Gcn4-Mediator Specificity Is Mediated by a Large and Dynamic Fuzzy Protein-Protein Complex

Directory of Open Access Journals (Sweden)

Lisa M. Tuttle

2018-03-01

Full Text Available Summary: Transcription activation domains (ADs are inherently disordered proteins that often target multiple coactivator complexes, but the specificity of these interactions is not understood. Efficient transcription activation by yeast Gcn4 requires its tandem ADs and four activator-binding domains (ABDs on its target, the Mediator subunit Med15. Multiple ABDs are a common feature of coactivator complexes. We find that the large Gcn4-Med15 complex is heterogeneous and contains nearly all possible AD-ABD interactions. Gcn4-Med15 forms via a dynamic fuzzy protein-protein interface, where ADs bind the ABDs in multiple orientations via hydrophobic regions that gain helicity. This combinatorial mechanism allows individual low-affinity and specificity interactions to generate a biologically functional, specific, and higher affinity complex despite lacking a defined protein-protein interface. This binding strategy is likely representative of many activators that target multiple coactivators, as it allows great flexibility in combinations of activators that can cooperate to regulate genes with variable coactivator requirements. : Tuttle et al. report a “fuzzy free-for-all” interaction mechanism that explains how seemingly unrelated transcription activators converge on a limited number of coactivator targets. The mechanism provides a rationale for the observation that individually weak and low-specificity interactions can combine to produce biologically critical function without requiring highly ordered structure. Keywords: transcription activation, intrinsically disordered proteins, fuzzy binding

Translation Initiation from Conserved Non-AUG Codons Provides Additional Layers of Regulation and Coding Capacity

Directory of Open Access Journals (Sweden)

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.

GCN2-Dependent Metabolic Stress Is Essential for Endotoxemic Cytokine Induction and Pathology

Science.gov (United States)

Liu, Haiyun; Huang, Lei; Bradley, Jillian; Liu, Kebin; Bardhan, Kankana; Ron, David; Mellor, Andrew L.; Munn, David H.

2014-01-01

Activated inflammatory macrophages can express indoleamine 2,3-dioxygenase (IDO) and thus actively deplete their own tryptophan supply; however, it is not clear how amino acid depletion influences macrophage behavior in inflammatory environments. In this report, we demonstrate that the stress response kinase GCN2 promotes macrophage inflammation and mortality in a mouse model of septicemia. In vitro, enzymatic amino acid consumption enhanced sensitivity of macrophages to the Toll-like receptor 4 (TLR4) ligand lipopolysaccharide (LPS) with significantly increased interleukin 6 (IL-6) production. Tryptophan withdrawal induced the stress response proteins ATF4 and CHOP/GADD153; however, LPS stimulation rapidly enhanced expression of both proteins. Moreover, LPS-driven cytokine production under amino acid-deficient conditions was dependent on GCN2, as GCN2 knockout (GCN2KO) macrophages had a significant reduction of cytokine gene expression after LPS stimulation. To test the in vivo relevance of these findings, monocytic-lineage-specific GCN2KO mice were challenged with a lethal dose of LPS intraperitoneally (i.p.). The GCN2KO mice showed reduced inflammatory responses, with decreased IL-6 and IL-12 expression correlating with significant reduction in animal mortality. Thus, the data show that amino acid depletion stress signals (via GCN2) synergize with proinflammatory signals to potently increase innate immune responsiveness. PMID:24248597

GCN5 Potentiates Glioma Proliferation and Invasion via STAT3 and AKT Signaling Pathways

Directory of Open Access Journals (Sweden)

Kun Liu

2015-09-01

Full Text Available The general control of nucleotide synthesis 5 (GCN5, which is one kind of lysine acetyltransferases, regulates a number of cellular processes, such as cell proliferation, differentiation, cell cycle and DNA damage repair. However, its biological role in human glioma development remains elusive. In the present study, we firstly reported that GCN5 was frequently overexpressed in human glioma tissues and GCN5 was positively correlated with proliferation of cell nuclear antigen PCNA and matrix metallopeptidase MMP9. Meanwhile, down-regulation of GCN5 by siRNA interfering inhibited glioma cell proliferation and invasion. In addition, GCN5 knockdown reduced expression of p-STAT3, p-AKT, PCNA and MMP9 and increased the expression of p21 in glioma cells. In conclusion, GCN5 exhibited critical roles in glioma development by regulating cell proliferation and invasion, which suggested that GCN5 might be a potential molecular target for glioma treatment.

Methods of NMR structure refinement: molecular dynamics simulations improve the agreement with measured NMR data of a C-terminal peptide of GCN4-p1

International Nuclear Information System (INIS)

Dolenc, Jozica; Missimer, John H.; Steinmetz, Michel O.; Gunsteren, Wilfred F. van

2010-01-01

The C-terminal trigger sequence is essential in the coiled-coil formation of GCN4-p1; its conformational properties are thus of importance for understanding this process at the atomic level. A solution NMR model structure of a peptide, GCN4p16-31, encompassing the GCN4-p1 trigger sequence was proposed a few years ago. Derived using a standard single-structure refinement protocol based on 172 nuclear Overhauser effect (NOE) distance restraints, 14 hydrogen-bond and 11 φ torsional-angle restraints, the resulting set of 20 NMR model structures exhibits regular α-helical structure. However, the set slightly violates some measured NOE bounds and does not reproduce all 15 measured 3 J(H N -H Cα )-coupling constants, indicating that different conformers of GCN4p16-31 might be present in solution. With the aim to resolve structures compatible with all NOE upper distance bounds and 3 J-coupling constants, we executed several structure refinement protocols employing unrestrained and restrained molecular dynamics (MD) simulations with two force fields. We find that only configurational ensembles obtained by applying simultaneously time-averaged NOE distance and 3 J-coupling constant restraining with either force field reproduce all the experimental data. Additionally, analyses of the simulated ensembles show that the conformational variability of GCN4p16-31 in solution admitted by the available set of 187 measured NMR data is larger than represented by the set of the NMR model structures. The conformations of GCN4p16-31 in solution differ in the orientation not only of the side-chains but also of the backbone. The inconsistencies between the NMR model structures and the measured NMR data are due to the neglect of averaging effects and the inclusion of hydrogen-bond and torsional-angle restraints that have little basis in the primary, i.e. measured NMR data.

Methods of NMR structure refinement: molecular dynamics simulations improve the agreement with measured NMR data of a C-terminal peptide of GCN4-p1.

Science.gov (United States)

Dolenc, Jozica; Missimer, John H; Steinmetz, Michel O; van Gunsteren, Wilfred F

2010-07-01

The C-terminal trigger sequence is essential in the coiled-coil formation of GCN4-p1; its conformational properties are thus of importance for understanding this process at the atomic level. A solution NMR model structure of a peptide, GCN4p16-31, encompassing the GCN4-p1 trigger sequence was proposed a few years ago. Derived using a standard single-structure refinement protocol based on 172 nuclear Overhauser effect (NOE) distance restraints, 14 hydrogen-bond and 11 phi torsional-angle restraints, the resulting set of 20 NMR model structures exhibits regular alpha-helical structure. However, the set slightly violates some measured NOE bounds and does not reproduce all 15 measured (3)J(H(N)-H(Calpha))-coupling constants, indicating that different conformers of GCN4p16-31 might be present in solution. With the aim to resolve structures compatible with all NOE upper distance bounds and (3)J-coupling constants, we executed several structure refinement protocols employing unrestrained and restrained molecular dynamics (MD) simulations with two force fields. We find that only configurational ensembles obtained by applying simultaneously time-averaged NOE distance and (3)J-coupling constant restraining with either force field reproduce all the experimental data. Additionally, analyses of the simulated ensembles show that the conformational variability of GCN4p16-31 in solution admitted by the available set of 187 measured NMR data is larger than represented by the set of the NMR model structures. The conformations of GCN4p16-31 in solution differ in the orientation not only of the side-chains but also of the backbone. The inconsistencies between the NMR model structures and the measured NMR data are due to the neglect of averaging effects and the inclusion of hydrogen-bond and torsional-angle restraints that have little basis in the primary, i.e. measured NMR data.

Subunits of ADA-two-A-containing (ATAC) or Spt-Ada-Gcn5-acetyltrasferase (SAGA) Coactivator Complexes Enhance the Acetyltransferase Activity of GCN5.

Science.gov (United States)

Riss, Anne; Scheer, Elisabeth; Joint, Mathilde; Trowitzsch, Simon; Berger, Imre; Tora, László

2015-11-27

Histone acetyl transferases (HATs) play a crucial role in eukaryotes by regulating chromatin architecture and locus specific transcription. GCN5 (KAT2A) is a member of the GNAT (Gcn5-related N-acetyltransferase) family of HATs. In metazoans this enzyme is found in two functionally distinct coactivator complexes, SAGA (Spt Ada Gcn5 acetyltransferase) and ATAC (Ada Two A-containing). These two multiprotein complexes comprise complex-specific and shared subunits, which are organized in functional modules. The HAT module of ATAC is composed of GCN5, ADA2a, ADA3, and SGF29, whereas in the SAGA HAT module ADA2b is present instead of ADA2a. To better understand how the activity of human (h) hGCN5 is regulated in the two related, but different, HAT complexes we carried out in vitro HAT assays. We compared the activity of hGCN5 alone with its activity when it was part of purified recombinant hATAC or hSAGA HAT modules or endogenous hATAC or hSAGA complexes using histone tail peptides and full-length histones as substrates. We demonstrated that the subunit environment of the HAT complexes into which GCN5 incorporates determines the enhancement of GCN5 activity. On histone peptides we show that all the tested GCN5-containing complexes acetylate mainly histone H3K14. Our results suggest a stronger influence of ADA2b as compared with ADA2a on the activity of GCN5. However, the lysine acetylation specificity of GCN5 on histone tails or full-length histones was not changed when incorporated in the HAT modules of ATAC or SAGA complexes. Our results thus demonstrate that the catalytic activity of GCN5 is stimulated by subunits of the ADA2a- or ADA2b-containing HAT modules and is further increased by incorporation of the distinct HAT modules in the ATAC or SAGA holo-complexes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Protein acetylation sites mediated by Schistosoma mansoni GCN5

International Nuclear Information System (INIS)

Moraes Maciel, Renata de; Furtado Madeiro da Costa, Rodrigo; Meirelles Bastosde Oliveira, Francisco; Rumjanek, Franklin David; Fantappie, Marcelo Rosado

2008-01-01

The transcriptional co-activator GCN5, a histone acetyltransferase (HAT), is part of large multimeric complexes that are required for chromatin remodeling and transcription activation. As in other eukaryotes, the DNA from the parasite Schistosome mansoni is organized into nucleosomes and the genome encodes components of chromatin-remodeling complexes. Using a series of synthetic peptides we determined that Lys-14 of histone H3 was acetylated by the recombinant SmGCN5-HAT domain. SmGCN5 was also able to acetylate schistosome non-histone proteins, such as the nuclear receptors SmRXR1 and SmNR1, and the co-activator SmNCoA-62. Electron microscopy revealed the presence of SmGCN5 protein in the nuclei of vitelline cells. Within the nucleus, SmGCN5 was found to be located in interchromatin granule clusters (IGCs), which are transcriptionally active structures. The data suggest that SmGCN5 is involved in transcription activation

Two-dimensional porous architecture of protonated GCN and reduced graphene oxide via electrostatic self-assembly strategy for high photocatalytic hydrogen evolution under visible light

Energy Technology Data Exchange (ETDEWEB)

Pu, Chenchen; Wan, Jun; Liu, Enzhou; Yin, Yunchao; Li, Juan; Ma, Yongning [School of Chemical Engineering, Northwest University, Xi’an 710069 (China); Fan, Jun, E-mail: fanjun@nwu.edu.cn [School of Chemical Engineering, Northwest University, Xi’an 710069 (China); Hu, Xiaoyun, E-mail: hxy3275@nwu.edu.cn [School of Physics, Northwest University, Xi’an 710069 (China)

2017-03-31

Highlights: • The protonated GCN (pGCN) is prepared by acidic cutting and hydrothermal process. • The pGCN coupled with rGO are synthesized via electrostatic self-assembly strategy. • The pGCN-5 wt% rGO is obtained with a high specific surface area of 115.64 m{sup 2}g{sup −1}. • The pGCN-5 wt% rGO photocatalysts exhibit superb photocatalytic reduction capacity. - Abstract: Herein, porous protonated graphitic carbon nitride (pGCN) is prepared from bulk g-C{sub 3}N{sub 4} (GCN) directly by acidic cutting and hydrothermal process. The holey structure not only provides a lot of bounds on the accelerated and photo induced charge transfer and thus reduce the aggregation, but also endows the GCN with more exposure to the active site. The pGCN is obtained with an increased band gap of 2.91 eV together with a higher specific surface area of 82.76 m{sup 2}g{sup −1}. Meanwhile, the positively charged GCN resulted from the protonation pretreatment is beneficial for improving the interaction with negatively charged GO sheets. Compared with GCN, pGCN-rGO displays a significant decrease of PL intensities and an apparently enhancement of visible-light absorption, resulting a lower charge recombination rate and a better light absorption. Besides, the enhanced charge separation is demonstrated by photoluminescence emission spectroscopy and the transient photocurrent measurement. The photocatalytic performance studies for the degradation of MB indicate that pGCN-rGO exhibits the highest adsorption ability towards dye molecules. In addition, the pGCN-5 wt% rGO composite shows the optimal photocatalytic activity, the photodegradation rate of MB is 99.4% after 80 min of irradiation and the H{sub 2} evolution performance up to 557 μmol g{sup −1}h{sup −1} under visible light, which is much higher than the other control samples.

Methods of NMR structure refinement: molecular dynamics simulations improve the agreement with measured NMR data of a C-terminal peptide of GCN4-p1

Energy Technology Data Exchange (ETDEWEB)

Dolenc, Jozica [Swiss Federal Institute of Technology, Laboratory of Physical Chemistry, ETH (Switzerland); Missimer, John H.; Steinmetz, Michel O. [Paul Scherrer Institut, Biomolecular Research (Switzerland); Gunsteren, Wilfred F. van, E-mail: wfvgn@igc.phys.chem.ethz.c [Swiss Federal Institute of Technology, Laboratory of Physical Chemistry, ETH (Switzerland)

2010-07-15

The C-terminal trigger sequence is essential in the coiled-coil formation of GCN4-p1; its conformational properties are thus of importance for understanding this process at the atomic level. A solution NMR model structure of a peptide, GCN4p16-31, encompassing the GCN4-p1 trigger sequence was proposed a few years ago. Derived using a standard single-structure refinement protocol based on 172 nuclear Overhauser effect (NOE) distance restraints, 14 hydrogen-bond and 11 {phi} torsional-angle restraints, the resulting set of 20 NMR model structures exhibits regular {alpha}-helical structure. However, the set slightly violates some measured NOE bounds and does not reproduce all 15 measured {sup 3}J(H{sub N}-H{sub C{alpha}})-coupling constants, indicating that different conformers of GCN4p16-31 might be present in solution. With the aim to resolve structures compatible with all NOE upper distance bounds and {sup 3}J-coupling constants, we executed several structure refinement protocols employing unrestrained and restrained molecular dynamics (MD) simulations with two force fields. We find that only configurational ensembles obtained by applying simultaneously time-averaged NOE distance and {sup 3}J-coupling constant restraining with either force field reproduce all the experimental data. Additionally, analyses of the simulated ensembles show that the conformational variability of GCN4p16-31 in solution admitted by the available set of 187 measured NMR data is larger than represented by the set of the NMR model structures. The conformations of GCN4p16-31 in solution differ in the orientation not only of the side-chains but also of the backbone. The inconsistencies between the NMR model structures and the measured NMR data are due to the neglect of averaging effects and the inclusion of hydrogen-bond and torsional-angle restraints that have little basis in the primary, i.e. measured NMR data.

Exploring the trigger sequence of the GCN4 coiled-coil: Biased molecular dynamics resolves apparent inconsistencies in NMR measurements

Science.gov (United States)

Missimer, John H; Dolenc, Jožica; Steinmetz, Michel O; van Gunsteren, Wilfred F

2010-01-01

Trigger sequences are indispensable elements for coiled-coil formation. The monomeric helical trigger sequence of the yeast transcriptional activator GCN4 has been investigated recently using several solution NMR observables including nuclear Overhauser enhancement (NOE) intensities and 3J(HN,HCα)-coupling constants, and a set of 20 model structures was proposed. Constrained to satisfy the NOE-derived distance bounds, the NMR model structures do not appear to reproduce all the measured 3J(HN-HCα)-coupling constant values, indicating that the α-helical propensity is not uniform along the GCN4 trigger sequence. A recent methodological study of unrestrained and restrained molecular dynamics (MD) simulations of the GCN4 trigger sequence in solution showed that only MD simulations incorporating time-averaged NOE distance restraints and instantaneous or local-elevation 3J-coupling restraints could satisfy the entire set of the experimental data. In this report, we assess by means of cluster analyses the model structures characteristic of the two simulations that are compatible with the measured data and compare them with the proposed 20 NMR model structures. Striking characteristics of the MD model structures are the variability of the simulated configurations and the indication of entropic stability mediated by the aromatic N-terminal residues 17Tyr and 18His, which are absent in the set of NMR model structures. PMID:20954244

GCN5 regulates the activation of PI3K/Akt survival pathway in B cells exposed to oxidative stress via controlling gene expressions of Syk and Btk.

Science.gov (United States)

Kikuchi, Hidehiko; Kuribayashi, Futoshi; Takami, Yasunari; Imajoh-Ohmi, Shinobu; Nakayama, Tatsuo

2011-02-25

Histone acetyltransferase(s) (HATs) are involved in the acetylation of core histones, which is an important event for transcription regulation through alterations in the chromatin structure in eukaryotes. General control non-depressible 5 (GCN5) was first identified as a global coactivator and transcription-related HAT. Here we report that GCN5 regulates the activation of phosphatidylinositol 3-kinase (PI3K)/acutely transforming retrovirus AKT8 in rodent T cell lymphoma (Akt) survival pathway in B cells exposed to oxidative stress via controlling gene expressions of spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (Btk). The GCN5-deficiency remarkably caused apoptotic cell death by treatment with exogenous hydrogen peroxide (H(2)O(2)) in chicken DT40 cells. In GCN5-deficient DT40 cells, gene expressions of Syk and Btk, which are involved in activation of PI3K/Akt survival pathway in DT40 cells exposed to exogenous H(2)O(2), were remarkably decreased compared with those in wild type DT40 cells. In addition, phosphorylation of Akt in H(2)O(2)-treated GCN5-deficient cells was remarkably suppressed as compared to that of DT40. Chromatin immunoprecipitation assay revealed that GCN5 binds to proximal 5'-upstream regions of Syk and Btk genes in vivo. These results suggest that GCN5 takes part in transcriptional regulations of the Syk and Btk genes, and plays a key role in epigenetic regulation of PI3K/Akt survival pathway in B cells exposed to reactive oxygen species such as H(2)O(2). Copyright © 2011 Elsevier Inc. All rights reserved.

GCN5 Regulates FGF Signaling and Activates Selective MYC Target Genes during Early Embryoid Body Differentiation

Directory of Open Access Journals (Sweden)

Li Wang

2018-01-01

Full Text Available Precise control of gene expression during development is orchestrated by transcription factors and co-regulators including chromatin modifiers. How particular chromatin-modifying enzymes affect specific developmental processes is not well defined. Here, we report that GCN5, a histone acetyltransferase essential for embryonic development, is required for proper expression of multiple genes encoding components of the fibroblast growth factor (FGF signaling pathway in early embryoid bodies (EBs. Gcn5−/− EBs display deficient activation of ERK and p38, mislocalization of cytoskeletal components, and compromised capacity to differentiate toward mesodermal lineage. Genomic analyses identified seven genes as putative direct targets of GCN5 during early differentiation, four of which are cMYC targets. These findings established a link between GCN5 and the FGF signaling pathway and highlighted specific GCN5-MYC partnerships in gene regulation during early differentiation.

Update of the Large-scale Concentration Maps for the Netherlands (GCN); De aangepaste GCN

Energy Technology Data Exchange (ETDEWEB)

Van den Elshout, S.; Molenaar, R. [DCMR Milieudienst Rijnmond, Rotterdam (Netherlands)

2011-04-15

Every year the RIVM and PBL publish the so-called Large-scale concentration maps of the Netherlands (GCN maps). These maps offer an approximation of the background concentrations of several air-polluting substances. Sometimes these maps need to be updated to realize a better approximation of the background concentrations. [Dutch] Jaarlijks publiceren het RIVM en het PBL de zogenoemde Grootschalige Concentratiekaarten van Nederland (GCN-kaarten). Deze kaarten geven een benadering van de achtergrondconcentraties van enkele luchtvervuilende stoffen. Soms is het nodig de kaarten aan te passen om tot een betere benadering van de achtergrondconcentratie te komen.

Diversification of the Histone Acetyltransferase GCN5 through Alternative Splicing in Brachypodium distachyon

Directory of Open Access Journals (Sweden)

Alexandre Martel

2017-12-01

Full Text Available The epigenetic modulatory SAGA complex is involved in various developmental and stress responsive pathways in plants. Alternative transcripts of the SAGA complex's enzymatic subunit GCN5 have been identified in Brachypodium distachyon. These splice variants differ based on the presence and integrity of their conserved domain sequences: the histone acetyltransferase domain, responsible for catalytic activity, and the bromodomain, involved in acetyl-lysine binding and genomic loci targeting. GCN5 is the wild-type transcript, while alternative splice sites result in the following transcriptional variants: L-GCN5, which is missing the bromodomain and S-GCN5, which lacks the bromodomain as well as certain motifs of the histone acetyltransferase domain. Absolute mRNA quantification revealed that, across eight B. distachyon accessions, GCN5 was the dominant transcript isoform, accounting for up to 90% of the entire transcript pool, followed by L-GCN5 and S-GCN5. A cycloheximide treatment further revealed that the S-GCN5 splice variant was degraded through the nonsense-mediated decay pathway. All alternative BdGCN5 transcripts displayed similar transcript profiles, being induced during early exposure to heat and displaying higher levels of accumulation in the crown, compared to aerial tissues. All predicted protein isoforms localize to the nucleus, which lends weight to their purported epigenetic functions. S-GCN5 was incapable of forming an in vivo protein interaction with ADA2, the transcriptional adaptor that links the histone acetyltransferase subunit to the SAGA complex, while both GCN5 and L-GCN5 interacted with ADA2, which suggests that a complete histone acetyltransferase domain is required for BdGCN5-BdADA2 interaction in vivo. Thus, there has been a diversification in BdGCN5 through alternative splicing that has resulted in differences in conserved domain composition, transcript fate and in vivo protein interaction partners. Furthermore, our

GCN2 in the Brain Programs PPARγ2 and Triglyceride Storage in the Liver during Perinatal Development in Response to Maternal Dietary Fat

Science.gov (United States)

Xu, Xu; Hu, Jingjie; McGrath, Barbara C.; Cavener, Douglas R.

2013-01-01

The liver plays a central role in regulating lipid metabolism and facilitates efficient lipid utilization and storage. We discovered that a modest increase in maternal dietary fat in mice programs triglyceride storage in the liver of their developing offspring. The activation of this programming is not apparent, however, until several months later at the adult stage. We found that the perinatal programming of adult hepatic triglyceride storage was controlled by the eIF2α kinase GCN2 (EIF2AK4) in the brain of the offspring, which stimulates epigenetic modification of the Pparγ2 gene in the neonatal liver. Genetic ablation of Gcn2 in the offspring exhibited reduced hepatic triglyceride storage and repressed expression of the peroxisome proliferator-activated receptor gamma 2 (Pparγ2) and two lipid droplet protein genes, Fsp27 and Cidea. Brain-specific, but not liver-specific, Gcn2 KO mice exhibit these same defects demonstrating that GCN2 in the developing brain programs hepatic triglyceride storage. GCN2 and nutrition-dependent programming of Pparγ2 is correlated with trimethylation of lysine 4 of histone 3 (H3K4me3) in the Pparγ2 promoter region during neonatal development. In addition to regulating hepatic triglyceride in response to modest changes in dietary fat, Gcn2 deficiency profoundly impacts the severity of the obese-diabetic phenotype of the leptin receptor mutant (db/db) mouse, by reducing hepatic steatosis and obesity but exacerbating the diabetic phenotype. We suggest that GCN2-dependent perinatal programming of hepatic triglyceride storage is an adaptation to couple early nutrition to anticipated needs for hepatic triglyceride storage in adults. However, increasing the hepatic triglyceride set point during perinatal development may predispose individuals to hepatosteatosis, while reducing circulating fatty acid levels that promote insulin resistance. PMID:24130751

The GRB coordinates network (GCN): A status report

International Nuclear Information System (INIS)

Barthelmy, S. D.; Takeshima, T.; Butterworth, P.; Cline, T. L.; Gehrels, N.; Marshall, F.; Connaughton, V.; Kippen, R. M.; Kouveliotou, C.; Robinson, C. R.

1998-01-01

A review of the GRB Coordinates Network (GCN) will be given. The GCN has recently replaced the BATSE Coordinates Distribution Network (BACODINE), maintaining all of BACODINE's original capabilities and services, but also providing new sources of GRB location information. These are: (1) source locations using the MSFC LOCBURST algorithm, (2) the Rossi-XTE detections (PCA and ASM), (3) the Interplanetary Network (IPN) locations, and (4) CGRO-COMPTEL locations. These new sources of locations are available for distribution in the minutes-to-hours-to-days time delay ranges, and they also have increasingly and significantly reduced error boxes, thus providing a broad range of time delays and error box sizes to fit within the observing capabilities of a broad range of follow-up instruments in the radio, optical, and TeV gamma-ray bands. Extreme-UV transients from ALEXIS are also now distributed. For all sources of location information, all the distribution methods are available (Internet Socket, E-mail, Alpha-numeric and Numeric Pagers, and Phone/modem) and several filters. Sites can choose which sources to receive and what filters to be applied. The GCN web site has been expanded to include a globally inclusive table of locations, light-curves, and fluence information which is automatically updated in real-time

N-Myc and GCN5 regulate significantly overlapping transcriptional programs in neural stem cells.

Directory of Open Access Journals (Sweden)

Verónica Martínez-Cerdeño

Full Text Available Here we examine the functions of the Myc cofactor and histone acetyltransferase, GCN5/KAT2A, in neural stem and precursor cells (NSC using a conditional knockout approach driven by nestin-cre. Mice with GCN5-deficient NSC exhibit a 25% reduction in brain mass with a microcephaly phenotype similar to that observed in nestin-cre driven knockouts of c- or N-myc. In addition, the loss of GCN5 inhibits precursor cell proliferation and reduces their populations in vivo, as does loss of N-myc. Gene expression analysis indicates that about one-sixth of genes whose expression is affected by loss of GCN5 are also affected in the same manner by loss of N-myc. These findings strongly support the notion that GCN5 protein is a key N-Myc transcriptional cofactor in NSC, but are also consistent with recruitment of GCN5 by other transcription factors and the use by N-Myc of other histone acetyltransferases. Putative N-Myc/GCN5 coregulated transcriptional pathways include cell metabolism, cell cycle, chromatin, and neuron projection morphogenesis genes. GCN5 is also required for maintenance of histone acetylation both at its putative specific target genes and at Myc targets. Thus, we have defined an important role for GCN5 in NSC and provided evidence that GCN5 is an important Myc transcriptional cofactor in vivo.

Gcn4p and the Crabtree effect of yeast: drawing the causal model of the Crabtree effect in Saccharomyces cerevisiae and explaining evolutionary trade-offs of adaptation to galactose through systems biology.

Science.gov (United States)

Martínez, José L; Bordel, Sergio; Hong, KuFk-Ki; Nielsen, Jens

2014-06-01

By performing an integrated comparative analysis on the physiology and transcriptome of four different S. cerevisiae strains growing on galactose and glucose, it was inferred that the transcription factors Bas1p, Pho2p, and Gcn4p play a central role in the regulatory events causing the Crabtree effect in S. cerevisiae. The analysis also revealed that a point mutation in the RAS2 observed in a galactose-adapted strain causes a lower Crabtree effect and growth rate on glucose by decreasing the activity of Gcn4p while at the same time is at the origin of higher growth rate on galactose due to a lower activity of the transcriptional repressor Sok2p. The role of Gcn4p on the trade-off effect observed on glucose was confirmed experimentally. This was done by showing that the point mutation in RAS2 does not result in a lower growth rate on glucose if it is introduced in a GCN4-negative background. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

In-depth analysis of cis-determinants that either promote or inhibit reinitiation on GCN4 mRNA after translation of its four short uORFs

Czech Academy of Sciences Publication Activity Database

Gunišová, Stanislava; Beznosková, Petra; Mohammad, Mahabub Pasha; Vlčková, Vladislava; Valášek, Leoš Shivaya

2016-01-01

Roč. 22, č. 4 (2016), s. 542-558 ISSN 1355-8382 R&D Projects: GA ČR(CZ) GAP305/11/0172 Institutional support: RVO:61388971 Keywords : translational control * reinitiation * uORF Subject RIV: CE - Biochemistry Impact factor: 4.605, year: 2016

Programmed cell death 4 protein (Pdcd4) and homeodomain-interacting protein kinase 2 (Hipk2) antagonistically control translation of Hipk2 mRNA.

Science.gov (United States)

Ohnheiser, Johanna; Ferlemann, Eva; Haas, Astrid; Müller, Jan P; Werwein, Eugen; Fehler, Olesja; Biyanee, Abhiruchi; Klempnauer, Karl-Heinz

2015-07-01

The tumor suppressor protein programmed cell death 4 (Pdcd4) is a highly conserved RNA-binding protein that inhibits the translation of specific mRNAs. Here, we have identified the homeobox-interacting protein kinase-2 (Hipk2) mRNA as a novel translational target of Pdcd4. Unlike most other protein kinases Hipk2 is constitutively active after being synthesized by the ribosome and its expression and activity are thought to be mainly controlled by modulation of the half-life of the kinase. Our work provides the first evidence that Hipk2 expression is also controlled on the level of translation. We show that Hipk2 stimulates the translation of its own mRNA and that Pdcd4 suppresses the translation of Hipk2 mRNA by interfering with this auto-regulatory feedback mechanism. We also show that the translation of the related kinase Hipk1 is controlled by a similar feedback loop and that Hipk2 also stimulates the translation of Hipk1 mRNA. Taken together, our work describes a novel mechanism of translational suppression by Pdcd4 and shows for the first time that Hipk2 controls its own synthesis by an auto-regulatory feedback mechanism. Furthermore, the effect of Hipk2 on the translation of Hipk1 RNA suggests that Hipk2 and Pdcd4 can act in similar manner to control the translation of other mRNAs. Copyright © 2015 Elsevier B.V. All rights reserved.

Swift Data Products in GCN

Science.gov (United States)

Barthelmy, Scott D.

2006-09-01

The Swift mission produces a much larger range of data products for the GRB Coordinates Distribution (GCN) system than any previous mission. Beyond the normal position-containing notices, the extra products are lightcurves, spectra, and images. We will present examples of these new data products and how they can be used to guide GRB follow-up observation campaigns.

Lysine acetyltransferase GCN5b interacts with AP2 factors and is required for Toxoplasma gondii proliferation.

Directory of Open Access Journals (Sweden)

Jiachen Wang

2014-01-01

Full Text Available Histone acetylation has been linked to developmental changes in gene expression and is a validated drug target of apicomplexan parasites, but little is known about the roles of individual histone modifying enzymes and how they are recruited to target genes. The protozoan parasite Toxoplasma gondii (phylum Apicomplexa is unusual among invertebrates in possessing two GCN5-family lysine acetyltransferases (KATs. While GCN5a is required for gene expression in response to alkaline stress, this KAT is dispensable for parasite proliferation in normal culture conditions. In contrast, GCN5b cannot be disrupted, suggesting it is essential for Toxoplasma viability. To further explore the function of GCN5b, we generated clonal parasites expressing an inducible HA-tagged dominant-negative form of GCN5b containing a point mutation that ablates enzymatic activity (E703G. Stabilization of this dominant-negative GCN5b was mediated through ligand-binding to a destabilization domain (dd fused to the protein. Induced accumulation of the ddHAGCN5b(E703G protein led to a rapid arrest in parasite replication. Growth arrest was accompanied by a decrease in histone H3 acetylation at specific lysine residues as well as reduced expression of GCN5b target genes in GCN5b(E703G parasites, which were identified using chromatin immunoprecipitation coupled with microarray hybridization (ChIP-chip. Proteomics studies revealed that GCN5b interacts with AP2-domain proteins, apicomplexan plant-like transcription factors, as well as a "core complex" that includes the co-activator ADA2-A, TFIID subunits, LEO1 polymerase-associated factor (Paf1 subunit, and RRM proteins. The dominant-negative phenotype of ddHAGCN5b(E703G parasites, considered with the proteomics and ChIP-chip data, indicate that GCN5b plays a central role in transcriptional and chromatin remodeling complexes. We conclude that GCN5b has a non-redundant and indispensable role in regulating gene expression required

IL-1β-specific recruitment of GCN5 histone acetyltransferase induces the release of PAF1 from chromatin for the de-repression of inflammatory response genes.

Science.gov (United States)

Kim, Nari; Sun, Hwa-Young; Youn, Min-Young; Yoo, Joo-Yeon

2013-04-01

To determine the functional specificity of inflammation, it is critical to orchestrate the timely activation and repression of inflammatory responses. Here, we explored the PAF1 (RNA polymerase II associated factor)-mediated signal- and locus-specific repression of genes induced through the pro-inflammatory cytokine interleukin (IL)-1β. Using microarray analysis, we identified the PAF1 target genes whose expression was further enhanced by PAF1 knockdown in IL-1β-stimulated HepG2 hepatocarcinomas. PAF1 bound near the transcription start sites of target genes and dissociated on stimulation. In PAF1-deficient cells, more elongating RNA polymerase II and acetylated histones were observed, although IL-1β-mediated activation and recruitment of nuclear factor κB (NF-κB) were not altered. Under basal conditions, PAF1 blocked histone acetyltransferase general control non-depressible 5 (GCN5)-mediated acetylation on H3K9 and H4K5 residues. On IL-1β stimulation, activated GCN5 discharged PAF1 from chromatin, allowing productive transcription to occur. PAF1 bound to histones but not to acetylated histones, and the chromatin-binding domain of PAF1 was essential for target gene repression. Moreover, IL-1β-induced cell migration was similarly controlled through counteraction between PAF1 and GCN5. These results suggest that the IL-1β signal-specific exchange of PAF1 and GCN5 on the target locus limits inappropriate gene induction and facilitates the timely activation of inflammatory responses.

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.

Nuclear Magnetic Resonance Structures of GCN4p Are Largely Conserved When Ion Pairs Are Disrupted at Acidic pH but Show a Relaxation of the Coiled Coil Superhelix.

Science.gov (United States)

Kaplan, Anne R; Brady, Megan R; Maciejewski, Mark W; Kammerer, Richard A; Alexandrescu, Andrei T

2017-03-21

To understand the roles ion pairs play in stabilizing coiled coils, we determined nuclear magnetic resonance structures of GCN4p at three pH values. At pH 6.6, all acidic residues are fully charged; at pH 4.4, they are half-charged, and at pH 1.5, they are protonated and uncharged. The α-helix monomer and coiled coil structures of GCN4p are largely conserved, except for a loosening of the coiled coil quaternary structure with a decrease in pH. Differences going from neutral to acidic pH include (i) an unwinding of the coiled coil superhelix caused by the loss of interchain ion pair contacts, (ii) a small increase in the separation of the monomers in the dimer, (iii) a loosening of the knobs-into-holes packing motifs, and (iv) an increased separation between oppositely charged residues that participate in ion pairs at neutral pH. Chemical shifts (HN, N, C', Cα, and Cβ) of GCN4p display a seven-residue periodicity that is consistent with α-helical structure and is invariant with pH. By contrast, periodicity in hydrogen exchange rates at neutral pH is lost at acidic pH as the exchange mechanism moves into the EX1 regime. On the basis of 1 H- 15 N nuclear Overhauser effect relaxation measurements, the α-helix monomers experience only small increases in picosecond to nanosecond backbone dynamics at acidic pH. By contrast, 13 C rotating frame T 1 relaxation (T 1ρ ) data evince an increase in picosecond to nanosecond side-chain dynamics at lower pH, particularly for residues that stabilize the coiled coil dimerization interface through ion pairs. The results on the structure and dynamics of GCNp4 over a range of pH values help rationalize why a single structure at neutral pH poorly predicts the pH dependence of the unfolding stability of the coiled coil.

Mitochondrial dysfunction enhances cisplatin resistance in human gastric cancer cells via the ROS-activated GCN2-eIF2α-ATF4-xCT pathway.

Science.gov (United States)

Wang, Sheng-Fan; Chen, Meng-Shian; Chou, Yueh-Ching; Ueng, Yune-Fang; Yin, Pen-Hui; Yeh, Tien-Shun; Lee, Hsin-Chen

2016-11-08

Mitochondrial DNA mutations and defects in mitochondrial enzymes have been identified in gastric cancers, and they might contribute to cancer progression. In previous studies, mitochondrial dysfunction was induced by oligomycin-enhanced chemoresistance to cisplatin. Herein, we dissected the regulatory mechanism for mitochondrial dysfunction-enhanced cisplatin resistance in human gastric cancer cells. Repeated cisplatin treatment-induced cisplatin-resistant cells exhibited high SLC7A11 (xCT) expression, and xCT inhibitors (sulfasalazine or erastin), xCT siRNA, or a GSH synthesis inhibitor (buthionine sulphoximine, BSO) could sensitize these cells to cisplatin. Clinically, the high expression of xCT was associated with a poorer prognosis for gastric cancer patients under adjuvant chemotherapy. Moreover, we found that mitochondrial dysfunction enhanced cisplatin resistance and up-regulated xCT expression, as well as intracellular glutathione (GSH). The xCT inhibitors, siRNA against xCT or BSO decreased mitochondrial dysfunction-enhanced cisplatin resistance. We further demonstrated that the upregulation of the eIF2α-ATF4 pathway contributed to mitochondrial dysfunction-induced xCT expression, and activated eIF2α kinase GCN2, but not PERK, stimulated the eIF2α-ATF4-xCT pathway in response to mitochondrial dysfunction-increased reactive oxygen species (ROS) levels. In conclusion, our results suggested that the ROS-activated GCN2-eIF2α-ATF4-xCT pathway might contribute to mitochondrial dysfunction-enhanced cisplatin resistance and could be a potential target for gastric cancer therapy.

SAGA complex and Gcn5 are necessary for respiration in budding yeast.

Science.gov (United States)

Canzonetta, Claudia; Leo, Manuela; Guarino, Salvatore Rocco; Montanari, Arianna; Francisci, Silvia; Filetici, Patrizia

2016-12-01

In budding yeast, growth through fermentation and/or respiration is dependent on the type of carbon source present in the medium. SAGA complex is the main acetylation complex and is required, together with Rtg factors, for nucleus-mitochondria communication and transcriptional activation of specific nuclear genes. Even though acetylation is necessary for mitochondria activity and respiratory pathways the direct role of histone acetyltransferases and SAGA complex has never been investigated directly. In this study we demonstrate, for the first time, that Gcn5 and SAGA are needed for respiratory metabolism and oxygen consumption. According to a central role for acetylation in respiration we find that the Gcn5 inhibitor CPTH2 had higher efficacy on cells grown in glycerol containing media. We also demonstrated that the opposing activities of Gcn5 and Hda1 modify selectively H3-AcK18 and are essential for respiration. Taken together our results suggest a novel paradigm coupling acetyltransferase activity to respiratory metabolism. Correspondingly we propose the selective utilization of KAT inhibitor CPTH2, combined to the modulation of the respiratory metabolism of the cell, as a promising novel tool of intervention in cancer cells. Copyright © 2016 Elsevier B.V. All rights reserved.

The histone acetyltransferase PsGcn5 mediates oxidative stress responses and is required for full virulence of Phytophthora sojae.

Science.gov (United States)

Zhao, Wei; Wang, Tao; Liu, Shusen; Chen, Qingqing; Qi, Rende

2015-10-01

In eukaryotic organisms, histone acetyltransferase complexes are coactivators that are important for transcriptional activation by modifying chromatin. In this study, a gene (PsGcn5) from Phytophthora sojae encoding a histone acetyltransferase was identified as a homolog of one component of the histone acetyltransferase complex from yeasts to mammals. PsGcn5 was constitutively expressed in each stage tested, but had a slightly higher expression in sporulating hyphae and 3 h after infection. PsGcn5-silenced mutants were generated using polyethylene glycol-mediated protoplast stable transformation. These mutants had normal development, but compared to wild type strains they had higher sensitivity to hydrogen peroxide (H2O2) and significantly reduced virulence in soybean. Diaminobenzidine staining revealed an accumulation of H2O2 around the infection sites of PsGcn5-silenced mutants but not for wild type strains. Inhibition of the plant NADPH oxidase by diphenyleneiodonium prevented host-derived H2O2 accumulation in soybean cells and restored infectious hyphal growth of the mutants. Thus, we concluded that PsGcn5 is important for growth under conditions of oxidative stress and contributes to the full virulence of P. sojae by suppressing the host-derived reactive oxygen species. Copyright © 2015 Elsevier Ltd. All rights reserved.

