Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells

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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.

Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms.

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

2005-01-01

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

Translation of field-reversed configurations in the FRX C/T experiment

Energy Technology Data Exchange (ETDEWEB)

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

1984-01-01

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

Translation of field-reversed configurations in the FRX C/T experiment

International Nuclear Information System (INIS)

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

1984-01-01

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

Evolutionary Conservation and Diversification of the Translation Initiation Apparatus in Trypanosomatids

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Alexandra Zinoviev

2012-01-01

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

Comparative genomic analysis of translation initiation mechanisms for genes lacking the Shine–Dalgarno sequence in prokaryotes

KAUST Repository

Nakagawa, So

2017-02-15

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

Comparative genomic analysis of translation initiation mechanisms for genes lacking the Shine–Dalgarno sequence in prokaryotes

KAUST Repository

Nakagawa, So; Niimura, Yoshihito; Gojobori, Takashi

2017-01-01

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

The distribution of synonymous codon choice in the translation initiation region of dengue virus.

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Jian-hua Zhou

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

The long non-coding RNA GAS5 cooperates with the eukaryotic translation initiation factor 4E to regulate c-Myc translation.

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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.

Entrainment to periodic initiation and transition rates in a computational model for gene translation.

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Michael Margaliot

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

A proposed vestigial translation initiation motif in VP1 of hepatitis A virus.

Science.gov (United States)

Kang, Jeong-Ah; Funkhouser, Ann W

2002-07-01

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

MetWAMer: eukaryotic translation initiation site prediction

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Brendel Volker

2008-09-01

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

Naked mole-rat has increased translational fidelity compared with the mouse, as well as a unique 28S ribosomal RNA cleavage.

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Azpurua, Jorge; Ke, Zhonghe; Chen, Iris X; Zhang, Quanwei; Ermolenko, Dmitri N; Zhang, Zhengdong D; Gorbunova, Vera; Seluanov, Andrei

2013-10-22

The naked mole-rat (Heterocephalus glaber) is a subterranean eusocial rodent with a markedly long lifespan and resistance to tumorigenesis. Multiple data implicate modulation of protein translation in longevity. Here we report that 28S ribosomal RNA (rRNA) of the naked mole-rat is processed into two smaller fragments of unequal size. The two breakpoints are located in the 28S rRNA divergent region 6 and excise a fragment of 263 nt. The excised fragment is unique to the naked mole-rat rRNA and does not show homology to other genomic regions. Because this hidden break site could alter ribosome structure, we investigated whether translation rate and amino acid incorporation fidelity were altered. We report that naked mole-rat fibroblasts have significantly increased translational fidelity despite having comparable translation rates with mouse fibroblasts. Although we cannot directly test whether the unique 28S rRNA structure contributes to the increased fidelity of translation, we speculate that it may change the folding or dynamics of the large ribosomal subunit, altering the rate of GTP hydrolysis and/or interaction of the large subunit with tRNA during accommodation, thus affecting the fidelity of protein synthesis. In summary, our results show that naked mole-rat cells produce fewer aberrant proteins, supporting the hypothesis that the more stable proteome of the naked mole-rat contributes to its longevity.

Modulation of Translation Initiation Efficiency in Classical Swine Fever Virus

DEFF Research Database (Denmark)

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

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

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

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Ivaylo P. Ivanov

2017-06-01

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

The nematode eukaryotic translation initiation factor 4E/G complex works with a trans-spliced leader stem-loop to enable efficient translation of trimethylguanosine-capped RNAs.

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

2010-04-01

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

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

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

2015-01-15

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

Translation initiation in bacterial polysomes through ribosome loading on a standby site on a highly translated mRNA

Science.gov (United States)

Andreeva, Irena

2018-01-01

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

The Innovative Medicines Initiative moves translational immunology forward.

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

2013-02-01

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

Lack of anomalous diffusion in linear translationally-invariant systems determined by only one initial condition

International Nuclear Information System (INIS)

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

2012-01-01

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

Lack of anomalous diffusion in linear translationally-invariant systems determined by only one initial condition

Energy Technology Data Exchange (ETDEWEB)

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

2012-01-16

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

Experimental Analysis of Mimivirus Translation Initiation Factor 4a Reveals Its Importance in Viral Protein Translation during Infection of Acanthamoeba polyphaga.

Science.gov (United States)

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

2018-05-15

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

The internal initiation of translation in bovine viral diarrhea virus RNA depends on the presence of an RNA pseudoknot upstream of the initiation codon.

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Moes, Lorin; Wirth, Manfred

2007-11-22

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

The internal initiation of translation in bovine viral diarrhea virus RNA depends on the presence of an RNA pseudoknot upstream of the initiation codon

Directory of Open Access Journals (Sweden)

Moes Lorin

2007-11-01

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

PTENα, a PTEN isoform translated through alternative initiation, regulates mitochondrial function and energy metabolism.