An investigation of nutrient-dependent mRNA translation in Drosophila larvae

Directory of Open Access Journals (Sweden)

Sabarish Nagarajan

2014-10-01

Full Text Available The larval period of the Drosophila life cycle is characterized by immense growth. In nutrient rich conditions, larvae increase in mass approximately two hundred-fold in five days. However, upon nutrient deprivation, growth is arrested. The prevailing view is that dietary amino acids drive this larval growth by activating the conserved insulin/PI3 kinase and Target of rapamycin (TOR pathways and promoting anabolic metabolism. One key anabolic process is protein synthesis. However, few studies have attempted to measure mRNA translation during larval development or examine the signaling requirements for nutrient-dependent regulation. Our work addresses this issue. Using polysome analyses, we observed that starvation rapidly (within thirty minutes decreased larval mRNA translation, with a maximal decrease at 6–18 hours. By analyzing individual genes, we observed that nutrient-deprivation led to a general reduction in mRNA translation, regardless of any starvation-mediated changes (increase or decrease in total transcript levels. Although sugars and amino acids are key regulators of translation in animal cells and are the major macronutrients in the larval diet, we found that they alone were not sufficient to maintain mRNA translation in larvae. The insulin/PI3 kinase and TOR pathways are widely proposed as the main link between nutrients and mRNA translation in animal cells. However, we found that genetic activation of PI3K and TOR signaling, or regulation of two effectors – 4EBP and S6K – could not prevent the starvation-mediated translation inhibition. Similarly, we showed that the nutrient stress-activated eIF2α kinases, GCN2 and PERK, were not required for starvation-induced inhibition of translation in larvae. These findings indicate that nutrient control of mRNA translation in larvae is more complex than simply amino acid activation of insulin and TOR signaling.

Epidermal Growth Factor Receptor (EGFR) gene copy number (GCN) correlates with clinical activity of irinotecan-cetuximab in K-RAS wild-type colorectal cancer: a fluorescence in situ (FISH) and chromogenic in situ hybridization (CISH) analysis

International Nuclear Information System (INIS)

Scartozzi, Mario; Galizia, Eva; Berardi, Rossana; Biscotti, Tommasina; Labianca, Roberto; Masi, Gianluca; Falcone, Alfredo; Cascinu, Stefano; Bearzi, Italo; Mandolesi, Alessandra; Pierantoni, Chiara; Loupakis, Fotios; Zaniboni, Alberto; Negri, Francesca; Quadri, Antonello; Zorzi, Fausto

2009-01-01

K-RAS wild type colorectal tumors show an improved response rate to anti-EGFR monoclonal antibodies. Nevertheless 70% to 40% of these patients still does not seem to benefit from this therapeutic approach. FISH EGFR GCN has been previously demonstrated to correlate with clinical outcome of colorectal cancer treated with anti-EGFR monoclonal antibodies. CISH also seemed able to provide accurate EGFR GCN information with the advantage of a simpler and reproducible technique involving immunohistochemistry and light microscopy. Based on these findings we investigated the correlation between both FISH and CISH EGFR GCN and clinical outcome in K-RAS wild-type colorectal cancer treated with irinotecan-cetuximab. Patients with advanced K-RAS wild-type, colorectal cancer receiving irinotecan-cetuximab after failure of irinotecan-based chemotherapy were eligible. A cut-off value for EGFR GCN of 2.6 and 2.12 for FISH and CISH respectively was derived from ROC curve analysis. Forty-four patients were available for analysis. We observed a partial remission in 9 (60%) and 2 (9%) cases with a FISH EGFR GCN ≥ 2.6 and < 2.6 respectively (p = 0.002) and in 10 (36%) and 1 (6%) cases with a CISH EGFR GCN ≥ 2.12 and < 2.12 respectively (p = 0.03). Median TTP was 7.7 and 6.4 months in patients showing increased FISH and CISH EGFR GCN whereas it was 2.9 and 3.1 months in those with low FISH and CISH EGFR GCN (p = 0.04 and 0.02 respectively). FISH and CISH EGFR GCN may both represent effective tools for a further patients selection in K-RAS wild-type colorectal cancer treated with cetuximab

Functional Characterization of the Role of the N-terminal Domain of the c/Nip1 Subunit of Eukaryotic Initiation Factor 3 (eIF3) in AUG Recognition

Czech Academy of Sciences Publication Activity Database

Karásková, Martina; Gunišová, Stanislava; Herrmannová, Anna; Wagner, Susan; Munzarová, Vanda; Valášek, Leoš Shivaya

2012-01-01

Roč. 287, č. 34 (2012), s. 28420-28434 ISSN 0021-9258 R&D Projects: GA ČR GAP305/10/0335 Institutional support: RVO:61388971 Keywords : START CODON SELECTION * 40S RIBOSOMAL-SUBUNIT * GCN4 TRANSLATIONAL CONTROL Subject RIV: CE - Biochemistry Impact factor: 4.651, year: 2012

Update of the Large-scale Concentration Maps for the Netherlands (GCN)

International Nuclear Information System (INIS)

Van den Elshout, S.; Molenaar, R.

2011-01-01

Every year the RIVM and PBL publish the so-called Large-scale concentration maps of the Netherlands (GCN maps). These maps offer an approximation of the background concentrations of several air-polluting substances. Sometimes these maps need to be updated to realize a better approximation of the background concentrations. [nl

ADA1, a novel component of the ADA/GCN5 complex, has broader effects than GCN5, ADA2, or ADA3.

OpenAIRE

Horiuchi, J; Silverman, N; Piña, B; Marcus, G A; Guarente, L

1997-01-01

The ADA genes encode factors which are proposed to function as transcriptional coactivators. Here we describe the cloning, sequencing, and initial characterization of a novel ADA gene, ADA1. Similar to the previously isolated ada mutants, ada1 mutants display decreases in transcription from various reporters. Furthermore, ADA1 interacts with the other ADAs in the ADA/GCN5 complex as demonstrated by partial purification of the complex and immunoprecipitation experiments. We estimate that the c...

Interplay among Gcn5, Sch9 and mitochondria during chronological aging of wine yeast is dependent on growth conditions.

Directory of Open Access Journals (Sweden)

Cecilia Picazo

Full Text Available Saccharomyces cerevisiae chronological life span (CLS is determined by a wide variety of environmental and genetic factors. Nutrient limitation without malnutrition, i.e. dietary restriction, expands CLS through the control of nutrient signaling pathways, of which TOR/Sch9 has proven to be the most relevant, particularly under nitrogen deprivation. The use of prototrophic wine yeast allows a better understanding of the role of nitrogen in longevity in natural and more demanding environments, such as grape juice fermentation. We previously showed that acetyltransferase Gcn5, a member of the SAGA complex, has opposite effects on CLS under laboratory and winemaking conditions, and is detrimental under the latter. Here we demonstrate that integrity of the SAGA complex is necessary for prolonged longevity, as its dismantling by SPT20 deletion causes a drop in CLS under both laboratory and winemaking conditions. The sch9Δ mutant is long-lived in synthetic SC medium, as expected, and the combined deletion of GCN5 partially suppresses this phenotype. However it is short-lived in grape juice, likely due to its low nitrogen/carbon ratio. Therefore, unbalance of nutrients can be more relevant for life span than total amounts of them. Deletion of RTG2, which codes for a protein associated with Gcn5 and is a component of the mitochondrial retrograde signal, and which communicates mitochondrial dysfunction to the nucleus, is detrimental under laboratory, but not under winemaking conditions, where respiration seems not so relevant for longevity. Transcription factor Rgm1 was found to be a novel CLS regulator Sch9-dependently.

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

The translational regulator Cup controls NMJ presynaptic terminal morphology.

Science.gov (United States)

Menon, Kaushiki P; Carrillo, Robert A; Zinn, Kai

2015-07-01

During oogenesis and early embryonic development in Drosophila, translation of proteins from maternally deposited mRNAs is tightly controlled. We and others have previously shown that translational regulatory proteins that function during oogenesis also have essential roles in the nervous system. Here we examine the role of Cup in neuromuscular system development. Maternal Cup controls translation of localized mRNAs encoding the Oskar and Nanos proteins and binds to the general translation initiation factor eIF4E. In this paper, we show that zygotic Cup protein is localized to presynaptic terminals at larval neuromuscular junctions (NMJs). cup mutant NMJs have strong phenotypes characterized by the presence of small clustered boutons called satellite boutons. They also exhibit an increase in the frequency of spontaneous glutamate release events (mEPSPs). Reduction of eIF4E expression synergizes with partial loss of Cup expression to produce satellite bouton phenotypes. The presence of satellite boutons is often associated with increases in retrograde bone morphogenetic protein (BMP) signaling, and we show that synaptic BMP signaling is elevated in cup mutants. cup genetically interacts with two genes, EndoA and Dap160, that encode proteins involved in endocytosis that are also neuronal modulators of the BMP pathway. Endophilin protein, encoded by the EndoA gene, is downregulated in a cup mutant. Our results are consistent with a model in which Cup and eIF4E work together to ensure efficient localization and translation of endocytosis proteins in motor neurons and control the strength of the retrograde BMP signal. Copyright © 2015 Elsevier Inc. All rights reserved.

Epidermal Growth Factor Receptor (EGFR) gene copy number (GCN) correlates with clinical activity of irinotecan-cetuximab in K-RAS wild-type colorectal cancer: a fluorescence in situ (FISH) and chromogenic in situ hybridization (CISH) analysis.

Science.gov (United States)

Scartozzi, Mario; Bearzi, Italo; Mandolesi, Alessandra; Pierantoni, Chiara; Loupakis, Fotios; Zaniboni, Alberto; Negri, Francesca; Quadri, Antonello; Zorzi, Fausto; Galizia, Eva; Berardi, Rossana; Biscotti, Tommasina; Labianca, Roberto; Masi, Gianluca; Falcone, Alfredo; Cascinu, Stefano

2009-08-27

K-RAS wild type colorectal tumors show an improved response rate to anti-EGFR monoclonal antibodies. Nevertheless 70% to 40% of these patients still does not seem to benefit from this therapeutic approach. FISH EGFR GCN has been previously demonstrated to correlate with clinical outcome of colorectal cancer treated with anti-EGFR monoclonal antibodies. CISH also seemed able to provide accurate EGFR GCN information with the advantage of a simpler and reproducible technique involving immunohistochemistry and light microscopy. Based on these findings we investigated the correlation between both FISH and CISH EGFR GCN and clinical outcome in K-RAS wild-type colorectal cancer treated with irinotecan-cetuximab. Patients with advanced K-RAS wild-type, colorectal cancer receiving irinotecan-cetuximab after failure of irinotecan-based chemotherapy were eligible. A cut-off value for EGFR GCN of 2.6 and 2.12 for FISH and CISH respectively was derived from ROC curve analysis. Forty-four patients were available for analysis. We observed a partial remission in 9 (60%) and 2 (9%) cases with a FISH EGFR GCN >or= 2.6 and CISH EGFR GCN >or= 2.12 and CISH EGFR GCN whereas it was 2.9 and 3.1 months in those with low FISH and CISH EGFR GCN (p = 0.04 and 0.02 respectively). FISH and CISH EGFR GCN may both represent effective tools for a further patients selection in K-RAS wild-type colorectal cancer treated with cetuximab.

Cell-specific differences in the requirements for translation quality control

DEFF Research Database (Denmark)

Reynolds, Noah M; Ling, Jiqiang; Roy, Hervé

2010-01-01

Protein synthesis has an overall error rate of approximately 10(-4) for each mRNA codon translated. The fidelity of translation is mainly determined by two events: synthesis of cognate amino acid:tRNA pairs by aminoacyl-tRNA synthetases (aaRSs) and accurate selection of aminoacyl-tRNAs (aa-tRNAs)...... divergent requirements for quality control in different cell compartments and suggest that the limits of translational accuracy may be largely determined by cellular physiology....

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.

Translational control is a major contributor to hypoxia induced gene expression

International Nuclear Information System (INIS)

Beucken, Twan van den; Magagnin, Michael G.; Jutten, Barry; Seigneuric, Renaud; Lambin, Philippe; Koritzinsky, Marianne; Wouters, Bradly G.

2011-01-01

Background and purpose: Hypoxia is a common feature of solid tumors that is associated with an aggressive phenotype, resistance to therapy and poor prognosis. Major contributors to these adverse effects are the transcriptional program activated by the HIF family of transcription factors as well as the translational response mediated by PERK-dependent phosphorylation of eIF2α and inhibition of mTORC1 activity. In this study we determined the relative contribution of both transcriptional and translational responses to changes in hypoxia induced gene expression. Material and methods: Total and efficiently translated (polysomal) mRNA was isolated from DU145 prostate carcinoma cells that were exposed for up to 24 h of hypoxia ( 2 ). Changes in transcription and translation were assessed using affymetrix microarray technology. Results: Our data reveal an unexpectedly large contribution of translation control on both induced and repressed gene expression at all hypoxic time points, particularly during acute hypoxia (2-4 h). Gene ontology analysis revealed that gene classes like transcription and signal transduction are stimulated by translational control whereas expression of genes involved in cell growth and protein metabolism are repressed during hypoxic conditions by translational control. Conclusions: Our data indicate that translation influences gene expression during hypoxia on a scale comparable to that of transcription.

Ground Operations Aerospace Language (GOAL). Volume 4: Interpretive code translator

Science.gov (United States)

1973-01-01

This specification identifies and describes the principal functions and elements of the Interpretive Code Translator which has been developed for use with the GOAL Compiler. This translator enables the user to convert a compliled GOAL program to a highly general binary format which is designed to enable interpretive execution. The translator program provides user controls which are designed to enable the selection of various output types and formats. These controls provide a means for accommodating many of the implementation options which are discussed in the Interpretive Code Guideline document. The technical design approach is given. The relationship between the translator and the GOAL compiler is explained and the principal functions performed by the Translator are described. Specific constraints regarding the use of the Translator are discussed. The control options are described. These options enable the user to select outputs to be generated by the translator and to control vrious aspects of the translation processing.

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.

The Gcn2 Regulator Yih1 Interacts with the Cyclin Dependent Kinase Cdc28 and Promotes Cell Cycle Progression through G2/M in Budding Yeast.

Directory of Open Access Journals (Sweden)

Richard C Silva

Full Text Available The Saccharomyces cerevisiae protein Yih1, when overexpressed, inhibits the eIF2 alpha kinase Gcn2 by competing for Gcn1 binding. However, deletion of YIH1 has no detectable effect on Gcn2 activity, suggesting that Yih1 is not a general inhibitor of Gcn2, and has no phenotypic defect identified so far. Thus, its physiological role is largely unknown. Here, we show that Yih1 is involved in the cell cycle. Yeast lacking Yih1 displays morphological patterns and DNA content indicative of a delay in the G2/M phases of the cell cycle, and this phenotype is independent of Gcn1 and Gcn2. Accordingly, the levels of phosphorylated eIF2α, which show a cell cycle-dependent fluctuation, are not altered in cells devoid of Yih1. We present several lines of evidence indicating that Yih1 is in a complex with Cdc28. Yih1 pulls down endogenous Cdc28 in vivo and this interaction is enhanced when Cdc28 is active, suggesting that Yih1 modulates the function of Cdc28 in specific stages of the cell cycle. We also demonstrate, by Bimolecular Fluorescence Complementation, that endogenous Yih1 and Cdc28 interact with each other, confirming Yih1 as a bona fide Cdc28 binding partner. Amino acid substitutions within helix H2 of the RWD domain of Yih1 enhance Yih1-Cdc28 association. Overexpression of this mutant, but not of wild type Yih1, leads to a phenotype similar to that of YIH1 deletion, supporting the view that Yih1 is involved through Cdc28 in the regulation of the cell cycle. We further show that IMPACT, the mammalian homologue of Yih1, interacts with CDK1, the mammalian counterpart of Cdc28, indicating that the involvement with the cell cycle is conserved. Together, these data provide insights into the cellular function of Yih1/IMPACT, and provide the basis for future studies on the role of this protein in the cell cycle.

Boron Stress Activates the General Amino Acid Control Mechanism and Inhibits Protein Synthesis

Science.gov (United States)

Uluisik, Irem; Kaya, Alaattin; Fomenko, Dmitri E.; Karakaya, Huseyin C.; Carlson, Bradley A.; Gladyshev, Vadim N.; Koc, Ahmet

2011-01-01

Boron is an essential micronutrient for plants, and it is beneficial for animals. However, at high concentrations boron is toxic to cells although the mechanism of this toxicity is not known. Atr1 has recently been identified as a boron efflux pump whose expression is upregulated in response to boron treatment. Here, we found that the expression of ATR1 is associated with expression of genes involved in amino acid biosynthesis. These mechanisms are strictly controlled by the transcription factor Gcn4 in response to boron treatment. Further analyses have shown that boron impaired protein synthesis by promoting phosphorylation of eIF2α in a Gcn2 kinase dependent manner. The uncharged tRNA binding domain (HisRS) of Gcn2 is necessary for the phosphorylation of eIF2α in the presence of boron. We postulate that boron exerts its toxic effect through activation of the general amino acid control system and inhibition of protein synthesis. Since the general amino acid control pathway is conserved among eukaryotes, this mechanism of boron toxicity may be of general importance. PMID:22114689

Boron stress activates the general amino acid control mechanism and inhibits protein synthesis.

Directory of Open Access Journals (Sweden)

Irem Uluisik

Full Text Available Boron is an essential micronutrient for plants, and it is beneficial for animals. However, at high concentrations boron is toxic to cells although the mechanism of this toxicity is not known. Atr1 has recently been identified as a boron efflux pump whose expression is upregulated in response to boron treatment. Here, we found that the expression of ATR1 is associated with expression of genes involved in amino acid biosynthesis. These mechanisms are strictly controlled by the transcription factor Gcn4 in response to boron treatment. Further analyses have shown that boron impaired protein synthesis by promoting phosphorylation of eIF2α in a Gcn2 kinase dependent manner. The uncharged tRNA binding domain (HisRS of Gcn2 is necessary for the phosphorylation of eIF2α in the presence of boron. We postulate that boron exerts its toxic effect through activation of the general amino acid control system and inhibition of protein synthesis. Since the general amino acid control pathway is conserved among eukaryotes, this mechanism of boron toxicity may be of general importance.

Translational coregulation of 5′TOP mRNAs by TIA-1 and TIAR

Science.gov (United States)

Damgaard, Christian Kroun; Lykke-Andersen, Jens

2011-01-01

The response of cells to changes in their environment often requires coregulation of gene networks, but little is known about how this can occur at the post-transcriptional level. An important example of post-transcriptional coregulation is the selective translational regulation in response to growth conditions of mammalian mRNAs that encode protein biosynthesis factors and contain hallmark 5′-terminal oligopyrimidine tracts (5′TOP). However, the responsible trans-factors and the mechanism by which they coregulate 5′TOP mRNAs have remained elusive. Here we identify stress granule-associated TIA-1 and TIAR proteins as key factors in human 5′TOP mRNA regulation, which upon amino acid starvation assemble onto the 5′ end of 5′TOP mRNAs and arrest translation at the initiation step, as evidenced by TIA-1/TIAR-dependent 5′TOP mRNA translation repression, polysome release, and accumulation in stress granules. This requires starvation-mediated activation of the GCN2 (general control nonderepressible 2) kinase and inactivation of the mTOR (mammalian target of rapamycin) signaling pathway. Our findings provide a mechanistic explanation to the long-standing question of how the network of 5′TOP mRNAs are coregulated according to amino acid availability, thereby allowing redirection of limited resources to mount a nutrient deprivation response. This presents a fundamental example of how a group of mRNAs can be translationally coregulated in response to changes in the cellular environment. PMID:21979918

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.

Epidermal Growth Factor Receptor (EGFR gene copy number (GCN correlates with clinical activity of irinotecan-cetuximab in K-RAS wild-type colorectal cancer: a fluorescence in situ (FISH and chromogenic in situ hybridization (CISH analysis

Directory of Open Access Journals (Sweden)

Scartozzi Mario

2009-08-01

Full Text Available Abstract Background K-RAS wild type colorectal tumors show an improved response rate to anti-EGFR monoclonal antibodies. Nevertheless 70% to 40% of these patients still does not seem to benefit from this therapeutic approach. FISH EGFR GCN has been previously demonstrated to correlate with clinical outcome of colorectal cancer treated with anti-EGFR monoclonal antibodies. CISH also seemed able to provide accurate EGFR GCN information with the advantage of a simpler and reproducible technique involving immunohistochemistry and light microscopy. Based on these findings we investigated the correlation between both FISH and CISH EGFR GCN and clinical outcome in K-RAS wild-type colorectal cancer treated with irinotecan-cetuximab. Methods Patients with advanced K-RAS wild-type, colorectal cancer receiving irinotecan-cetuximab after failure of irinotecan-based chemotherapy were eligible. A cut-off value for EGFR GCN of 2.6 and 2.12 for FISH and CISH respectively was derived from ROC curve analysis. Results Forty-four patients were available for analysis. We observed a partial remission in 9 (60% and 2 (9% cases with a FISH EGFR GCN ≥ 2.6 and Conclusion FISH and CISH EGFR GCN may both represent effective tools for a further patients selection in K-RAS wild-type colorectal cancer treated with cetuximab.

Dysregulated Translational Control: From Brain Disorders to Psychoactive Drugs

Directory of Open Access Journals (Sweden)

Emanuela eSantini

2011-11-01

Full Text Available In the last decade, a plethora of studies utilizing pharmacological, biochemical, and genetic approaches have shown that precise translational control is required for long-lasting synaptic plasticity and the formation of long-term memory. Moreover, more recent studies indicate that alterations in translational control are a common pathophysiological feature of human neurological disorders, including developmental disorders, neuropsychiatric disorders, and neurodegenerative diseases. Finally, translational control mechanisms are susceptible to modification by psychoactive drugs. Taken together, these findings point to a central role for translational control in the regulation of synaptic function and behavior.

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.

The nutrient transceptor/PKA pathway functions independently of TOR and responds to leucine and Gcn2 in a TOR-independent manner.

Science.gov (United States)

Conrad, Michaela; Kankipati, Harish Nag; Kimpe, Marlies; Van Zeebroeck, Griet; Zhang, Zhiqiang; Thevelein, Johan M

2017-08-01

Two nutrient-controlled signalling pathways, the PKA and TOR pathway, play a major role in nutrient regulation of growth as well as growth-correlated properties in yeast. The relationship between the two pathways is not well understood. We have used Gap1 and Pho84 transceptor-mediated activation of trehalase and phosphorylation of fragmented Sch9 as a read-out for rapid nutrient activation of PKA or TORC1, respectively. We have identified conditions in which L-citrulline-induced activation of Sch9 phosphorylation is compromised, but not activation of trehalase: addition of the TORC1 inhibitor, rapamycin and low levels of L-citrulline. The same disconnection was observed for phosphate activation in phosphate-starved cells. The leu2 auxotrophic mutation reduces amino acid activation of trehalase, which is counteracted by deletion of GCN2. Both effects were also independent of TORC1. Our results show that rapid activation of the TOR pathway by amino acids is not involved in rapid activation of the PKA pathway and that effects of Gcn2 inactivation as well as leu2 auxotrophy all act independently of the TOR pathway. Hence, rapid nutrient signalling to PKA and TOR in cells arrested by nutrient starvation acts through parallel pathways. © FEMS 2017.

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

Aminoacyl-tRNA quality control is required for efficient activation of the TOR pathway regulator Gln3p.

Science.gov (United States)

Mohler, Kyle; Mann, Rebecca; Kyle, Amanda; Reynolds, Noah; Ibba, Michael

2017-09-14

The aminoacylation status of the cellular tRNA pool regulates both general amino acid control (GAAC) and target of rapamycin (TOR) stress response pathways in yeast. Consequently, fidelity of translation at the level of aminoacyl-tRNA synthesis plays a central role in determining accuracy and sensitivity of stress responses. To investigate effects of translational quality control (QC) on cell physiology under stress conditions, phenotypic microarray analyses were used to identify changes in QC deficient cells. Nitrogen source growth assays showed QC deficient yeast grew differently compared to WT. The QC deficient strain was more tolerant to caffeine treatment than wild type through altered interactions with the TOR and GAAC pathways. Increased caffeine tolerance of the QC deficient strain was consistent with the observation that the activity of Gln3p, a transcription factor controlled by the TOR pathway, is decreased in the QC deficient strain compared to WT. GCN4 translation, which is typically repressed in the absence of nutritional stress, was enhanced in the QC deficient strain through TOR inhibition. QC did not impact cell cycle regulation; however, the chronological lifespan of QC deficient yeast strains decreased compared to wild type, likely due to translational errors and alteration of the TOR-associated regulon. These findings support the idea that changes in translational fidelity provide a mechanism of cellular adaptation by modulating TOR activity. This, in turn, supports a central role for aminoacyl-tRNA synthesis QC in the integrated stress response by maintaining the proper aa-tRNA pools necessary to coordinate the GAAC and TOR.

Grammatical Metaphor, Controlled Languageand Machine Translation

DEFF Research Database (Denmark)

Møller, Margrethe

2003-01-01

It is a general assumption that 1) the readability and clarity of LSP texts written in a controlled language are better than uncontrolled texts and 2) that controlled languages produce better results with machine translation than uncontrolled languages. Controlled languages impose lexical...

Validation of AIRS V6 Surface Temperature over Greenland with GCN and NOAA Stations

Science.gov (United States)

Lee, Jae N.; Hearty, Thomas; Cullather, Richard; Nowicki, Sophie; Susskind, Joel

2016-01-01

This work compares the temporal and spatial characteristics of the AIRSAMSU (Atmospheric Infrared Sounder Advanced Microwave Sounding Unit A) Version 6 and MODIS (Moderate resolution Imaging Spectroradiometer) Collection 5 derived surface temperatures over Greenland. To estimate uncertainties in space-based surface temperature measurements, we re-projected the MODIS Ice Surface Temperature (IST) to 0.5 by 0.5 degree spatial resolution. We also re-gridded AIRS Skin Temperature (Ts) into the same grid but classified with different cloud conditions and surface types. These co-located data sets make intercomparison between the two instruments relatively straightforward. Using this approach, the spatial comparison between the monthly mean AIRS Ts and MODIS IST is in good agreement with RMS 2K for May 2012. This approach also allows the detection of any long-term calibration drift and the careful examination of calibration consistency in the MODIS and AIRS temperature data record. The temporal correlations between temperature data are also compared with those from in-situ measurements from GC-Net (GCN) and NOAA stations. The coherent time series of surface temperature evident in the correlation between AIRS Ts and GCN temperatures suggest that at monthly time scales both observations capture the same climate signal over Greenland. It is also suggested that AIRS surface air temperature (Ta) can be used to estimate the boundary layer inversion.

DW4TR: A Data Warehouse for Translational Research.

Science.gov (United States)

Hu, Hai; Correll, Mick; Kvecher, Leonid; Osmond, Michelle; Clark, Jim; Bekhash, Anthony; Schwab, Gwendolyn; Gao, De; Gao, Jun; Kubatin, Vladimir; Shriver, Craig D; Hooke, Jeffrey A; Maxwell, Larry G; Kovatich, Albert J; Sheldon, Jonathan G; Liebman, Michael N; Mural, Richard J

2011-12-01

The linkage between the clinical and laboratory research domains is a key issue in translational research. Integration of clinicopathologic data alone is a major task given the number of data elements involved. For a translational research environment, it is critical to make these data usable at the point-of-need. Individual systems have been developed to meet the needs of particular projects though the need for a generalizable system has been recognized. Increased use of Electronic Medical Record data in translational research will demand generalizing the system for integrating clinical data to support the study of a broad range of human diseases. To ultimately satisfy these needs, we have developed a system to support multiple translational research projects. This system, the Data Warehouse for Translational Research (DW4TR), is based on a light-weight, patient-centric modularly-structured clinical data model and a specimen-centric molecular data model. The temporal relationships of the data are also part of the model. The data are accessed through an interface composed of an Aggregated Biomedical-Information Browser (ABB) and an Individual Subject Information Viewer (ISIV) which target general users. The system was developed to support a breast cancer translational research program and has been extended to support a gynecological disease program. Further extensions of the DW4TR are underway. We believe that the DW4TR will play an important role in translational research across multiple disease types. Copyright © 2011 Elsevier Inc. All rights reserved.

Translational coregulation of 5'TOP mRNAs by TIA-1 and TIAR

DEFF Research Database (Denmark)

Damgaard, Christian Kroun; Lykke-Andersen, Jens

2011-01-01

in stress granules. This requires starvation-mediated activation of the GCN2 (general control nonderepressible 2) kinase and inactivation of the mTOR (mammalian target of rapamycin) signaling pathway. Our findings provide a mechanistic explanation to the long-standing question of how the network of 5'TOP m...

The Online Translator: Implementing National Standard 4.1.

Science.gov (United States)

Burton, Christine

2003-01-01

A pedagogical idea for addressing National Standard 4.1 (Students demonstrate understanding of the nature of language through comparisons of language studied and their own) suggests the deliberate use of the online translator to illustrate to students the syntactical errors that occur when translating idioms from one language to another. (VWL)

Structure of N-acetyl-[beta]-D-glucosaminidase (GcnA) from the Endocarditis Pathogen Streptococcus gordonii and its Complex with the Mechanism-based Inhibitor NAG-thiazoline

Energy Technology Data Exchange (ETDEWEB)

Langley, David B.; Harty, Derek W.S.; Jacques, Nicholas A.; Hunter, Neil; Guss, J. Mitchell; Collyer, Charles A. (Sydney); (Westmead)

2008-09-17

The crystal structure of GcnA, an N-acetyl-{beta}-D-glucosaminidase from Streptococcus gordonii, was solved by multiple wavelength anomalous dispersion phasing using crystals of selenomethionine-substituted protein. GcnA is a homodimer with subunits each comprised of three domains. The structure of the C-terminal {alpha}-helical domain has not been observed previously and forms a large dimerization interface. The fold of the N-terminal domain is observed in all structurally related glycosidases although its function is unknown. The central domain has a canonical ({beta}/{alpha}){sub 8} TIM-barrel fold which harbours the active site. The primary sequence and structure of this central domain identifies the enzyme as a family 20 glycosidase. Key residues implicated in catalysis have different conformations in two different crystal forms, which probably represent active and inactive conformations of the enzyme. The catalytic mechanism for this class of glycoside hydrolase, where the substrate rather than the enzyme provides the cleavage-inducing nucleophile, has been confirmed by the structure of GcnA complexed with a putative reaction intermediate analogue, N-acetyl-{beta}-D-glucosamine-thiazoline. The catalytic mechanism is discussed in light of these and other family 20 structures.

Comprehensive approach to study complement C4 in systemic lupus erythematosus: Gene polymorphisms, protein levels and functional activity.

Science.gov (United States)

Tsang-A-Sjoe, M W P; Bultink, I E M; Korswagen, L A; van der Horst, A; Rensink, I; de Boer, M; Hamann, D; Voskuyl, A E; Wouters, D

2017-12-01

Genetic variation of the genes encoding complement component C4 is strongly associated with systemic lupus erythematosus (SLE), a chronic multi-organ auto-immune disease. This study examined C4 and its isotypes on a genetic, protein, and functional level in 140 SLE patients and 104 healthy controls. Gene copy number (GCN) variation, silencing CT-insertion, and the retroviral HERV-K(C4) insertion) were analyzed with multiplex ligation-dependent probe amplification. Increased susceptibility to SLE was found for low GCN (≪2) of C4A. Serositis was the only clinical manifestation associated with low C4A GCN. One additional novel silencing mutation in the C4A gene was found by Sanger sequencing. This mutation causes a premature stop codon in exon 11. Protein concentrations of C4 isoforms C4A and C4B were determined with ELISA and were significantly lower in SLE patients compared to healthy controls. To study C4 isotypes on a functional level, a new C4 assay was developed, which distinguishes C4A from C4B by its binding capacity to amino or hydroxyl groups, respectively. This assay showed high correlation with ELISA and detected crossing over of Rodgers and Chido antigens in 3.2% (8/244) of individuals. The binding capacity of available C4 to its substrates was unaffected in SLE. Our study provides, for the first time, a complete overview of C4 in SLE from genetic variation to binding capacity using a novel test. As this test detects crossing over of Rodgers and Chido antigens, it will allow for more accurate measurement of C4 in future studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modulation of translation-initiation in CHO-K1 cells by rapamycin-induced heterodimerization of engineered eIF4G fusion proteins.

Science.gov (United States)

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.

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.

Targeting the eIF4F translation initiation complex: a critical nexus for cancer development.

Science.gov (United States)

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.

eIF4E Phosphorylation Influences Bdnf mRNA Translation in Mouse Dorsal Root Ganglion Neurons

Directory of Open Access Journals (Sweden)

Jamie K. Moy

2018-02-01

Full Text Available Plasticity in dorsal root ganglion (DRG neurons that promotes pain requires activity-dependent mRNA translation. Protein synthesis inhibitors block the ability of many pain-promoting molecules to enhance excitability in DRG neurons and attenuate behavioral signs of pain plasticity. In line with this, we have recently shown that phosphorylation of the 5′ cap-binding protein, eIF4E, plays a pivotal role in plasticity of DRG nociceptors in models of hyperalgesic priming. However, mRNA targets of eIF4E phosphorylation have not been elucidated in the DRG. Brain-derived neurotrophic factor (BDNF signaling from nociceptors in the DRG to spinal dorsal horn neurons is an important mediator of hyperalgesic priming. Regulatory mechanisms that promote pain plasticity via controlling BDNF expression that is involved in promoting pain plasticity have not been identified. We show that phosphorylation of eIF4E is paramount for Bdnf mRNA translation in the DRG. Bdnf mRNA translation is reduced in mice lacking eIF4E phosphorylation (eIF4ES209A and pro-nociceptive factors fail to increase BDNF protein levels in the DRGs of these mice despite robust upregulation of Bdnf-201 mRNA levels. Importantly, bypassing the DRG by giving intrathecal injection of BDNF in eIF4ES209A mice creates a strong hyperalgesic priming response that is normally absent or reduced in these mice. We conclude that eIF4E phosphorylation-mediated translational control of BDNF expression is a key mechanism for nociceptor plasticity leading to hyperalgesic priming.

Chloroplast Translation: Structural and Functional Organization, Operational Control, and Regulation[OPEN

Science.gov (United States)

2018-01-01

Chloroplast translation is essential for cellular viability and plant development. Its positioning at the intersection of organellar RNA and protein metabolism makes it a unique point for the regulation of gene expression in response to internal and external cues. Recently obtained high-resolution structures of plastid ribosomes, the development of approaches allowing genome-wide analyses of chloroplast translation (i.e., ribosome profiling), and the discovery of RNA binding proteins involved in the control of translational activity have greatly increased our understanding of the chloroplast translation process and its regulation. In this review, we provide an overview of the current knowledge of the chloroplast translation machinery, its structure, organization, and function. In addition, we summarize the techniques that are currently available to study chloroplast translation and describe how translational activity is controlled and which cis-elements and trans-factors are involved. Finally, we discuss how translational control contributes to the regulation of chloroplast gene expression in response to developmental, environmental, and physiological cues. We also illustrate the commonalities and the differences between the chloroplast and bacterial translation machineries and the mechanisms of protein biosynthesis in these two prokaryotic systems. PMID:29610211

The Triticum Mosaic Virus 5' Leader Binds to Both eIF4G and eIFiso4G for Translation.

Directory of Open Access Journals (Sweden)

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.

The Fusarium graminearum Histone Acetyltransferases Are Important for Morphogenesis, DON Biosynthesis, and Pathogenicity

Directory of Open Access Journals (Sweden)

Xiangjiu Kong

2018-04-01

Full Text Available Post-translational modifications of chromatin structure by histone acetyltransferase (HATs play a central role in the regulation of gene expression and various biological processes in eukaryotes. Although HAT genes have been studied in many fungi, few of them have been functionally characterized. In this study, we identified and characterized four putative HATs (FgGCN5, FgRTT109, FgSAS2, FgSAS3 in the plant pathogenic ascomycete Fusarium graminearum, the causal agent of Fusarium head blight of wheat and barley. We replaced the genes and all mutant strains showed reduced growth of F. graminearum. The ΔFgSAS3 and ΔFgGCN5 mutant increased sensitivity to oxidative and osmotic stresses. Additionally, ΔFgSAS3 showed reduced conidia sporulation and perithecium formation. Mutant ΔFgGCN5 was unable to generate any conidia and lost its ability to form perithecia. Our data showed also that FgSAS3 and FgGCN5 are pathogenicity factors required for infecting wheat heads as well as tomato fruits. Importantly, almost no Deoxynivalenol (DON was produced either in ΔFgSAS3 or ΔFgGCN5 mutants, which was consistent with a significant downregulation of TRI genes expression. Furthermore, we discovered for the first time that FgSAS3 is indispensable for the acetylation of histone site H3K4, while FgGCN5 is essential for the acetylation of H3K9, H3K18, and H3K27. H3K14 can be completely acetylated when FgSAS3 and FgGCN5 were both present. The RNA-seq analyses of the two mutant strains provide insight into their functions in development and metabolism. Results from this study clarify the functional divergence of HATs in F. graminearum, and may provide novel targeted strategies to control secondary metabolite expression and infections of F. graminearum.

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.

Cap-dependent translational control of oncolytic measles virus infection in malignant mesothelioma.

Science.gov (United States)

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.

Ectopic expression of eIF4E-transporter triggers the movement of eIF4E into P-bodies, inhibiting steady-state translation but not the pioneer round of translation

International Nuclear Information System (INIS)

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

Does eIF3 promote reinitiation after translation of short upstream ORFs also in mammalian cells?

Czech Academy of Sciences Publication Activity Database

Hronová, Vladislava; Mohammad, Mahabub Pasha; Wagner, Susan; Pánek, Josef; Gunišová, Stanislava; Zeman, Jakub; Poncová, Kristýna; Valášek, Leoš Shivaya

2017-01-01

Roč. 14, č. 12 (2017), s. 1660-1667 ISSN 1547-6286 R&D Projects: GA ČR GA15-10116S Institutional support: RVO:61388971 Keywords : ATF4 * eIF3 * GCN4 Subject RIV: EE - Microbiology, Virology OBOR OECD: Developmental biology Impact factor: 3.900, year: 2016

Translation initiation factor AteIF(iso4E is involved in selective mRNA translation in Arabidopsis thaliana seedlings.

Directory of Open Access Journals (Sweden)

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.

IRES-dependent translational control during virus-induced endoplasmic reticulum stress and apoptosis

Directory of Open Access Journals (Sweden)

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.

Translational control of ceruloplasmin gene expression: Beyond the IRE

Directory of Open Access Journals (Sweden)

BARSANJIT MAZUMDER

2006-01-01

Full Text Available Translational control is a common regulatory mechanism for the expression of iron-related proteins. For example, three enzymes involved in erythrocyte development are regulated by three different control mechanisms: globin synthesis is modulated by heme-regulated translational inhibitor; erythroid 5-aminolevulinate synthase translation is inhibited by binding of the iron regulatory protein to the iron response element in the 5'-untranslated region (UTR; and 15-lipoxygenase is regulated by specific proteins binding to the 3'-UTR. Ceruloplasmin (Cp is a multi-functional, copper protein made primarily by the liver and by activated macrophages. Cp has important roles in iron homeostasis and in inflammation. Its role in iron metabolism was originally proposed because of its ferroxidase activity and because of its ability to stimulate iron loading into apo-transferrin and iron efflux from liver. We have shown that Cp mRNA is induced by interferon (IFN-γ in U937 monocytic cells, but synthesis of Cp protein is halted by translational silencing. The silencing mechanism requires binding of a cytosolic inhibitor complex, IFN-Gamma-Activated Inhibitor of Translation (GAIT, to a specific GAIT element in the Cp 3'-UTR. Here, we describe our studies that define and characterize the GAIT element and elucidate the specific trans-acting proteins that bind the GAIT element. Our experiments describe a new mechanism of translational control of an iron-related protein and may shed light on the role that macrophage-derived Cp plays at the intersection of iron homeostasis and inflammation.

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.

Analysis of the interacting partners eIF4F and 3'-CITE required for Melon necrotic spot virus cap-independent translation.

Science.gov (United States)

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.

Mitochondrial protein acetylation mediates nutrient sensing of mitochondrial protein synthesis and mitonuclear protein balance.

Science.gov (United States)

Di Domenico, Antonella; Hofer, Annette; Tundo, Federica; Wenz, Tina

2014-11-01

Changes in nutrient supply require global metabolic reprogramming to optimize the utilization of the nutrients. Mitochondria as a central component of the cellular metabolism play a key role in this adaptive process. Since mitochondria harbor their own genome, which encodes essential enzymes, mitochondrial protein synthesis is a determinant of metabolic adaptation. While regulation of cytoplasmic protein synthesis in response to metabolic challenges has been studied in great detail, mechanisms which adapt mitochondrial translation in response to metabolic challenges remain elusive. Our results suggest that the mitochondrial acetylation status controlled by Sirt3 and its proposed opponent GCN5L1 is an important regulator of the metabolic adaptation of mitochondrial translation. Moreover, both proteins modulate regulators of cytoplasmic protein synthesis as well as the mitonuclear protein balance making Sirt3 and GCN5L1 key players in synchronizing mitochondrial and cytoplasmic translation. Our results thereby highlight regulation of mitochondrial translation as a novel component in the cellular nutrient sensing scheme and identify mitochondrial acetylation as a new regulatory principle for the metabolic competence of mitochondrial protein synthesis. © 2014 International Union of Biochemistry and Molecular Biology.

Translational control of Nrf2 within the open reading frame

International Nuclear Information System (INIS)

Perez-Leal, Oscar; Barrero, Carlos A.; Merali, Salim

2013-01-01

Highlights: •Identification of a novel Nrf2 translational repression mechanism. •The repressor is within the 3′ portion of the Nrf2 ORF. •The translation of Nrf2 or eGFP is reduced by the regulatory element. •The translational repression can be reversed with synonymous codon substitutions. •The molecular mechanism requires the mRNA sequence, but not the encoded amino acids. -- Abstract: Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) is a transcription factor that is essential for the regulation of an effective antioxidant and detoxifying response. The regulation of its activity can occur at transcription, translation and post-translational levels. Evidence suggests that under environmental stress conditions, new synthesis of Nrf2 is required – a process that is regulated by translational control and is not fully understood. Here we described the identification of a novel molecular process that under basal conditions strongly represses the translation of Nrf2 within the open reading frame (ORF). This mechanism is dependent on the mRNA sequence within the 3′ portion of the ORF of Nrf2 but not in the encoded amino acid sequence. The Nrf2 translational repression can be reversed with the use of synonymous codon substitutions. This discovery suggests an additional layer of control to explain the reason for the low Nrf2 concentration under quiescent state

Translational Control of Cell Division by Elongator

Directory of Open Access Journals (Sweden)

Fanelie Bauer

2012-05-01

Full Text Available Elongator is required for the synthesis of the mcm5s2 modification found on tRNAs recognizing AA-ending codons. In order to obtain a global picture of the role of Elongator in translation, we used reverse protein arrays to screen the fission yeast proteome for translation defects. Unexpectedly, this revealed that Elongator inactivation mainly affected three specific functional groups including proteins implicated in cell division. The absence of Elongator results in a delay in mitosis onset and cytokinesis defects. We demonstrate that the kinase Cdr2, which is a central regulator of mitosis and cytokinesis, is under translational control by Elongator due to the Lysine codon usage bias of the cdr2 coding sequence. These findings uncover a mechanism by which the codon usage, coupled to tRNA modifications, fundamentally contributes to gene expression and cellular functions.

IMPLEMENTASI NETWORK ADDRESS TRANSLATION (NAT MENGGUNAKAN KERIO CONTROL VERSI 7.4.1 DI PUSAT PENELITIAN BIOTEKNOLOGI – LIPI

Directory of Open Access Journals (Sweden)

Tutang Tutang

2016-03-01

Full Text Available Biotechnology Research Center as an institution engaged in the research, the need for data and updated information is an absolute thing. This requirement can be met one of them is the use of information technology either by using the internet. With the increasing number of Internet users in Biotechnology Research Center and order for all users who are members of the Local Area Network (LAN can utilize the internet needed a good network management. While, during the network management Indonesian Institute of Sciences (LIPI, under the supervision of the Joint Network Team (TGJ – LIPI only provide one local IP segment which is limited to only 250 users. While number of internet users in Biotechnology Research Center and more than that number will continue to grow. To overcome these problems, then the LAN network at the Research Center for Biotechnology service facility utilizes Network Address Translation (NAT contained in Kerio Control software version 7.4.1. The subject of this article is limited to the implementation and configuration of NAT using Kerio Control 7.4.1 version. From these results, we concluded that the implementation of NAT helps all users in the network LAN Biotechnology Research Center get Public IP, so that it can connect to the internet properly.

Ribonuclease inhibitor 1 regulates erythropoiesis by controlling GATA1 translation.

Science.gov (United States)

Chennupati, Vijaykumar; Veiga, Diogo Ft; Maslowski, Kendle M; Andina, Nicola; Tardivel, Aubry; Yu, Eric Chi-Wang; Stilinovic, Martina; Simillion, Cedric; Duchosal, Michel A; Quadroni, Manfredo; Roberts, Irene; Sankaran, Vijay G; MacDonald, H Robson; Fasel, Nicolas; Angelillo-Scherrer, Anne; Schneider, Pascal; Hoang, Trang; Allam, Ramanjaneyulu

2018-04-02

Ribosomal proteins (RP) regulate specific gene expression by selectively translating subsets of mRNAs. Indeed, in Diamond-Blackfan anemia and 5q- syndrome, mutations in RP genes lead to a specific defect in erythroid gene translation and cause anemia. Little is known about the molecular mechanisms of selective mRNA translation and involvement of ribosomal-associated factors in this process. Ribonuclease inhibitor 1 (RNH1) is a ubiquitously expressed protein that binds to and inhibits pancreatic-type ribonucleases. Here, we report that RNH1 binds to ribosomes and regulates erythropoiesis by controlling translation of the erythroid transcription factor GATA1. Rnh1-deficient mice die between embryonic days E8.5 and E10 due to impaired production of mature erythroid cells from progenitor cells. In Rnh1-deficient embryos, mRNA levels of Gata1 are normal, but GATA1 protein levels are decreased. At the molecular level, we found that RNH1 binds to the 40S subunit of ribosomes and facilitates polysome formation on Gata1 mRNA to confer transcript-specific translation. Further, RNH1 knockdown in human CD34+ progenitor cells decreased erythroid differentiation without affecting myelopoiesis. Our results reveal an unsuspected role for RNH1 in the control of GATA1 mRNA translation and erythropoiesis.

Translational control of auditory imprinting and structural plasticity by eIF2α

Science.gov (United States)

Batista, Gervasio; Johnson, Jennifer Leigh; Dominguez, Elena; Costa-Mattioli, Mauro; Pena, Jose L

2016-01-01

The formation of imprinted memories during a critical period is crucial for vital behaviors, including filial attachment. Yet, little is known about the underlying molecular mechanisms. Using a combination of behavior, pharmacology, in vivo surface sensing of translation (SUnSET) and DiOlistic labeling we found that, translational control by the eukaryotic translation initiation factor 2 alpha (eIF2α) bidirectionally regulates auditory but not visual imprinting and related changes in structural plasticity in chickens. Increasing phosphorylation of eIF2α (p-eIF2α) reduces translation rates and spine plasticity, and selectively impairs auditory imprinting. By contrast, inhibition of an eIF2α kinase or blocking the translational program controlled by p-eIF2α enhances auditory imprinting. Importantly, these manipulations are able to reopen the critical period. Thus, we have identified a translational control mechanism that selectively underlies auditory imprinting. Restoring translational control of eIF2α holds the promise to rejuvenate adult brain plasticity and restore learning and memory in a variety of cognitive disorders. DOI: http://dx.doi.org/10.7554/eLife.17197.001 PMID:28009255

An empirical evaluation of the translation to Brazilian Portuguese of the Loss of Control over Eating Scale (LOCES

Directory of Open Access Journals (Sweden)

Felipe Q. da Luz

2016-02-01

Full Text Available Abstract Background Loss of control over eating is a key feature of the most prevalent eating disorders. The Loss of Control over Eating Scale (LOCES enables a thorough assessment of loss of control over eating. Objective This study empirically evaluated the translation of the LOCES from English to Brazilian Portuguese. Methods The scale was translated to Brazilian Portuguese and back translated to English in order to check accuracy of the translation. Two hundred and ninety-three medicine and nursing students, 60 males and 233 females, 18-55 years old, with mean body mass index (BMI 23.2 kg/m2 (SD 4.1, recruited between August and December 2014, answered the Brazilian Portuguese LOCES. An exploratory factor analysis was performed. Results Exploratory factor analysis of the Brazilian Portuguese LOCES showed three distinct factors of the loss of control over eating (disgust/negative sensations, cognitive experiences/dissociation, and “positive” effects as well as moderate consistency with previous reports of exploratory factor analysis of the English version. Discussion This study showed satisfactory translation of the LOCES from English to Brazilian Portuguese, which is now ready for further validation.

Eukaryotic Initiation Factor 4H Is under Transcriptional Control of p65/NF-κB

Science.gov (United States)

Fiume, Giuseppe; Rossi, Annalisa; de Laurentiis, Annamaria; Falcone, Cristina; Pisano, Antonio; Vecchio, Eleonora; Pontoriero, Marilena; Scala, Iris; Scialdone, Annarita; Masci, Francesca Fasanella; Mimmi, Selena; Palmieri, Camillo; Scala, Giuseppe; Quinto, Ileana

2013-01-01

Protein synthesis is mainly regulated at the initiation step, allowing the fast, reversible and spatial control of gene expression. Initiation of protein synthesis requires at least 13 translation initiation factors to assemble the 80S ribosomal initiation complex. Loss of translation control may result in cell malignant transformation. Here, we asked whether translational initiation factors could be regulated by NF-κB transcription factor, a major regulator of genes involved in cell proliferation, survival, and inflammatory response. We show that the p65 subunit of NF-κB activates the transcription of eIF4H gene, which is the regulatory subunit of eIF4A, the most relevant RNA helicase in translation initiation. The p65-dependent transcriptional activation of eIF4H increased the eIF4H protein content augmenting the rate of global protein synthesis. In this context, our results provide novel insights into protein synthesis regulation in response to NF-κB activation signalling, suggesting a transcription-translation coupled mechanism of control. PMID:23776612

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

Time of action of 4.5 S RNA in Escherichia coli translation

DEFF Research Database (Denmark)

Brown, S

1989-01-01

A new class of suppressor mutants helps to define the role of 4.5 S RNA in translation. The suppressors reduce the requirement for 4.5 S RNA by increasing the intracellular concentration of uncharged tRNA. Suppression probably occurs by prolonging the period in which translating ribosomes have...... translocated but not yet released the uncharged tRNA, indicating that this is the point at which 4.5 S RNA enters translation. The release of 4.5 S RNA from polysomes is affected by antibiotics that inhibit protein synthesis. The antibiotic-sensitivity of this release indicates that 4.5 S RNA exits...... the ribosome following translocation and prior to release of protein synthesis elongation factor G. These results indicate that 4.5 S RNA acts immediately after ribosomal translocation. A model is proposed in which 4.5 S RNA stabilizes the post-translocation state by replacing 23 S ribosomal RNA as a binding...

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.

Science.gov (United States)

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.

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.

Temporal Translational Control by a Metastable RNA Structure

DEFF Research Database (Denmark)

Møller-Jensen, Jakob; Franch, Thomas; Gerdes, Kenn

2001-01-01

Programmed cell death by the hok/sok locus of plasmid R1 relies on a complex translational control mechanism. The highly stable hok mRNA is activated by 3'-end exonucleolytical processing. Removal of the mRNA 3' end releases a 5'-end sequence that triggers refolding of the mRNA. The refolded hok m......-transcriptional control mechanism....

Essential role of eIF5-mimic protein in animal development is linked to control of ATF4 expression

Science.gov (United States)

Translational control of ATF4 through upstream ORFs (uORFs) plays an important role in eukaryotic gene regulation. While ATF4 translation is typically induced by inhibitory phosphorylation of eIF2, ATF4 translation can be also induced by expression of a new translational inhibitor protein, eIF5-mimi...

Translation-coupling systems

Science.gov (United States)

Pfleger, Brian; Mendez-Perez, Daniel

2013-11-05

Disclosed are systems and methods for coupling translation of a target gene to a detectable response gene. A version of the invention includes a translation-coupling cassette. The translation-coupling cassette includes a target gene, a response gene, a response-gene translation control element, and a secondary structure-forming sequence that reversibly forms a secondary structure masking the response-gene translation control element. Masking of the response-gene translation control element inhibits translation of the response gene. Full translation of the target gene results in unfolding of the secondary structure and consequent translation of the response gene. Translation of the target gene is determined by detecting presence of the response-gene protein product. The invention further includes RNA transcripts of the translation-coupling cassettes, vectors comprising the translation-coupling cassettes, hosts comprising the translation-coupling cassettes, methods of using the translation-coupling cassettes, and gene products produced with the translation-coupling cassettes.

Synaptic control of local translation: the plot thickens with new characters.

Science.gov (United States)

Thomas, María Gabriela; Pascual, Malena Lucía; Maschi, Darío; Luchelli, Luciana; Boccaccio, Graciela Lidia

2014-06-01

The production of proteins from mRNAs localized at the synapse ultimately controls the strength of synaptic transmission, thereby affecting behavior and cognitive functions. The regulated transcription, processing, and transport of mRNAs provide dynamic control of the dendritic transcriptome, which includes thousands of messengers encoding multiple cellular functions. Translation is locally modulated by synaptic activity through a complex network of RNA-binding proteins (RBPs) and various types of non-coding RNAs (ncRNAs) including BC-RNAs, microRNAs, piwi-interacting RNAs, and small interference RNAs. The RBPs FMRP and CPEB play a well-established role in synaptic translation, and additional regulatory factors are emerging. The mRNA repressors Smaug, Nanos, and Pumilio define a novel pathway for local translational control that affects dendritic branching and spines in both flies and mammals. Recent findings support a role for processing bodies and related synaptic mRNA-silencing foci (SyAS-foci) in the modulation of synaptic plasticity and memory formation. The SyAS-foci respond to different stimuli with changes in their integrity thus enabling regulated mRNA release followed by translation. CPEB, Pumilio, TDP-43, and FUS/TLS form multimers through low-complexity regions related to prion domains or polyQ expansions. The oligomerization of these repressor RBPs is mechanistically linked to the aggregation of abnormal proteins commonly associated with neurodegeneration. Here, we summarize the current knowledge on how specificity in mRNA translation is achieved through the concerted action of multiple pathways that involve regulatory ncRNAs and RBPs, the modification of translation factors, and mRNA-silencing foci dynamics.

Tunable translational control using site-specific unnatural amino acid incorporation in Escherichia coli

Directory of Open Access Journals (Sweden)

Yusuke Kato

2015-04-01

Full Text Available Translation of target gene transcripts in Escherichia coli harboring UAG amber stop codons can be switched on by the amber-codon-specific incorporation of an exogenously supplied unnatural amino acid, 3-iodo-L-tyrosine. Here, we report that this translational switch can control the translational efficiency at any intermediate magnitude by adjustment of the 3-iodo-L-tyrosine concentration in the medium, as a tunable translational controller. The translational efficiency of a target gene reached maximum levels with 10−5 M 3-iodo-L-tyrosine, and intermediate levels were observed with suboptimal concentrations (approximately spanning a 2-log10 concentration range, 10−7–10−5 M. Such intermediate-level expression was also confirmed in individual bacteria.

Air Pollution Translations: A Bibliography with Abstracts - Volume 4.

Science.gov (United States)

Environmental Protection Agency, Research Triangle Park, NC. Air Pollution Technical Information Center.

This volume is the fourth in a series of compilations presenting abstracts and indexes of translations of technical air pollution literature. The entries are grouped into 12 subject categories: Emission Sources, Control Methods, Measurement Methods, Air Quality Measurements, Atmospheric Interaction, Basic Science and Technology, Effects--Human…

Fragile X mental retardation protein: A paradigm for translational control by RNA-binding proteins.

Science.gov (United States)

Chen, Eileen; Joseph, Simpson

2015-07-01

Translational control is a common mechanism used to regulate gene expression and occur in bacteria to mammals. Typically in translational control, an RNA-binding protein binds to a unique sequence in the mRNA to regulate protein synthesis by the ribosomes. Alternatively, a protein may bind to or modify a translation factor to globally regulate protein synthesis by the cell. Here, we review translational control by the fragile X mental retardation protein (FMRP), the absence of which causes the neurological disease, fragile X syndrome (FXS). Copyright © 2015 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.

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.

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.

Translation initiation complex eIF4F is a therapeutic target for dual mTOR kinase inhibitors in non-Hodgkin lymphoma

Science.gov (United States)

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

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 ▿ †

Science.gov (United States)

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 Not5 subunit of the ccr4-not complex connects transcription and translation.

Directory of Open Access Journals (Sweden)

Zoltan Villanyi

2014-10-01

Full Text Available Recent studies have suggested that a sub-complex of RNA polymerase II composed of Rpb4 and Rpb7 couples the nuclear and cytoplasmic stages of gene expression by associating with newly made mRNAs in the nucleus, and contributing to their translation and degradation in the cytoplasm. Here we show by yeast two hybrid and co-immunoprecipitation experiments, followed by ribosome fractionation and fluorescent microscopy, that a subunit of the Ccr4-Not complex, Not5, is essential in the nucleus for the cytoplasmic functions of Rpb4. Not5 interacts with Rpb4; it is required for the presence of Rpb4 in polysomes, for interaction of Rpb4 with the translation initiation factor eIF3 and for association of Rpb4 with mRNAs. We find that Rpb7 presence in the cytoplasm and polysomes is much less significant than that of Rpb4, and that it does not depend upon Not5. Hence Not5-dependence unlinks the cytoplasmic functions of Rpb4 and Rpb7. We additionally determine with RNA immunoprecipitation and native gel analysis that Not5 is needed in the cytoplasm for the co-translational assembly of RNA polymerase II. This stems from the importance of Not5 for the association of the R2TP Hsp90 co-chaperone with polysomes translating RPB1 mRNA to protect newly synthesized Rpb1 from aggregation. Hence taken together our results show that Not5 interconnects translation and transcription.

Deregulation of protein translation control, a potential game-changing hypothesis for Parkinson's disease pathogenesis.

Science.gov (United States)

Taymans, Jean-Marc; Nkiliza, Aurore; Chartier-Harlin, Marie-Christine

2015-08-01

Protein translation is one of the most fundamental and exquisitely controlled processes in biology, and is energetically demanding. The deregulation of this process is deleterious to cells, as demonstrated by several diseases caused by mutations in protein translation machinery. Emerging evidence now points to a role for protein translation in the pathogenesis of Parkinson's disease (PD); a debilitating neurodegenerative movement disorder. In this paper, we propose a hypothesis that protein translation machinery, PD-associated proteins and PD pathology are connected in a functional network linking cell survival to protein translation control. This hypothesis is a potential game changer in the field of the molecular pathogenesis of PD, with implications for the development of PD diagnostics and disease-modifying therapies. Copyright © 2015 Elsevier Ltd. 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

Translation of selected papers published in Nuclear Constants 4, 1986

International Nuclear Information System (INIS)

1989-08-01

The document includes the English translation of 7 papers published in the Russian journal Nuclear Constants 4, 1986 and dealing with neutron data evaluations for actinide nuclei and iron. Refs, figs and tab

Translating research into policy: lessons learned from eclampsia treatment and malaria control in three southern African countries.

Science.gov (United States)

Woelk, Godfrey; Daniels, Karen; Cliff, Julie; Lewin, Simon; Sevene, Esperança; Fernandes, Benedita; Mariano, Alda; Matinhure, Sheillah; Oxman, Andrew D; Lavis, John N; Lundborg, Cecilia Stålsby

2009-12-30

Little is known about the process of knowledge translation in low- and middle-income countries. We studied policymaking processes in Mozambique, South Africa and Zimbabwe to understand the factors affecting the use of research evidence in national policy development, with a particular focus on the findings from randomized control trials (RCTs). We examined two cases: the use of magnesium sulphate (MgSO(4)) in the treatment of eclampsia in pregnancy (a clinical case); and the use of insecticide treated bed nets and indoor residual household spraying for malaria vector control (a public health case). We used a qualitative case-study methodology to explore the policy making process. We carried out key informants interviews with a range of research and policy stakeholders in each country, reviewed documents and developed timelines of key events. Using an iterative approach, we undertook a thematic analysis of the data. Prior experience of particular interventions, local champions, stakeholders and international networks, and the involvement of researchers in policy development were important in knowledge translation for both case studies. Key differences across the two case studies included the nature of the evidence, with clear evidence of efficacy for MgSO(4 )and ongoing debate regarding the efficacy of bed nets compared with spraying; local researcher involvement in international evidence production, which was stronger for MgSO(4 )than for malaria vector control; and a long-standing culture of evidence-based health care within obstetrics. Other differences were the importance of bureaucratic processes for clinical regulatory approval of MgSO(4), and regional networks and political interests for malaria control. In contrast to treatment policies for eclampsia, a diverse group of stakeholders with varied interests, differing in their use and interpretation of evidence, was involved in malaria policy decisions in the three countries. Translating research knowledge into

Translating research into policy: lessons learned from eclampsia treatment and malaria control in three southern African countries

Directory of Open Access Journals (Sweden)

Matinhure Sheillah

2009-12-01

Full Text Available Abstract Background Little is known about the process of knowledge translation in low- and middle-income countries. We studied policymaking processes in Mozambique, South Africa and Zimbabwe to understand the factors affecting the use of research evidence in national policy development, with a particular focus on the findings from randomized control trials (RCTs. We examined two cases: the use of magnesium sulphate (MgSO4 in the treatment of eclampsia in pregnancy (a clinical case; and the use of insecticide treated bed nets and indoor residual household spraying for malaria vector control (a public health case. Methods We used a qualitative case-study methodology to explore the policy making process. We carried out key informants interviews with a range of research and policy stakeholders in each country, reviewed documents and developed timelines of key events. Using an iterative approach, we undertook a thematic analysis of the data. Findings Prior experience of particular interventions, local champions, stakeholders and international networks, and the involvement of researchers in policy development were important in knowledge translation for both case studies. Key differences across the two case studies included the nature of the evidence, with clear evidence of efficacy for MgSO4 and ongoing debate regarding the efficacy of bed nets compared with spraying; local researcher involvement in international evidence production, which was stronger for MgSO4 than for malaria vector control; and a long-standing culture of evidence-based health care within obstetrics. Other differences were the importance of bureaucratic processes for clinical regulatory approval of MgSO4, and regional networks and political interests for malaria control. In contrast to treatment policies for eclampsia, a diverse group of stakeholders with varied interests, differing in their use and interpretation of evidence, was involved in malaria policy decisions in the three

Multiple post-translational modifications in hepatocyte nuclear factor 4α

International Nuclear Information System (INIS)

Yokoyama, Atsushi; Katsura, Shogo; Ito, Ryo; Hashiba, Waka; Sekine, Hiroki; Fujiki, Ryoji; Kato, Shigeaki

2011-01-01

Highlights: → We performed comprehensive PTM analysis for HNF4α protein. → We identified 8 PTMs in HNF4α protein including newly identified PTMs. → Among them, we found acetylation at lysine 458 was one of the prime PTMs for HNF4α function. → Acetylation at lysine 458 was inhibitory for HNF4α transcription function. → This modification fluctuated in response to extracellular condition. -- Abstract: To investigate the role of post-translational modifications (PTMs) in the hepatocyte nuclear factor 4α (HNF4α)-mediated transcription, we took a comprehensive survey of PTMs in HNF4α protein by massspectrometry and identified totally 8 PTM sites including newly identified ubiquitilation and acetylation sites. To assess the impact of identified PTMs in HNF4α-function, we introduced point mutations at the identified PTM sites and, tested transcriptional activity of the HNF4α. Among the point-mutations, an acetylation site at lysine 458 was found significant in the HNF4α-mediated transcriptional control. An acetylation negative mutant at lysine 458 showed an increased transcriptional activity by about 2-fold, while an acetylation mimic mutant had a lowered transcriptional activation. Furthermore, this acetylation appeared to be fluctuated in response to extracellular nutrient conditions. Thus, by applying an comprehensive analysis of PTMs, multiple PTMs were newly identified in HNF4α and unexpected role of an HNF4α acetylation could be uncovered.

PCAF/GCN5-Mediated Acetylation of RPA1 Promotes Nucleotide Excision Repair

Directory of Open Access Journals (Sweden)

Meimei Zhao

2017-08-01

Full Text Available The RPA complex can integrate multiple stress signals into diverse responses by activating distinct DNA repair pathways. However, it remains unclear how RPA1 elects to activate a specific repair pathway during different types of DNA damage. Here, we report that PCAF/GCN5-mediated K163 acetylation of RPA1 is crucial for nucleotide excision repair (NER but is dispensable for other DNA repair pathways. Mechanistically, we demonstrate that the acetylation of RPA1 is critical for the steady accumulation of XPA at damaged DNA sites and preferentially activates the NER pathway. DNA-PK phosphorylates and activates PCAF upon UV damage and consequently promotes the acetylation of RPA1. Moreover, the acetylation of RPA1 is tightly regulated by HDAC6 and SIRT1. Together, our results demonstrate that the K163 acetylation of RPA1 plays a key role in the repair of UV-induced DNA damage and reveal how the specific RPA1 modification modulates the choice of distinct DNA repair pathways.

Passivity-Based Control of Rotational and Translational Timoshenko Arms

Directory of Open Access Journals (Sweden)

Minoru Sasaki

2012-01-01

Full Text Available It is shown that the alternate passivity-based control schemes can be designed which explicitly exploit the passivity properties of the Timoshenko model. This approach has the advantage over the conventional methods in the respect that it allows one to deal directly with the system's partial differential equations without resorting to approximations. Numerical results for the tracking control of a translational and rotational flexible Timoshenko arm are presented and compared. They verify that the proposed control schemes are effective at controlling flexible dynamical systems.

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.

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.

Operational controlling - a tool of translating strategy into action

Directory of Open Access Journals (Sweden)

2011-03-01

Full Text Available . Enterprises have a lot of problems with realization their strategic aims in the fast changing and competitive business arena from many years. Effective execution of strategic plan needs its translating into action, task results and indicators of everyday activities. The success on the market is attainable by communicating strategic and operating goals on the each level of organizational structure and their connecting with budget of units or employee motivation. The scorecards balancing in finance, customer, process and development perspectives is very useful for pointing - what do we control with? or - what do we have to achieve? But doesn't answer to question about ways of enterprise managing. Main aim of the article is proving that operational controlling system is a essential tool for translating strategy into action. The Balanced Scorecard methodology should to take into consideration system and process connection of enterprise with procurement, co-operation or distribution supply chain also.

Predicted RNA Binding Proteins Pes4 and Mip6 Regulate mRNA Levels, Translation, and Localization during Sporulation in Budding Yeast.

Science.gov (United States)

Jin, Liang; Zhang, Kai; Sternglanz, Rolf; Neiman, Aaron M

2017-05-01

In response to starvation, diploid cells of Saccharomyces cerevisiae undergo meiosis and form haploid spores, a process collectively referred to as sporulation. The differentiation into spores requires extensive changes in gene expression. The transcriptional activator Ndt80 is a central regulator of this process, which controls many genes essential for sporulation. Ndt80 induces ∼300 genes coordinately during meiotic prophase, but different mRNAs within the NDT80 regulon are translated at different times during sporulation. The protein kinase Ime2 and RNA binding protein Rim4 are general regulators of meiotic translational delay, but how differential timing of individual transcripts is achieved was not known. This report describes the characterization of two related NDT80 -induced genes, PES4 and MIP6 , encoding predicted RNA binding proteins. These genes are necessary to regulate the steady-state expression, translational timing, and localization of a set of mRNAs that are transcribed by NDT80 but not translated until the end of meiosis II. Mutations in the predicted RNA binding domains within PES4 alter the stability of target mRNAs. PES4 and MIP6 affect only a small portion of the NDT80 regulon, indicating that they act as modulators of the general Ime2/Rim4 pathway for specific transcripts. Copyright © 2017 American Society for Microbiology.

In Salmonella enterica, the Gcn5-Related Acetyltransferase MddA (Formerly YncA) Acetylates Methionine Sulfoximine and Methionine Sulfone, Blocking Their Toxic Effects

Science.gov (United States)

Hentchel, Kristy L.

2014-01-01

Protein and small-molecule acylation reactions are widespread in nature. Many of the enzymes catalyzing acylation reactions belong to the Gcn5-related N-acetyltransferase (GNAT; PF00583) family, named after the yeast Gcn5 protein. The genome of Salmonella enterica serovar Typhimurium LT2 encodes 26 GNATs, 11 of which have no known physiological role. Here, we provide in vivo and in vitro evidence for the role of the MddA (methionine derivative detoxifier; formerly YncA) GNAT in the detoxification of oxidized forms of methionine, including methionine sulfoximine (MSX) and methionine sulfone (MSO). MSX and MSO inhibited the growth of an S. enterica ΔmddA strain unless glutamine or methionine was present in the medium. We used an in vitro spectrophotometric assay and mass spectrometry to show that MddA acetylated MSX and MSO. An mddA+ strain displayed biphasic growth kinetics in the presence of MSX and glutamine. Deletion of two amino acid transporters (GlnHPQ and MetNIQ) in a ΔmddA strain restored growth in the presence of MSX. Notably, MSO was transported by GlnHPQ but not by MetNIQ. In summary, MddA is the mechanism used by S. enterica to respond to oxidized forms of methionine, which MddA detoxifies by acetyl coenzyme A-dependent acetylation. PMID:25368301

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.

mTORC1 Balances Cellular Amino Acid Supply with Demand for Protein Synthesis through Post-transcriptional Control of ATF4

Directory of Open Access Journals (Sweden)

Yeonwoo Park

2017-05-01

Full Text Available The mammalian target of rapamycin complex 1 (mTORC1 is a master regulator of cell growth that is commonly deregulated in human diseases. Here we find that mTORC1 controls a transcriptional program encoding amino acid transporters and metabolic enzymes through a mechanism also used to regulate protein synthesis. Bioinformatic analysis of mTORC1-responsive mRNAs identified a promoter element recognized by activating transcription factor 4 (ATF4, a key effector of the integrated stress response. ATF4 translation is normally induced by the phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α through a mechanism that requires upstream open reading frames (uORFs in the ATF4 5′ UTR. mTORC1 also controls ATF4 translation through uORFs, but independently of changes in eIF2α phosphorylation. mTORC1 instead employs the 4E-binding protein (4E-BP family of translation repressors. These results link mTORC1-regulated demand for protein synthesis with an ATF4-regulated transcriptional program that controls the supply of amino acids to the translation machinery.

MRF Family Genes Are Involved in Translation Control, Especially under Energy-Deficient Conditions, and Their Expression and Functions Are Modulated by the TOR Signaling Pathway[OPEN

Science.gov (United States)

Lee, Du-Hwa; Park, Seung Jun; Ahn, Chang Sook

2017-01-01

Dynamic control of protein translation in response to the environment is essential for the survival of plant cells. Target of rapamycin (TOR) coordinates protein synthesis with cellular energy/nutrient availability through transcriptional modulation and phosphorylation of the translation machinery. However, mechanisms of TOR-mediated translation control are poorly understood in plants. Here, we report that Arabidopsis thaliana MRF (MA3 DOMAIN-CONTAINING TRANSLATION REGULATORY FACTOR) family genes encode translation regulatory factors under TOR control, and their functions are particularly important in energy-deficient conditions. Four MRF family genes (MRF1-MRF4) are transcriptionally induced by dark and starvation (DS). Silencing of multiple MRFs increases susceptibility to DS and treatment with a TOR inhibitor, while MRF1 overexpression decreases susceptibility. MRF proteins interact with eIF4A and cofractionate with ribosomes. MRF silencing decreases translation activity, while MRF1 overexpression increases it, accompanied by altered ribosome patterns, particularly in DS. Furthermore, MRF deficiency in DS causes altered distribution of mRNAs in sucrose gradient fractions and accelerates rRNA degradation. MRF1 is phosphorylated in vivo and phosphorylated by S6 kinases in vitro. MRF expression and MRF1 ribosome association and phosphorylation are modulated by cellular energy status and TOR activity. We discuss possible mechanisms of the function of MRF family proteins under normal and energy-deficient conditions and their functional link with the TOR pathway. PMID:29084871

MRF Family Genes Are Involved in Translation Control, Especially under Energy-Deficient Conditions, and Their Expression and Functions Are Modulated by the TOR Signaling Pathway.

Science.gov (United States)

Lee, Du-Hwa; Park, Seung Jun; Ahn, Chang Sook; Pai, Hyun-Sook

2017-11-01

Dynamic control of protein translation in response to the environment is essential for the survival of plant cells. Target of rapamycin (TOR) coordinates protein synthesis with cellular energy/nutrient availability through transcriptional modulation and phosphorylation of the translation machinery. However, mechanisms of TOR-mediated translation control are poorly understood in plants. Here, we report that Arabidopsis thaliana MRF (MA3 DOMAIN-CONTAINING TRANSLATION REGULATORY FACTOR) family genes encode translation regulatory factors under TOR control, and their functions are particularly important in energy-deficient conditions. Four MRF family genes ( MRF1 - MRF4 ) are transcriptionally induced by dark and starvation (DS). Silencing of multiple MRFs increases susceptibility to DS and treatment with a TOR inhibitor, while MRF1 overexpression decreases susceptibility. MRF proteins interact with eIF4A and cofractionate with ribosomes. MRF silencing decreases translation activity, while MRF1 overexpression increases it, accompanied by altered ribosome patterns, particularly in DS. Furthermore, MRF deficiency in DS causes altered distribution of mRNAs in sucrose gradient fractions and accelerates rRNA degradation. MRF1 is phosphorylated in vivo and phosphorylated by S6 kinases in vitro. MRF expression and MRF1 ribosome association and phosphorylation are modulated by cellular energy status and TOR activity. We discuss possible mechanisms of the function of MRF family proteins under normal and energy-deficient conditions and their functional link with the TOR pathway. © 2017 American Society of Plant Biologists. All rights reserved.

First Steps Towards Translating HZD Control of Bipedal Robots to Decentralized Control of Exoskeletons

OpenAIRE

Agrawal, Ayush; Harib, Omar; Hereid, Ayonga; Finet, Sylvain; Masselin, Matthieu; Praly, Laurent; Ames, Aaron D.; Sreenath, Koushil; Grizzle, Jessy W.

2017-01-01

This paper presents preliminary results toward translating gait and control design for bipedal robots to decentralized control of an exoskeleton aimed at restoring mobility to patients with lower limb paralysis, without the need for crutches. A mathematical hybrid dynamical model of the human-exoskeleton system is developed and a library of dynamically feasible periodic walking gaits for different walking speeds is found through nonlinear constrained optimization using the full-order dynamica...

Translational Capacity of a Cell Is Determined during Transcription Elongation via the Ccr4-Not Complex

Directory of Open Access Journals (Sweden)

Ishaan Gupta

2016-05-01

Full Text Available The current understanding of gene expression considers transcription and translation to be independent processes. Challenging this notion, we found that translation efficiency is determined during transcription elongation through the imprinting of mRNAs with Not1, the central scaffold of the Ccr4-Not complex. We determined that another subunit of the complex, Not5, defines Not1 binding to specific mRNAs, particularly those produced from ribosomal protein genes. This imprinting mechanism specifically regulates ribosomal protein gene expression, which in turn determines the translational capacity of cells. We validate our model by SILAC and polysome profiling experiments. As a proof of concept, we demonstrate that enhanced translation compensates for transcriptional elongation stress. Taken together, our data indicate that in addition to defining mRNA stability, components of the Ccr4-Not imprinting complex regulate RNA translatability, thus ensuring global gene expression homeostasis.

Strategies to regulate transcription factor-mediated gene positioning and interchromosomal clustering at the nuclear periphery.

Science.gov (United States)

Randise-Hinchliff, Carlo; Coukos, Robert; Sood, Varun; Sumner, Michael Chas; Zdraljevic, Stefan; Meldi Sholl, Lauren; Garvey Brickner, Donna; Ahmed, Sara; Watchmaker, Lauren; Brickner, Jason H

2016-03-14

In budding yeast, targeting of active genes to the nuclear pore complex (NPC) and interchromosomal clustering is mediated by transcription factor (TF) binding sites in the gene promoters. For example, the binding sites for the TFs Put3, Ste12, and Gcn4 are necessary and sufficient to promote positioning at the nuclear periphery and interchromosomal clustering. However, in all three cases, gene positioning and interchromosomal clustering are regulated. Under uninducing conditions, local recruitment of the Rpd3(L) histone deacetylase by transcriptional repressors blocks Put3 DNA binding. This is a general function of yeast repressors: 16 of 21 repressors blocked Put3-mediated subnuclear positioning; 11 of these required Rpd3. In contrast, Ste12-mediated gene positioning is regulated independently of DNA binding by mitogen-activated protein kinase phosphorylation of the Dig2 inhibitor, and Gcn4-dependent targeting is up-regulated by increasing Gcn4 protein levels. These different regulatory strategies provide either qualitative switch-like control or quantitative control of gene positioning over different time scales. © 2016 Randise-Hinchliff et al.

Design control for clinical translation of 3D printed modular scaffolds.

Science.gov (United States)

Hollister, Scott J; Flanagan, Colleen L; Zopf, David A; Morrison, Robert J; Nasser, Hassan; Patel, Janki J; Ebramzadeh, Edward; Sangiorgio, Sophia N; Wheeler, Matthew B; Green, Glenn E

2015-03-01

The primary thrust of tissue engineering is the clinical translation of scaffolds and/or biologics to reconstruct tissue defects. Despite this thrust, clinical translation of tissue engineering therapies from academic research has been minimal in the 27 year history of tissue engineering. Academic research by its nature focuses on, and rewards, initial discovery of new phenomena and technologies in the basic research model, with a view towards generality. Translation, however, by its nature must be directed at specific clinical targets, also denoted as indications, with associated regulatory requirements. These regulatory requirements, especially design control, require that the clinical indication be precisely defined a priori, unlike most academic basic tissue engineering research where the research target is typically open-ended, and furthermore requires that the tissue engineering therapy be constructed according to design inputs that ensure it treats or mitigates the clinical indication. Finally, regulatory approval dictates that the constructed system be verified, i.e., proven that it meets the design inputs, and validated, i.e., that by meeting the design inputs the therapy will address the clinical indication. Satisfying design control requires (1) a system of integrated technologies (scaffolds, materials, biologics), ideally based on a fundamental platform, as compared to focus on a single technology, (2) testing of design hypotheses to validate system performance as opposed to mechanistic hypotheses of natural phenomena, and (3) sequential testing using in vitro, in vivo, large preclinical and eventually clinical tests against competing therapies, as compared to single experiments to test new technologies or test mechanistic hypotheses. Our goal in this paper is to illustrate how design control may be implemented in academic translation of scaffold based tissue engineering therapies. Specifically, we propose to (1) demonstrate a modular platform approach

Cap-proximal nucleotides via differential eIF4E binding and alternative promoter usage mediate translational response to energy stress.

Science.gov (United States)

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.

Robotic real-time translational and rotational head motion correction during frameless stereotactic radiosurgery

Energy Technology Data Exchange (ETDEWEB)

Liu, Xinmin; Belcher, Andrew H.; Grelewicz, Zachary; Wiersma, Rodney D., E-mail: rwiersma@uchicago.edu [Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois 60637 (United States)

2015-06-15

Purpose: To develop a control system to correct both translational and rotational head motion deviations in real-time during frameless stereotactic radiosurgery (SRS). Methods: A novel feedback control with a feed-forward algorithm was utilized to correct for the coupling of translation and rotation present in serial kinematic robotic systems. Input parameters for the algorithm include the real-time 6DOF target position, the frame pitch pivot point to target distance constant, and the translational and angular Linac beam off (gating) tolerance constants for patient safety. Testing of the algorithm was done using a 4D (XY Z + pitch) robotic stage, an infrared head position sensing unit and a control computer. The measured head position signal was processed and a resulting command was sent to the interface of a four-axis motor controller, through which four stepper motors were driven to perform motion compensation. Results: The control of the translation of a brain target was decoupled with the control of the rotation. For a phantom study, the corrected position was within a translational displacement of 0.35 mm and a pitch displacement of 0.15° 100% of the time. For a volunteer study, the corrected position was within displacements of 0.4 mm and 0.2° over 98.5% of the time, while it was 10.7% without correction. Conclusions: The authors report a control design approach for both translational and rotational head motion correction. The experiments demonstrated that control performance of the 4D robotic stage meets the submillimeter and subdegree accuracy required by SRS.

Robotic real-time translational and rotational head motion correction during frameless stereotactic radiosurgery

International Nuclear Information System (INIS)

Liu, Xinmin; Belcher, Andrew H.; Grelewicz, Zachary; Wiersma, Rodney D.

2015-01-01

Purpose: To develop a control system to correct both translational and rotational head motion deviations in real-time during frameless stereotactic radiosurgery (SRS). Methods: A novel feedback control with a feed-forward algorithm was utilized to correct for the coupling of translation and rotation present in serial kinematic robotic systems. Input parameters for the algorithm include the real-time 6DOF target position, the frame pitch pivot point to target distance constant, and the translational and angular Linac beam off (gating) tolerance constants for patient safety. Testing of the algorithm was done using a 4D (XY Z + pitch) robotic stage, an infrared head position sensing unit and a control computer. The measured head position signal was processed and a resulting command was sent to the interface of a four-axis motor controller, through which four stepper motors were driven to perform motion compensation. Results: The control of the translation of a brain target was decoupled with the control of the rotation. For a phantom study, the corrected position was within a translational displacement of 0.35 mm and a pitch displacement of 0.15° 100% of the time. For a volunteer study, the corrected position was within displacements of 0.4 mm and 0.2° over 98.5% of the time, while it was 10.7% without correction. Conclusions: The authors report a control design approach for both translational and rotational head motion correction. The experiments demonstrated that control performance of the 4D robotic stage meets the submillimeter and subdegree accuracy required by SRS

Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma.

Science.gov (United States)

Ambrosio, Maria R; Rocca, Bruno J; Barone, Aurora; Onorati, Monica; Mundo, Lucia; Crivelli, Filippo; Di Nuovo, Franca; De Falco, Giulia; del Vecchio, Maria T; Tripodi, Sergio A; Tosi, Piero

2015-01-01

Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis.

From Controlled Trial to Community Adoption: The Multisite Translational Community Trial

Science.gov (United States)

Murimi, Mary; Gonzalez, Anjelica; Njike, Valentine; Green, Lawrence W.

2011-01-01

Methods for translating the findings of controlled trials, such as the Diabetes Prevention Program, into real-world community application have not been clearly defined. A standardized research methodology for making and evaluating such a transition is needed. We introduce the multisite translational community trial (mTCT) as the research analog to the multisite randomized controlled trial. The mTCT is adapted to incorporate the principles and practices of community-based participatory research and the increased relevance and generalizability gained from diverse community settings. The mTCT is a tool designed to bridge the gap between what a clinical trial demonstrates can work in principle and what is needed to make it workable and effective in real-world settings. Its utility could be put to the test, in particular with practice-based research networks such as the Prevention Research Centers. PMID:21680935

Modeling and control of lateral vibration of an axially translating flexible link

Energy Technology Data Exchange (ETDEWEB)

Shin, Heon Seop; Rhim, Sung Soo [Kyung Hee University, Yongin (Korea, Republic of)

2015-01-15

Manipulators used for the transportation of large panel-shape payloads often adopt long and slender links (or forks) with translational joins to carry the payloads. As the size of the payload increases, the length of the links also increases to hold the payload securely. The increased length of the link inevitably amplifies the effect of the flexure in the link. Intuitively, the translational motion of the link in its longitudinal direction should have no effect on the lateral vibration of the link because of the orthogonality between the direction of the translational motion and the lateral vibration. If, however, the link was flexible and translated horizontally (perpendicular to the gravitational field) the asymmetric deflection of the link caused by gravity would break the orthogonality between the two directions, and the longitudinal motion of the link would excite lateral motion in the link. In this paper, the lateral oscillatory motion of the flexible link in a large-scale solar cell panel handling robot is investigated where the links carry the panel in its longitudinal direction. The Newtonian approach in conjunction with the assumed modes method is used for derivation of the equation of motion for the flexible forks where non-zero control force is applied at the base of the link. The analysis illustrates the effect of longitudinal motion on the lateral vibration and dynamic stiffening effect (variation of the natural frequency) of the link due to the translational velocity. Lateral vibration behavior is simulated using the derived equations of the motion. A robust vibration control scheme, the input shaping filter technique, is implemented on the model and the effectiveness of the scheme is verified numerically.