Science.gov (United States)

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

2014-05-06

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

Designing Course An Initial Approach To Translation Teaching

Directory of Open Access Journals (Sweden)

Roswani Siregar

2017-09-01

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

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

Neural Network Prediction of Translation Initiation Sites in Eukaryotes: Perspectives for EST and Genome analysis

DEFF Research Database (Denmark)

Pedersen, Anders Gorm; Nielsen, Henrik

1997-01-01

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

The N-terminal region of eukaryotic translation initiation factor 5A signals to nuclear localization of the protein

International Nuclear Information System (INIS)

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

2007-01-01

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

Viral Genome-Linked Protein (VPg Is Essential for Translation Initiation of Rabbit Hemorrhagic Disease Virus (RHDV.

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Jie Zhu

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

Dragon TIS Spotter: An Arabidopsis-derived predictor of translation initiation sites in plants

KAUST Repository

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

2012-01-01

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

Dragon TIS Spotter: An Arabidopsis-derived predictor of translation initiation sites in plants

KAUST Repository

Magana-Mora, Arturo

2012-10-30

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

Compositional translation

NARCIS (Netherlands)

Appelo, Lisette; Janssen, Theo; Jong, de F.M.G.; Landsbergen, S.P.J.

1994-01-01

This book provides an in-depth review of machine translation by discussing in detail a particular method, called compositional translation, and a particular system, Rosetta, which is based on this method. The Rosetta project is a unique combination of fundamental research and large-scale

From what we know to what we do: lessons learned from the translational CLAHRC initiative in England.

Science.gov (United States)

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

2013-10-01

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

Harmonization in preclinical epilepsy research: A joint AES/ILAE translational initiative.

Science.gov (United States)

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

2017-11-01

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

Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms

OpenAIRE

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

2005-01-01

Translation initiation is a multistep process involving several canonical translation factors, which assemble at the 5′-end of the mRNA to promote the recruitment of the ribosome. Although the 3′ poly(A) tail of eukaryotic mRNAs and its major bound protein, the poly(A)-binding protein (PABP), have been studied extensively, their mechanism of action in translation is not well understood and is confounded by differences between in vivo and in vitro systems. Here, we provide direct evidence for ...

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.

Regulation of cap-dependent translation initiation in the early stage porcine parthenotes

Czech Academy of Sciences Publication Activity Database

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

2008-01-01

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

Dragon TIS Spotter: an Arabidopsis-derived predictor of translation initiation sites in plants.

Science.gov (United States)

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

2013-01-01

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

OvidSP Medline-to-PubMed search filter translation: a methodology for extending search filter range to include PubMed's unique content.

Science.gov (United States)

Damarell, Raechel A; Tieman, Jennifer J; Sladek, Ruth M

2013-07-02

PubMed translations of OvidSP Medline search filters offer searchers improved ease of access. They may also facilitate access to PubMed's unique content, including citations for the most recently published biomedical evidence. Retrieving this content requires a search strategy comprising natural language terms ('textwords'), rather than Medical Subject Headings (MeSH). We describe a reproducible methodology that uses a validated PubMed search filter translation to create a textword-only strategy to extend retrieval to PubMed's unique heart failure literature. We translated an OvidSP Medline heart failure search filter for PubMed and established version equivalence in terms of indexed literature retrieval. The PubMed version was then run within PubMed to identify citations retrieved by the filter's MeSH terms (Heart failure, Left ventricular dysfunction, and Cardiomyopathy). It was then rerun with the same MeSH terms restricted to searching on title and abstract fields (i.e. as 'textwords'). Citations retrieved by the MeSH search but not the textword search were isolated. Frequency analysis of their titles/abstracts identified natural language alternatives for those MeSH terms that performed less effectively as textwords. These terms were tested in combination to determine the best performing search string for reclaiming this 'lost set'. This string, restricted to searching on PubMed's unique content, was then combined with the validated PubMed translation to extend the filter's performance in this database. The PubMed heart failure filter retrieved 6829 citations. Of these, 834 (12%) failed to be retrieved when MeSH terms were converted to textwords. Frequency analysis of the 834 citations identified five high frequency natural language alternatives that could improve retrieval of this set (cardiac failure, cardiac resynchronization, left ventricular systolic dysfunction, left ventricular diastolic dysfunction, and LV dysfunction). Together these terms reclaimed

A guide to the translation of the Global Initiative for Asthma (GINA) strategy into improved care

DEFF Research Database (Denmark)

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

2012-01-01

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

ER stress inducer tunicamycin suppresses the self-renewal of glioma-initiating cell partly through inhibiting Sox2 translation.

Science.gov (United States)

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

2016-06-14

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

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

KAUST Repository

Kuwahara, Hiroyuki

2015-11-04

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

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

KAUST Repository

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

2015-01-01

solutions, previous models to capture this noise source had to assume translation to be initiation-limited, representing the burst size by a specific type of a long-tail distribution. However, there is increasing evidence suggesting that the initiation

Identifying intrinsic and extrinsic determinants that regulate internal initiation of translation mediated by the FMR1 5' leader

Directory of Open Access Journals (Sweden)

Timmerman Stephanie

2008-10-01

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

HIV-1 transcripts use IRES-initiation under conditions where Cap-dependent translation is restricted by poliovirus 2A protease.