Modeling and control of lateral vibration of an axially translating flexible link

International Nuclear Information System (INIS)

Shin, Heon Seop; Rhim, Sung Soo

2015-01-01

Manipulators used for the transportation of large panel-shape payloads often adopt long and slender links (or forks) with translational joins to carry the payloads. As the size of the payload increases, the length of the links also increases to hold the payload securely. The increased length of the link inevitably amplifies the effect of the flexure in the link. Intuitively, the translational motion of the link in its longitudinal direction should have no effect on the lateral vibration of the link because of the orthogonality between the direction of the translational motion and the lateral vibration. If, however, the link was flexible and translated horizontally (perpendicular to the gravitational field) the asymmetric deflection of the link caused by gravity would break the orthogonality between the two directions, and the longitudinal motion of the link would excite lateral motion in the link. In this paper, the lateral oscillatory motion of the flexible link in a large-scale solar cell panel handling robot is investigated where the links carry the panel in its longitudinal direction. The Newtonian approach in conjunction with the assumed modes method is used for derivation of the equation of motion for the flexible forks where non-zero control force is applied at the base of the link. The analysis illustrates the effect of longitudinal motion on the lateral vibration and dynamic stiffening effect (variation of the natural frequency) of the link due to the translational velocity. Lateral vibration behavior is simulated using the derived equations of the motion. A robust vibration control scheme, the input shaping filter technique, is implemented on the model and the effectiveness of the scheme is verified numerically.

Speed Controls in Translating Secretory Proteins in Eukaryotes - an Evolutionary Perspective

Science.gov (United States)

Mahlab, Shelly; Linial, Michal

2014-01-01

Protein translation is the most expensive operation in dividing cells from bacteria to humans. Therefore, managing the speed and allocation of resources is subject to tight control. From bacteria to humans, clusters of relatively rare tRNA codons at the N′-terminal of mRNAs have been implicated in attenuating the process of ribosome allocation, and consequently the translation rate in a broad range of organisms. The current interpretation of “slow” tRNA codons does not distinguish between protein translations mediated by free- or endoplasmic reticulum (ER)-bound ribosomes. We demonstrate that proteins translated by free- or ER-bound ribosomes exhibit different overall properties in terms of their translation efficiency and speed in yeast, fly, plant, worm, bovine and human. We note that only secreted or membranous proteins with a Signal peptide (SP) are specified by segments of “slow” tRNA at the N′-terminal, followed by abundant codons that are considered “fast.” Such profiles apply to 3100 proteins of the human proteome that are composed of secreted and signal peptide (SP)-assisted membranous proteins. Remarkably, the bulks of the proteins (12,000), or membranous proteins lacking SP (3400), do not have such a pattern. Alternation of “fast” and “slow” codons was found also in proteins that translocate to mitochondria through transit peptides (TP). The differential clusters of tRNA adapted codons is not restricted to the N′-terminal of transcripts. Specifically, Glycosylphosphatidylinositol (GPI)-anchored proteins are unified by clusters of low adapted tRNAs codons at the C′-termini. Furthermore, selection of amino acids types and specific codons was shown as the driving force which establishes the translation demands for the secretory proteome. We postulate that “hard-coded” signals within the secretory proteome assist the steps of protein maturation and folding. Specifically, “speed control” signals for delaying the translation

Translating Colored Control Flow Nets into Readable Java via Annotated Java Workflow Nets

DEFF Research Database (Denmark)

Lassen, Kristian Bisgaard; Tjell, Simon

2007-01-01

In this paper, we present a method for developing Java applications from Colored Control Flow Nets (CCFNs), which is a special kind of Colored Petri Nets (CPNs) that we introduce. CCFN makes an explicit distinction between the representation of: The system, the environment of the system, and the ......In this paper, we present a method for developing Java applications from Colored Control Flow Nets (CCFNs), which is a special kind of Colored Petri Nets (CPNs) that we introduce. CCFN makes an explicit distinction between the representation of: The system, the environment of the system......, and the interface between the system and the environment. Our translation maps CCFNs into Anno- tated Java Workflow Nets (AJWNs) as an intermediate step, and these AJWNs are finally mapped to Java. CCFN is intended to enforce the modeler to describe the system in an imperative manner which makes the subsequent...... translation to Java easier to define. The translation to Java preserves data dependencies and control-flow aspects of the source CCFN. This paper contributes to the model-driven software development paradigm, by showing how to model a system, environment, and their interface, as a CCFN and presenting a fully...

Topical Review: Translating Translational Research in Behavioral Science.

Science.gov (United States)

Hommel, Kevin A; Modi, Avani C; Piazza-Waggoner, Carrie; Myers, James D

2015-01-01

To present a model of translational research for behavioral science that communicates the role of behavioral research at each phase of translation. A task force identified gaps in knowledge regarding behavioral translational research processes and made recommendations regarding advancement of knowledge. A comprehensive model of translational behavioral research was developed. This model represents T1, T2, and T3 research activities, as well as Phase 1, 2, 3, and 4 clinical trials. Clinical illustrations of translational processes are also offered as support for the model. Behavioral science has struggled with defining a translational research model that effectively articulates each stage of translation and complements biomedical research. Our model defines key activities at each phase of translation from basic discovery to dissemination/implementation. This should be a starting point for communicating the role of behavioral science in translational research and a catalyst for better integration of biomedical and behavioral research. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Loss of FTO in adipose tissue decreases Angptl4 translation and alters triglyceride metabolism.

Science.gov (United States)

Wang, Chao-Yung; Shie, Shian-Sen; Wen, Ming-Shien; Hung, Kuo-Chun; Hsieh, I-Chang; Yeh, Ta-Sen; Wu, Delon

2015-12-15

A common variant of the FTO (fat mass- and obesity-associated) gene is a risk factor for obesity. We found that mice with an adipocyte-specific deletion of FTO gained more weight than control mice on a high-fat diet. Analysis of mice lacking FTO in adipocytes fed a normal diet or adipocytes from these mice revealed alterations in triglyceride metabolism that would be expected to favor increased fatty acid storage by adipose tissue. Mice lacking FTO in adipocytes showed increased serum triglyceride breakdown and clearance, which was associated with lower serum triglyceride concentrations. In addition, lipolysis in response to β-adrenergic stimulation was decreased in adipocytes and ex vivo adipose explants from the mutant mice. FTO is a nucleic acid demethylase that removes N(6)-methyladenosine (m(6)A) from mRNAs. We found that FTO bound to Angptl4, which encodes an adipokine that stimulates intracellular lipolysis in adipocytes. Unexpectedly, the adipose tissue of fasted or fed mice lacking FTO in adipocytes had greater Angptl4 mRNA abundance. However, after high-fat feeding, the mutant mice had less Angptl4 protein and more m(6)A-modified Angptl4 than control mice, suggesting that lack of FTO prevented the translation of Angptl4. Injection of Angptl4-encoding adenovirus into mice lacking FTO in adipocytes restored serum triglyceride concentrations and lipolysis to values similar to those in control mice and abolished excessive weight gain from a high-fat diet. These results reveal that FTO regulates fatty acid mobilization in adipocytes and thus body weight in part through posttranscriptional regulation of Angptl4. Copyright © 2015, American Association for the Advancement of Science.

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

Regulation of protein translation initiation in response to ionizing radiation

International Nuclear Information System (INIS)

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

Directory of Open Access Journals (Sweden)

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.

GCN2 and FGF21 are likely mediators of the protection from cancer, autoimmunity, obesity, and diabetes afforded by vegan diets.

Science.gov (United States)

McCarty, Mark F

2014-09-01

Third World quasi-vegan cultures have been characterized by low risks for "Western" cancers, autoimmune disorders, obesity, and diabetes. The relatively low essential amino acid contents of many vegan diets may play a role in this regard. It is proposed that such diets modestly activate the kinase GCN2 - a physiological detector of essential amino acid paucity - within the liver, resulting in up-regulated production of fibroblast growth factor 21 (FGF21). FGF21, by opposing the stimulatory effect of growth hormone on hepatic IGF-I production, may be responsible for the down-regulation of plasma IGF-I observed in vegans consuming diets of modest protein content. Decreased IGF-I bioactivity throughout life can be expected to have a favorable impact on cancer risk, as observed in rodents that are calorie restricted or genetically defective in IGF-I activity. Increased FGF21 in vegans might also contribute to their characteristic leanness and low LDL cholesterol by promoting hepatic lipid oxidation while inhibiting lipogenesis. Direct trophic effects of FGF21 on pancreatic beta-cells may help to explain the low risk for diabetes observed in vegans, and the utility of vegan diets in diabetes management. And up-regulation of GCN2 in immune cells, by boosting T regulatory activity, might play some role in the reduced risk for autoimmunity reported in some quasi-vegan cultures. The fact that bone density tends to be no greater in vegans than omnivores, despite consumption of a more "alkaline" diet, might be partially attributable to the fact that FGF21 opposes osteoblastogenesis and decreases IGF-I. If these speculations have merit, it should be possible to demonstrate that adoption of a vegan diet of modest protein content increases plasma FGF21 levels. Copyright © 2014 Elsevier Ltd. All rights reserved.

The control of translational accuracy is a determinant of healthy ageing in yeast.

Science.gov (United States)

von der Haar, Tobias; Leadsham, Jane E; Sauvadet, Aimie; Tarrant, Daniel; Adam, Ilectra S; Saromi, Kofo; Laun, Peter; Rinnerthaler, Mark; Breitenbach-Koller, Hannelore; Breitenbach, Michael; Tuite, Mick F; Gourlay, Campbell W

2017-01-01

Life requires the maintenance of molecular function in the face of stochastic processes that tend to adversely affect macromolecular integrity. This is particularly relevant during ageing, as many cellular functions decline with age, including growth, mitochondrial function and energy metabolism. Protein synthesis must deliver functional proteins at all times, implying that the effects of protein synthesis errors like amino acid misincorporation and stop-codon read-through must be minimized during ageing. Here we show that loss of translational accuracy accelerates the loss of viability in stationary phase yeast. Since reduced translational accuracy also reduces the folding competence of at least some proteins, we hypothesize that negative interactions between translational errors and age-related protein damage together overwhelm the cellular chaperone network. We further show that multiple cellular signalling networks control basal error rates in yeast cells, including a ROS signal controlled by mitochondrial activity, and the Ras pathway. Together, our findings indicate that signalling pathways regulating growth, protein homeostasis and energy metabolism may jointly safeguard accurate protein synthesis during healthy ageing. © 2017 The Authors.

Rainfall Simulations of Typhoon Morakot with Controlled Translation Speed Based on EnKF Data Assimilation

Directory of Open Access Journals (Sweden)

Tzu-Hsiung Yen

2011-01-01

Full Text Available Typhoon Morakot produced record-breaking accumulated rainfall over southern Taiwan in August 2009. The combination of several factors resulted in this extreme weather event: the steep terrain in Taiwan, the prevailing south-westerly flow in the monsoon trough, Typhoon Goni over the northern South China Sea, and the slow translation speed of Morakot itself over Taiwan. In this study, the influence of the translation speed is particularly emphasized. Based on the EnKF data assimilation, an innovative method is applied to perform ensemble simulations with several designated translation speeds of Morakot using the WRF model. Thus the influence of the translation speed on the amount of accumulated rainfall over Taiwan can be quantitatively evaluated. In the control simulation with observed translation speed, the maximum amount and geographic pattern of accumulated rainfall during the landfall period of Morakot are generally consistent with the observations, though the detailed overall distributions of accumulated rainfall is mostly underestimated, resulting in the low bias of the frequency distribution of the accumulated rainfall. In a simulation with nearly-doubled translation speed of Morakot, the maximum accumulated rainfall is decreased by 33% than that in the control simulation, while the rainfall distribution over Taiwan remains similar. In addition, the 28 ensemble members can further provide additional information in terms of their spread and other statistics. The results from ensemble members reveal the usefulness of ensemble simulations for the quantitative precipitation forecast.

A Stable Formation Control Using Approximation of Translational and Angular Accelerations

Directory of Open Access Journals (Sweden)

Viet-Hong Tran

2011-03-01

Full Text Available In this paper, a stable leader-following formation control for multiple non-holonomic mobile robot systems using only limited on-board sensor information is proposed. The control can be used for the conventional single leader – single follower (SLSF or for novel two leaders – single follower (TLSF schemes. The control algorithm utilizes estimations of the leaders' translational and angular accelerations in a simple form to reduce the measurement of indirect information. Simulation results show that the TLSF scheme can suppress the oscillation and damping in formation of large robot teams.

Post-translational control of RIPK3 and MLKL mediated necroptotic cell death [version 1; referees: 4 approved

Directory of Open Access Journals (Sweden)

James M. Murphy

2015-11-01

Full Text Available Several programmed lytic and necrotic-like cell death mechanisms have now been uncovered, including the recently described receptor interacting protein kinase-3 (RIPK3-mixed lineage kinase domain-like (MLKL-dependent necroptosis pathway. Genetic experiments have shown that programmed necrosis, including necroptosis, can play a pivotal role in regulating host-resistance against microbial infections. Alternatively, excess or unwarranted necroptosis may be pathological in autoimmune and autoinflammatory diseases. This review highlights the recent advances in our understanding of the post-translational control of RIPK3-MLKL necroptotic signaling. We discuss the critical function of phosphorylation in the execution of necroptosis, and highlight the emerging regulatory roles for several ubiquitin ligases and deubiquitinating enzymes. Finally, based on current evidence, we discuss the potential mechanisms by which the essential, and possibly terminal, necroptotic effector, MLKL, triggers the disruption of cellular membranes to cause cell lysis.

Motion Perception and Manual Control Performance During Passive Tilt and Translation Following Space Flight

Science.gov (United States)

Clement, Gilles; Wood, Scott J.

2010-01-01

This joint ESA-NASA study is examining changes in motion perception following Space Shuttle flights and the operational implications of post-flight tilt-translation ambiguity for manual control performance. Vibrotactile feedback of tilt orientation is also being evaluated as a countermeasure to improve performance during a closed-loop nulling task. METHODS. Data has been collected on 5 astronaut subjects during 3 preflight sessions and during the first 8 days after Shuttle landings. Variable radius centrifugation (216 deg/s) combined with body translation (12-22 cm, peak-to-peak) is utilized to elicit roll-tilt perception (equivalent to 20 deg, peak-to-peak). A forward-backward moving sled (24-390 cm, peak-to-peak) with or without chair tilting in pitch is utilized to elicit pitch tilt perception (equivalent to 20 deg, peak-to-peak). These combinations are elicited at 0.15, 0.3, and 0.6 Hz for evaluating the effect of motion frequency on tilt-translation ambiguity. In both devices, a closed-loop nulling task is also performed during pseudorandom motion with and without vibrotactile feedback of tilt. All tests are performed in complete darkness. PRELIMINARY RESULTS. Data collection is currently ongoing. Results to date suggest there is a trend for translation motion perception to be increased at the low and medium frequencies on landing day compared to pre-flight. Manual control performance is improved with vibrotactile feedback. DISCUSSION. The results of this study indicate that post-flight recovery of motion perception and manual control performance is complete within 8 days following short-duration space missions. Vibrotactile feedback of tilt improves manual control performance both before and after flight.

Reversible pH-controlled DNA-binding peptide nanotweezers: An in-silico study

Directory of Open Access Journals (Sweden)

Gaurav Sharma

2008-11-01

Full Text Available Gaurav Sharma1, Kaushal Rege2,3, David E Budil4, Martin L Yarmush2,5, Constantinos Mavroidis11Department of Mechanical and Industrial Engineering; 4Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA; 2The Center for Engineering in Medicine (CEM, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; 3Department of Chemical Engineering, Arizona State University, Tempe, AZ, USA; 5Department of Biomedical Engineering, Rutgers University, NJ, USAAbstract: We describe the molecular dynamics (MD-aided engineering design of mutant peptides based on the α-helical coiled-coil GCN4 leucine zipper peptide (GCN4-p1 in order to obtain environmentally-responsive nanotweezers. The actuation mechanism of the nanotweezers depends on the modification of electrostatic charges on the residues along the length of the coiled coil. Modulating the solution pH between neutral and acidic values results in the reversible movement of helices toward and away from each other and creates a complete closed-open-closed transition cycle between the helices. Our results indicate that the mutants show a reversible opening of up to 15 Å (1.5 nm; approximately 150% of the initial separation upon pH actuation. Investigation on the physicochemical phenomena that influence conformational properties, structural stability, and reversibility of the coiled-coil peptide-based nanotweezers revealed that a rationale- and design-based approach is needed to engineer stable peptide or macromolecules into stimuli-responsive devices. The efficacy of the mutant that demonstrated the most significant reversible actuation for environmentally responsive modulation of DNA-binding activity was also demonstrated. Our results have significant implications in bioseparations and in the engineering of novel transcription factors.Keywords: bionanotechnology, nanotweezers, coiled-coil, GCN4, leucine zipper, molecular dynamics, environmentally

The significance of translation regulation in the stress response

Science.gov (United States)

2013-01-01

Background The stress response in bacteria involves the multistage control of gene expression but is not entirely understood. To identify the translational response of bacteria in stress conditions and assess its contribution to the regulation of gene expression, the translational states of all mRNAs were compared under optimal growth condition and during nutrient (isoleucine) starvation. Results A genome-scale study of the translational response to nutritional limitation was performed in the model bacterium Lactococcus lactis. Two measures were used to assess the translational status of each individual mRNA: the fraction engaged in translation (ribosome occupancy) and ribosome density (number of ribosomes per 100 nucleotides). Under isoleucine starvation, half of the mRNAs considered were translationally down-regulated mainly due to decreased ribosome density. This pattern concerned genes involved in growth-related functions such as translation, transcription, and the metabolism of fatty acids, phospholipids and bases, contributing to the slowdown of growth. Only 4% of the mRNAs were translationally up-regulated, mostly related to prophagic expression in response to stress. The remaining genes exhibited antagonistic regulations of the two markers of translation. Ribosome occupancy increased significantly for all the genes involved in the biosynthesis of isoleucine, although their ribosome density had decreased. The results revealed complex translational regulation of this pathway, essential to cope with isoleucine starvation. To elucidate the regulation of global gene expression more generally, translational regulation was compared to transcriptional regulation under isoleucine starvation and to other post-transcriptional regulations related to mRNA degradation and mRNA dilution by growth. Translational regulation appeared to accentuate the effects of transcriptional changes for down-regulated growth-related functions under isoleucine starvation although m

The Spt-Ada-Gcn5 Acetyltransferase (SAGA complex in Aspergillus nidulans.

Directory of Open Access Journals (Sweden)

Paraskevi Georgakopoulos

Full Text Available A mutation screen in Aspergillus nidulans uncovered mutations in the acdX gene that led to altered repression by acetate, but not by glucose. AcdX of A. nidulans is highly conserved with Spt8p of Saccharomyces cerevisiae, and since Spt8p is a component of the Spt-Ada-Gcn5 Acetyltransferase (SAGA complex, the SAGA complex may have a role in acetate repression in A. nidulans. We used a bioinformatic approach to identify genes encoding most members of the SAGA complex in A. nidulans, and a proteomic analysis to confirm that most protein components identified indeed exist as a complex in A. nidulans. No apparent compositional differences were detected in mycelia cultured in acetate compared to glucose medium. The methods used revealed apparent differences between Yeast and A. nidulans in the deubiquitination (DUB module of the complex, which in S. cerevisiae consists of Sgf11p, Sus1p, and Ubp8p. Although a convincing homologue of S. cerevisiae Ubp8p was identified in the A. nidulans genome, there were no apparent homologues for Sus1p and Sgf11p. In addition, when the SAGA complex was purified from A. nidulans, members of the DUB module were not co-purified with the complex, indicating that functional homologues of Sus1p and Sgf11p were not part of the complex. Thus, deubiquitination of H2B-Ub in stress conditions is likely to be regulated differently in A. nidulans compared to S. cerevisiae.

Translation and cultural adaptation of a specific instrument for measuring asthma control and asthma status: the Asthma Control and Communication Instrument

Directory of Open Access Journals (Sweden)

Michelle Gonçalves de Souza Tavares

Full Text Available ABSTRACT Objective: To translate the Asthma Control and Communication Instrument (ACCI to Portuguese and adapt it for use in Brazil. Methods: The ACCI was translated to Portuguese and adapted for use in Brazil in accordance with internationally accepted guidelines. The protocol included the following steps: permission and rights of use granted by the original author; translation of the ACCI from English to Portuguese; reconciliation; back-translation; review and harmonization of the back-translation; approval from the original author; review of the Portuguese version of the ACCI by an expert panel; cognitive debriefing (the clarity, understandability, and acceptability of the translated version being tested in a sample of the target population; and reconciliation and preparation of the final version. Results: During the cognitive debriefing process, 41 asthma patients meeting the inclusion criteria completed the ACCI and evaluated the clarity of the questions/statements. The clarity index for all ACCI items was > 0.9, meaning that all items were considered to be clear. Conclusions: The ACCI was successfully translated to Portuguese and culturally adapted for use in Brazil, the translated version maintaining the psychometric properties of the original version. The ACCI can be used in clinical practice because it is easy to understand and easily applied.

Translation and cultural adaptation of a specific instrument for measuring asthma control and asthma status: the Asthma Control and Communication Instrument

Science.gov (United States)

Tavares, Michelle Gonçalves de Souza; Brümmer, Carolina Finardi; Nicolau, Gabriela Valente; de Melo, José Tavares; Nazário, Nazaré Otilia; Steidle, Leila John Marques; Patino, Cecília Maria; Pizzichini, Marcia Margaret Menezes; Pizzichini, Emílio

2017-01-01

ABSTRACT Objective: To translate the Asthma Control and Communication Instrument (ACCI) to Portuguese and adapt it for use in Brazil. Methods: The ACCI was translated to Portuguese and adapted for use in Brazil in accordance with internationally accepted guidelines. The protocol included the following steps: permission and rights of use granted by the original author; translation of the ACCI from English to Portuguese; reconciliation; back-translation; review and harmonization of the back-translation; approval from the original author; review of the Portuguese version of the ACCI by an expert panel; cognitive debriefing (the clarity, understandability, and acceptability of the translated version being tested in a sample of the target population); and reconciliation and preparation of the final version. Results: During the cognitive debriefing process, 41 asthma patients meeting the inclusion criteria completed the ACCI and evaluated the clarity of the questions/statements. The clarity index for all ACCI items was > 0.9, meaning that all items were considered to be clear. Conclusions: The ACCI was successfully translated to Portuguese and culturally adapted for use in Brazil, the translated version maintaining the psychometric properties of the original version. The ACCI can be used in clinical practice because it is easy to understand and easily applied. PMID:29365000

Methods for CT automatic exposure control protocol translation between scanner platforms.

Science.gov (United States)

McKenney, Sarah E; Seibert, J Anthony; Lamba, Ramit; Boone, John M

2014-03-01

An imaging facility with a diverse fleet of CT scanners faces considerable challenges when propagating CT protocols with consistent image quality and patient dose across scanner makes and models. Although some protocol parameters can comfortably remain constant among scanners (eg, tube voltage, gantry rotation time), the automatic exposure control (AEC) parameter, which selects the overall mA level during tube current modulation, is difficult to match among scanners, especially from different CT manufacturers. Objective methods for converting tube current modulation protocols among CT scanners were developed. Three CT scanners were investigated, a GE LightSpeed 16 scanner, a GE VCT scanner, and a Siemens Definition AS+ scanner. Translation of the AEC parameters such as noise index and quality reference mAs across CT scanners was specifically investigated. A variable-diameter poly(methyl methacrylate) phantom was imaged on the 3 scanners using a range of AEC parameters for each scanner. The phantom consisted of 5 cylindrical sections with diameters of 13, 16, 20, 25, and 32 cm. The protocol translation scheme was based on matching either the volumetric CT dose index or image noise (in Hounsfield units) between two different CT scanners. A series of analytic fit functions, corresponding to different patient sizes (phantom diameters), were developed from the measured CT data. These functions relate the AEC metric of the reference scanner, the GE LightSpeed 16 in this case, to the AEC metric of a secondary scanner. When translating protocols between different models of CT scanners (from the GE LightSpeed 16 reference scanner to the GE VCT system), the translation functions were linear. However, a power-law function was necessary to convert the AEC functions of the GE LightSpeed 16 reference scanner to the Siemens Definition AS+ secondary scanner, because of differences in the AEC functionality designed by these two companies. Protocol translation on the basis of

Glenohumeral joint translation and muscle activity in patients with symptomatic rotator cuff pathology: An ultrasonographic and electromyographic study with age-matched controls.

Science.gov (United States)

Rathi, Sangeeta; Taylor, Nicholas F; Soo, Brendan; Green, Rodney A

2018-03-02

To determine whether patients with symptomatic rotator cuff pathology had more glenohumeral joint translation and different patterns of rotator cuff muscle activity compared to controls. Repeated measurements of glenohumeral translation and muscle activity in two positions and six testing conditions in two groups. Twenty participants with a symptomatic and diagnosed rotator cuff tear and 20 age, and gender matched controls were included. Neuromuscular activity was tested by inserting intramuscular electrodes in the rotator cuff muscles. Anterior and posterior glenohumeral translations were measured using real time ultrasound in testing conditions (with and without translation force, with and without isometric internal and external rotation), in two positions (shoulder neutral, 90° of abduction) and two force directions (anterior, posterior). Symptomatic pathology group demonstrated increased passive glenohumeral translation with posterior translation force (protator cuff muscle contraction in the pathology group limited joint translation in a similar manner to the control group, but they did not show the normal direction specific pattern in the neutral posterior position (protator cuff still controlled glenohumeral translation. These results highlight the need to consider joint translation in the assessment and management of patients with rotator cuff injury. Copyright © 2018 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Immunohistochemical localization of translationally controlled tumor protein in the mouse digestive system.

Science.gov (United States)

Sheverdin, Vadim; Jung, Jiwon; Lee, Kyunglim

2013-09-01

Translationally controlled tumor protein (TCTP) is a housekeeping protein, highly conserved among various species. It plays a major role in cell differentiation, growth, proliferation, apoptosis and carcinogenesis. Studies reported so far on TCTP expression in different digestive organs have not led to any understanding of the role of TCTP in digestion, so we localized TCTP in organs of the mouse digestive system employing immunohistochemical techniques. Translationally controlled tumor protein was found expressed in all organs studied: tongue, salivary glands, esophagus, stomach, small and large intestines, liver and pancreas. The expression of TCTP was found to be predominant in epithelia and neurons of myenteric nerve ganglia; high in serous glands (parotid, submandibular, gastric, intestinal crypts, pancreatic acini) and in neurons of myenteric nerve ganglia, and moderate to low in epithelia. In epithelia, expression of TCTP varied depending on its type and location. In enteric neurons, TCTP was predominantly expressed in the processes. Translationally controlled tumor protein expression in the liver followed porto-central gradient with higher expression in pericentral hepatocytes. In the pancreas, TCTP was expressed in both acini and islet cells. Our finding of nearly universal localization and expression of TCTP in mouse digestive organs points to the hitherto unrecognized functional importance of TCTP in the digestive system and suggests the need for further studies of the possible role of TCTP in the proliferation, secretion, absorption and neural regulation of the digestive process and its importance in the physiology and pathology of digestive process. © 2013 Anatomical Society.

p16(INK4a translation suppressed by miR-24.

Directory of Open Access Journals (Sweden)

Ashish Lal

2008-03-01

Full Text Available Expression of the tumor suppressor p16(INK4a increases during aging and replicative senescence.Here, we report that the microRNA miR-24 suppresses p16 expression in human diploid fibroblasts and cervical carcinoma cells. Increased p16 expression with replicative senescence was associated with decreased levels of miR-24, a microRNA that was predicted to associate with the p16 mRNA coding and 3'-untranslated regions. Ectopic miR-24 overexpression reduced p16 protein but not p16 mRNA levels. Conversely, introduction of antisense (AS-miR-24 blocked miR-24 expression and markedly enhanced p16 protein levels, p16 translation, and the production of EGFP-p16 reporter bearing the miR-24 target recognition sites.Together, our results suggest that miR-24 represses the initiation and elongation phases of p16 translation.

SRSF3 represses the expression of PDCD4 protein by coordinated regulation of alternative splicing, export and translation

Energy Technology Data Exchange (ETDEWEB)

Park, Seung Kuk; Jeong, Sunjoo, E-mail: sjsj@dankook.ac.kr

2016-02-05

Gene expression is regulated at multiple steps, such as transcription, splicing, export, degradation and translation. Considering diverse roles of SR proteins, we determined whether the tumor-related splicing factor SRSF3 regulates the expression of the tumor-suppressor protein, PDCD4, at multiple steps. As we have reported previously, knockdown of SRSF3 increased the PDCD4 protein level in SW480 colon cancer cells. More interestingly, here we showed that the alternative splicing and the nuclear export of minor isoforms of pdcd4 mRNA were repressed by SRSF3, but the translation step was unaffected. In contrast, only the translation step of the major isoform of pdcd4 mRNA was repressed by SRSF3. Therefore, overexpression of SRSF3 might be relevant to the repression of all isoforms of PDCD4 protein levels in most types of cancer cell. We propose that SRSF3 could act as a coordinator of the expression of PDCD4 protein via two mechanisms on two alternatively spliced mRNA isoforms.

Inhibition of mTORC1 Enhances the Translation of Chikungunya Proteins via the Activation of the MnK/eIF4E Pathway

Science.gov (United States)

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.

Directory of Open Access Journals (Sweden)

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.

Translational control by eIF2α phosphorylation regulates vulnerability to the synaptic and behavioral effects of cocaine

Science.gov (United States)

Huang, Wei; Placzek, Andon N; Viana Di Prisco, Gonzalo; Khatiwada, Sanjeev; Sidrauski, Carmela; Krnjević, Krešimir; Walter, Peter; Dani, John A; Costa-Mattioli, Mauro

2016-01-01

Adolescents are especially prone to drug addiction, but the underlying biological basis of their increased vulnerability remains unknown. We reveal that translational control by phosphorylation of the translation initiation factor eIF2α (p-eIF2α) accounts for adolescent hypersensitivity to cocaine. In adolescent (but not adult) mice, a low dose of cocaine reduced p-eIF2α in the ventral tegmental area (VTA), potentiated synaptic inputs to VTA dopaminergic neurons, and induced drug-reinforced behavior. Like adolescents, adult mice with reduced p-eIF2α-mediated translational control were more susceptible to cocaine-induced synaptic potentiation and behavior. Conversely, like adults, adolescent mice with increased p-eIF2α became more resistant to cocaine's effects. Accordingly, metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD)—whose disruption is postulated to increase vulnerability to drug addiction—was impaired in both adolescent mice and adult mice with reduced p-eIF2α mediated translation. Thus, during addiction, cocaine hijacks translational control by p-eIF2α, initiating synaptic potentiation and addiction-related behaviors. These insights may hold promise for new treatments for addiction. DOI: http://dx.doi.org/10.7554/eLife.12052.001 PMID:26928234

DOE translation tool: Faster and better than ever

International Nuclear Information System (INIS)

El-Chakieh, T.; Vincent, C.

2006-01-01

CAE's constant push to advance power plant simulation practices involves continued investment in our technologies. This commitment has yielded many advances in our simulation technologies and tools to provide faster maintenance updates, easier process updates and higher fidelity models for power plant simulators. Through this quest, a comprehensive, self-contained and user-friendly DCS translation tool for plant control system emulation was created. The translation tool converts an ABB Advant AC160 and/or AC450 control system, used in both gas turbine-based, fossil and nuclear power plants, into Linux or Windows-based ROSE[reg] simulation schematics. The translation for a full combined-cycle gas turbine (CCGT) plant that comprises more than 5,300 function plans distributed over 15 nodes is processed in less than five hours on a dual 2.8Ghz Xeon Linux platform in comparison to the 12 hours required by CAE's previous translation tool. The translation process, using the plant configuration files, includes the parsing of the control algorithms, the databases, the graphic and the interconnection between nodes. A Linux or Windows API is then used to automatically populate the ROSE[reg] database. Without such a translation, tool or if ?stimulation? of real control system is not feasible or too costly, simulation of the DCS manually takes months of error prone manual coding. The translation can be performed for all the nodes constituting the configuration files of the whole plant DCS, or in order to provide faster maintenance updates and easier process updates, partial builds are possible at 3 levels: a. single schematic updates, b. multi-schematic updates and c. single node updates based on the user inputs into the Graphical User Interface. improvements including: - Process time reduction of over 60%; - All communication connections between nodes are fully automated; - New partial build for one schematic, a group of schematics or a single node; - Availability on PC

Translational models of infection prevention and control: lessons from studying high risk aging populations.

Science.gov (United States)

Mody, Lona

2018-06-13

The present review describes our research experiences and efforts in advancing the field of infection prevention and control in nursing facilities including postacute and long-term care settings. There are over two million infections in postacute and long-term care settings each year in the United States and $4 billion in associated costs. To define a target group most amenable to infection prevention and control interventions, we sought to quantify the relation between indwelling device use and microbial colonization in nursing facility patients. Using various methodologies including survey methods, observational epidemiology, randomized controlled studies, and collaboratives, we showed that indwelling device type is related to the site of multidrug-resistant organism (MDRO) colonization; multianatomic site colonization with MDROs is common; community-associated methicillin-resistant Staphylococcus aureus (MRSA) appeared in the nursing facility setting almost immediately following its emergence in acute care; (4) MDRO prevalence and catheter-associated infection rates can be reduced through a multimodal targeted infection prevention intervention; and (5) using a collaborative approach, such an intervention can be successfully scaled up. Our work advances the infection prevention field through translational research utilizing various methodologies, including quantitative and qualitative surveys, patient-oriented randomized controlled trials, and clinical microbiologic and molecular methods. The resulting interventions employ patient-oriented methods to reduce infections and antimicrobial resistance, and with partnerships from major national entities, can be implemented nationally.

Translational Control Protein 80 Stimulates IRES-Mediated Translation of p53 mRNA in Response to DNA Damage

Directory of Open Access Journals (Sweden)

Marie-Jo Halaby

2015-01-01

Full Text Available Synthesis of the p53 tumor suppressor increases following DNA damage. This increase and subsequent activation of p53 are essential for the protection of normal cells against tumorigenesis. We previously discovered an internal ribosome entry site (IRES that is located at the 5′-untranslated region (UTR of p53 mRNA and found that the IRES activity increases following DNA damage. However, the mechanism underlying IRES-mediated p53 translation in response to DNA damage is still poorly understood. In this study, we discovered that translational control protein 80 (TCP80 has increased binding to the p53 mRNA in vivo following DNA damage. Overexpression of TCP80 also leads to increased p53 IRES activity in response to DNA damage. TCP80 has increased association with RNA helicase A (RHA following DNA damage and overexpression of TCP80, along with RHA, leads to enhanced expression of p53. Moreover, we found that MCF-7 breast cancer cells with decreased expression of TCP80 and RHA exhibit defective p53 induction following DNA damage and diminished expression of its downstream target PUMA, a proapoptotic protein. Taken together, our discovery of the function of TCP80 and RHA in regulating p53 IRES and p53 induction following DNA damage provides a better understanding of the mechanisms that regulate IRES-mediated p53 translation in response to genotoxic stress.

A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism

Directory of Open Access Journals (Sweden)

Meera Shah

2016-08-01

Full Text Available The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer.

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.

Translator from the symbol coding language for the BUTs-20 processor of the in-core reactor control system

International Nuclear Information System (INIS)

Vorob'ev, D.M.; Golovanov, M.N.; Levin, G.L.; Parfenova, T.K.; Filatov, V.P.

1978-01-01

A symbolic-language code translator is described; it has been developed for automation of making up programs for in-core control systems. The translator is written in the ASSEMBLER language which is included in the software of the M-6000 computer. Two scannings of the source program are required for making up the operating program in the internal language of the BUTs-2O processor. The flowsheet and listing of the interrogation program of an analog-to-digital converter are presented. It is emphasized that the translator proposed allows a time reduction for constructing programs for the in-core control systems by a factor of 10-15 and an improvement of their quality

Program X4TOC4 (Version 86-1). Translation of experimental data from the EXFOR format to a computation format

International Nuclear Information System (INIS)

Cullen, D.E.

1986-09-01

Experimental nuclear reaction data are world-wide compiled in EXFOR format. The computer program X4TOC4 described in the present document translates data from the rather flexible EXFOR format to the more rigid ''computation format'' which is suitable for input to further computer processing of the data including graphical plotting. The program is available costfree from the IAEA Nuclear Data Section, upon request. (author)

SU-G-TeP4-15: The Roucoulette: A Set of Quality Control Tests for Dynamic Trajectory (4Pi) Treatment Delivery Techniques

Energy Technology Data Exchange (ETDEWEB)

Teke, T [BC Cancer Agency, Centre for the Southern Interior, Kelowna, BC (Canada)

2016-06-15

Purpose: To present and validate a set of quality control tests for trajectory treatment delivery using synchronized dynamic couch (translation and rotation), MLC and collimator motion. Methods: The quality control tests are based on the Picket fence test, which consist of 5 narrow band 2mm width spaced at 2.5cm intervals, and adds progressively synchronized dynamic motions. The tests were exposed on GafChromic EBT3 films. The first test is a regular (no motion and MLC static while beam is on) Picket Fence test used as baseline. The second test includes simultaneous collimator and couch rotation, each stripe corresponding to a different rotation speed. Errors in these tests were introduced (0.5 degree and 1 degree error in rotation synchronization) to assess the error sensitivity of this test. The second test is similar to the regular Picket Fence but now including dynamic MLC motion and couch translation (including acceleration during delivery) while the beam is on. Finally in the third test, which is a combination of the first and second test, the Picket Fence pattern is delivered using synchronized collimator and couch rotation and synchronized dynamic MLC and couch translation including acceleration. Films were analyzed with FilmQA Pro. Results: The distance between the peaks in the dose profile where measured (18.5cm away from the isocentre in the inplane direction where non synchronized rotation would have the largest effect) and compared to the regular Picket Fence tests. For well synchronized motions distances between peaks where between 24.9–25.4 mm identical to the regular Picket Fence test. This range increased to 24.4–26.4mm and 23.4–26.4mm for 0.5 degree and 1 degree error respectively. The amplitude also decreased up to 15% when errors are introduced. Conclusion: We demonstrated that the Roucoulette tests can be used as a quality control tests for trajectory treatment delivery using synchronized dynamic motion.

Inhibition of Group I Metabotropic Glutamate Receptors Reverses Autistic-Like Phenotypes Caused by Deficiency of the Translation Repressor eIF4E Binding Protein 2.

Science.gov (United States)

Aguilar-Valles, Argel; Matta-Camacho, Edna; Khoutorsky, Arkady; Gkogkas, Christos; Nader, Karim; Lacaille, Jean-Claude; Sonenberg, Nahum

2015-08-05

Exacerbated mRNA translation during brain development has been linked to autism spectrum disorders (ASDs). Deletion of the eukaryotic initiation factor 4E (eIF4E)-binding protein 2 gene (Eif4ebp2), encoding the suppressor of mRNA translation initiation 4E-BP2, leads to an imbalance in excitatory-to-inhibitory neurotransmission and ASD-like behaviors. Inhibition of group I metabotropic glutamate receptors (mGluRs) mGluR1 and mGluR5 reverses the autistic phenotypes in several ASD mouse models. Importantly, these receptors control synaptic physiology via activation of mRNA translation. We investigated the potential reversal of autistic-like phenotypes in Eif4ebp2(-/-) mice by using antagonists of mGluR1 (JNJ16259685) or mGluR5 (fenobam). Augmented hippocampal mGluR-induced long-term depression (LTD; or chemically induced mGluR-LTD) in Eif4ebp2(-/-) mice was rescued by mGluR1 or mGluR5 antagonists. While rescue by mGluR5 inhibition occurs through the blockade of a protein synthesis-dependent component of LTD, normalization by mGluR1 antagonists requires the activation of protein synthesis. Synaptically induced LTD was deficient in Eif4ebp2(-/-) mice, and this deficit was not rescued by group I mGluR antagonists. Furthermore, a single dose of mGluR1 (0.3 mg/kg) or mGluR5 (3 mg/kg) antagonists in vivo reversed the deficits in social interaction and repetitive behaviors (marble burying) in Eif4ebp2(-/-) mice. Our results demonstrate that Eif4ebp2(-/-) mice serve as a relevant model to test potential therapies for ASD symptoms. In addition, we provide substantive evidence that the inhibition of mGluR1/mGluR5 is an effective treatment for physiological and behavioral alterations caused by exacerbated mRNA translation initiation. Exacerbated mRNA translation during brain development is associated with several autism spectrum disorders (ASDs). We recently demonstrated that the deletion of a negative regulator of mRNA translation initiation, the eukaryotic initiation factor 4E

Characterization of the pumpkin Translationally-Controlled Tumor Protein CmTCTP.

Science.gov (United States)

Hinojosa-Moya, J Jesús; Xoconostle-Cázares, Beatriz; Toscano-Morales, Roberto; Ramírez-Ortega, Francisco; Cabrera-Ponce, José Luis; Ruiz-Medrano, Roberto

2013-01-01

In higher plants, the phloem plays a central role in the delivery of nutrients and signals from source to sink tissues. These signals likely coordinate different aspects of plant development, as well as its response to environmental cues. Although some phloem-transported proteins and RNAs may function as signaling molecules in plants, their mode of action remains poorly understood. Previous analysis of transcripts from CMV-infected pumpkin (Cucurbita maxima cv Big Max) identified a Translationally-Controlled Tumor Protein (TCTP) mRNA homolog, designated CmTCTP. In the present work this transcript was analyzed in terms of its expression pattern. This RNA accumulates, both in healthy and CMV-infected plants, in developing and mature phloem in petiole and roots, as well as in apices at high levels. The protein was present at lower levels in most cell types, and almost no signal was detected in apices, suggesting translational regulation of this RNA. Additionally, CmTCTP harbored by Agrobacterium rhizogenes is capable of inducing whole plant regeneration. These data suggest a role for CmTCTP in growth regulation, possibly through long-distance signaling.

Characterization of the pumpkin Translationally-Controlled Tumor Protein CmTCTP

Science.gov (United States)

Hinojosa-Moya, J Jesús; Xoconostle-Cázares, Beatriz; Toscano-Morales, Roberto; Ramírez-Ortega, Francisco; Luis Cabrera-Ponce, José; Ruiz-Medrano, Roberto

2013-01-01

In higher plants, the phloem plays a central role in the delivery of nutrients and signals from source to sink tissues. These signals likely coordinate different aspects of plant development, as well as its response to environmental cues. Although some phloem-transported proteins and RNAs may function as signaling molecules in plants, their mode of action remains poorly understood. Previous analysis of transcripts from CMV-infected pumpkin (Cucurbita maxima cv Big Max) identified a Translationally-Controlled Tumor Protein (TCTP) mRNA homolog, designated CmTCTP. In the present work this transcript was analyzed in terms of its expression pattern. This RNA accumulates, both in healthy and CMV-infected plants, in developing and mature phloem in petiole and roots, as well as in apices at high levels. The protein was present at lower levels in most cell types, and almost no signal was detected in apices, suggesting translational regulation of this RNA. Additionally, CmTCTP harbored by Agrobacterium rhizogenes is capable of inducing whole plant regeneration. These data suggest a role for CmTCTP in growth regulation, possibly through long-distance signaling. PMID:24065051

Crystal structure of a minimal eIF4E–Cup complex reveals a general mechanism of eIF4E regulation in translational repression

Science.gov (United States)

Kinkelin, Kerstin; Veith, Katharina; Grünwald, Marlene; Bono, Fulvia

2012-01-01

Cup is an eIF4E-binding protein (4E-BP) that plays a central role in translational regulation of localized mRNAs during early Drosophila development. In particular, Cup is required for repressing translation of the maternally contributed oskar, nanos, and gurken mRNAs, all of which are essential for embryonic body axis determination. Here, we present the 2.8 Å resolution crystal structure of a minimal eIF4E–Cup assembly, consisting of the interacting regions of the two proteins. In the structure, two separate segments of Cup contact two orthogonal faces of eIF4E. The eIF4E-binding consensus motif of Cup (YXXXXLΦ) binds the convex side of eIF4E similarly to the consensus of other eIF4E-binding proteins, such as 4E-BPs and eIF4G. The second, noncanonical, eIF4E-binding site of Cup binds laterally and perpendicularly to the eIF4E β-sheet. Mutations of Cup at this binding site were shown to reduce binding to eIF4E and to promote the destabilization of the associated mRNA. Comparison with the binding mode of eIF4G to eIF4E suggests that Cup and eIF4G binding would be mutually exclusive at both binding sites. This shows how a common molecular surface of eIF4E might recognize different proteins acting at different times in the same pathway. The structure provides insight into the mechanism by which Cup disrupts eIF4E–eIF4G interaction and has broader implications for understanding the role of 4E-BPs in translational regulation. PMID:22832024

Role of post-translational modifications at the β-subunit ectodomain in complex association with a promiscuous plant P4-ATPase.

Science.gov (United States)

Costa, Sara R; Marek, Magdalena; Axelsen, Kristian B; Theorin, Lisa; Pomorski, Thomas G; López-Marqués, Rosa L

2016-06-01

P-type ATPases of subfamily IV (P4-ATPases) constitute a major group of phospholipid flippases that form heteromeric complexes with members of the Cdc50 (cell division control 50) protein family. Some P4-ATPases interact specifically with only one β-subunit isoform, whereas others are promiscuous and can interact with several isoforms. In the present study, we used a site-directed mutagenesis approach to assess the role of post-translational modifications at the plant ALIS5 β-subunit ectodomain in the functionality of the promiscuous plant P4-ATPase ALA2. We identified two N-glycosylated residues, Asn(181) and Asn(231) Whereas mutation of Asn(231) seems to have a small effect on P4-ATPase complex formation, mutation of evolutionarily conserved Asn(181) disrupts interaction between the two subunits. Of the four cysteine residues located in the ALIS5 ectodomain, mutation of Cys(86) and Cys(107) compromises complex association, but the mutant β-subunits still promote complex trafficking and activity to some extent. In contrast, disruption of a conserved disulfide bond between Cys(158) and Cys(172) has no effect on the P4-ATPase complex. Our results demonstrate that post-translational modifications in the β-subunit have different functional roles in different organisms, which may be related to the promiscuity of the P4-ATPase. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

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.

Broca Pars Triangularis Constitutes a “Hub” of the Language-Control Network during Simultaneous Language Translation

Directory of Open Access Journals (Sweden)

Stefan Elmer

2016-09-01

Full Text Available Until now, several branches of research have fundamentally contributed to a better understanding of the ramifications of bilingualism, multilingualism, and language expertise on psycholinguistic-, cognitive-, and neural implications. In this context, it is noteworthy to mention that from a cognitive perspective, there is a strong convergence of data pointing to an influence of multilingual speech competence on a variety of cognitive functions, including attention, short-term- and working memory, set shifting, switching, and inhibition. In addition, complementary neuroimaging findings have highlighted a specific set of cortical and subcortical brain regions which fundamentally contribute to administrate cognitive control in the multilingual brain, namely Broca’s area, the middle-anterior cingulate cortex, the inferior parietal lobe, and the basal ganglia. However, a disadvantage of focusing on group analyses is that this procedure only enables an approximation of the neural networks shared within a population while at the same time smoothing inter-individual differences. In order to address both commonalities (i.e., within group analyses and inter-individual variability (i.e., single-subject analyses in language control mechanisms, here I measured five professional simultaneous interpreters while the participants overtly translated or repeated sentences with a simple subject-verb-object structure. Results demonstrated that pars triangularis was commonly activated across participants during backward translation (i.e., from L2 to L1, whereas the other brain regions of the control network showed a strong inter-individual variability during both backward and forward (i.e., from L1 to L2 translation. Thus, I propose that pars triangularis plays a crucial role within the language-control network and behaves as a fundamental processing entity supporting simultaneous language translation.

Controlled rotation and translation of spherical particles or living cells by surface acoustic waves.

Science.gov (United States)

Bernard, Ianis; Doinikov, Alexander A; Marmottant, Philippe; Rabaud, David; Poulain, Cédric; Thibault, Pierre

2017-07-11

We show experimental evidence of the acoustically-assisted micromanipulation of small objects like solid particles or blood cells, combining rotation and translation, using high frequency surface acoustic waves. This was obtained from the leakage in a microfluidic channel of two standing waves arranged perpendicularly in a LiNbO 3 piezoelectric substrate working at 36.3 MHz. By controlling the phase lag between the emitters, we could, in addition to translation, generate a swirling motion of the emitting surface which, in turn, led to the rapid rotation of spherical polystyrene Janus beads suspended in the channel and of human red and white blood cells up to several rounds per second. We show that these revolution velocities are compatible with a torque caused by the acoustic streaming that develops at the particles surface, like that first described by [F. Busse et al., J. Acoust. Soc. Am., 1981, 69(6), 1634-1638]. This device, based on standard interdigitated transducers (IDTs) adjusted to emit at equal frequencies, opens a way to a large range of applications since it allows the simultaneous control of the translation and rotation of hard objects, as well as the investigation of the response of cells to shear stress.

Behavioral and electrophysiological signatures of word translation processes.

Science.gov (United States)

Jost, Lea B; Radman, Narges; Buetler, Karin A; Annoni, Jean-Marie

2018-01-31

Translation is a demanding process during which a message is analyzed, translated and communicated from one language to another. Despite numerous studies on translation mechanisms, the electrophysiological processes underlying translation with overt production remain largely unexplored. Here, we investigated how behavioral response patterns and spatial-temporal brain dynamics differ in a translation compared to a control within-language word-generation task. We also investigated how forward and backward translation differs on the behavioral and electrophysiological level. To address these questions, healthy late bilingual subjects performed a translation and a within-language control task while a 128-channel EEG was recorded. Behavioral data showed faster responses for translation compared to within-language word generation and faster responses for backward than forward translation. The ERP-analysis revealed stronger early ( processes for between than within word generation. Later (424-630ms) differences were characterized by distinct engagement of domain-general control networks, namely self-monitoring and lexical access interference. Language asymmetry effects occurred at a later stage (600ms), reflecting differences in conceptual processing characterized by a larger involvement of areas implicated in attention, arousal and awareness for forward versus backward translation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Deregulation of sucrose-controlled translation of a bZIP-type transcription factor results in sucrose accumulation in leaves.

Directory of Open Access Journals (Sweden)

Sunil Kumar Thalor

Full Text Available Sucrose is known to repress the translation of Arabidopsis thaliana AtbZIP11 transcript which encodes a protein belonging to the group of S (S--stands for small basic region-leucine zipper (bZIP-type transcription factor. This repression is called sucrose-induced repression of translation (SIRT. It is mediated through the sucrose-controlled upstream open reading frame (SC-uORF found in the AtbZIP11 transcript. The SIRT is reported for 4 other genes belonging to the group of S bZIP in Arabidopsis. Tobacco tbz17 is phylogenetically closely related to AtbZIP11 and carries a putative SC-uORF in its 5'-leader region. Here we demonstrate that tbz17 exhibits SIRT mediated by its SC-uORF in a manner similar to genes belonging to the S bZIP group of the Arabidopsis genus. Furthermore, constitutive transgenic expression of tbz17 lacking its 5'-leader region containing the SC-uORF leads to production of tobacco plants with thicker leaves composed of enlarged cells with 3-4 times higher sucrose content compared to wild type plants. Our finding provides a novel strategy to generate plants with high sucrose content.

Deregulation of sucrose-controlled translation of a bZIP-type transcription factor results in sucrose accumulation in leaves.

Science.gov (United States)

Thalor, Sunil Kumar; Berberich, Thomas; Lee, Sung Shin; Yang, Seung Hwan; Zhu, Xujun; Imai, Ryozo; Takahashi, Yoshihiro; Kusano, Tomonobu

2012-01-01

Sucrose is known to repress the translation of Arabidopsis thaliana AtbZIP11 transcript which encodes a protein belonging to the group of S (S--stands for small) basic region-leucine zipper (bZIP)-type transcription factor. This repression is called sucrose-induced repression of translation (SIRT). It is mediated through the sucrose-controlled upstream open reading frame (SC-uORF) found in the AtbZIP11 transcript. The SIRT is reported for 4 other genes belonging to the group of S bZIP in Arabidopsis. Tobacco tbz17 is phylogenetically closely related to AtbZIP11 and carries a putative SC-uORF in its 5'-leader region. Here we demonstrate that tbz17 exhibits SIRT mediated by its SC-uORF in a manner similar to genes belonging to the S bZIP group of the Arabidopsis genus. Furthermore, constitutive transgenic expression of tbz17 lacking its 5'-leader region containing the SC-uORF leads to production of tobacco plants with thicker leaves composed of enlarged cells with 3-4 times higher sucrose content compared to wild type plants. Our finding provides a novel strategy to generate plants with high sucrose content.

A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism.

Science.gov (United States)

Shah, Meera; Su, Dan; Scheliga, Judith S; Pluskal, Tomáš; Boronat, Susanna; Motamedchaboki, Khatereh; Campos, Alexandre Rosa; Qi, Feng; Hidalgo, Elena; Yanagida, Mitsuhiro; Wolf, Dieter A

2016-08-16

The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Selective regulation of YB-1 mRNA translation by the mTOR signaling pathway is not mediated by 4E-binding protein.

Science.gov (United States)

Lyabin, D N; Ovchinnikov, L P

2016-03-02

The Y-box binding protein 1 (YB-1) is a key regulator of gene expression at the level of both translation and transcription. The mode of its action on cellular events depends on its subcellular distribution and the amount in the cell. So far, the regulatory mechanisms of YB-1 synthesis have not been adequately studied. Our previous finding was that selective inhibition of YB-1 mRNA translation was caused by suppression of activity of the mTOR signaling pathway. It was suggested that this event may be mediated by phosphorylation of the 4E-binding protein (4E-BP). Here, we report that 4E-BP alone can only slightly inhibit YB-1 synthesis both in the cell and in vitro, although it essentially decreases binding of the 4F-group translation initiation factors to mRNA. With inhibited mTOR kinase, the level of mRNA binding to the eIF4F-group factors was decreased, while that to 4E-BP1 was increased, as was observed for both mTOR kinase-sensitive mRNAs and those showing low sensitivity. This suggests that selective inhibition of translation of YB-1 mRNA, and probably some other mRNAs as well, by mTOR kinase inhibitors is not mediated by the action of the 4E-binding protein upon functions of the 4F-group translation initiation factors.

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.

Translation at Risk: the Script List as Hermeneutic Control

Directory of Open Access Journals (Sweden)

Richart, Mabel

2012-07-01

Full Text Available This paper intends to carry out a description and analysis of one of the first elements in any dubbing process: the script list delivered by a film distribution company to a dubbing studio for its translation. This is done with a twofold purpose: first, to offer a close description of a document that is not normally included in audiovisual translation studies, and second, to present it as one of the symptoms of the risks involved in any translation: misinterpretation and manipulation. At the same time, this paper provides some documents that support the analysis.

Characterisation of a novel homodimeric N-acetyl-β-D-glucosaminidase from Streptococcus gordonii

International Nuclear Information System (INIS)

Harty, Derek W.S.; Chen Yingjian; Simpson, Christine L.; Berg, Tracey; Cook, Simon L.; Mayo, John A.; Hunter, Neil; Jacques, Nicholas A.

2004-01-01

An N-acetyl-β-D-glucosaminidase (GcnA) from Streptococcus gordonii FSS2 was cloned and sequenced. GcnA had a deduced molecular mass of 72,120 Da. The molecular weight after gel-filtration chromatography was 140,000 Da and by SDS-PAGE was 70,000 Da, indicating that the native protein was a homodimer. The deduced amino acid sequence had significant homology to a glycosyl hydrolase from Streptococcus pneumoniae and the conserved catalytic domain of the Family 20 glycosyl hydrolases. GcnA catalysed the hydrolysis of the synthetic substrates, 4-methylumbelliferyl (4MU)-N-acetyl-β-D-glucosaminide, 4MU-N-acetyl-β-D-galactosaminide, 4-MU-β-D-N,N ' -diacetylchitobioside, and 4-MU-β-D-N,N ' ,N''-chitotrioside as well as the respective chito-oligosaccharides. GcnA was optimally active at pH 6.6 and 42 deg. C. The K m for 4-MU-β-D-N,N ' ,N''-chitotrioside, 45 μM, was the lowest for all the substrates tested. Hg 2+ , Cu 2+ , Fe 2+ , and Zn 2+ completely inhibited while Co 2+ , Mn 2+ , and Ni 2+ partially inhibited activity. S. gordonii FSS2 and a GcnA negative mutant grew equally well on chito-oligosaccharides as substrates. The S. gordonii sequencing projects indicate two further N-acetyl-β-D-glucosaminidase activities

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.

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.

Helper component proteinase of the genus Potyvirus is an interaction partner of translation initiation factors eIF(iso)4E and eIF4E and contains a 4E binding motif.

Science.gov (United States)

Ala-Poikela, Marjo; Goytia, Elisa; Haikonen, Tuuli; Rajamäki, Minna-Liisa; Valkonen, Jari P T

2011-07-01

The multifunctional helper component proteinase (HCpro) of potyviruses (genus Potyvirus; Potyviridae) shows self-interaction and interacts with other potyviral and host plant proteins. Host proteins that are pivotal to potyvirus infection include the eukaryotic translation initiation factor eIF4E and the isoform eIF(iso)4E, which interact with viral genome-linked protein (VPg). Here we show that HCpro of Potato virus A (PVA) interacts with both eIF4E and eIF(iso)4E, with interactions with eIF(iso)4E being stronger, as judged by the data of a yeast two-hybrid system assay. A bimolecular fluorescence complementation assay on leaves of Nicotiana benthamiana showed that HCpro from three potyviruses (PVA, Potato virus Y, and Tobacco etch virus) interacted with the eIF(iso)4E and eIF4E of tobacco (Nicotiana tabacum); interactions with eIF(iso)4E and eIF4E of potato (Solanum tuberosum) were weaker. In PVA-infected cells, interactions between HCpro and tobacco eIF(iso)4E were confined to round structures that colocalized with 6K2-induced vesicles. Point mutations introduced to a 4E binding motif identified in the C-terminal region of HCpro debilitated interactions of HCpro with translation initiation factors and were detrimental to the virulence of PVA in plants. The 4E binding motif conserved in HCpro of potyviruses and HCpro-initiation factor interactions suggest new roles for HCpro and/or translation factors in the potyvirus infection cycle.

Immunization of rabbits with highly purified, soluble, trimeric human immunodeficiency virus type 1 envelope glycoprotein induces a vigorous B cell response and broadly cross-reactive neutralization.

Directory of Open Access Journals (Sweden)

Gerald V Quinnan

Full Text Available Previously we described induction of cross-reactive HIV-1 neutralizing antibody responses in rabbits using a soluble HIV-1 gp140 envelope glycoprotein (Env in an adjuvant containing monophosphoryl lipid A (MPL and QS21 (AS02A. Here, we compared different forms of the same HIV-1 strain R2 Env for antigenic and biophysical characteristics, and in rabbits characterized the extent of B cell induction for specific antibody expression and secretion and neutralizing responses. The forms of this Env that were produced in and purified from stably transformed 293T cells included a primarily dimeric gp140, a trimeric gp140 appended to a GCN4 trimerization domain (gp140-GCN4, gp140-GCN4 with a 15 amino acid flexible linker between the gp120 and gp41 ectodomain (gp140-GCN4-L, also trimeric, and a gp140 with the flexible linker purified from cell culture supernatants as either dimer (gp140-L(D or monomer (gp140-L(M. Multimeric states of the Env proteins were assessed by native gel electrophoresis and analytical ultracentrifugation. The different forms of gp140 bound broadly cross-reactive neutralizing (BCN human monoclonal antibodies (mAbs similarly in ELISA and immunoprecipitation assays. All Envs bound CD4i mAbs in the presence and absence of sCD4, as reported for the R2 Env. Weak neutralization of some strains of HIV-1 was seen after two additional doses in AS02A. Rabbits that were given a seventh dose of gp140-GCN4-L developed BCN responses that were weak to moderate, similar to our previous report. The specificity of these responses did not appear similar to that of any of the known BCN human mAbs. Induction of spleen B cell and plasma cells producing immunoglobulins that bound trimeric gp140-GCN4-L was vigorous, based on ELISpot and flow cytometry analyses. The results demonstrate that highly purified gp140-GCN4-L trimer in adjuvant elicits BCN responses in rabbits accompanied by vigorous B cell induction.

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…

Engineering in translational medicine

CERN Document Server

2014-01-01

This book covers a broad area of engineering research in translational medicine. Leaders in academic institutions around the world contributed focused chapters on a broad array of topics such as: cell and tissue engineering (6 chapters), genetic and protein engineering (10 chapters), nanoengineering (10 chapters), biomedical instrumentation (4 chapters), and theranostics and other novel approaches (4 chapters). Each chapter is a stand-alone review that summarizes the state-of-the-art of the specific research area. Engineering in Translational Medicine gives readers a comprehensive and in-depth overview of a broad array of related research areas, making this an excellent reference book for scientists and students both new to engineering/translational medicine and currently working in this area.

Effect of boron and phosphorus codoping on the electronic and optical properties of graphitic carbon nitride monolayers: First-principle simulations

Science.gov (United States)

Yousefi, Mahdieh; Faraji, Monireh; Asgari, Reza; Moshfegh, Alireza Z.

2018-05-01

We study the effect of boron (B) and phosphorous (P) doping and B/P codoping on electronic and optical properties of graphitic carbon nitride (g-C3N4 or GCN) monolayers using density functional simulations. The energy band structure indicates that the incorporation of both B and P into a hexagonal lattice of GCN reduces the energy band gap from 3.1 for pristine GCN to 1.9 eV, thus extending light absorption toward the visible region. Moreover, on the basis of calculating absorption spectra and dielectric function, the codoped system exhibits an improved absorption intensity in the visible region and more electronic transitions, which named π* electronic transitions that occurred and were prohibited in the pristine GCN. These transitions can be attributed to charge redistribution upon doping, caused by distorted configurable B/P-codoped GCN confirmed by both electron density and Mulliken charge population. Therefore, B/P-codoped GCN is expected to be an auspicious candidate to be used as a promising photoelectrode in photoelectrochemical water splitting reactions leading to efficient solar H2 production.

The Effect of Holly Quran Voice With and Without Translation on Stress, Anxiety and Depression During Pregnancy: A Randomized Controlled Trial.

Science.gov (United States)

Jabbari, Batoul; Mirghafourvand, Mojgan; Sehhatie, Fahimeh; Mohammad-Alizadeh-Charandabi, Sakineh

2017-05-30

This study aimed to investigate the effect of Holy Quran on stress, anxiety and depression in Iranian pregnant women. A total of 168 participants were allocated randomly into three groups. Group I received broadcast of the Holy Quran with translation, group II received broadcast of the Holy Quran without translation, and group III was the control group. After intervention, scores of perceived stress, state anxiety, trait anxiety and depression in group I and group II were significantly lower compared with the control group. The Holly Quran with translation and without it, both are the effective for reducing stress, anxiety and depression during pregnancy.

Model of cap-dependent translation initiation in sea urchin: a step towards the eukaryotic translation regulation network.

Science.gov (United States)

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.

Translating Alcohol Research

Science.gov (United States)

Batman, Angela M.; Miles, Michael F.

2015-01-01

Alcohol use disorder (AUD) and its sequelae impose a major burden on the public health of the United States, and adequate long-term control of this disorder has not been achieved. Molecular and behavioral basic science research findings are providing the groundwork for understanding the mechanisms underlying AUD and have identified multiple candidate targets for ongoing clinical trials. However, the translation of basic research or clinical findings into improved therapeutic approaches for AUD must become more efficient. Translational research is a multistage process of streamlining the movement of basic biomedical research findings into clinical research and then to the clinical target populations. This process demands efficient bidirectional communication across basic, applied, and clinical science as well as with clinical practitioners. Ongoing work suggests rapid progress is being made with an evolving translational framework within the alcohol research field. This is helped by multiple interdisciplinary collaborative research structures that have been developed to advance translational work on AUD. Moreover, the integration of systems biology approaches with collaborative clinical studies may yield novel insights for future translational success. Finally, appreciation of genetic variation in pharmacological or behavioral treatment responses and optimal communication from bench to bedside and back may strengthen the success of translational research applications to AUD. PMID:26259085

A new method for the construction of a mutant library with a predictable occurrence rate using Poisson distribution.

Science.gov (United States)

Seong, Ki Moon; Park, Hweon; Kim, Seong Jung; Ha, Hyo Nam; Lee, Jae Yung; Kim, Joon

2007-06-01

A yeast transcriptional activator, Gcn4p, induces the expression of genes that are involved in amino acid and purine biosynthetic pathways under amino acid starvation. Gcn4p has an acidic activation domain in the central region and a bZIP domain in the C-terminus that is divided into the DNA-binding motif and dimerization leucine zipper motif. In order to identify amino acids in the DNA-binding motif of Gcn4p which are involved in transcriptional activation, we constructed mutant libraries in the DNA-binding motif through an innovative application of random mutagenesis. Mutant library made by oligonucleotides which were mutated randomly using the Poisson distribution showed that the actual mutation frequency was in good agreement with expected values. This method could save the time and effort to create a mutant library with a predictable mutation frequency. Based on the studies using the mutant libraries constructed by the new method, the specific residues of the DNA-binding domain in Gcn4p appear to be involved in the transcriptional activities on a conserved binding site.

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.

Particle Swarm-Based Translation Control for Immersed Tunnel Element in the Hong Kong-Zhuhai-Macao Bridge Project

Science.gov (United States)

Li, Jun-jun; Yang, Xiao-jun; Xiao, Ying-jie; Xu, Bo-wei; Wu, Hua-feng

2018-03-01

Immersed tunnel is an important part of the Hong Kong-Zhuhai-Macao Bridge (HZMB) project. In immersed tunnel floating, translation which includes straight and transverse movements is the main working mode. To decide the magnitude and direction of the towing force for each tug, a particle swarm-based translation control method is presented for non-power immersed tunnel element. A sort of linear weighted logarithmic function is exploited to avoid weak subgoals. In simulation, the particle swarm-based control method is evaluated and compared with traditional empirical method in the case of the HZMB project. Simulation results show that the presented method delivers performance improvement in terms of the enhanced surplus towing force.

Coordinated Control of Three-Dimensional Components of Smooth Pursuit to Rotating and Translating Textures.

Science.gov (United States)

Edinger, Janick; Pai, Dinesh K; Spering, Miriam

2017-01-01

The neural control of pursuit eye movements to visual textures that simultaneously translate and rotate has largely been neglected. Here we propose that pursuit of such targets-texture pursuit-is a fully three-dimensional task that utilizes all three degrees of freedom of the eye, including torsion. Head-fixed healthy human adults (n = 8) tracked a translating and rotating random dot pattern, shown on a computer monitor, with their eyes. Horizontal, vertical, and torsional eye positions were recorded with a head-mounted eye tracker. The torsional component of pursuit is a function of the rotation of the texture, aligned with its visual properties. We observed distinct behaviors between those trials in which stimulus rotation was in the same direction as that of a rolling ball ("natural") in comparison to those with the opposite rotation ("unnatural"): Natural rotation enhanced and unnatural rotation reversed torsional velocity during pursuit, as compared to torsion triggered by a nonrotating random dot pattern. Natural rotation also triggered pursuit with a higher horizontal velocity gain and fewer and smaller corrective saccades. Furthermore, we show that horizontal corrective saccades are synchronized with torsional corrective saccades, indicating temporal coupling of horizontal and torsional saccade control. Pursuit eye movements have a torsional component that depends on the visual stimulus. Horizontal and torsional eye movements are separated in the motor periphery. Our findings suggest that translational and rotational motion signals might be coordinated in descending pursuit pathways.

Translator/Revisor | IDRC - International Development Research ...

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

On request, performs quality control of texts translated or written by clients or ... of the Official Languages Act, the IDRC Translation Unit provides service for the ... Resources and Communications documents for the purposes of internal and ...

The impact of new translation technologies on specialized texts

Directory of Open Access Journals (Sweden)

Matthieu LeBlanc

2016-03-01

Full Text Available The introduction of translation technologies, especially translation memory software, has had a significant impact on both the translator’s professional practice and the target text itself. Apart from the fact that he or she must translate in a non-linear fashion due to the design of translation memory systems, the translator is now called upon to increase output and, in many cases, recycle what has already been translated by others. As a result, the translator, used to having full control over his or her text, is in some regards losing control over the translation process, which brings him or her to reflect on the quality of the final product and, in turn, on the transformations the field of specialized translation is undergoing. In this paper, I will present the results of an important ethnographic study conducted in three Canadian translation environments. I will focus mostly on the effects translation technologies and newly implemented practices have had on the quality of specialized texts destined for the Canadian market, where most of the specialized texts produced in French are in fact translations. Special attention will be given to the comments made by specialized translators during semi-directed interviews.

The small molecule '1-(4-biphenylylcarbonyl)-4-(5-bromo-2-methoxybenzyl) piperazine oxalate' and its derivatives regulate global protein synthesis by inactivating eukaryotic translation initiation factor 2-alpha.

Science.gov (United States)

Hong, Mi-Na; Nam, Ky-Youb; Kim, Kyung Kon; Kim, So-Young; Kim, InKi

2016-05-01

By environmental stresses, cells can initiate a signaling pathway in which eukaryotic translation initiation factor 2-alpha (eIF2-α) is involved to regulate the response. Phosphorylation of eIF2-α results in the reduction of overall protein neogenesis, which allows cells to conserve resources and to reprogram energy usage for effective stress control. To investigate the role of eIF2-α in cell stress responses, we conducted a viability-based compound screen under endoplasmic reticulum (ER) stress condition, and identified 1-(4-biphenylylcarbonyl)-4-(5-bromo-2-methoxybenzyl) piperazine oxalate (AMC-01) and its derivatives as eIF2-α-inactivating chemical. Molecular characterization of this signaling pathway revealed that AMC-01 induced inactivation of eIF2-α by phosphorylating serine residue 51 in a dose- and time-dependent manner, while the negative control compounds did not affect eIF2-α phosphorylation. In contrast with ER stress induction by thapsigargin, phosphorylation of eIF2-α persisted for the duration of incubation with AMC-01. By pathway analysis, AMC-01 clearly induced the activation of protein kinase RNA-activated (PKR) kinase and nuclear factor-κB (NF-κB), whereas it did not modulate the activity of PERK or heme-regulated inhibitor (HRI). Finally, we could detect a lower protein translation rate in cells incubated with AMC-01, establishing AMC-01 as a potent chemical probe that can regulate eIF2-α activity. We suggest from these data that AMC-01 and its derivative compounds can be used as chemical probes in future studies of the role of eIF2-α in protein synthesis-related cell physiology.

Enterovirus Control of Translation and RNA Granule Stress Responses.

Science.gov (United States)

Lloyd, Richard E

2016-03-30

Enteroviruses such as poliovirus (PV) and coxsackievirus B3 (CVB3) have evolved several parallel strategies to regulate cellular gene expression and stress responses to ensure efficient expression of the viral genome. Enteroviruses utilize their encoded proteinases to take over the cellular translation apparatus and direct ribosomes to viral mRNAs. In addition, viral proteinases are used to control and repress the two main types of cytoplasmic RNA granules, stress granules (SGs) and processing bodies (P-bodies, PBs), which are stress-responsive dynamic structures involved in repression of gene expression. This review discusses these processes and the current understanding of the underlying mechanisms with respect to enterovirus infections. In addition, the review discusses accumulating data suggesting linkage exists between RNA granule formation and innate immune sensing and activation.

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...

Post-translational Control of Intracellular Pathogen Sensing Pathways.

Science.gov (United States)

Chiang, Cindy; Gack, Michaela U

2017-01-01

Mammalian cells recognize virus-derived nucleic acids using a defined set of intracellular sensors including the DNA sensors cyclic GMP-AMP (cGAMP) synthase (cGAS) and interferon gamma (IFNγ)-inducible protein 16 (IFI16) as well as viral RNA receptors of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family. Following innate immune recognition, these sensors launch an immune response that is characterized by the transcriptional upregulation of many antiviral molecules, including proinflammatory cytokines, chemokines, and IFN-stimulated genes. Recent studies have demonstrated that the signal transduction initiated by these sensors is sophisticatedly regulated by post-translational modifications (PTMs) resulting in a robust yet 'tunable' cytokine response to maintain immune homeostasis. Here we summarize recent advances in our understanding of how PTMs and regulatory enzymes control the signaling activity of RLRs, cGAS, and IFI16 as well as their proximal adaptor proteins. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Translation as a Way of Intercultural Communication

Directory of Open Access Journals (Sweden)

Marina Alexeevna Laskovets

2014-09-01

Full Text Available The article focuses on the role of translation in teaching foreign languages to non-linguistic students and postgraduates. The translation is a way of intercultural communication. At present, the translation is not only a means of teaching and control, but also an objective of foreign language teaching and additional qualification, which is “translator of vocationally oriented texts”. The article highlights a number of issues of teaching specialized translation to non-linguistic students and postgraduates as a part of higher education in the Russian Federation.

Metal-free hybrids of graphitic carbon nitride and nanodiamonds for photoelectrochemical and photocatalytic applications.

Science.gov (United States)

Zhou, Li; Zhang, Huayang; Guo, Xiaochen; Sun, Hongqi; Liu, Shaomin; Tade, Moses O; Wang, Shaobin

2017-05-01

Graphitic carbon nitride (g-C 3 N 4 ) has been considered as a metal-free, cost-effective, eco-friendly and efficient catalyst for various photoelectrochemical applications. However, compared to conventional metal-based photocatalysts, its photocatalytic activity is still low because of the low mobility of carriers restricted by the polymer nature. Herein, a series of hybrids of g-C 3 N 4 (GCN) and nanodiamonds (NDs) were synthesized using a solvothermal method. The photoelectrochemical performance and photocatalytic efficiency of the GCN/NDs were investigated by means of the generation of photocurrent and photodegradation of methylene blue (MB) solutions under UV-visible light irradiations. In this study, the sample of GCN/ND-33% derived from 0.1g GCN and 0.05g NDs displayed the highest photocatalytic activity and the strongest photocurrent density. The mechanism of enhanced photoelectrochemical and photocatalytic performances was also discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Cap-independent translation of plant viral RNAs.

Science.gov (United States)

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.

Eukaryotic elongation factor 2 controls TNF-α translation in LPS-induced hepatitis

Science.gov (United States)

González-Terán, Bárbara; Cortés, José R.; Manieri, Elisa; Matesanz, Nuria; Verdugo, ρngeles; Rodríguez, María E.; González-Rodríguez, ρgueda; Valverde, ρngela; Martín, Pilar; Davis, Roger J.; Sabio, Guadalupe

2012-01-01

Bacterial LPS (endotoxin) has been implicated in the pathogenesis of acute liver disease through its induction of the proinflammatory cytokine TNF-α. TNF-α is a key determinant of the outcome in a well-established mouse model of acute liver failure during septic shock. One possible mechanism for regulating TNF-α expression is through the control of protein elongation during translation, which would allow rapid cell adaptation to physiological changes. However, the regulation of translational elongation is poorly understood. We found that expression of p38γ/δ MAPK proteins is required for the elongation of nascent TNF-α protein in macrophages. The MKK3/6-p38γ/δ pathway mediated an inhibitory phosphorylation of eukaryotic elongation factor 2 (eEF2) kinase, which in turn promoted eEF2 activation (dephosphorylation) and subsequent TNF-α elongation. These results identify a new signaling pathway that regulates TNF-α production in LPS-induced liver damage and suggest potential cell-specific therapeutic targets for liver diseases in which TNF-α production is involved. PMID:23202732

Composition of the SAGA complex in plants and its role in controlling gene expression in response to abiotic stresses.

Directory of Open Access Journals (Sweden)

Felipe eMoraga

2015-10-01

Full Text Available Protein complexes involved in epigenetic regulation of transcription have evolved as molecular strategies to face environmental stress in plants. SAGA (Spt–Ada–Gcn5 Acetyltransferase is a transcriptional co-activator complex that regulates numerous cellular processes through the coordination of multiple post-translational histone modifications, including acetylation, deubiquitination, and chromatin recognition. The diverse functions of the SAGA complex involve distinct modules that are highly conserved between yeast, flies, and mammals. In this review, the composition of the SAGA complex in plants is described and its role in gene expression regulation under stress conditions summarized. Some of these proteins are likely involved in the regulation of the inducible expression of genes under light, cold, drought, salt, and iron stress, although the functions of several of its components remain unknown.

Hindi translation and validation of Cambridge-Hopkins Diagnostic Questionnaire for RLS (CHRLSq).

Science.gov (United States)

Gupta, Ravi; Allan, Richard P; Pundeer, Ashwini; Das, Sourav; Dhyani, Mohan; Goel, Deepak

2015-01-01

Restless legs syndrome also known as Willis-Ekbom's Disease (RLS/WED) is a common illness. Cambridge-Hopkins diagnostic questionnaire for RLS (CHRLSq) is a good diagnostic tool and can be used in the epidemiological studies. However, its Hindi version is not available. Thus, this study was conducted to translate and validate it in the Hindi speaking population. After obtaining the permission from the author of the CHRLSq, it was translated into Hindi language by two independent translators. After a series of forward and back translations, the finalized Hindi version was administered to two groups by one of the authors, who were blinded to the clinical diagnosis. First group consisted of RLS/WED patients, where diagnosis was made upon face to face interview and the other group - the control group included subjects with somatic symptoms disorders or exertional myalgia or chronic insomnia. Each group had 30 subjects. Diagnosis made on CHRLSq was compared with the clinical diagnosis. Analysis was done using Statistical Package for Social Sciences (SPSS) v 21.0. Descriptive statistics was calculated. Proportions were compared using chi-square test; whereas, categorical variables were compared using independent sample t-test. Sensitivity, specificity, and positive predictive value of the translated version of questionnaire were calculated. Average age was comparable between the cases and control group (RLS/WED = 39.1 ± 10.1 years vs 36.2 ± 11.4 years in controls; P = 0.29). Women outnumbered men in the RLS/WED group (87% in RLS/WED group vs 57% among controls; χ(2) = 6.64; P = 0.01). Both the sensitivity and specificity of the translated version was 83.3%. It had the positive predictive value of 86.6%. Hindi version of CHRLSq has positive predictive value of 87% and it can be used to diagnose RLS in Hindi speaking population.

The translational repressor Crc controls the Pseudomonas putida benzoate and alkane catabolic pathways using a multi-tier regulation strategy.

Science.gov (United States)

Hernández-Arranz, Sofía; Moreno, Renata; Rojo, Fernando

2013-01-01

Metabolically versatile bacteria usually perceive aromatic compounds and hydrocarbons as non-preferred carbon sources, and their assimilation is inhibited if more preferable substrates are available. This is achieved via catabolite repression. In Pseudomonas putida, the expression of the genes allowing the assimilation of benzoate and n-alkanes is strongly inhibited by catabolite repression, a process controlled by the translational repressor Crc. Crc binds to and inhibits the translation of benR and alkS mRNAs, which encode the transcriptional activators that induce the expression of the benzoate and alkane degradation genes respectively. However, sequences similar to those recognized by Crc in benR and alkS mRNAs exist as well in the translation initiation regions of the mRNA of several structural genes of the benzoate and alkane pathways, which suggests that Crc may also regulate their translation. The present results show that some of these sites are functional, and that Crc inhibits the induction of both pathways by limiting not only the translation of their transcriptional activators, but also that of genes coding for the first enzyme in each pathway. Crc may also inhibit the translation of a gene involved in benzoate uptake. This multi-tier approach probably ensures the rapid regulation of pathway genes, minimizing the assimilation of non-preferred substrates when better options are available. A survey of possible Crc sites in the mRNAs of genes associated with other catabolic pathways suggested that targeting substrate uptake, pathway induction and/or pathway enzymes may be a common strategy to control the assimilation of non-preferred compounds. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

Role of post-translational modifications at the β-subunit ectodomain in complex association with a promiscuous plant P4-ATPase

DEFF Research Database (Denmark)

Costa, Sara; Marek, Magdalena; Axelsen, Kristian Buhl

2016-01-01

and can interact with several isoforms. In the present study, we used a site-directed mutagenesis approach to assess the role of post-translational modifications at the plant ALIS5 β-subunit ectodomain in the functionality of the promiscuous plant P4-ATPase ALA2. We identified two N-glycosylated residues......) compromises complex association, but the mutant β-subunits still promote complex trafficking and activity to some extent. In contrast, disruption of a conserved disulfide bond between Cys(158) and Cys(172) has no effect on the P4-ATPase complex. Our results demonstrate that post-translational modifications...

Pioneer round of translation occurs during serum starvation

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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.

Dengue virus-induced regulation of the host cell translational machinery

Directory of Open Access Journals (Sweden)

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.

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....

Regulation of mRNA translation during mitosis.

Science.gov (United States)

Tanenbaum, Marvin E; Stern-Ginossar, Noam; Weissman, Jonathan S; Vale, Ronald D

2015-08-25

Passage through mitosis is driven by precisely-timed changes in transcriptional regulation and protein degradation. However, the importance of translational regulation during mitosis remains poorly understood. Here, using ribosome profiling, we find both a global translational repression and identified ~200 mRNAs that undergo specific translational regulation at mitotic entry. In contrast, few changes in mRNA abundance are observed, indicating that regulation of translation is the primary mechanism of modulating protein expression during mitosis. Interestingly, 91% of the mRNAs that undergo gene-specific regulation in mitosis are translationally repressed, rather than activated. One of the most pronounced translationally-repressed genes is Emi1, an inhibitor of the anaphase promoting complex (APC) which is degraded during mitosis. We show that full APC activation requires translational repression of Emi1 in addition to its degradation. These results identify gene-specific translational repression as a means of controlling the mitotic proteome, which may complement post-translational mechanisms for inactivating protein function.

47 CFR 74.733 - UHF translator signal boosters.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false UHF translator signal boosters. 74.733 Section... Translator, and TV Booster Stations § 74.733 UHF translator signal boosters. (a) The licensee of a UHF television broadcast translator station may be authorized to operate one or more signal boosters for the...

Recent FRC translation experiments on FRX-C/T

International Nuclear Information System (INIS)

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

1985-01-01

Since the last CT Symposium, several accomplishments have been realized from the FRC translation studies on the FRX-C/T device: (1) FRCs have been launched into, and trapped in, a dc magnetic guide field region without the use of any pulsed ''gate'' coils; (2) detailed studies of translation dynamics have been performed which are consistent with energy conservation, adiabatic compression theory, and 2-D MHD simulations; (3) the confinement properties of translated FRC has been evaluated; (4) translation through either puff or static deuterium gas fill has been demonstrated; (5) higher density (n less than or equal to 4 x 10 15 cm -3 ) FRCs have been translated over 10-m lengths; (6) the n = 2 rotational instability has been stabilized by FRC translation into a weak helical quadrupole field

The plasticity of descending controls in pain: translational probing.

Science.gov (United States)

Bannister, Kirsty; Dickenson, A H

2017-07-01

Descending controls, comprising pathways that originate in midbrain and brainstem regions and project onto the spinal cord, have long been recognised as key links in the multiple neural networks that interact to produce the overall pain experience. There is clear evidence from preclinical and clinical studies that both peripheral and central sensitisation play important roles in determining the level of pain perceived. Much emphasis has been put on spinal cord mechanisms in central excitability, but it is now becoming clear that spinal hyperexcitability can be regulated by descending pathways from the brain that originate from predominantly noradrenergic and serotonergic systems. One pain can inhibit another. In this respect diffuse noxious inhibitory controls (DNIC) are a unique form of endogenous descending inhibitory pathway since they can be easily evoked and quantified in animals and man. The spinal pharmacology of pathways that subserve DNIC are complicated; in the normal situation these descending controls produce a final inhibitory effect through the actions of noradrenaline at spinal α 2 -adrenoceptors, although serotonin, acting on facilitatory spinal 5-HT 3 receptors, influences the final expression of DNIC also. These descending pathways are altered in neuropathy and the effects of excess serotonin may now become inhibitory through activation of spinal 5-HT 7 receptors. Conditioned pain modulation (CPM) is the human counterpart of DNIC and requires a descending control also. Back and forward translational studies between DNIC and CPM, gauged between bench and bedside, are key for the development of analgesic therapies that exploit descending noradrenergic and serotonergic control pathways. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Development Of Translational Motion Of Unmanned Aerial Vehicle Using MATLAB

Directory of Open Access Journals (Sweden)

Thwe Thwe Htoo

2015-08-01

Full Text Available This research work describes the translational motion analysis of unmanned aerial vehicle UAV. Since the center of mass of the receiver is timevarying the equations are written in a reference frame that is geometrically fixed in the aircraft. Due to the fact that aerial vehicle simulation and control deal with the position and orientation of the UAV the equations of motion are derived in terms of the translational and rotational position and velocity with respect to the aircraft location. The formation relative motion control is a challenging problem due to the coupled translational and rotational dynamics. As the translational vector depends on the current attitude and its angular velocity and some of the attitude constraints also couple the position and attitude of the spacecraft it makes the formation control problem high dimensional. This work develops UAV stability conditions including translational vector maneuverability condition and included angle condition between the translational and the rotational motion of UAV system and then presents two methods to calculate the UAV attitude. Both of the two methods need first design the optimal trajectory of the translational vector and then use geometric and nonlinear programming methods to calculate the target trajectory. The validity of the proposed approach is demonstrated in a UAV by using MATLAB. The performance of the translational motion control is evaluated by the simulated results.

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

Translation of an FRC plasma into a quasi-spherical confinement region

International Nuclear Information System (INIS)

Sekiguchi, Jun'ichi; Asai, Tomohiko; Takahashi, Tsutomu; Takahashi, Toshiki

2014-01-01

Translation of a Field-Reversed Configuration (FRC) into a quasi-spherical confinement region with super-alfvenic translation speed has been successfully conducted. Translation speed can be controlled in the range from 80 to 150 km/s by changing statically filled gas pressure. The translated FRC experiences radial decompression process rapidly when it enters into the confinement chamber. The separatrix shape of translated FRC is controlled through the translation process. Especially, in the case of FRC translation into deuterium gas atmosphere, elongation of the FRC is roughly unity. It indicates possible application of center solenoid onto the high-beta compact torus of FRC. Also, as a new finding, a rotational instability with an n=2 deformation has been observed in the translated FRC. (author)

Magnetic Control of Fe3O4 Nanomaterial for Fat Ablation in Microchannel

Directory of Open Access Journals (Sweden)

Ming Chang

2015-11-01

Full Text Available In this study, surface modification of iron (II, III oxide Fe3O4 nanoparticles by oleic acid (OA coating is investigated for the microablation of fat in a microchannel. The nanoparticles are synthesized by the co-precipitation method and then dispersed in organic solvent prior to mixing with the OA. The magnetization, agglomeration, and particle size distribution properties of the OA-coated Fe3O4 nanoparticles are characterized. The surface modification of the Fe3O4 nanoparticles reveals that upon injection into a microchannel, the lipophilicity of the OA coating influences the movement of the nanoparticles across an oil-phase barrier. The motion of the nanoparticles is controlled using an AC magnetic field to induce magnetic torque and a static gradient field to control linear translation. The fat microablation process in a microchannel is demonstrated using an oscillating driving field of less than 1200 Am−1.

The membrane-topogenic vectorial behaviour of Nrf1 controls its post-translational modification and transactivation activity.

Science.gov (United States)

Zhang, Yiguo; Hayes, John D

2013-01-01

The integral membrane-bound Nrf1 transcription factor fulfils important functions in maintaining cellular homeostasis and organ integrity, but how it is controlled vectorially is unknown. Herein, creative use of Gal4-based reporter assays with protease protection assays (GRAPPA), and double fluorescence protease protection (dFPP), reveals that the membrane-topogenic vectorial behaviour of Nrf1 dictates its post-translational modification and transactivation activity. Nrf1 is integrated within endoplasmic reticulum (ER) membranes through its NHB1-associated TM1 in cooperation with other semihydrophobic amphipathic regions. The transactivation domains (TADs) of Nrf1, including its Asn/Ser/Thr-rich (NST) glycodomain, are transiently translocated into the ER lumen, where it is glycosylated in the presence of glucose to become a 120-kDa isoform. Thereafter, the NST-adjoining TADs are partially repartitioned out of membranes into the cyto/nucleoplasmic side, where Nrf1 is subject to deglycosylation and/or proteolysis to generate 95-kDa and 85-kDa isoforms. Therefore, the vectorial process of Nrf1 controls its target gene expression.

Post-translational control of nitrate reductase activity responding to light and photosynthesis evolved already in the early vascular plants.

Science.gov (United States)

Nemie-Feyissa, Dugassa; Królicka, Adriana; Førland, Nina; Hansen, Margarita; Heidari, Behzad; Lillo, Cathrine

2013-05-01

Regulation of nitrate reductase (NR) by reversible phosphorylation at a conserved motif is well established in higher plants, and enables regulation of NR in response to rapid fluctuations in light intensity. This regulation is not conserved in algae NR, and we wished to test the evolutionary origin of the regulatory mechanism by physiological examination of ancient land plants. Especially a member of the lycophytes is of interest since their NR is candidate for regulation by reversible phosphorylation based on sequence analysis. We compared Selaginella kraussiana, a member of the lycophytes and earliest vascular plants, with the angiosperm Arabidopsis thaliana, and also tested the moss Physcomitrella patens. Interestingly, optimization of assay conditions revealed that S. kraussiana NR used NADH as an electron donor like A. thaliana, whereas P. patens NR activity depended on NADPH. Examination of light/darkness effects showed that S. kraussiana NR was rapidly regulated similar to A. thaliana NR when a differential (Mg(2+) contra EDTA) assay was used to reveal activity state of NR. This implies that already existing NR enzyme was post-translationally activated by light in both species. Light had a positive effect also on de novo synthesis of NR in S. kraussiana, which could be shown after the plants had been exposed to a prolonged dark period (7 days). Daily variations in NR activity were mainly caused by post-translational modifications. As for angiosperms, the post-translational light activation of NR in S. kraussiana was inhibited by 3-(3,4-dichlorophenyl)-1*1-dimethylurea (DCMU), an inhibitor of photosynthesis and stomata opening. Evolutionary, a post-translational control mechanism for NR have occurred before or in parallel with development of vascular tissue in land plants, and appears to be part of a complex mechanisms for coordination of CO2 and nitrogen metabolism in these plants. Copyright © 2013 Elsevier GmbH. All rights reserved.

Bi-polarized translation of ascidian maternal mRNA determinant pem-1 associated with regulators of the translation machinery on cortical Endoplasmic Reticulum (cER).

Science.gov (United States)

Paix, Alexandre; Le Nguyen, Phuong Ngan; Sardet, Christian

2011-09-01

Polarized cortical mRNA determinants such as maternal macho-1 and pem-1 in ascidians, like budding yeast mating factor ASH1 reside on the cER-mRNA domain a subdomain of cortical Endoplasmic Reticulum(ER) and are translated in its vicinity. Using high resolution imaging and isolated cortical fragments prepared from eggs and embryos we now find that macho-1 and pem-1 RNAs co-localize with phospho-protein regulators of translation initiation (MnK/4EBP/S6K). Translation of cortical pem-1 RNA follows its bi-polarized relocalization. About 10 min after fertilization or artificial activation with a calcium ionophore, PEM1 protein is detected in the vegetal cortex in the vicinity of pem-1 RNA. About 40 min after fertilization-when pem-1 RNA and P-MnK move to the posterior pole-PEM1 protein remains in place forming a network of cortical patches anchored at the level of the zygote plasma membrane before disappearing. Cortical PEM1 protein is detected again at the 4 cell stage in the posterior centrosome attracting body (CAB) region where the cER-mRNA domain harboring pem-1/P-MnK/P-4EBP/P-S6K is concentrated. Bi-polarized PEM1 protein signals are not detected when pem-1 morpholinos are injected into eggs or zygotes or when MnK is inhibited. We propose that localized translation of the pem-1 RNA determinant is triggered by the fertilization/calcium wave and that the process is controlled by phospho-protein regulators of translation initiation co-localized with the RNA determinant on a sub-domain of the cortical Endoplasmic Reticulum. Copyright © 2011 Elsevier Inc. All rights reserved.

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...

Structural basis for the Nanos-mediated recruitment of the CCR4-NOT complex and translational repression.

Science.gov (United States)

Bhandari, Dipankar; Raisch, Tobias; Weichenrieder, Oliver; Jonas, Stefanie; Izaurralde, Elisa

2014-04-15

The RNA-binding proteins of the Nanos family play an essential role in germ cell development and survival in a wide range of metazoan species. They function by suppressing the expression of target mRNAs through the recruitment of effector complexes, which include the CCR4-NOT deadenylase complex. Here, we show that the three human Nanos paralogs (Nanos1-3) interact with the CNOT1 C-terminal domain and determine the structural basis for the specific molecular recognition. Nanos1-3 bind CNOT1 through a short CNOT1-interacting motif (NIM) that is conserved in all vertebrates and some invertebrate species. The crystal structure of the human Nanos1 NIM peptide bound to CNOT1 reveals that the peptide opens a conserved hydrophobic pocket on the CNOT1 surface by inserting conserved aromatic residues. The substitutions of these aromatic residues in the Nanos1-3 NIMs abolish binding to CNOT1 and abrogate the ability of the proteins to repress translation. Our findings provide the structural basis for the recruitment of the CCR4-NOT complex by vertebrate Nanos, indicate that the NIMs are the major determinants of the translational repression mediated by Nanos, and identify the CCR4-NOT complex as the main effector complex for Nanos function.

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...

Cell type-specific translational repression of Cyclin B during meiosis in males.

Science.gov (United States)

Baker, Catherine Craig; Gim, Byung Soo; Fuller, Margaret T

2015-10-01

The unique cell cycle dynamics of meiosis are controlled by layers of regulation imposed on core mitotic cell cycle machinery components by the program of germ cell development. Although the mechanisms that regulate Cdk1/Cyclin B activity in meiosis in oocytes have been well studied, little is known about the trans-acting factors responsible for developmental control of these factors in male gametogenesis. During meiotic prophase in Drosophila males, transcript for the core cell cycle protein Cyclin B1 (CycB) is expressed in spermatocytes, but the protein does not accumulate in spermatocytes until just before the meiotic divisions. Here, we show that two interacting proteins, Rbp4 and Fest, expressed at the onset of spermatocyte differentiation under control of the developmental program of male gametogenesis, function to direct cell type- and stage-specific repression of translation of the core G2/M cell cycle component cycB during the specialized cell cycle of male meiosis. Binding of Fest to Rbp4 requires a 31-amino acid region within Rbp4. Rbp4 and Fest are required for translational repression of cycB in immature spermatocytes, with Rbp4 binding sequences in a cell type-specific shortened form of the cycB 3' UTR. Finally, we show that Fest is required for proper execution of meiosis I. © 2015. Published by The Company of Biologists Ltd.

Involvement of yeast HSP90 isoforms in response to stress and cell death induced by acetic acid.

Directory of Open Access Journals (Sweden)

Alexandra Silva

Full Text Available Acetic acid-induced apoptosis in yeast is accompanied by an impairment of the general protein synthesis machinery, yet paradoxically also by the up-regulation of the two isoforms of the heat shock protein 90 (HSP90 chaperone family, Hsc82p and Hsp82p. Herein, we show that impairment of cap-dependent translation initiation induced by acetic acid is caused by the phosphorylation and inactivation of eIF2α by Gcn2p kinase. A microarray analysis of polysome-associated mRNAs engaged in translation in acetic acid challenged cells further revealed that HSP90 mRNAs are over-represented in this polysome fraction suggesting preferential translation of HSP90 upon acetic acid treatment. The relevance of HSP90 isoform translation during programmed cell death (PCD was unveiled using genetic and pharmacological abrogation of HSP90, which suggests opposing roles for HSP90 isoforms in cell survival and death. Hsc82p appears to promote survival and its deletion leads to necrotic cell death, while Hsp82p is a pro-death molecule involved in acetic acid-induced apoptosis. Therefore, HSP90 isoforms have distinct roles in the control of cell fate during PCD and their selective translation regulates cellular response to acetic acid stress.

Dynamic Modeling of GAIT System Reveals Transcriptome Expansion and Translational Trickle Control Device

Science.gov (United States)

Yao, Peng; Potdar, Alka A.; Arif, Abul; Ray, Partho Sarothi; Mukhopadhyay, Rupak; Willard, Belinda; Xu, Yichi; Yan, Jun; Saidel, Gerald M.; Fox, Paul L.

2012-01-01

SUMMARY Post-transcriptional regulatory mechanisms superimpose “fine-tuning” control upon “on-off” switches characteristic of gene transcription. We have exploited computational modeling with experimental validation to resolve an anomalous relationship between mRNA expression and protein synthesis. Differential GAIT (Gamma-interferon Activated Inhibitor of Translation) complex activation repressed VEGF-A synthesis to a low, constant rate despite high, variable VEGFA mRNA expression. Dynamic model simulations indicated the presence of an unidentified, inhibitory GAIT element-interacting factor. We discovered a truncated form of glutamyl-prolyl tRNA synthetase (EPRS), the GAIT constituent that binds the 3’-UTR GAIT element in target transcripts. The truncated protein, EPRSN1, prevents binding of functional GAIT complex. EPRSN1 mRNA is generated by a remarkable polyadenylation-directed conversion of a Tyr codon in the EPRS coding sequence to a stop codon (PAY*). By low-level protection of GAIT element-bearing transcripts, EPRSN1 imposes a robust “translational trickle” of target protein expression. Genome-wide analysis shows PAY* generates multiple truncated transcripts thereby contributing to transcriptome expansion. PMID:22386318

Hindi translation and validation of Cambridge-Hopkins Diagnostic Questionnaire for RLS (CHRLSq

Directory of Open Access Journals (Sweden)

Ravi Gupta

2015-01-01

Full Text Available Background: Restless legs syndrome also known as Willis-Ekbom′s Disease (RLS/WED is a common illness. Cambridge-Hopkins diagnostic questionnaire for RLS (CHRLSq is a good diagnostic tool and can be used in the epidemiological studies. However, its Hindi version is not available. Thus, this study was conducted to translate and validate it in the Hindi speaking population. Materials and Methods: After obtaining the permission from the author of the CHRLSq, it was translated into Hindi language by two independent translators. After a series of forward and back translations, the finalized Hindi version was administered to two groups by one of the authors, who were blinded to the clinical diagnosis. First group consisted of RLS/WED patients, where diagnosis was made upon face to face interview and the other group - the control group included subjects with somatic symptoms disorders or exertional myalgia or chronic insomnia. Each group had 30 subjects. Diagnosis made on CHRLSq was compared with the clinical diagnosis. Statistical Analysis: Analysis was done using Statistical Package for Social Sciences (SPSS v 21.0. Descriptive statistics was calculated. Proportions were compared using chi-square test; whereas, categorical variables were compared using independent sample t-test. Sensitivity, specificity, and positive predictive value of the translated version of questionnaire were calculated. Results: Average age was comparable between the cases and control group (RLS/WED = 39.1 ± 10.1 years vs 36.2 ± 11.4 years in controls; P = 0.29. Women outnumbered men in the RLS/WED group (87% in RLS/WED group vs 57% among controls; χ2 = 6.64; P = 0.01. Both the sensitivity and specificity of the translated version was 83.3%. It had the positive predictive value of 86.6%. Conclusion: Hindi version of CHRLSq has positive predictive value of 87% and it can be used to diagnose RLS in Hindi speaking population.

Translational Creativity

DEFF Research Database (Denmark)

Nielsen, Sandro

2010-01-01

A long-established approach to legal translation focuses on terminological equivalence making translators strictly follow the words of source texts. Recent research suggests that there is room for some creativity allowing translators to deviate from the source texts. However, little attention...... is given to genre conventions in source texts and the ways in which they can best be translated. I propose that translators of statutes with an informative function in expert-to-expert communication may be allowed limited translational creativity when translating specific types of genre convention....... This creativity is a result of translators adopting either a source-language or a target-language oriented strategy and is limited by the pragmatic principle of co-operation. Examples of translation options are provided illustrating the different results in target texts. The use of a target-language oriented...

Clinical significance of overexpression of NRG1 and its receptors, HER3 and HER4, in gastric cancer patients.

Science.gov (United States)

Yun, Sumi; Koh, Jiwon; Nam, Soo Kyung; Park, Jung Ok; Lee, Sung Mi; Lee, Kyoungyul; Lee, Kyu Sang; Ahn, Sang-Hoon; Park, Do Joong; Kim, Hyung-Ho; Choe, Gheeyoung; Kim, Woo Ho; Lee, Hye Seung

2018-03-01

Neuregulin 1 (NRG1), a ligand for human epidermal growth factor (HER) 3 and HER4, can activates cell signaling pathways to promote carcinogenesis and metastasis. To investigate the clinicopathologic significance of NRG1 and its receptors, immunohistochemistry was performed for NRG1, HER3, and HER4 in 502 consecutive gastric cancers (GCs). Furthermore, HER2, microsatellite instability (MSI), and Epstein-Barr virus (EBV) status were investigated. NRG1 gene copy number (GCN) was determined by dual-color fluorescence in situ hybridization (FISH) in 388 available GCs. NRG1 overexpression was observed in 141 (28.1%) GCs and closely correlated with HER3 (P = 0.034) and HER4 (P overexpression was significantly associated with aggressive features, including infiltrative tumor growth, lymphovascular, and neural invasion, high pathologic stage, and poor prognosis (all P overexpression as an independent prognostic factor for survival (P = 0.040). HER3 and HER4 expressions were observed in 157 (31.3%) and 277 (55.2%), respectively. In contrast to NRG1, expression of these proteins was not associated with survival. NRG1 GCN gain (GCN ≥ 2.5) was detected in 14.7% patients, including two cases of amplification, and was moderately correlated with NRG1 overexpression (κ, 0.459; P overexpression in GC, overexpression of their ligand, NRG1, was associated with aggressive clinical features and represented an independent unfavorable prognostic factor. Therefore, NRG1 is a potential prognostic and therapeutic biomarker in GC patients.

Programming Post-Translational Control over the Metabolic Labeling of Cellular Proteins with a Noncanonical Amino Acid.

Science.gov (United States)

Thomas, Emily E; Pandey, Naresh; Knudsen, Sarah; Ball, Zachary T; Silberg, Jonathan J

2017-08-18

Transcriptional control can be used to program cells to label proteins with noncanonical amino acids by regulating the expression of orthogonal aminoacyl tRNA synthetases (aaRSs). However, we cannot yet program cells to control labeling in response to aaRS and ligand binding. To identify aaRSs whose activities can be regulated by interactions with ligands, we used a combinatorial approach to discover fragmented variants of Escherichia coli methionyl tRNA synthetase (MetRS) that require fusion to associating proteins for maximal activity. We found that these split proteins could be leveraged to create ligand-dependent MetRS using two approaches. When a pair of MetRS fragments was fused to FKBP12 and the FKBP-rapamycin binding domain (FRB) of mTOR and mutations were introduced that direct substrate specificity toward azidonorleucine (Anl), Anl metabolic labeling was significantly enhanced in growth medium containing rapamycin, which stabilizes the FKBP12-FRB complex. In addition, fusion of MetRS fragments to the termini of the ligand-binding domain of the estrogen receptor yielded proteins whose Anl metabolic labeling was significantly enhanced when 4-hydroxytamoxifen (4-HT) was added to the growth medium. These findings suggest that split MetRS can be fused to a range of ligand-binding proteins to create aaRSs whose metabolic labeling activities depend upon post-translational interactions with ligands.

Finite translation surfaces with maximal number of translations

OpenAIRE

Schlage-Puchta, Jan-Christoph; Weitze-Schmithuesen, Gabriela

2013-01-01

The natural automorphism group of a translation surface is its group of translations. For finite translation surfaces of genus g > 1 the order of this group is naturally bounded in terms of g due to a Riemann-Hurwitz formula argument. In analogy with classical Hurwitz surfaces, we call surfaces which achieve the maximal bound Hurwitz translation surfaces. We study for which g there exist Hurwitz translation surfaces of genus g.

Regulation by nitrate of protein synthesis and translation of RNA in maize roots

International Nuclear Information System (INIS)

McClure, P.R.; Bouthyette, P.Y.

1986-01-01

Roots of maize seedlings were exposed to 35 S-methionine in the presence or absence of nitrate. Using SDS-PAGE, nitrate-induced changes in labeled polypeptides were noted in the soluble (at 92, 63 and 21kD) and organellar(at 14kD) fractions, as well as in a membrane fraction of putative tonoplast origin (at 31kD). No nitrate-induced changes were noted in a plasmamembrane-enriched fraction or in a membrane fraction of mixed origin. Total RNA from nitrate-treated and control roots was translated in a rabbit reticulocyte system. Five translation products (94, 63, 41, 39 and 21kD) were identified as nitrate-inducible by comparative gel electrophoresis. Changes in protein synthesis and translation of mRNA were apparent within 2-3 h after introduction of nitrate. Within 4-6 h after removal of nitrate, the level of nitrate-inducible translation products diminished to that of control roots. In contrast, the 31kD tonoplast polypeptide was still labeled 26 h after removal of external nitrate and 35 S-methionine. The results will be discussed in relation to the nitrate induction of nitrate reductase, nitrite reductase, and the nitrate uptake system

Machine Translation Tools - Tools of The Translator's Trade

DEFF Research Database (Denmark)

Kastberg, Peter

2012-01-01

In this article three of the more common types of translation tools are presented, discussed and critically evaluated. The types of translation tools dealt with in this article are: Fully Automated Machine Translation (or FAMT), Human Aided Machine Translation (or HAMT) and Machine Aided Human...... Translation (or MAHT). The strengths and weaknesses of the different types of tools are discussed and evaluated by means of a number of examples. The article aims at two things: at presenting a sort of state of the art of what is commonly referred to as “machine translation” as well as at providing the reader...... with a sound basis for considering what translation tool (if any) is the most appropriate in order to meet his or her specific translation needs....

Magnetic super-hydrophilic carbon nanotubes/graphene oxide composite as nanocarriers of mesenchymal stem cells: Insights into the time and dose dependences.

Science.gov (United States)

Granato, Alessandro E C; Rodrigues, Bruno V M; Rodrigues-Junior, Dorival M; Marciano, Fernanda R; Lobo, Anderson O; Porcionatto, Marimelia A

2016-10-01

Among nanostructured materials, multi-walled carbon nanotubes (MWCNT) have demonstrated great potential for biomedical applications in recent years. After oxygen plasma etching, we can obtain super-hydrophilic MWCNT that contain graphene oxide (GO) at their tips. This material exhibits good dispersion in biological systems due to the presence of polar groups and its excellent magnetic properties due to metal particle residues from the catalyst that often remain trapped in its walls and tips. Here, we show for the first time a careful biological investigation using magnetic superhydrophilic MWCNT/GO (GCN composites). The objective of this study was to investigate the application of GCN for the in vitro immobilization of mesenchymal stem cells. Our ultimate goal was to develop a system to deliver mesenchymal stem cells to different tissues and organs. We show here that mesenchymal stem cells were able to internalize GCN with a consequent migration when subjected to a magnetic field. The cytotoxicity of GCN was time- and dose-dependent. We also observed that GCN internalization caused changes in the gene expression of the proteins involved in cell adhesion and migration, such as integrins, laminins, and the chemokine CXCL12, as well as its receptor CXCR4. These results suggest that GCN represents a potential new platform for mesenchymal stem cell immobilization at injury sites. Copyright © 2016 Elsevier B.V. All rights reserved.

Translation Techniques

OpenAIRE

Marcia Pinheiro

2015-01-01

In this paper, we discuss three translation techniques: literal, cultural, and artistic. Literal translation is a well-known technique, which means that it is quite easy to find sources on the topic. Cultural and artistic translation may be new terms. Whilst cultural translation focuses on matching contexts, artistic translation focuses on matching reactions. Because literal translation matches only words, it is not hard to find situations in which we should not use this technique.  Because a...

eIF2α Kinases Control Chalone Production in Dictyostelium discoideum ▿

Science.gov (United States)

Bowman, Robert L.; Xiong, Yanhua; Kirsten, Janet H.; Singleton, Charles K.

2011-01-01

Growing Dictyostelium cells secrete CfaD and AprA, two proteins that have been characterized as chalones. They exist within a high-molecular-weight complex that reversibly inhibits cell proliferation, but not growth, via cell surface receptors and a signaling pathway that includes G proteins. How the production of these two proteins is regulated is unknown. Dictyostelium cells possess three GCN2-type eukaryotic initiation factor 2 α subunit (eIF2α) kinases, proteins that phosphorylate the translational initiation factor eIF2α and possess a tRNA binding domain involved in their regulation. The Dictyostelium kinases have been shown to function during development in regulating several processes. We show here that expression of an unregulated, activated kinase domain greatly inhibits cell proliferation. The inhibitory effect on proliferation is not due to a general inhibition of translation. Instead, it is due to enhanced production of a secreted factor(s). Indeed, extracellular CfaD and AprA proteins, but not their mRNAs, are overproduced in cells expressing the activated kinase domain. The inhibition of proliferation is not seen when the activated kinase domain is expressed in cells lacking CfaD or AprA or in cells that contain a nonphosphorylatable eIF2α. We conclude that production of the chalones CfaD and AprA is translationally regulated by eIF2α phosphorylation. Both proteins are upregulated at the culmination of development, and this enhanced production is lacking in a strain that possesses a nonphosphorylatable eIF2α. PMID:21278229

Translation Ambiguity but Not Word Class Predicts Translation Performance

Science.gov (United States)

Prior, Anat; Kroll, Judith F.; Macwhinney, Brian

2013-01-01

We investigated the influence of word class and translation ambiguity on cross-linguistic representation and processing. Bilingual speakers of English and Spanish performed translation production and translation recognition tasks on nouns and verbs in both languages. Words either had a single translation or more than one translation. Translation…

Examining English-German Translation Ambiguity Using Primed Translation Recognition

Science.gov (United States)

Eddington, Chelsea M.; Tokowicz, Natasha

2013-01-01

Many words have more than one translation across languages. Such "translation-ambiguous" words are translated more slowly and less accurately than their unambiguous counterparts. We examine the extent to which word context and translation dominance influence the processing of translation-ambiguous words. We further examine how these factors…

A GRAMMATICAL ADJUSTMENT ANALYSIS OF STATISTICAL MACHINE TRANSLATION METHOD USED BY GOOGLE TRANSLATE COMPARED TO HUMAN TRANSLATION IN TRANSLATING ENGLISH TEXT TO INDONESIAN

Directory of Open Access Journals (Sweden)

Eko Pujianto

2017-04-01

Full Text Available Google translate is a program which provides fast, free and effortless translating service. This service uses a unique method to translate. The system is called ―Statistical Machine Translation‖, the newest method in automatic translation. Machine translation (MT is an area of many kinds of different subjects of study and technique from linguistics, computers science, artificial intelligent (AI, translation theory, and statistics. SMT works by using statistical methods and mathematics to process the training data. The training data is corpus-based. It is a compilation of sentences and words of the languages (SL and TL from translation done by human. By using this method, Google let their machine discovers the rules for themselves. They do this by analyzing millions of documents that have already been translated by human translators and then generate the result based on the corpus/training data. However, questions arise when the results of the automatic translation prove to be unreliable in some extent. This paper questions the dependability of Google translate in comparison with grammatical adjustment that naturally characterizes human translators' specific advantage. The attempt is manifested through the analysis of the TL of some texts translated by the SMT. It is expected that by using the sample of TL produced by SMT we can learn the potential flaws of the translation. If such exists, the partial of more substantial undependability of SMT may open more windows to the debates of whether this service may suffice the users‘ need.

Selected translated abstracts of Russian-language climate-change publications. 4: General circulation models

Energy Technology Data Exchange (ETDEWEB)

Burtis, M.D. [comp.] [Oak Ridge National Lab., TN (United States). Carbon Dioxide Information Analysis Center; Razuvaev, V.N.; Sivachok, S.G. [All-Russian Research Inst. of Hydrometeorological Information--World Data Center, Obninsk (Russian Federation)

1996-10-01

This report presents English-translated abstracts of important Russian-language literature concerning general circulation models as they relate to climate change. Into addition to the bibliographic citations and abstracts translated into English, this report presents the original citations and abstracts in Russian. Author and title indexes are included to assist the reader in locating abstracts of particular interest.

Analysis of Histones H3 and H4 Reveals Novel and Conserved Post-Translational Modifications in Sugarcane.

Science.gov (United States)

Moraes, Izabel; Yuan, Zuo-Fei; Liu, Shichong; Souza, Glaucia Mendes; Garcia, Benjamin A; Casas-Mollano, J Armando

2015-01-01

Histones are the main structural components of the nucleosome, hence targets of many regulatory proteins that mediate processes involving changes in chromatin. The functional outcome of many pathways is "written" in the histones in the form of post-translational modifications that determine the final gene expression readout. As a result, modifications, alone or in combination, are important determinants of chromatin states. Histone modifications are accomplished by the addition of different chemical groups such as methyl, acetyl and phosphate. Thus, identifying and characterizing these modifications and the proteins related to them is the initial step to understanding the mechanisms of gene regulation and in the future may even provide tools for breeding programs. Several studies over the past years have contributed to increase our knowledge of epigenetic gene regulation in model organisms like Arabidopsis, yet this field remains relatively unexplored in crops. In this study we identified and initially characterized histones H3 and H4 in the monocot crop sugarcane. We discovered a number of histone genes by searching the sugarcane ESTs database. The proteins encoded correspond to canonical histones, and their variants. We also purified bulk histones and used them to map post-translational modifications in the histones H3 and H4 using mass spectrometry. Several modifications conserved in other plants, and also novel modified residues, were identified. In particular, we report O-acetylation of serine, threonine and tyrosine, a recently identified modification conserved in several eukaryotes. Additionally, the sub-nuclear localization of some well-studied modifications (i.e., H3K4me3, H3K9me2, H3K27me3, H3K9ac, H3T3ph) is described and compared to other plant species. To our knowledge, this is the first report of histones H3 and H4 as well as their post-translational modifications in sugarcane, and will provide a starting point for the study of chromatin regulation in

The Role of Semantics in Translation Recognition: Effects of Number of Translations, Dominance of Translations and Semantic Relatedness of Multiple Translations

Science.gov (United States)

Laxen, Jannika; Lavaur, Jean-Marc

2010-01-01

This study aims to examine the influence of multiple translations of a word on bilingual processing in three translation recognition experiments during which French-English bilinguals had to decide whether two words were translations of each other or not. In the first experiment, words with only one translation were recognized as translations…

Translational control by the DEAD Box RNA helicase belle regulates ecdysone-triggered transcriptional cascades.

Directory of Open Access Journals (Sweden)

Robert J Ihry

Full Text Available Steroid hormones act, through their respective nuclear receptors, to regulate target gene expression. Despite their critical role in development, physiology, and disease, however, it is still unclear how these systemic cues are refined into tissue-specific responses. We identified a mutation in the evolutionarily conserved DEAD box RNA helicase belle/DDX3 that disrupts a subset of responses to the steroid hormone ecdysone during Drosophila melanogaster metamorphosis. We demonstrate that belle directly regulates translation of E74A, an ets transcription factor and critical component of the ecdysone-induced transcriptional cascade. Although E74A mRNA accumulates to abnormally high levels in belle mutant tissues, no E74A protein is detectable, resulting in misregulation of E74A-dependent ecdysone response genes. The accumulation of E74A mRNA in belle mutant salivary glands is a result of auto-regulation, fulfilling a prediction made by Ashburner nearly 40 years ago. In this model, Ashburner postulates that, in addition to regulating secondary response genes, protein products of primary response genes like E74A also inhibit their own ecdysone-induced transcription. Moreover, although ecdysone-triggered transcription of E74A appears to be ubiquitous during metamorphosis, belle-dependent translation of E74A mRNA is spatially restricted. These results demonstrate that translational control plays a critical, and previously unknown, role in refining transcriptional responses to the steroid hormone ecdysone.

Effect of display location on control-display stereotype strength for translational and rotational controls with linear displays.

Science.gov (United States)

Chan, Alan H S; Hoffmann, Errol R

2015-01-01

Experiments were designed to investigate the effects of control type and display location, relative to the operator, on the strength of control/display stereotypes. The Worringham and Beringer Visual Field principle and an extension of this principle for rotary controls (Hoffmann E.R., and Chan A.H.S. 2013). "The Worringham and Beringer 'Visual Field' Principle for Rotary Controls. Ergonomics." 56 (10): 1620-1624) indicated that, for a number of different control types (rotary and lever) on different planes, there should be no significant effect of the display location relative to the seated operator. Past data were surveyed and stereotype strengths listed. Experiments filled gaps where data are not available. Six different control types and seven display locations were used, as in the Frame of Reference Transformation Tool (FORT) model of Wickens et al. (Wickens, C.D., Keller, J.W., and Small, R.L. (2010). "Left. No, Right! Development of the Frame of Reference Transformation Tool (FORT)." Proceedings of the Human Factors and Ergonomics Society 54th Annual Meeting September 2010, 54: 1022-1026). Control/display arrangements with high stereotype strengths were evaluated yielding data for designers of complex control/display arrangements where the control and display are in different planes and for where the operator is moving. It was found possible to predict display/control arrangements with high stereotype strength, based on past data. Practitioner Summary: Controls and displays in complex arrangements need to have high compatibility. These experiments provide arrangements for six different controls (rotary and translational) and seven different display locations relative to the operator.

Translational profiling in childhood acute lymphoblastic leukemia: no evidence for glucocorticoid regulation of mRNA translation.

Science.gov (United States)

Aneichyk, Tatsiana; Bindreither, Daniel; Mantinger, Christine; Grazio, Daniela; Goetsch, Katrin; Kofler, Reinhard; Rainer, Johannes

2013-12-01

Glucocorticoids (GCs) are natural stress induced steroid hormones causing cell cycle arrest and cell death in lymphoid tissues. Therefore they are the central component in the treatment of lymphoid malignancies, in particular childhood acute lymphoblastic leukemia (chALL). GCs act mainly via regulating gene transcription, which has been intensively studied by us and others. GC control of mRNA translation has also been reported but has never been assessed systematically. In this study we investigate the effect of GCs on mRNA translation on a genome-wide scale. Childhood T- (CCRF-CEM) and precursor B-ALL (NALM6) cells were exposed to GCs and subjected to "translational profiling", a technique combining sucrose-gradient fractionation followed by Affymetrix Exon microarray analysis of mRNA from different fractions, to assess the translational efficiency of the expressed genes. Analysis of GC regulation in ribosome-bound fractions versus transcriptional regulation revealed no significant differences, i.e., GC did not entail a significant shift between ribosomal bound and unbound mRNAs. In the present study we analyzed for the first time possible effects of GC on the translational efficiency of expressed genes in two chALL model systems employing whole genome polysome profiling. Our results did not reveal significant differences in translational efficiency of expressed genes thereby arguing against a potential widespread regulatory effect of GCs on translation at least in the investigated in vitro systems.

PERSONALITY TYPE AND TRANSLATION PERFORMANCE OF PERSIAN TRANSLATOR TRAINEES

Directory of Open Access Journals (Sweden)

Reza Shaki

2017-09-01

Full Text Available The study investigated the relationship between the personality typology of a sample of Iranian translation students and their translation quality in terms of expressive, appellative, and informative text types. The study also attempted to identify the personality types that can perform better in English to Persian translation of the three text types. For that purpose, the personality type and the translation quality of the participants was assessed using Myers-Briggs Type Indicator (MBTI personality test and translation quality assessment (TQA, respectively. The analysis of the data revealed that the personality type of the participants seemed relevant to the translation quality of all the text types. The translation quality of the participants with intuitive and thinking types was significantly better than the sensing type counterparts in translating expressive texts. The participants with intuitive and feeling types also performed better than their counterparts with sensing type in translation of the informative text. Moreover, the participants with intuitive, feeling, and thinking personality types performed more successfully than the participants with sensing type in translation of the appellative text. The findings of the study are discussed in light of the existing research literature.

Type 2 Translational Research for CKD

OpenAIRE

Tuttle, Katherine R.; Tuot, Delphine S.; Corbett, Cynthia L.; Setter, Stephen M.; Powe, Neil R.

2013-01-01

Strategies to effectively treat people with CKD have been identified by conventional clinical research. Despite this evidence, awareness, screening, detection, diagnosis, risk factor control, treatment, and outcomes remain substandard. Translating clinical evidence into actionable measures that reduce the burden of CKD is a pressing need. Expansion from a “bench-to-bedside” paradigm (conventional type 1 translation) to research that encompasses “clinic and community” is the core concept of ty...

JOVIAL (J73) to Ada Translator.

Science.gov (United States)

1982-06-01

editors, file managers , and other APSE , the Translator will Provide significant (though not total) Ltion of the conversion of J73 Proorams for use...vlobal knowlede only of compool declarationsi externals are not resolved until the compiled modules are linked. Creatinv a vlobal data base durin...translation (as shown in Figure 2-1) will require the Job control, file management , and text editing capabilities which are provided by a typical

Reassessment of the role of TSC, mTORC1 and microRNAs in amino acids-meditated translational control of TOP mRNAs.

Directory of Open Access Journals (Sweden)

Ilona Patursky-Polischuk

Full Text Available TOP mRNAs encode components of the translational apparatus, and repression of their translation comprises one mechanism, by which cells encountering amino acid deprivation downregulate the biosynthesis of the protein synthesis machinery. This mode of regulation involves TSC as knockout of TSC1 or TSC2 rescued TOP mRNAs translation in amino acid-starved cells. The involvement of mTOR in translational control of TOP mRNAs is demonstrated by the ability of constitutively active mTOR to relieve the translational repression of TOP mRNA upon amino acid deprivation. Consistently, knockdown of this kinase as well as its inhibition by pharmacological means blocked amino acid-induced translational activation of these mRNAs. The signaling of amino acids to TOP mRNAs involves RagB, as overexpression of active RagB derepressed the translation of these mRNAs in amino acid-starved cells. Nonetheless, knockdown of raptor or rictor failed to suppress translational activation of TOP mRNAs by amino acids, suggesting that mTORC1 or mTORC2 plays a minor, if any, role in this mode of regulation. Finally, miR10a has previously been suggested to positively regulate the translation of TOP mRNAs. However, we show here that titration of this microRNA failed to downregulate the basal translation efficiency of TOP mRNAs. Moreover, Drosha knockdown or Dicer knockout, which carries out the first and second processing steps in microRNAs biosynthesis, respectively, failed to block the translational activation of TOP mRNAs by amino acid or serum stimulation. Evidently, these results are questioning the positive role of microRNAs in this mode of regulation.

Translation initiation mediated by nuclear cap-binding protein complex.

Science.gov (United States)

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].

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.

Science.gov (United States)

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.

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.

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

Comparing three knowledge communication strategies - Diffusion, Dissemination and Translation - through randomized controlled studies.

Science.gov (United States)

Lane, Joseph P; Stone, Vathsala I

2015-01-01

This paper describes a series of three randomized controlled case studies comparing the effectiveness of three strategies for communicating new research-based knowledge (Diffusion, Dissemination, Translation), to different Assistive Technology (AT) stakeholder groups. Pre and post intervention measures for level of knowledge use (unaware, aware, interested, using) via the LOKUS instrument, assessed the relative effectiveness of the three strategies. The latter two approaches were both more effective than diffusion but also equally effective. The results question the value added by tailoring research findings to specific audiences, and instead supports the critical yet neglected role for relevance in determining knowledge use by stakeholders.

Translation, modification and cellular distribution of two AC4 variants of African cassava mosaic virus in yeast and their pathogenic potential in plants

International Nuclear Information System (INIS)

Hipp, Katharina; Rau, Peter; Schäfer, Benjamin; Pfannstiel, Jens; Jeske, Holger

2016-01-01

Plant infecting geminiviruses encode a small (A)C4 protein within the open reading frame of the replication-initiator protein. In African cassava mosaic virus, two in-frame start codons may be used for the translation of a longer and a shorter AC4 variant. Both were fused to green fluorescent protein or glutathione-S-transferase genes and expressed in fission yeast. The longer variant accumulated in discrete spots in the cytoplasm, whereas the shorter variant localized to the plasma membrane. A similar expression pattern was found in plants. A myristoylation motif may promote a targeting of the shorter variant to the plasma membrane. Mass spectrometry analysis of the yeast-expressed shorter variant detected the corresponding myristoylation. The biological relevance of the second start codon was confirmed using mutated infectious clones. Whereas mutating the first start codon had no effect on the infectivity in Nicotiana benthamiana plants, the second start codon proved to be essential. -- Highlights: •The ACMV AC4 may be translated from one or the other in-frame start codon. •Both AC4 variants are translated in fission yeast. •The long AC4 protein localizes to the cytoplasm, the short to the plasma membrane. •The short variant is myristoylated in yeast and may promote membrane localization. •Only the shorter AC4 variant has an impact on viral infections in plants.

Translation, modification and cellular distribution of two AC4 variants of African cassava mosaic virus in yeast and their pathogenic potential in plants

Energy Technology Data Exchange (ETDEWEB)

Hipp, Katharina, E-mail: katharina.hipp@bio.uni-stuttgart.de [University of Stuttgart, Institute of Biomaterials and biomolecular Systems, Department of Molecular Biology and Plant Virology, Pfaffenwaldring 57, 70550 Stuttgart (Germany); Rau, Peter; Schäfer, Benjamin [University of Stuttgart, Institute of Biomaterials and biomolecular Systems, Department of Molecular Biology and Plant Virology, Pfaffenwaldring 57, 70550 Stuttgart (Germany); Pfannstiel, Jens [University of Hohenheim, Mass Spectrometry Core Facility, August-von-Hartmann-Straße 3, 70599 Stuttgart (Germany); Jeske, Holger [University of Stuttgart, Institute of Biomaterials and biomolecular Systems, Department of Molecular Biology and Plant Virology, Pfaffenwaldring 57, 70550 Stuttgart (Germany)

2016-11-15

Plant infecting geminiviruses encode a small (A)C4 protein within the open reading frame of the replication-initiator protein. In African cassava mosaic virus, two in-frame start codons may be used for the translation of a longer and a shorter AC4 variant. Both were fused to green fluorescent protein or glutathione-S-transferase genes and expressed in fission yeast. The longer variant accumulated in discrete spots in the cytoplasm, whereas the shorter variant localized to the plasma membrane. A similar expression pattern was found in plants. A myristoylation motif may promote a targeting of the shorter variant to the plasma membrane. Mass spectrometry analysis of the yeast-expressed shorter variant detected the corresponding myristoylation. The biological relevance of the second start codon was confirmed using mutated infectious clones. Whereas mutating the first start codon had no effect on the infectivity in Nicotiana benthamiana plants, the second start codon proved to be essential. -- Highlights: •The ACMV AC4 may be translated from one or the other in-frame start codon. •Both AC4 variants are translated in fission yeast. •The long AC4 protein localizes to the cytoplasm, the short to the plasma membrane. •The short variant is myristoylated in yeast and may promote membrane localization. •Only the shorter AC4 variant has an impact on viral infections in plants.

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.

Assessing Aptitude and Attitude Development in a Translation Skills Course

Science.gov (United States)

Mekheimer, Mohamed Amin A.

2012-01-01

This study investigates the effects on EFL students of using Blackboard technology and online dictionaries in developing translating skills and building positive attitudes towards translation in male Saudi college students. The study compares two groups of students in a translation course; one in a traditional, face-to-face setting (control) and…

The Equivalence of Translated Songs Lyrics and their Effects - The Case of Translated Ecclesial Songs

Directory of Open Access Journals (Sweden)

S. Suharto

2015-01-01

Full Text Available This study aimed at describing the equivalence of eclessial song lyrics, which belong to the content word, the meaning of the sentences and their effect on church songs. The method used in this study is descriptive and qualitative by using music, language, and interdiciline approach. The data collection method used questionnaires technique, interview, documents and content analysis. The data used are 5 documents of songs chosen purposively as the primary data. Based on the data being analyzed, the results of this study were: 1 The translated content word located in the same bars and equivalent was around 27.07%, the translated content word located in the same bars, but not equivalent was 18.34%, the translated content word located in the different bars, but equivalent was 11.79%, the translated content word located in the different bars and not equivalent was 2.62%, and the untranslated words were 4.17%. 2 The translation of equivalence beautiful lyrics showed the beauty of the song was equivalent at 17.02%, the beauty of the song was less equivalent at 29.78%, the beauty of the song was not equivalent of 61.70%. 3. The differences of structure caused the incorrect dictions or choice of words and missing words in the translated lyrics.

Post-translational processing of synaptophysin in the rat retina is disrupted by diabetes.

Directory of Open Access Journals (Sweden)

Travis S D'Cruz

Full Text Available Synaptophysin, is an abundant presynaptic protein involved in synaptic vesicle recycling and neurotransmitter release. Previous work shows that its content is significantly reduced in the rat retina by streptozotocin (STZ-diabetes. This study tested the hypothesis that STZ-diabetes alters synaptophysin protein turnover and glycosylation in the rat retina. Whole explant retinas from male Sprague-Dawley rats were used in this study. Rats were made diabetic by a single intraperitoneal STZ injection (65 mg/kg body weight in 10 mM sodium citrate, pH 4.5. mRNA translation was measured using a (35S-methionine labeling assay followed by synaptophysin immunoprecipitation and autoradiography. A pulse-chase study was used to determine the depletion of newly synthesized synaptophysin. Depletion of total synaptophysin was determined after treatment with cycloheximide. Mannose rich N-glycosylated synaptophysin was detected by treating retinal lysates with endoglycosidase H followed by immunoblot analysis. Synaptophysin mRNA translation was significantly increased after 1 month (p<0.001 and 2 months (p<0.05 of STZ-diabetes, compared to age-matched controls. Newly synthesized synaptophysin degradation was significantly accelerated in the retina after 1 and 2 months of diabetes compared to controls (p<0.05. Mannose rich glycosylated synaptophysin was significantly increased after 1 month of STZ-diabetes compared to controls (p<0.05.These data suggest that diabetes increases mRNA translation of synaptophysin in the retina, resulting in an accumulation of mannose rich glycosylated synaptophysin, a transient post-translational state of the protein. This diabetes-induced irregularity in post-translational processing could explain the accelerated degradation of retinal synaptophysin in diabetes.

Pauses by Student and Professional Translators in Translation Process

Directory of Open Access Journals (Sweden)

Rusdi Noor Rosa

2018-01-01

Full Text Available Translation as a process of meaning making activity requires a cognitive process one of which is realized in a pause, a temporary stop or a break indicating doing other than typing activities in a certain period of translation process. Scholars agree that pauses are an indicator of cognitive process without which there will never be any translation practices. Despite such agreement, pauses are debatable as well, either in terms of their length or in terms of the activities managed by a translator while taking pauses. This study, in particular, aims at finding out how student translators and professional translators managed the pauses in a translation process. This was a descriptive research taking two student translators and two professional translators as the participants who were asked to translate a text from English into bahasa Indonesia. The source text (ST was a historical recount text entitled ‘Early History of Yellowstone National Park’ downloaded from http://www.nezperce.com/yelpark9.html composed of 230-word long from English into bahasa Indonesia. The data were collected using Translog protocols, think aloud protocols (TAPs and screen recording. Based on the data analysis, it was found that student translators took the longest pauses in the drafting phase spent to solve the problems related to finding out the right equivalent for the ST words or terms and to solve the difficulties encountered in encoding their ST understanding in the TL; meanwhile, professional translators took the longest pauses in the pos-drafting phase spent to ensure whether their TT had been natural and whether their TT had corresponded to the prevailing grammatical rules of the TL.

Performance limitations of translationally symmetric nonimaging devices

Science.gov (United States)

Bortz, John C.; Shatz, Narkis E.; Winston, Roland

2001-11-01

The component of the optical direction vector along the symmetry axis is conserved for all rays propagated through a translationally symmetric optical device. This quality, referred to herein as the translational skew invariant, is analogous to the conventional skew invariant, which is conserved in rotationally symmetric optical systems. The invariance of both of these quantities is a consequence of Noether's theorem. We show how performance limits for translationally symmetric nonimaging optical devices can be derived from the distributions of the translational skew invariant for the optical source and for the target to which flux is to be transferred. Examples of computed performance limits are provided. In addition, we show that a numerically optimized non-tracking solar concentrator utilizing symmetry-breaking surface microstructure can overcome the performance limits associated with translational symmetry. The optimized design provides a 47.4% increase in efficiency and concentration relative to an ideal translationally symmetric concentrator.

Machine translation

Energy Technology Data Exchange (ETDEWEB)

Nagao, M

1982-04-01

Each language has its own structure. In translating one language into another one, language attributes and grammatical interpretation must be defined in an unambiguous form. In order to parse a sentence, it is necessary to recognize its structure. A so-called context-free grammar can help in this respect for machine translation and machine-aided translation. Problems to be solved in studying machine translation are taken up in the paper, which discusses subjects for semantics and for syntactic analysis and translation software. 14 references.

Sulfur availability regulates plant growth via glucose-TOR signaling.

Science.gov (United States)

Dong, Yihan; Silbermann, Marleen; Speiser, Anna; Forieri, Ilaria; Linster, Eric; Poschet, Gernot; Allboje Samami, Arman; Wanatabe, Mutsumi; Sticht, Carsten; Teleman, Aurelio A; Deragon, Jean-Marc; Saito, Kazuki; Hell, Rüdiger; Wirtz, Markus

2017-10-27

Growth of eukaryotic cells is regulated by the target of rapamycin (TOR). The strongest activator of TOR in metazoa is amino acid availability. The established transducers of amino acid sensing to TOR in metazoa are absent in plants. Hence, a fundamental question is how amino acid sensing is achieved in photo-autotrophic organisms. Here we demonstrate that the plant Arabidopsis does not sense the sulfur-containing amino acid cysteine itself, but its biosynthetic precursors. We identify the kinase GCN2 as a sensor of the carbon/nitrogen precursor availability, whereas limitation of the sulfur precursor is transduced to TOR by downregulation of glucose metabolism. The downregulated TOR activity caused decreased translation, lowered meristematic activity, and elevated autophagy. Our results uncover a plant-specific adaptation of TOR function. In concert with GCN2, TOR allows photo-autotrophic eukaryotes to coordinate the fluxes of carbon, nitrogen, and sulfur for efficient cysteine biosynthesis under varying external nutrient supply.

Translational Control of Host Gene Expression by a Cys-Motif Protein Encoded in a Bracovirus.

Directory of Open Access Journals (Sweden)

Eunseong Kim

Full Text Available Translational control is a strategy that various viruses use to manipulate their hosts to suppress acute antiviral response. Polydnaviruses, a group of insect double-stranded DNA viruses symbiotic to some endoparasitoid wasps, are divided into two genera: ichnovirus (IV and bracovirus (BV. In IV, some Cys-motif genes are known as host translation-inhibitory factors (HTIF. The genome of endoparasitoid wasp Cotesia plutellae contains a Cys-motif gene (Cp-TSP13 homologous to an HTIF known as teratocyte-secretory protein 14 (TSP14 of Microplitis croceipes. Cp-TSP13 consists of 129 amino acid residues with a predicted molecular weight of 13.987 kDa and pI value of 7.928. Genomic DNA region encoding its open reading frame has three introns. Cp-TSP13 possesses six conserved cysteine residues as other Cys-motif genes functioning as HTIF. Cp-TSP13 was expressed in Plutella xylostella larvae parasitized by C. plutellae. C. plutellae bracovirus (CpBV was purified and injected into non-parasitized P. xylostella that expressed Cp-TSP13. Cp-TSP13 was cloned into a eukaryotic expression vector and used to infect Sf9 cells to transiently express Cp-TSP13. The synthesized Cp-TSP13 protein was detected in culture broth. An overlaying experiment showed that the purified Cp-TSP13 entered hemocytes. It was localized in the cytosol. Recombinant Cp-TSP13 significantly inhibited protein synthesis of secretory proteins when it was added to in vitro cultured fat body. In addition, the recombinant Cp-TSP13 directly inhibited the translation of fat body mRNAs in in vitro translation assay using rabbit reticulocyte lysate. Moreover, the recombinant Cp-TSP13 significantly suppressed cellular immune responses by inhibiting hemocyte-spreading behavior. It also exhibited significant insecticidal activities by both injection and feeding routes. These results indicate that Cp-TSP13 is a viral HTIF.

Structural basis for the Nanos-mediated recruitment of the CCR4–NOT complex and translational repression

Science.gov (United States)

Bhandari, Dipankar; Raisch, Tobias; Weichenrieder, Oliver; Jonas, Stefanie; Izaurralde, Elisa

2014-01-01

The RNA-binding proteins of the Nanos family play an essential role in germ cell development and survival in a wide range of metazoan species. They function by suppressing the expression of target mRNAs through the recruitment of effector complexes, which include the CCR4–NOT deadenylase complex. Here, we show that the three human Nanos paralogs (Nanos1–3) interact with the CNOT1 C-terminal domain and determine the structural basis for the specific molecular recognition. Nanos1–3 bind CNOT1 through a short CNOT1-interacting motif (NIM) that is conserved in all vertebrates and some invertebrate species. The crystal structure of the human Nanos1 NIM peptide bound to CNOT1 reveals that the peptide opens a conserved hydrophobic pocket on the CNOT1 surface by inserting conserved aromatic residues. The substitutions of these aromatic residues in the Nanos1–3 NIMs abolish binding to CNOT1 and abrogate the ability of the proteins to repress translation. Our findings provide the structural basis for the recruitment of the CCR4–NOT complex by vertebrate Nanos, indicate that the NIMs are the major determinants of the translational repression mediated by Nanos, and identify the CCR4–NOT complex as the main effector complex for Nanos function. PMID:24736845

47 CFR 74.1233 - Processing FM translator and booster station applications.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Processing FM translator and booster station... SERVICES FM Broadcast Translator Stations and FM Broadcast Booster Stations § 74.1233 Processing FM translator and booster station applications. (a) Applications for FM translator and booster stations are...

Translation elicits a growth rate-dependent, genome-wide, differential protein production in Bacillus subtilis.

Science.gov (United States)

Borkowski, Olivier; Goelzer, Anne; Schaffer, Marc; Calabre, Magali; Mäder, Ulrike; Aymerich, Stéphane; Jules, Matthieu; Fromion, Vincent

2016-05-17

Complex regulatory programs control cell adaptation to environmental changes by setting condition-specific proteomes. In balanced growth, bacterial protein abundances depend on the dilution rate, transcript abundances and transcript-specific translation efficiencies. We revisited the current theory claiming the invariance of bacterial translation efficiency. By integrating genome-wide transcriptome datasets and datasets from a library of synthetic gfp-reporter fusions, we demonstrated that translation efficiencies in Bacillus subtilis decreased up to fourfold from slow to fast growth. The translation initiation regions elicited a growth rate-dependent, differential production of proteins without regulators, hence revealing a unique, hard-coded, growth rate-dependent mode of regulation. We combined model-based data analyses of transcript and protein abundances genome-wide and revealed that this global regulation is extensively used in B. subtilis We eventually developed a knowledge-based, three-step translation initiation model, experimentally challenged the model predictions and proposed that a growth rate-dependent drop in free ribosome abundance accounted for the differential protein production. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Evaluating Translational Research: A Process Marker Model

Science.gov (United States)

Trochim, William; Kane, Cathleen; Graham, Mark J.; Pincus, Harold A.

2011-01-01

Abstract Objective: We examine the concept of translational research from the perspective of evaluators charged with assessing translational efforts. One of the major tasks for evaluators involved in translational research is to help assess efforts that aim to reduce the time it takes to move research to practice and health impacts. Another is to assess efforts that are intended to increase the rate and volume of translation. Methods: We offer an alternative to the dominant contemporary tendency to define translational research in terms of a series of discrete “phases.”Results: We contend that this phased approach has been confusing and that it is insufficient as a basis for evaluation. Instead, we argue for the identification of key operational and measurable markers along a generalized process pathway from research to practice. Conclusions: This model provides a foundation for the evaluation of interventions designed to improve translational research and the integration of these findings into a field of translational studies. Clin Trans Sci 2011; Volume 4: 153–162 PMID:21707944

Hypothalamic eIF2α Signaling Regulates Food Intake

Directory of Open Access Journals (Sweden)

Anne-Catherine Maurin

2014-02-01

Full Text Available The reversible phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α is a highly conserved signal implicated in the cellular adaptation to numerous stresses such as the one caused by amino acid limitation. In response to dietary amino acid deficiency, the brain-specific activation of the eIF2α kinase GCN2 leads to food intake inhibition. We report here that GCN2 is rapidly activated in the mediobasal hypothalamus (MBH after consumption of a leucine-deficient diet. Furthermore, knockdown of GCN2 in this particular area shows that MBH GCN2 activity controls the onset of the aversive response. Importantly, pharmacological experiments demonstrate that the sole phosphorylation of eIF2α in the MBH is sufficient to regulate food intake. eIF2α signaling being at the crossroad of stress pathways activated in several pathological states, our study indicates that hypothalamic eIF2α phosphorylation could play a critical role in the onset of anorexia associated with certain diseases.

Translating Alcohol Research: Opportunities and Challenges.

Science.gov (United States)

Batman, Angela M; Miles, Michael F

2015-01-01

Alcohol use disorder (AUD) and its sequelae impose a major burden on the public health of the United States, and adequate long-term control of this disorder has not been achieved. Molecular and behavioral basic science research findings are providing the groundwork for understanding the mechanisms underlying AUD and have identified multiple candidate targets for ongoing clinical trials. However, the translation of basic research or clinical findings into improved therapeutic approaches for AUD must become more efficient. Translational research is a multistage process of stream-lining the movement of basic biomedical research findings into clinical research and then to the clinical target populations. This process demands efficient bidirectional communication across basic, applied, and clinical science as well as with clinical practitioners. Ongoing work suggests rapid progress is being made with an evolving translational framework within the alcohol research field. This is helped by multiple interdisciplinary collaborative research structures that have been developed to advance translational work on AUD. Moreover, the integration of systems biology approaches with collaborative clinical studies may yield novel insights for future translational success. Finally, appreciation of genetic variation in pharmacological or behavioral treatment responses and optimal communication from bench to bedside and back may strengthen the success of translational research applications to AUD.

Machine vs. human translation of SNOMED CT terms.

Science.gov (United States)

Schulz, Stefan; Bernhardt-Melischnig, Johannes; Kreuzthaler, Markus; Daumke, Philipp; Boeker, Martin

2013-01-01

In the context of past and current SNOMED CT translation projects we compare three kinds of SNOMED CT translations from English to German by: (t1) professional medical translators; (t2) a free Web-based machine translation service; (t3) medical students. 500 SNOMED CT fully specified names from the (English) International release were randomly selected. Based on this, German translations t1, t2, and t3 were generated. A German and an Austrian physician rated the translations for linguistic correctness and content fidelity. Kappa for inter-rater reliability was 0.4 for linguistic correctness and 0.23 for content fidelity. Average ratings of linguistic correctness did not differ significantly between human translation scenarios. Content fidelity was rated slightly better for student translators compared to professional translators. Comparing machine to human translation, the linguistic correctness differed about 0.5 scale units in favour of the human translation and about 0.25 regarding content fidelity, equally in favour of the human translation. The results demonstrate that low-cost translation solutions of medical terms may produce surprisingly good results. Although we would not recommend low-cost translation for producing standardized preferred terms, this approach can be useful for creating additional language-specific entry terms. This may serve several important use cases. We also recommend testing this method to bootstrap a crowdsourcing process, by which term translations are gathered, improved, maintained, and rated by the user community.

Translationally invariant and non-translationally invariant empirical effective interactions

International Nuclear Information System (INIS)

Golin, M.; Zamick, L.

1975-01-01

In this work empirical deficiencies of the core-renormalized realistic effective interactions are examined and simple corrective potentials are sought. The inability of the current realistic interactions to account for the energies of isobaric analog states is noted, likewise they are unable to reproduce the changes in the single-particle energies, as one goes from one closed shell to another. It is noted that the Schiffer interaction gives better results for these gross properties and this is attributed to a combination of several facts. First, to the inclusion of long range terms in the Schiffer potential, then to the presence of relative p-state terms (l=1), in addition to the usual relative s-state terms (l=0). The strange shape of the above interaction is further attributed to the fact that it is translationally invariant whereas the theory of core-polarization yields non-translationally invariant potentials. Consequently, as a correction to the monopole deficiencies of the realistic interactions the term Vsub(mon)=ar 2 (1)r 2 (2)+r 2 (1)+β[r 4 (1)r 2 (2)r 4 (2) ] is proposed. (Auth.)

Visible light photocatalytic activities of template free porous graphitic carbon nitride-BiOBr composite catalysts towards the mineralization of reactive dyes

Science.gov (United States)

Kanagaraj, Thamaraiselvi; Thiripuranthagan, Sivakumar; Paskalis, Sahaya Murphin Kumar; Abe, Hideki

2017-12-01

Template free porous g-C3N4 (pGCN) and flower like bismuth oxybromide catalysts were synthesized by poly condensation and precipitation methods respectively. Various weight percentages of porous GCN-BiOBr composite catalysts (x% pGCN-BiOBr where x = 5, 10, 30, 50 & 70 wt% of pGCN) were synthesized by impregnation method. All the synthesized catalysts were characterized by X-Ray diffractometer, Fourier transform infrared spectrophotometer, BET surface area analyzer, UV Visible diffuse reflectance spectrophotometer, X-Ray photoelectron spectrophotometer, SEM with Energy dispersive X-ray analyzer (SEM/EDAX) and elemental mapping, Transmission electron microscope, Photoluminescence spectrophotometer and Electrochemical impedance. Photocatalytic degradation of all the synthesized catalysts were tested towards the harmful reactive dyes such as reactive blue 198 (RB 198), reactive black 5 (RB 5) and reactive yellow 145 (RY 145) in presence of visible irradiation. Among the catalysts 30% pGCN-BiOBr resulted in the highest photocatalytic activity towards the degradation of all the three dyes in presence of UV, visible and solar irradiations. Kinetics studies on the photocatalytic mineralization of dyes indicated that it followed pseudo first order. HPLC, TOC and COD studies confirm that the dyes are mineralized into CO2, water and mineral salts.

Translating Inclusion

DEFF Research Database (Denmark)

Fallov, Mia Arp; Birk, Rasmus

2018-01-01

The purpose of this paper is to explore how practices of translation shape particular paths of inclusion for people living in marginalized residential areas in Denmark. Inclusion, we argue, is not an end-state, but rather something which must be constantly performed. Active citizenship, today......, is not merely a question of participation, but of learning to become active in all spheres of life. The paper draws on empirical examples from a multi-sited field work in 6 different sites of local community work in Denmark, to demonstrate how different dimensions of translation are involved in shaping active...... citizenship. We propose the following different dimensions of translation: translating authority, translating language, translating social problems. The paper takes its theoretical point of departure from assemblage urbanism, arguing that cities are heterogeneous assemblages of socio-material interactions...

Evaluation of a nurse-led dementia education and knowledge translation programme in primary care: A cluster randomized controlled trial.

Science.gov (United States)

Wang, Yao; Xiao, Lily Dongxia; Ullah, Shahid; He, Guo-Ping; De Bellis, Anita

2017-02-01

The lack of dementia education programmes for health professionals in primary care is one of the major factors contributing to the unmet demand for dementia care services. To determine the effectiveness of a nurse-led dementia education and knowledge translation programme for health professionals in primary care; participants' satisfaction with the programme; and to understand participants' perceptions of and experiences in the programme. A cluster randomized controlled trial was used as the main methodology to evaluate health professionals' knowledge, attitudes and care approach. Focus groups were used at the end of the project to understand health professionals' perceptions of and experiences in the programme. Fourteen community health service centres in a province in China participated in the study. Seven centres were randomly assigned to the intervention or control group respectively and 85 health professionals in each group completed the programme. A train-the-trainer model was used to implement a dementia education and knowledge translation programme. Outcome variables were measured at baseline, on the completion of the programme and at 3-month follow-up. A mixed effect linear regression model was applied to compare the significant differences of outcome measures over time between the two groups. Focus groups were guided by four semi-structured questions and analysed using content analysis. Findings revealed significant effects of the education and knowledge translation programme on participants' knowledge, attitudes and a person-centred care approach. Focus groups confirmed that the programme had a positive impact on dementia care practice. A dementia education and knowledge translation programme for health professionals in primary care has positive effects on their knowledge, attitudes, care approach and care practice. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthesis and photocatalytic properties of graphitic carbon nitride nanofibers using porous anodic alumina templates

Science.gov (United States)

Suchitra, S. M.; Udayashankar, N. K.

2017-12-01

In the present study, we describe an effective method for the synthesis of Graphitic carbon nitride (GCN) nanostructures using porous anodic alumina (AAO) membrane as template by simple thermal condensation of cyanamide. Synthesized nanostructure was fully analysed by various techniques to detect its crystalline nature, morphology, luminescent properties followed by the evaluation of its photocatalytic activity in the degradation of Methylene blue dye. Structural analysis of synthesized GCNNF was systematically carried out using x-ray powder diffraction (XRD) and scanning electron microscope (SEM), and. The results confirmed the growth of GCN inside the nanochannels of anodic alumina templates. Luminescent properties of GCNNF were studied using photoluminescence (PL) spectroscopy. PL analysis showed the presence of a strong emission peak in the wavelength range of 350-600 nm in blue region. GCNNF displays higher photocatalytic performance in the photodegradation of methylene blue compare to the bulk GCN. Highlights 1. In the present paper, we report the synthesis of graphitic carbon nitride nanofibers (GCNNF) using porous anodic aluminium oxide membranes as templates through thermal condensation of cyanamide at 500 °C. 2. The synthesis of Graphitic carbon nitride nanofibers using porous andic alumina template is the efficient approach for increasing crystallinity and surface area. 3. The high surface area of graphitic carbon nitride nanofibers has a good impact on novel optical and photocatalytic properties of the bulkGCN. 4. AAO templating of GCN is one of the versatile method to produce tailorable GCN nanostructures with higher surface area and less number of structural defects. 5. Towards photocatalytic degradation of dyes, the tuning of physical properties is very essential thing hence we are succeeded in achieving better catalytic performance of GCN nanostructures by making use of AAO templates.

Translating the foundational model of anatomy into french using knowledge-based and lexical methods

Directory of Open Access Journals (Sweden)

Merabti Tayeb

2011-10-01

Full Text Available Abstract Background The Foundational Model of Anatomy (FMA is the reference ontology regarding human anatomy. FMA vocabulary was integrated into the Health Multi Terminological Portal (HMTP developed by CISMeF based on the CISMeF Information System which also includes 26 other terminologies and controlled vocabularies, mainly in French. However, FMA is primarily in English. In this context, the translation of FMA English terms into French could also be useful for searching and indexing French anatomy resources. Various studies have investigated automatic methods to assist the translation of medical terminologies or create multilingual medical vocabularies. The goal of this study was to facilitate the translation of FMA vocabulary into French. Methods We compare two types of approaches to translate the FMA terms into French. The first one is UMLS-based on the conceptual information of the UMLS metathesaurus. The second method is lexically-based on several Natural Language Processing (NLP tools. Results The UMLS-based approach produced a translation of 3,661 FMA terms into French whereas the lexical approach produced a translation of 3,129 FMA terms into French. A qualitative evaluation was made on 100 FMA terms translated by each method. For the UMLS-based approach, among the 100 translations, 52% were manually rated as "very good" and only 7% translations as "bad". For the lexical approach, among the 100 translations, 47% were rated as "very good" and 20% translations as "bad". Conclusions Overall, a low rate of translations were demonstrated by the two methods. The two approaches permitted us to semi-automatically translate 3,776 FMA terms from English into French, this was to added to the existing 10,844 French FMA terms in the HMTP (4,436 FMA French terms and 6,408 FMA terms manually translated.

Novel polysome messages and changes in translational activity appear after induction of adipogenesis in 3T3-L1 cells

Directory of Open Access Journals (Sweden)

Fromm-Dornieden Carolin

2012-03-01

Full Text Available Abstract Background Control of translation allows for rapid adaptation of the cell to stimuli, rather than the slower transcriptional control. We presume that translational control is an essential process in the control of adipogenesis, especially in the first hours after hormonal stimulation. 3T3-L1 preadipocytes were cultured to confluency and adipogenesis was induced by standard protocols using a hormonal cocktail. Cells were harvested before and 6 hours after hormonal induction. mRNAs attached to ribosomes (polysomal mRNAs were separated from unbound mRNAs by velocity sedimentation. Pools of polysomal and unbound mRNA fractions were analyzed by microarray analysis. Changes in relative abundance in unbound and polysomal mRNA pools were calculated to detect putative changes in translational activity. Changes of expression levels of selected genes were verified by qPCR and Western blotting. Results We identified 43 genes that shifted towards the polysomal fraction (up-regulated and 2 genes that shifted towards free mRNA fraction (down-regulated. Interestingly, we found Ghrelin to be down-regulated. Up-regulated genes comprise factors that are nucleic acid binding (eIF4B, HSF1, IRF6, MYC, POLR2a, RPL18, RPL27a, RPL6, RPL7a, RPS18, RPSa, TSC22d3, form part of ribosomes (RPL18, RPL27a, RPL6, RPL7a, RPS18, RPSa, act on the regulation of translation (eIF4B or transcription (HSF1, IRF6, MYC, TSC22d3. Others act as chaperones (BAG3, HSPA8, HSP90ab1 or in other metabolic or signals transducing processes. Conclusions We conclude that a moderate reorganisation of the functionality of the ribosomal machinery and translational activity are very important steps for growth and gene expression control in the initial phase of adipogenesis.

Control of PNG kinase, a key regulator of mRNA translation, is coupled to meiosis completion at egg activation.

Science.gov (United States)

Hara, Masatoshi; Petrova, Boryana; Orr-Weaver, Terry L

2017-05-30

The oocyte-to-embryo transition involves extensive changes in mRNA translation, regulated in Drosophila by the PNG kinase complex whose activity we show here to be under precise developmental control. Despite presence of the catalytic PNG subunit and the PLU and GNU activating subunits in the mature oocyte, GNU is phosphorylated at Cyclin B/CDK1sites and unable to bind PNG and PLU. In vitro phosphorylation of GNU by CyclinB/CDK1 blocks activation of PNG. Meiotic completion promotes GNU dephosphorylation and PNG kinase activation to regulate translation. The critical regulatory effect of phosphorylation is shown by replacement in the oocyte with a phosphorylation-resistant form of GNU, which promotes PNG-GNU complex formation, elevation of Cyclin B, and meiotic defects consistent with premature PNG activation. After PNG activation GNU is destabilized, thus inactivating PNG. This short-lived burst in kinase activity links development with maternal mRNA translation and ensures irreversibility of the oocyte-to-embryo transition.

DISSEMINATING MULTICULTURALISM THROUGH THE TEACHING OF TRANSLATION

Directory of Open Access Journals (Sweden)

Arido Laksono

2013-12-01

Full Text Available 800x600 ABSTRACT Students are expected to change the world. Their perspectives represent the way they view the world and its phenomena. The broader knowledge they possess, the more tolerance they have in interpreting life. In the global era, students should understand the importance of having good knowledge in multiculturalism. They will involve in an inter-cultural encounter since sources of information are widely offered. The willingness to have such an open mind is required in order to develop a better place to live and work. One way to disseminate multiculturalism values is using text containing information about culture and social values. The text written in English or Bahasa Indonesia for the class designed in disseminating multiculturalism is Translation. Here, students are taught to interpret the messages conveyed and translate the information from the source language to the target language correctly. Teacher must have good and creative technique in delivering the material so that students really enjoy the class and deeply understand the topic. The teaching and learning process in Translation class, therefore, is an effective medium to achieve the expected purpose as stated above. Theory of translation will not be the one and only theory to do the translation job, but it also needs comprehensive knowledge on other social sciences. Hence, translation class will not only discuss lines of words in a paragraph, but also reciprocal discussion among the members of the class. At the end, students will have the ability to translate such information in a text correctly and to establish civic society with more open comprehension over society and its culture. Keywords: theory of translation, multiculturalism, teaching-learning process, globalization. Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0

Translation and Culture:Translation as a Cross-cultural Mediation

Institute of Scientific and Technical Information of China (English)

叶谋锦

2013-01-01

Translation is a complex activity which involves language competence as well as proficiency in multiculturalism. From the perspective of multiculturalism, translation resembles recreation of source text by grasping essential meanings to produce a sub-tle target text which can be clearly perceived by target readers. Ignoring cultural issues can present serious mistranslations in the field of advertising translation. This paper aims to explore the significance of connotation confined by the framework of culture and point out that verbal translation is a dangerous inclination by illustrating three business examples. This paper argues that cross-cultural mediation plays an important role in translation.

eIF4A inhibition allows translational regulation of mRNAs encoding proteins involved in Alzheimer's disease.

Directory of Open Access Journals (Sweden)

Andrew Bottley

2010-09-01

Full Text Available Alzheimer's disease (AD is the main cause of dementia in our increasingly aging population. The debilitating cognitive and behavioral symptoms characteristic of AD make it an extremely distressing illness for patients and carers. Although drugs have been developed to treat AD symptoms and to slow disease progression, there is currently no cure. The incidence of AD is predicted to increase to over one hundred million by 2050, placing a heavy burden on communities and economies, and making the development of effective therapies an urgent priority. Two proteins are thought to have major contributory roles in AD: the microtubule associated protein tau, also known as MAPT; and the amyloid-beta peptide (A-beta, a cleavage product of amyloid precursor protein (APP. Oxidative stress is also implicated in AD pathology from an early stage. By targeting eIF4A, an RNA helicase involved in translation initiation, the synthesis of APP and tau, but not neuroprotective proteins, can be simultaneously and specifically reduced, representing a novel avenue for AD intervention. We also show that protection from oxidative stress is increased upon eIF4A inhibition. We demonstrate that the reduction of these proteins is not due to changes in mRNA levels or increased protein degradation, but is a consequence of translational repression conferred by inhibition of the helicase activity of eIF4A. Inhibition of eIF4A selectively and simultaneously modulates the synthesis of proteins involved in Alzheimer's disease: reducing A-beta and tau synthesis, while increasing proteins predicted to be neuroprotective.

Knowledge translation interventions for critically ill patients: a systematic review*.

Science.gov (United States)

Sinuff, Tasnim; Muscedere, John; Adhikari, Neill K J; Stelfox, Henry T; Dodek, Peter; Heyland, Daren K; Rubenfeld, Gordon D; Cook, Deborah J; Pinto, Ruxandra; Manoharan, Venika; Currie, Jan; Cahill, Naomi; Friedrich, Jan O; Amaral, Andre; Piquette, Dominique; Scales, Damon C; Dhanani, Sonny; Garland, Allan

2013-11-01

We systematically reviewed ICU-based knowledge translation studies to assess the impact of knowledge translation interventions on processes and outcomes of care. We searched electronic databases (to July, 2010) without language restrictions and hand-searched reference lists of relevant studies and reviews. Two reviewers independently identified randomized controlled trials and observational studies comparing any ICU-based knowledge translation intervention (e.g., protocols, guidelines, and audit and feedback) to management without a knowledge translation intervention. We focused on clinical topics that were addressed in greater than or equal to five studies. Pairs of reviewers abstracted data on the clinical topic, knowledge translation intervention(s), process of care measures, and patient outcomes. For each individual or combination of knowledge translation intervention(s) addressed in greater than or equal to three studies, we summarized each study using median risk ratio for dichotomous and standardized mean difference for continuous process measures. We used random-effects models. Anticipating a small number of randomized controlled trials, our primary meta-analyses included randomized controlled trials and observational studies. In separate sensitivity analyses, we excluded randomized controlled trials and collapsed protocols, guidelines, and bundles into one category of intervention. We conducted meta-analyses for clinical outcomes (ICU and hospital mortality, ventilator-associated pneumonia, duration of mechanical ventilation, and ICU length of stay) related to interventions that were associated with improvements in processes of care. From 11,742 publications, we included 119 investigations (seven randomized controlled trials, 112 observational studies) on nine clinical topics. Interventions that included protocols with or without education improved continuous process measures (seven observational studies and one randomized controlled trial; standardized

The significance of translation regulation in the stress response

OpenAIRE

Picard, Flora; Loubière, Pascal; Girbal, Laurence; Bousquet, Muriel

2013-01-01

Background: The stress response in bacteria involves the multistage control of gene expression but is not entirely understood. To identify the translational response of bacteria in stress conditions and assess its contribution to the regulation of gene expression, the translational states of all mRNAs were compared under optimal growth condition and during nutrient (isoleucine) starvation. Results: A genome-scale study of the translational response to nutritional limitation was performed in t...

The Effect of Translators' Emotional Intelligence on Their Translation Quality

Science.gov (United States)

Varzande, Mohsen; Jadidi, Esmaeil

2015-01-01

Translators differ from each other in many ways in terms of their knowledge, professional and psychological conditions that may directly influence their translation. The present study aimed at investigating the impact of translators' Emotional Intelligence on their translation quality. Following a "causal-comparative study," a sample of…

Translating India

CERN Document Server

Kothari, Rita

2014-01-01

The cultural universe of urban, English-speaking middle class in India shows signs of growing inclusiveness as far as English is concerned. This phenomenon manifests itself in increasing forms of bilingualism (combination of English and one Indian language) in everyday forms of speech - advertisement jingles, bilingual movies, signboards, and of course conversations. It is also evident in the startling prominence of Indian Writing in English and somewhat less visibly, but steadily rising, activity of English translation from Indian languages. Since the eighties this has led to a frenetic activity around English translation in India's academic and literary circles. Kothari makes this very current phenomenon her chief concern in Translating India.   The study covers aspects such as the production, reception and marketability of English translation. Through an unusually multi-disciplinary approach, this study situates English translation in India amidst local and global debates on translation, representation an...

The Impact of Translators' Academic Experience on Their Translation Quality

Science.gov (United States)

Varzande, Mohsen; Jadidi, Esmaeil

2015-01-01

Translators differ from each other in many ways in terms of their knowledge and professional conditions that may directly influence their translation. The present study aimed at investigating the impact of translators' academic experience on their translation quality. Following a "causal-comparative study", a sample of 100 male and…

Performance of an online translation tool when applied to patient educational material.

Science.gov (United States)

Khanna, Raman R; Karliner, Leah S; Eck, Matthias; Vittinghoff, Eric; Koenig, Christopher J; Fang, Margaret C

2011-11-01

Language barriers may prevent clinicians from tailoring patient educational material to the needs of individuals with limited English proficiency. Online translation tools could fill this gap, but their accuracy is unknown. We evaluated the accuracy of an online translation tool for patient educational material. We selected 45 sentences from a pamphlet available in both English and Spanish, and translated it into Spanish using GoogleTranslate™ (GT). Three bilingual Spanish speakers then performed a blinded evaluation on these 45 sentences, comparing GT-translated sentences to those translated professionally, along four domains: fluency (grammatical correctness), adequacy (information preservation), meaning (connotation maintenance), and severity (perceived dangerousness of an error if present). In addition, evaluators indicated whether they had a preference for either the GT-translated or professionally translated sentences. The GT-translated sentences had significantly lower fluency scores compared to the professional translation (3.4 vs. 4.7, P educational material, GT performed comparably to professional human translation in terms of preserving information and meaning, though it was slightly worse in preserving grammar. In situations where professional human translations are unavailable or impractical, online translation may someday fill an important niche. Copyright © 2011 Society of Hospital Medicine.

12 CFR 574.4 - Control.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Control. 574.4 Section 574.4 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY ACQUISITION OF CONTROL OF SAVINGS ASSOCIATIONS § 574.4 Control. (a) Conclusive control. (1) An acquiror shall be deemed to have acquired control of a...

Translating Legal Collocations in Contract Agreements by Iraqi EFL Students-Translators

Directory of Open Access Journals (Sweden)

Muntaha A. Abdulwahid

2017-01-01

Full Text Available Legal translation of contract agreements is a challenge to translators as it involves combining the literary translation with the technical terminological precision. In translating legal contract agreements, a legal translator must utilize the lexical or syntactic precision and, more importantly, the pragmatic awareness of the context. This will guarantee an overall communicative process and avoid inconsistency in legal translation. However, the inability of the translator to meet these two functions in translating the contract item not only affects the contractors’ comprehension of the contract item but also affects the parties’ contractual obligations. In light of this, the purpose of this study was to find out how legal collocations used in contract agreements are translated from Arabic into English by student-translators in terms of (1 purely technical, (2 semi-technical, and (3 everyday vocabulary collocations. For the data collection, a multiple-choice collocation test was used to be answered by 35 EFL Iraqi undergraduate translator-students to decide on the aspects of weaknesses and strengths of their translation, thus decide on the aspects of correction. The findings showed that these students had serious problems in translating legal collocations as they lack the linguistic knowledge and pragmatic awareness needed to achieve the legal meaning and effect. They were also unable to make a difference among the three categories of legal collocations, purely technical, semi-technical, and everyday vocabulary collocations. These students should be exposed to more legal translation practices to obtain the required experience needed for their future career.

Hurdles in Basic Science Translation

Directory of Open Access Journals (Sweden)

Christina J. Perry

2017-07-01

Full Text Available In the past century there have been incredible advances in the field of medical research, but what hinders translation of this knowledge into effective treatment for human disease? There is an increasing focus on the failure of many research breakthroughs to be translated through the clinical trial process and into medical practice. In this mini review, we will consider some of the reasons that findings in basic medical research fail to become translated through clinical trials and into basic medical practices. We focus in particular on the way that human disease is modeled, the understanding we have of how our targets behave in vivo, and also some of the issues surrounding reproducibility of basic research findings. We will also look at some of the ways that have been proposed for overcoming these issues. It appears that there needs to be a cultural shift in the way we fund, publish and recognize quality control in scientific research. Although this is a daunting proposition, we hope that with increasing awareness and focus on research translation and the hurdles that impede it, the field of medical research will continue to inform and improve medical practice across the world.

Translation Analysis on Civil Engineering Text Produced by Machine Translator

Directory of Open Access Journals (Sweden)

Sutopo Anam

2018-01-01

Full Text Available Translation is extremely needed in communication since people have serious problem in the language used. Translation activity is done by the person in charge for translating the material. Translation activity is also able to be done by machine. It is called machine translation, reflected in the programs developed by programmer. One of them is Transtool. Many people used Transtool for helping them in solving the problem related with translation activities. This paper wants to deliver how important is the Transtool program, how effective is Transtool program and how is the function of Transtool for human business. This study applies qualitative research. The sources of data were document and informant. This study used documentation and in dept-interviewing as the techniques for collecting data. The collected data were analyzed by using interactive analysis. The results of the study show that, first; Transtool program is helpful for people in translating the civil engineering text and it functions as the aid or helper, second; the working of Transtool software program is effective enough and third; the result of translation produced by Transtool is good for short and simple sentences and not readable, not understandable and not accurate for long sentences (compound, complex and compound complex thought the result is informative. The translated material must be edited by the professional translator.

Translation Analysis on Civil Engineering Text Produced by Machine Translator

Science.gov (United States)

Sutopo, Anam

2018-02-01

Translation is extremely needed in communication since people have serious problem in the language used. Translation activity is done by the person in charge for translating the material. Translation activity is also able to be done by machine. It is called machine translation, reflected in the programs developed by programmer. One of them is Transtool. Many people used Transtool for helping them in solving the problem related with translation activities. This paper wants to deliver how important is the Transtool program, how effective is Transtool program and how is the function of Transtool for human business. This study applies qualitative research. The sources of data were document and informant. This study used documentation and in dept-interviewing as the techniques for collecting data. The collected data were analyzed by using interactive analysis. The results of the study show that, first; Transtool program is helpful for people in translating the civil engineering text and it functions as the aid or helper, second; the working of Transtool software program is effective enough and third; the result of translation produced by Transtool is good for short and simple sentences and not readable, not understandable and not accurate for long sentences (compound, complex and compound complex) thought the result is informative. The translated material must be edited by the professional translator.

CDC 1604-A translator from the SLANG autocode for the TRA computer

International Nuclear Information System (INIS)

Belyaev, A.V.

1976-01-01

A SLANG - TRA translator has been devised for faster, easier programing. The program is realized on a SDS-1604A computer, input data are read from 80 column punch cards and translated into the standard Hollerith 026 code. Programs are processed in batches. A SDS-1604A teletype enables the operator to control the translation. The translator makes it possible to evaluate program processing time. The translator's high speed simplifies program editing and saves manpower

Translation: between what can be translated and what must be translated

Directory of Open Access Journals (Sweden)

Magda Jeanrenaud

2016-02-01

Full Text Available Starting from a disconcerting interpretation of Jacques Derrida, our analysis aims at investigating and also tries to explain the blockage which appears in the English, French and Romanian translations (signed by Maurice de Gandillac, Antoine Berman, Laurent Lamy, Alexis Nouss, Harry Zohn, Steven Rendall, Martine Broda, Catrinel Pleșu etc. of a well-known text of Walter Benjamin, Die Aufgabe des Übersetzers, when translators transpose in their target languages the two quotations given by Benjamin: one of Mallarmé, left untranslated in the source text, and another, signed by Pannwitz. The fact is that both quotations have something in common: a discoursive form which results from an unusual syntax, as if they were already, in a certain sense, „translations”. As if the translators feared—a feature of the translator’s psychology?—not to render their text sufficiently accessible, even when the source text is not intended to be accessible. Hence the painful dilemma of the intentional fallacy (not only of the text to be translated.

The translation initiation factor eIF4E regulates the sex-specific expression of the master switch gene Sxl in Drosophila melanogaster.

Directory of Open Access Journals (Sweden)

Patricia L Graham

2011-07-01

Full Text Available In female fruit flies, Sex-lethal (Sxl turns off the X chromosome dosage compensation system by a mechanism involving a combination of alternative splicing and translational repression of the male specific lethal-2 (msl-2 mRNA. A genetic screen identified the translation initiation factor eif4e as a gene that acts together with Sxl to repress expression of the Msl-2 protein. However, eif4e is not required for Sxl mediated repression of msl-2 mRNA translation. Instead, eif4e functions as a co-factor in Sxl-dependent female-specific alternative splicing of msl-2 and also Sxl pre-mRNAs. Like other factors required for Sxl regulation of splicing, eif4e shows maternal-effect female-lethal interactions with Sxl. This female lethality can be enhanced by mutations in other co-factors that promote female-specific splicing and is caused by a failure to properly activate the Sxl-positive autoregulatory feedback loop in early embryos. In this feedback loop Sxl proteins promote their own synthesis by directing the female-specific alternative splicing of Sxl-Pm pre-mRNAs. Analysis of pre-mRNA splicing when eif4e activity is compromised demonstrates that Sxl-dependent female-specific splicing of both Sxl-Pm and msl-2 pre-mRNAs requires eif4e activity. Consistent with a direct involvement in Sxl-dependent alternative splicing, eIF4E is associated with unspliced Sxl-Pm pre-mRNAs and is found in complexes that contain early acting splicing factors--the U1/U2 snRNP protein Sans-fils (Snf, the U1 snRNP protein U1-70k, U2AF38, U2AF50, and the Wilms' Tumor 1 Associated Protein Fl(2d--that have been directly implicated in Sxl splicing regulation.

Integrating Automatic Speech Recognition and Machine Translation for Better Translation Outputs

DEFF Research Database (Denmark)

Liyanapathirana, Jeevanthi

translations, combining machine translation with computer assisted translation has drawn attention in current research. This combines two prospects: the opportunity of ensuring high quality translation along with a significant performance gain. Automatic Speech Recognition (ASR) is another important area......, which caters important functionalities in language processing and natural language understanding tasks. In this work we integrate automatic speech recognition and machine translation in parallel. We aim to avoid manual typing of possible translations as dictating the translation would take less time...... to the n-best list rescoring, we also use word graphs with the expectation of arriving at a tighter integration of ASR and MT models. Integration methods include constraining ASR models using language and translation models of MT, and vice versa. We currently develop and experiment different methods...

Tradução e adaptação cultural do Asthma Control Scoring System (Sistema de Escore para Controle Abrangente da Asma para uso no Brasil The Asthma Control Scoring System: translation and cross-cultural adaptation for use in Brazil

Directory of Open Access Journals (Sweden)

Michelle Gonçalves de Souza Tavares

2010-12-01

Full Text Available OBJETIVO: Traduzir e adaptar culturalmente, para uso no Brasil, um instrumento específico de escore para o controle abrangente da asma, denominado Asthma Control Scoring System (ACSS. MÉTODOS: O protocolo incluiu dez etapas: autorização escrita do autor do ACSS; tradução do instrumento para a língua portuguesa do Brasil por três tradutores; análise e comparação das três versões por um comitê revisor; retradução literal para o inglês; revisão e harmonização da retradução; aprovação do autor do ACSS; revisão da tradução por especialistas; desdobramento cognitivo: teste da clareza, compreensão e aceitabilidade junto à população alvo (avaliação da tradução por 10 profissionais da área da saúde; segundo desdobramento cognitivo: revisão da nova versão por um segundo grupo de profissionais da área de saúde; e reconciliação e elaboração da versão final pelo comitê revisor. RESULTADOS: A versão do ACSS em português do Brasil apresentou clareza, compreensão e aceitabilidade. O instrumento foi considerado abrangente por englobar as manifestações clínicas, funcionais e inflamatórias da asma. CONCLUSÕES: Com o uso desta metodologia criteriosa empregada para a adaptação transcultural do ACSS, asseguramos sua adequação cultural para uso no Brasil. O uso desse instrumento poderá facilitar futuros estudos sobre o controle da asma.OBJECTIVE: The translation and cross-cultural adaptation of a specific scoring instrument for the comprehensive control of asthma, the Asthma Control Scoring System (ACSS, for use in Brazil. METHODS: The protocol included ten steps: acquisition of written permission from the author of the ACSS; translation of the instrument to Brazilian Portuguese, carried out by three separate translators; analysis and comparison of the three versions by a review committee; literal back-translation to English; review and harmonization of the back-translation; acquisition of the approval of the

(Con)figuring gender in Bible translation: Cultural, translational and ...

African Journals Online (AJOL)

The gendered intersection of cultural studies and Bible translation is under acknowledged. Accounting for gender criticism in translation work requires, besides responsible theory and practice of translation, also attention to interwoven gender critical aspects. After a brief investigation of the intersections between biblical, ...

Translation and identity: Translation of the Freedom Charter into ...

African Journals Online (AJOL)

A comparative analysis of the Afrikaans translations reveals how the respective translators struggled sporadically through certain ideological constraints in order to provide a satisfactory narrative. Their inability to internalise the principles contained in the Freedom Charter resulted in them presenting a 'framed' translation ...

The emergence of translational epidemiology: from scientific discovery to population health impact.

Science.gov (United States)

Khoury, Muin J; Gwinn, Marta; Ioannidis, John P A

2010-09-01

Recent emphasis on translational research (TR) is highlighting the role of epidemiology in translating scientific discoveries into population health impact. The authors present applications of epidemiology in TR through 4 phases designated T1-T4, illustrated by examples from human genomics. In T1, epidemiology explores the role of a basic scientific discovery (e.g., a disease risk factor or biomarker) in developing a "candidate application" for use in practice (e.g., a test used to guide interventions). In T2, epidemiology can help to evaluate the efficacy of a candidate application by using observational studies and randomized controlled trials. In T3, epidemiology can help to assess facilitators and barriers for uptake and implementation of candidate applications in practice. In T4, epidemiology can help to assess the impact of using candidate applications on population health outcomes. Epidemiology also has a leading role in knowledge synthesis, especially using quantitative methods (e.g., meta-analysis). To explore the emergence of TR in epidemiology, the authors compared articles published in selected issues of the Journal in 1999 and 2009. The proportion of articles identified as translational doubled from 16% (11/69) in 1999 to 33% (22/66) in 2009 (P = 0.02). Epidemiology is increasingly recognized as an important component of TR. By quantifying and integrating knowledge across disciplines, epidemiology provides crucial methods and tools for TR.

Predicting Translation Initiation Rates for Designing Synthetic Biology

International Nuclear Information System (INIS)

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.

Excessive lateral patellar translation on axial computed tomography indicates positive patellar J sign.

Science.gov (United States)

Xue, Zhe; Song, Guan-Yang; Liu, Xin; Zhang, Hui; Wu, Guan; Qian, Yi; Feng, Hua

2018-03-20

The purpose of the study was to quantify the patellar J sign using traditional computed tomography (CT) scans. Fifty-three patients (fifty-three knees) who suffered from recurrent patellar instability were included and analyzed. The patellar J sign was evaluated pre-operatively during active knee flexion and extension. It was defined as positive when there was obvious lateral patellar translation, and negative when there was not. The CT scans were performed in all patients with full knee extension; and the parameters including bisect offset index (BOI), patellar-trochlear-groove (PTG) distance, and patellar lateral tilt angle (PLTA) were measured on the axial slices. All the three parameters were compared between the J sign-positive group (study group) and the J sign-negative group (control group). In addition, the optimal thresholds of the three CT scan parameters for predicting the positive patellar J sign were determined with receiver operating characteristic (ROC) curves, and the diagnostic values were assessed by the area under the curve (AUC). Among the fifty-three patients (fifty-three knees), thirty-seven (70%) showed obvious lateral patellar translation, which were defined as positive J sign (study group), and the remaining sixteen (30%) who showed no lateral translation were defined as negative J sign (control group). The mean values of the three CT parameters in the study group were all significantly larger compared to the control group, including BOI (121 ± 28% vs 88 ± 12%, P = 0.038), PTG distance (5.2 ± 6.6 mm vs - 4.4 ± 5.2 mm, P J sign was 97.5% (Sensitivity = 83.3%, Specificity = 87.5%). In this study, the prevalence of positive patellar J sign was 70%. The BOI measured from the axial CT scans of the knee joint can be used as an appropriate predictor to differentiate the positive J sign from the negative J sign, highlighting that the excessive lateral patellar translation on axial CT scan indicates positive

Post-translational regulation enables robust p53 regulation.

Science.gov (United States)

Shin, Yong-Jun; Chen, Kai-Yuan; Sayed, Ali H; Hencey, Brandon; Shen, Xiling

2013-08-30

The tumor suppressor protein p53 plays important roles in DNA damage repair, cell cycle arrest and apoptosis. Due to its critical functions, the level of p53 is tightly regulated by a negative feedback mechanism to increase its tolerance towards fluctuations and disturbances. Interestingly, the p53 level is controlled by post-translational regulation rather than transcriptional regulation in this feedback mechanism. We analyzed the dynamics of this feedback to understand whether post-translational regulation provides any advantages over transcriptional regulation in regard to disturbance rejection. When a disturbance happens, even though negative feedback reduces the steady-state error, it can cause a system to become less stable and transiently overshoots, which may erroneously trigger downstream reactions. Therefore, the system needs to balance the trade-off between steady-state and transient errors. Feedback control and adaptive estimation theories revealed that post-translational regulation achieves a better trade-off than transcriptional regulation, contributing to a more steady level of p53 under the influence of noise and disturbances. Furthermore, post-translational regulation enables cells to respond more promptly to stress conditions with consistent amplitude. However, for better disturbance rejection, the p53- Mdm2 negative feedback has to pay a price of higher stochastic noise. Our analyses suggest that the p53-Mdm2 feedback favors regulatory mechanisms that provide the optimal trade-offs for dynamic control.

Word translation entropy in translation

DEFF Research Database (Denmark)

Schaeffer, Moritz; Dragsted, Barbara; Hvelplund, Kristian Tangsgaard

2016-01-01

This study reports on an investigation into the relationship between the number of translation alternatives for a single word and eye movements on the source text. In addition, the effect of word order differences between source and target text on eye movements on the source text is studied....... In particular, the current study investigates the effect of these variables on early and late eye movement measures. Early eye movement measures are indicative of processes that are more automatic while late measures are more indicative of conscious processing. Most studies that found evidence of target...... language activation during source text reading in translation, i.e. co-activation of the two linguistic systems, employed late eye movement measures or reaction times. The current study therefore aims to investigate if and to what extent earlier eye movement measures in reading for translation show...

(Configuring gender in Bible translation: Cultural, translational and gender critical intersections

Directory of Open Access Journals (Sweden)

Jeremy Punt

2014-06-01

Full Text Available The gendered intersection of cultural studies and Bible translation is under acknowledged. Accounting for gender criticism in translation work requires, besides responsible theory and practice of translation, also attention to interwoven gender critical aspects. After a brief investigation of the intersections between biblical, translation and gender studies, translation in a few Pauline texts with bearing on gender and sexuality are investigated.

'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 ...

Deficiency in mTORC1-controlled C/EBP beta-mRNA translation improves metabolic health in mice

NARCIS (Netherlands)

Zidek, Laura M.; Ackermann, Tobias; Hartleben, Goetz; Eichwald, Sabrina; Kortman, Gertrud; Kiehntopf, Michael; Leutz, Achim; Sonenberg, Nahum; Wang, Zhao-Qi; von Maltzahn, Julia; Mueller, Christine; Calkhoven, Cornelis F.

The mammalian target of rapamycin complex 1 (mTORC1) is a central regulator of physiological adaptations in response to changes in nutrient supply. Major downstream targets of mTORC1 signalling are the mRNA translation regulators p70 ribosomal protein S6 kinase 1 (S6K1p70) and the 4E-binding

Literal Translation using Google Translate in Translating the Text from French to English in Digital Tourism Brochure “Bienvenue À Paris”

Directory of Open Access Journals (Sweden)

Rila Hilma

2011-05-01

Full Text Available Translation is basically change of form. The form from which the translation is made will be called the source language and the form into which it is to be changed will be called the receptor language. Translation consists of transferring the meaning of the source language into the receptor language. Translating is not an easy job to do because many things to be considered to do this activity because translation means determining the meaning of a text, then reconstructing this same meaning using the appropriate structure and form in the receptor language. Translation is basically divided by two types of translation, one is literal and the other is idiomatic. Literal translation is really strict to the structure and form then often can not well express the true meaning of source language. Idiomatic translation makes every effort to communicate the meaning of the source language text in the natural forms of the receptor language. Then the most popular translation machine, Google Translate, in this study shows the results of translation which remain odd, unnatural, and nonsensical because the unsuccessful of message delivery, which is notably the typically error of literal translation.

Rotational and translational stability of different methods for direct acromioclavicular ligament repair in anatomic acromioclavicular joint reconstruction.

Science.gov (United States)

Beitzel, Knut; Obopilwe, Elifho; Apostolakos, John; Cote, Mark P; Russell, Ryan P; Charette, Ryan; Singh, Hardeep; Arciero, Robert A; Imhoff, Andreas B; Mazzocca, Augustus D

2014-09-01

Many reconstructions of acromioclavicular (AC) joint dislocations have focused on the coracoclavicular (CC) ligaments and neglected the functional contribution of the AC ligaments and the deltotrapezial fascia. To compare the modifications of previously published methods for direct AC reconstruction in addition to a CC reconstruction. The hypothesis was that there would be significant differences within the variations of surgical reconstructions. Controlled laboratory study. A total of 24 cadaveric shoulders were tested with a servohydraulic testing system. Two digitizing cameras evaluated the 3-dimensional movement. All reconstructions were based on a CC reconstruction using 2 clavicle tunnels and a tendon graft. The following techniques were used to reconstruct the AC ligaments: a graft was shuttled underneath the AC joint back from anterior and again sutured to the acromial side of the joint (group 1), a graft was fixed intramedullary in the acromion and distal clavicle (group 2), a graft was passed over the acromion and into an acromial tunnel (group 3), and a FiberTape was fixed in a cruciate configuration (group 4). Anterior, posterior, and superior translation, as well as anterior and posterior rotation, were tested. Group 1 showed significantly less posterior translation compared with the 3 other groups (P < .05) but did not show significant differences compared with the native joint. Groups 3 and 4 demonstrated significantly more posterior translation than the native joint. Group 1 showed significantly less anterior translation compared with groups 2 and 3. Group 3 demonstrated significantly more anterior translation than the native joint. Group 1 demonstrated significantly less superior translation compared with the other groups and with the native joint. The AC joint of group 1 was pulled apart less compared with all other reconstructions. Only group 1 reproduced the native joint for the anterior rotation at the posterior marker. Group 4 showed

On the structure of translational gauge theories of gravitation

International Nuclear Information System (INIS)

Wallner, R.P.

1982-01-01

Guided by decoupling processes in general gauge theories, we examine the translation limit in U 4 -theories. It is shown that this leads to Einstein's gravity theory as the appropriate choice for a translational gauge theory of gravitation. (Author)

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.

Human Immunodeficiency Virus Tat-Activated Expression of Poliovirus Protein 2A Inhibits mRNA Translation

Science.gov (United States)

Sun, Xiao-Hong; Baltimore, David

1989-04-01

To study the effect of poliovirus protein 2A on cellular RNA translation, the tat control system of human immunodeficiency virus (HIV) was used. Protein 2A was expressed from a plasmid construct (pHIV/2A) incorporating the HIV long terminal repeat. Protein synthesis was measured by using chloramphenicol acetyltransferase as a reporter gene driven by the Rous sarcoma virus long terminal repeat. When HIV/2A was contransfected with the reporter, addition of a tat-producing plasmid caused at least a 50-fold drop in chloramphenicol acetyltransferase synthesis. A HeLa cell line carrying HIV/2A was established. In it, tat expression caused more than a 10-fold drop in chloramphenicol acetyltransferase synthesis from the reporter plasmid. Furthermore, 2A induction by tat caused cleavage of the cellular translation factor P220, a part of eukaryotic translation initiation factor 4F. Thus protein 2A can, by itself, carry out the inhibition of cellular protein synthesis characteristic of a poliovirus infection. Also, the HIV tat activation provides a very effective method to control gene expression in mammalian cells.

The ICNP BaT - from translation tool to translation web service.

Science.gov (United States)

Schrader, Ulrich

2009-01-01

The ICNP BaT has been developed as a web application to support the collaborative translation of different versions of the ICNP into different languages. A prototype of a web service is described that could reuse the translations in the database of the ICNP BaT to provide automatic translations of nursing content based on the ICNP terminology globally. The translation web service is based on a service-oriented architecture making it easy to interoperate with different applications. Such a global translation server would free individual institutions from the maintenance costs of realizing their own translation services.

Pseudouridylation of tRNA-Derived Fragments Steers Translational Control in Stem Cells

DEFF Research Database (Denmark)

Guzzi, Nicola; Cieśla, Maciej; Ngoc, Phuong Cao Thi

2018-01-01

early embryogenesis. Mechanistically, the Ψ "writer" PUS7 modifies and activates a novel network of tRNA-derived small fragments (tRFs) targeting the translation initiation complex. PUS7 inactivation in embryonic stem cells impairs tRF-mediated translation regulation, leading to increased protein...... biosynthesis and defective germ layer specification. Remarkably, dysregulation of this posttranscriptional regulatory circuitry impairs hematopoietic stem cell commitment and is common to aggressive subtypes of human myelodysplastic syndromes. Our findings unveil a critical function of Ψ in directing...

On Various Negative Translations

Directory of Open Access Journals (Sweden)

Gilda Ferreira

2011-01-01

Full Text Available Several proof translations of classical mathematics into intuitionistic mathematics have been proposed in the literature over the past century. These are normally referred to as negative translations or double-negation translations. Among those, the most commonly cited are translations due to Kolmogorov, Godel, Gentzen, Kuroda and Krivine (in chronological order. In this paper we propose a framework for explaining how these different translations are related to each other. More precisely, we define a notion of a (modular simplification starting from Kolmogorov translation, which leads to a partial order between different negative translations. In this derived ordering, Kuroda and Krivine are minimal elements. Two new minimal translations are introduced, with Godel and Gentzen translations sitting in between Kolmogorov and one of these new translations.

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

Lost in translation?

DEFF Research Database (Denmark)

Granas, Anne Gerd; Nørgaard, Lotte Stig; Sporrong, Sofia Kälvemark

2014-01-01

OBJECTIVE: The "Beliefs about Medicines Questionnaire" (BMQ) assess balance of necessity and concern of medicines. The BMQ has been translated from English to many languages. However, the original meaning of statements, such as "My medicine is a mystery to me", may be lost in translation. The aim...... of this study is to compare three Scandinavian translations of the BMQ. (1) How reliable are the translations? (2) Are they still valid after translation? METHODS: Translated Norwegian, Swedish and Danish versions of the BMQ were scrutinized by three native Scandinavian researchers. Linguistic differences...... and ambiguities in the 5-point Likert scale and the BMQ statements were compared. RESULTS: In the Scandinavian translations, the Likert scale expanded beyond the original version at one endpoint (Swedish) or both endpoints (Danish). In the BMQ statements, discrepancies ranged from smaller inaccuracies toward...

Differential Effect of Correct Name Translation on Human and Automated Judgments of Translation Acceptability: A Pilot Study

National Research Council Canada - National Science Library

Vanni, Michelle; Walrath, James

2008-01-01

.... Twenty Arabic sentences, each with average name density of 3.7 names in 22 words, were translated into English with a research-grade MT system, to produce a 20-output-sentence Control Stimulus Set...

Folate Receptor-targeted Bioflavonoid Genistein-loaded Chitosan Nanoparticles for Enhanced Anticancer Effect in Cervical Cancers

Science.gov (United States)

Cai, Limei; Yu, Rufen; Hao, Xi; Ding, Xiangcui

2017-08-01

In this study, novel folic acid-conjugated chitosan nanoparticle was formulated for specific delivery of bioflavonoid, Genistein (GEN), to the cervical cancer cells. The prepared GEN-loaded chitosan nanoparticles (GCN) and folic acid-conjugated GCN (FGCN) showed smaller size with a controlled drug release profile. FGCN exhibited enhanced internalization potential in HeLa cells than that of GCN. The specific internalization of FGCN was mainly due to the affinity of folic acid (FA) with FRs-α which is present in large numbers in HeLa cells. The results revealed that FGCN has a specific affinity towards HeLa cells that will contribute to the better treatment. Folic acid-tagged nanoformulations exhibited a superior cytotoxic effect compared to that of non-targeted formulations. Consistently, IC50 value of GEN decreased from 33.8 to 14.6 μg/ml when treated with FGCN after 24 h incubation. The apoptosis studies indicated that the FGCN nanoparticles were then either GCN or free GEN in terms of anticancer activity. Overall, results revealed that folate conjugation to the delivery system might have great effect on the survival of cervical cancers that will be beneficial for overall cancer treatment.

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

Systematic Review of Knowledge Translation Strategies to Promote Research Uptake in Child Health Settings.

Science.gov (United States)

Albrecht, Lauren; Archibald, Mandy; Snelgrove-Clarke, Erna; Scott, Shannon D

2016-01-01

Strategies to assist evidence-based decision-making for healthcare professionals are crucial to ensure high quality patient care and outcomes. The goal of this systematic review was to identify and synthesize the evidence on knowledge translation interventions aimed at putting explicit research evidence into child health practice. A comprehensive search of thirteen electronic databases was conducted, restricted by date (1985-2011) and language (English). Articles were included if: 1) studies were randomized controlled trials (RCT), controlled clinical trials (CCT), or controlled before-and-after (CBA) studies; 2) target population was child health professionals; 3) interventions implemented research in child health practice; and 4) outcomes were measured at the professional/process, patient, or economic level. Two reviewers independently extracted data and assessed methodological quality. Study data were aggregated and analyzed using evidence tables. Twenty-one studies (13 RCT, 2 CCT, 6 CBA) were included. The studies employed single (n=9) and multiple interventions (n=12). The methodological quality of the included studies was largely moderate (n=8) or weak (n=11). Of the studies with moderate to strong methodological quality ratings, three demonstrated consistent, positive effect(s) on the primary outcome(s); effective knowledge translation interventions were two single, non-educational interventions and one multiple, educational intervention. This multidisciplinary systematic review in child health setting identified effective knowledge translation strategies assessed by the most rigorous research designs. Given the overall poor quality of the research literature, specific recommendations were made to improve knowledge translation efforts in child health. Copyright © 2016 Elsevier Inc. All rights reserved.

An Evergreen Challenge for Translators – The Translation of Idioms

Directory of Open Access Journals (Sweden)

Kovács Gabriella

2016-12-01

Full Text Available Translating idioms has always been a challenging decision-making process for translators mainly because not all idioms have direct equivalents in the target language. Translators usually and ideally have a solid knowledge of the target language and its cultural aspects, but even so they cannot match the ability of a native speaker in deciding when – i.e. in what context and text type – an idiom would or would not be appropriate. This study aims to explore the main characteristics of idioms and the difficulties which might occur when translating them. A needs analysis will also be presented, where the various solutions which a group of translator trainees chose while translating certain idioms from the novel “A Game of Thrones” by George R. R. Martin into Hungarian are examined. Their strategies and the appropriateness of their choices are analysed and compared with the options of the experienced literary translator (Tamás Pétersz. We consider this an important endeavour because, based on our experience, we believe that the topic of the translation of idioms should be included into the curriculum and appropriate materials and tasks should be designed to develop the translator trainees’ knowledge and skills in this domain. Therefore, the aim of this analysis is to obtain a clearer view of the difficulties they are dealing with and bear them in mind when designing teaching materials for them.

Translation in Language Teaching: Insights from Professional Translator Training

Science.gov (United States)

Carreres, Angeles; Noriega-Sanchez, Maria

2011-01-01

The past three decades have seen vast changes in attitudes towards translation, both as an academic discipline and as a profession. The insights we have gained in recent years, in particular in the area of professional translator training, call for a reassessment of the role of translation in language teaching. Drawing on research and practices in…

Lost in translation

DEFF Research Database (Denmark)

Hedegaard, Steffen; Simonsen, Jakob Grue

2011-01-01

of translated texts. Our results suggest (i) that frame-based classifiers are usable for author attribution of both translated and untranslated texts; (ii) that framebased classifiers generally perform worse than the baseline classifiers for untranslated texts, but (iii) perform as well as, or superior...... to the baseline classifiers on translated texts; (iv) that—contrary to current belief—naïve classifiers based on lexical markers may perform tolerably on translated texts if the combination of author and translator is present in the training set of a classifier....

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

Science.gov (United States)

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

2014-02-19

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

Writing Through: Practising Translation

Directory of Open Access Journals (Sweden)

Joel Scott

2010-05-01

Full Text Available This essay exists as a segment in a line of study and writing practice that moves between a critical theory analysis of translation studies conceptions of language, and the practical questions of what those ideas might mean for contemporary translation and writing practice. Although the underlying preoccupation of this essay, and my more general line of inquiry, is translation studies and practice, in many ways translation is merely a way into a discussion on language. For this essay, translation is the threshold of language. But the two trails of the discussion never manage to elude each other, and these concatenations have informed two experimental translation methods, referred to here as Live Translations and Series Translations. Following the essay are a number of poems in translation, all of which come from Blanco Nuclear by the contemporary Spanish poet, Esteban Pujals Gesalí. The first group, the Live Translations consist of transcriptions I made from audio recordings read in a public setting, in which the texts were translated in situ, either off the page of original Spanish-language poems, or through a process very much like that carried out by simultaneous translators, for which readings of the poems were played back to me through headphones at varying speeds to be translated before the audience. The translations collected are imperfect renderings, attesting to a moment in language practice rather than language objects. The second method involves an iterative translation process, by which three versions of any one poem are rendered, with varying levels of fluency, fidelity and servility. All three translations are presented one after the other as a series, with no version asserting itself as the primary translation. These examples, as well as the translation methods themselves, are intended as preliminary experiments within an endlessly divergent continuum of potential methods and translations, and not as a complete representation of

9.4 T small animal MRI using clinical components for direct translational studies.

Science.gov (United States)

Felder, Jörg; Celik, A Avdo; Choi, Chang-Hoon; Schwan, Stefan; Shah, N Jon

2017-12-28

Magnetic resonance is a major preclinical and clinical imaging modality ideally suited for longitudinal studies, e.g. in pharmacological developments. The lack of a proven platform that maintains an identical imaging protocol between preclinical and clinical platforms is solved with the construction of an animal scanner based on clinical hard- and software. A small animal magnet and gradient system were connected to a clinical MR system. Several hardware components were either modified or built in-house to achieve compatibility. The clinical software was modified to account for the different field-of-view of a preclinical MR system. The established scanner was evaluated using clinical QA protocols, and platform compatibility for translational research was verified against clinical scanners of different field strength. The constructed animal scanner operates with the majority of clinical imaging sequences. Translational research is greatly facilitated as protocols can be shared between preclinical and clinical platforms. Hence, when maintaining sequences parameters, maximum similarity between pulses played out on a human or an animal system is maintained. Coupling of a small animal magnet with a clinical MR system is a flexible, easy to use way to establish and advance translational imaging capability. It provides cost and labor efficient translational capability as no tedious sequence reprogramming between moieties is required and cross-platform compatibility of sequences facilitates multi-center studies.

Speaking your Translation

DEFF Research Database (Denmark)

Dragsted, Barbara; Mees, Inger M.; Gorm Hansen, Inge

2011-01-01

In this article we discuss the translation processes and products of 14 MA students who produced translations from Danish (L1) into English (L2) under different working conditions: (1) written translation, (2) sight translation, and (3) sight translation with a speech recognition (SR) tool. Audio......, since students were dictating in their L2, we looked into the number and types of error that occurred when using the SR software. Items that were misrecognised by the program could be divided into three categories: homophones, hesitations, and incorrectly pronounced words. Well over fifty per cent...

47 CFR 74.707 - Low power TV and TV translator station protection.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Low power TV and TV translator station... SERVICES Low Power TV, TV Translator, and TV Booster Stations § 74.707 Low power TV and TV translator station protection. (a)(1) A low power TV or TV translator will be protected from interference from other...

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.

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.

Science.gov (United States)

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.

Struggling with Translations

DEFF Research Database (Denmark)

Obed Madsen, Søren

This paper shows empirical how actors have difficulties with translating strategy texts. The paper uses four cases as different examples of what happens, and what might be difficult, when actors translate organizational texts. In order to explore this, it draws on a translation training method from...... translation theory. The study shows that for those who have produced the text, it is difficult to translate a strategy where they have to change the words so others who don’t understand the language in the text can understand it. It also shows that for those who haven’t been a part of the production, it very...... challenge the notion that actors understand all texts and that managers per se can translate a text....

Datin, a yeast poly(dA:dT)-binding protein, behaves as an activator of the wild-type ILV1 promoter and interacts synergistically with Reb1p

DEFF Research Database (Denmark)

Moreira, José Manuel Alfonso; Remacle, J E; Kielland-Brandt, Morten

1998-01-01

A cis-acting element required for GCN4-independent basal-level transcription of ILV1 was previously identified in our laboratories as a binding site for the REB1 protein (Reb1p). Further deletion analysis of the ILV1 promoter region identified a second element also required for GCN4-independent...... basal-level ILV1 expression. This second element is an A.T-rich tract (26 As out of 32 nucleotides) situated 15 bp downstream of the Reb1p-binding site. Deletion of both the Reblp site and the poly(dA:dT) element totally eliminates basal activity of the ILV1 promoter. We show that the two elements act...... synergistically to control ILV1 expression and that the synergistic effect is distance dependent. We demonstrate that (i) datin (Dat1p), the only known poly (dA:dT)-binding protein in yeast, specifically binds to the ILV1 poly(dA:dT) element in vitro; (ii) Dat1p functions as a trans-activating factor in the ILV1...

Acetyl coenzyme A synthetase is acetylated on multiple lysine residues by a protein acetyltransferase with a single Gcn5-type N-acetyltransferase (GNAT) domain in Saccharopolyspora erythraea.

Science.gov (United States)

You, Di; Yao, Li-Li; Huang, Dan; Escalante-Semerena, Jorge C; Ye, Bang-Ce

2014-09-01

Reversible lysine acetylation (RLA) is used by cells of all domains of life to modulate protein function. To date, bacterial acetylation/deacetylation systems have been studied in a few bacteria (e.g., Salmonella enterica, Bacillus subtilis, Escherichia coli, Erwinia amylovora, Mycobacterium tuberculosis, and Geobacillus kaustophilus), but little is known about RLA in antibiotic-producing actinomycetes. Here, we identify the Gcn5-like protein acetyltransferase AcuA of Saccharopolyspora erythraea (SacAcuA, SACE_5148) as the enzyme responsible for the acetylation of the AMP-forming acetyl coenzyme A synthetase (SacAcsA, SACE_2375). Acetylated SacAcsA was deacetylated by a sirtuin-type NAD(+)-dependent consuming deacetylase (SacSrtN, SACE_3798). In vitro acetylation/deacetylation of SacAcsA enzyme was studied by Western blotting, and acetylation of lysine residues Lys(237), Lys(380), Lys(611), and Lys(628) was confirmed by mass spectrometry. In a strain devoid of SacAcuA, none of the above-mentioned Lys residues of SacAcsA was acetylated. To our knowledge, the ability of SacAcuA to acetylate multiple Lys residues is unique among AcuA-type acetyltransferases. Results from site-specific mutagenesis experiments showed that the activity of SacAcsA was controlled by lysine acetylation. Lastly, immunoprecipitation data showed that in vivo acetylation of SacAcsA was influenced by glucose and acetate availability. These results suggested that reversible acetylation may also be a conserved regulatory posttranslational modification strategy in antibiotic-producing actinomycetes. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

A Comparative Study of "Google Translate" Translations: An Error Analysis of English-to-Persian and Persian-to-English Translations

Science.gov (United States)

Ghasemi, Hadis; Hashemian, Mahmood

2016-01-01

Both lack of time and the need to translate texts for numerous reasons brought about an increase in studying machine translation with a history spanning over 65 years. During the last decades, Google Translate, as a statistical machine translation (SMT), was in the center of attention for supporting 90 languages. Although there are many studies on…

Deregulation of cap-dependent mRNA translation increases tumour radiosensitivity through reduction of the hypoxic fraction

International Nuclear Information System (INIS)

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.

Bean Soup Translation: Flexible, Linguistically-Motivated Syntax for Machine Translation

Science.gov (United States)

Mehay, Dennis Nolan

2012-01-01

Machine translation (MT) systems attempt to translate texts from one language into another by translating words from a "source language" and rearranging them into fluent utterances in a "target language." When the two languages organize concepts in very different ways, knowledge of their general sentence structure, or…

EGFR gene copy number as a prognostic marker in colorectal cancer patients treated with cetuximab or panitumumab: a systematic review and meta analysis.

Directory of Open Access Journals (Sweden)

Zheng Jiang

Full Text Available The epidermal growth factor receptor (EGFR gene copy number (GCN has been previously demonstrated to correlate with the clinical outcome of colorectal cancer (CRC treated with anti-EGFR monoclonal antibodies (mAbs, although it remains controversial. We conducted a systematic review and meta-analysis to assess EGFR GCN as a potential biomarker of survival for patients with advanced CRC receiving treatment with anti-EGFR mAbs.We systematically identified articles investigating EGFR GCN by fluorescent or chromogenic in situ hybridization or other detection techniques in patients with metastatic CRC treated with panitumumab or cetuximab, (last search: 10 August 2012. Eligible studies had to report on overall survival (OS, progression-free survival (PFS or time-to-progression (TTP, stratified by EGFR GCN. Summary hazard ratios (HRs were calculated using random-effects models.Among 13 identified studies, 10 (776 patients, 302 with increased GCN, 8 (893 patients, 282 with increased GCN and 3 (149 patients, 66 with increased GCN were eligible for the OS, PFS and TTP meta-analyses, respectively. Increased EGFR GCN was associated with increased OS (HR = 0.62; 95% CI 0.50-0.77; P<0.001, PFS (HR = 0.65; 95% CI 0.47-0.89; P = 0.008 but not TTP (HR = 0.71; 95% CI 0.44-1.14; P = 0.157. It was also shown that EGFR GCN is independent of other factors such as KRAS status. Among those populations received second-line or higher treatment, increased EGFR GCN was strongly associated with improved survival (for OS, HR = 0.60; 95% CI 0.47-0.75; P<0.001; for PFS, HR = 0.59; 95% CI 0.47-0.75; P<0.001, whereas it did not influence survival in patients that received first-line therapy.Among the anti-EGFR-treated patients, increased EGFR GCN appears to be associated with improved survival outcomes. The effect on survival appears to be related to patients receiving the line of treatment.

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.

47 CFR 73.4195 - Political advertising by UHF translators.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Political advertising by UHF translators. 73.4195 Section 73.4195 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO... advertising by UHF translators. See Public Notice, FCC 76936, dated October 8, 1976. 62 FCC 2d 896; 41 FR...

Translational research in medicine

Directory of Open Access Journals (Sweden)

Bakir Mehić

2011-05-01

Full Text Available Translational medicine is a medical practice based on interventional epidemiology. It is regarded by its proponents as a natural progression from Evidence-Based Medicine. It integrates research from the basic sciences, social sciences and political sciences with the aim of optimizing patient care and preventive measures which may extend beyond healthcare services. In short, it is the process of turning appropriate biological discoveries into drugs and medical devices that can be used in the treatment of patients.[1]Scientific research and the development of modern powerful techniques are crucial for improving patient care in a society that is increasingly demanding the highest quality health services.[2] Indeed, effective patient care requires the continuous improvement of knowledge on the pathophysiology of the diseases, diagnostic procedures and therapeutic tools available. To this end, development of both clinical and basic research in health sciences is required. However, what is most effective in improving medical knowledge, and hence patient care, is the cross-fertilization between basic and clinical science. This has been specifically highlighted in recent years with the coining of the term “translational research”.[3] Translational research is of great importance in all medical specialties.Translational Research is the basis for Translational Medicine. It is the process which leads from evidence based medicine to sustainable solutions for public health problems.[4] It aims to improve the health and longevity of the world’s populations and depends on developing broad-based teams of scientists and scholars who are able to focus their efforts to link basic scientific discoveries with the arena of clinical investigation, and translating the results of clinical trials into changes in clinical practice, informed by evidence from the social and political sciences. Clinical science and ecological support from effective policies can�

Structural and Functional Diversity of Plant Virus 3'-Cap-Independent Translation Enhancers (3'-CITEs).

Science.gov (United States)

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.

47 CFR 74.790 - Permissible service of digital TV translator and LPTV stations.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Permissible service of digital TV translator... DISTRIBUTIONAL SERVICES Low Power TV, TV Translator, and TV Booster Stations § 74.790 Permissible service of digital TV translator and LPTV stations. (a) Digital TV translator stations provide a means whereby the...

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.

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

Promised Land No More: Dynamic Shifts in Slovene Translation Market and Translator Education

Directory of Open Access Journals (Sweden)

Nike K. Pokorn

2016-12-01

Full Text Available The article outlines the changes of the translation market, the development of Higher Education (HE translator training and of the profession of translator in Slovenia. First, three HE translator-training programmes in Slovenia are briefly described. Second, through an analysis of the public database containing information on all business entities in Slovenia, a description of the translation market in 2014 is made and the findings are compared to those of a similar study carried out in 2007. Then two surveys of translation graduates of University of Ljubljana are presented, focusing in particular on graduate employment statistics and average earnings of junior translators. The results show that despite the fact that the Slovene translation market is thriving, this growth is not reflected in the average earnings of individual translators. Finally, in view of the fact that translation rates are constantly falling, it is argued that the role of professional associations becomes vital.

Interaction in vitro between the proteinase of Tomato ringspot virus (genus Nepovirus) and the eukaryotic translation initiation factor iso4E from Arabidopsis thaliana.

Science.gov (United States)

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.

Evolutionary Conservation and Diversification of the Translation Initiation Apparatus in Trypanosomatids

Directory of Open Access Journals (Sweden)

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.

Translation in ESL Classes

Directory of Open Access Journals (Sweden)

Nagy Imola Katalin

2015-12-01

Full Text Available The problem of translation in foreign language classes cannot be dealt with unless we attempt to make an overview of what translation meant for language teaching in different periods of language pedagogy. From the translation-oriented grammar-translation method through the complete ban on translation and mother tongue during the times of the audio-lingual approaches, we have come today to reconsider the role and status of translation in ESL classes. This article attempts to advocate for translation as a useful ESL class activity, which can completely fulfil the requirements of communicativeness. We also attempt to identify some activities and games, which rely on translation in some books published in the 1990s and the 2000s.

Motion perception during tilt and translation after space flight

Science.gov (United States)

Clément, Gilles; Wood, Scott J.

2013-11-01

Preliminary results of an ongoing study examining the effects of space flight on astronauts' motion perception induced by independent tilt and translation motions are presented. This experiment used a sled and a variable radius centrifuge that translated the subjects forward-backward or laterally, and simultaneously tilted them in pitch or roll, respectively. Tests were performed on the ground prior to and immediately after landing. The astronauts were asked to report about their perceived motion in response to different combinations of body tilt and translation in darkness. Their ability to manually control their own orientation was also evaluated using a joystick with which they nulled out the perceived tilt while the sled and centrifuge were in motion. Preliminary results confirm that the magnitude of perceived tilt increased during static tilt in roll after space flight. A deterioration in the crewmember to control tilt using non-visual inertial cues was also observed post-flight. However, the use of a tactile prosthesis indicating the direction of down on the subject's trunk improved manual control performance both before and after space flight.