Directory of Open Access Journals (Sweden)

Raquel Amorim

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

Molecular modeling of the human eukaryotic translation initiation factor 5A (eIF5A) based on spectroscopic and computational analyses

International Nuclear Information System (INIS)

Costa-Neto, Claudio M.; Parreiras-e-Silva, Lucas T.; Ruller, Roberto; Oliveira, Eduardo B.; Miranda, Antonio; Oliveira, Laerte; Ward, Richard J.

2006-01-01

The eukaryotic translation initiation factor 5A (eIF5A) is a protein ubiquitously present in archaea and eukarya, which undergoes a unique two-step post-translational modification called hypusination. Several studies have shown that hypusination is essential for a variety of functional roles for eIF5A, including cell proliferation and synthesis of proteins involved in cell cycle control. Up to now neither a totally selective inhibitor of hypusination nor an inhibitor capable of directly binding to eIF5A has been reported in the literature. The discovery of such an inhibitor might be achieved by computer-aided drug design based on the 3D structure of the human eIF5A. In this study, we present a molecular model for the human eIF5A protein based on the crystal structure of the eIF5A from Leishmania brasiliensis, and compare the modeled conformation of the loop bearing the hypusination site with circular dichroism data obtained with a synthetic peptide of this loop. Furthermore, analysis of amino acid variability between different human eIF5A isoforms revealed peculiar structural characteristics that are of functional relevance

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.

Tuning of Recombinant Protein Expression in Escherichia coli by Manipulating Transcription, Translation Initiation Rates, and Incorporation of Noncanonical Amino Acids.

Science.gov (United States)

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

2017-06-16

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

Knowledge Translation Interventions to Improve the Timing of Dialysis Initiation: Protocol for a Cluster Randomized Trial.

Science.gov (United States)

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

2016-01-01

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

Androgen signaling promotes translation of TMEFF2 in prostate cancer cells via phosphorylation of the α subunit of the translation initiation factor 2.

Directory of Open Access Journals (Sweden)

Ryan F Overcash

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

Translation between cultures

Directory of Open Access Journals (Sweden)

Henrique de Oliveira Lee

2016-05-01

Full Text Available This article will question the pertinence of understanding interculturality in terms of translation between cultures. I shall study this hypothesis in two ways : 1 / the cosmopolitan horizon, which the idea of translation may implicate ; 2 / the critique of the premises of unique origin and homogeneity of cultures which this hypothesis makes possible.

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.

'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 ...

Origins of robustness in translational control via eukaryotic translation initiation factor (eIF) 2.

Science.gov (United States)

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

2018-05-14

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

A Novel Quality Measure and Correction Procedure for the Annotation of Microbial Translation Initiation Sites

NARCIS (Netherlands)

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

2015-01-01

The identification of translation initiation sites (TISs) constitutes an important aspect of sequence-based genome analysis. An erroneous TIS annotation can impair the identification of regulatory elements and N-terminal signal peptides, and also may flaw the determination of descent, for any

Biological insights into the expression of translation initiation factors from recombinant CHOK1SV cell lines and their relationship to enhanced productivity.

Science.gov (United States)

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

2015-12-15

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

Initiatives and evaluation of teaching-learning process in translation training

OpenAIRE

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

2010-01-01

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

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.

PKC δ Regulates Translation Initiation through PKR and eIF2 α in Response to Retinoic Acid in Acute Myeloid Leukemia Cells

OpenAIRE

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

2012-01-01

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

N-terminal Proteomics Assisted Profiling of the Unexplored Translation Initiation Landscape in Arabidopsis thaliana.

Science.gov (United States)

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

2017-06-01

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

Crystallization and preliminary crystallographic studies of the W2 domain of Drosophila melanogaster eukaryotic translation initiation factor 5C domain-containing protein

International Nuclear Information System (INIS)

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

2012-01-01

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

Advancing System Flexibility for High Penetration Renewable Integration (Chinese Translation)

Energy Technology Data Exchange (ETDEWEB)

Milligan, Michael [National Renewable Energy Lab. (NREL), Golden, CO (United States); Frew, Bethany [National Renewable Energy Lab. (NREL), Golden, CO (United States); Zhou, Ella [National Renewable Energy Lab. (NREL), Golden, CO (United States); Arent, Douglas J. [Joint Inst. for Strategic Energy Analysis, Golden, CO (United States)

2015-10-01

This is a Chinese translation of NREL/TP-6A20-64864. This report summarizes some of the issues discussed during the engagement on power system flexibility. By design, the focus is on flexibility options used in the United States. Exploration of whether and how U.S. experiences can inform Chinese energy planning will be part of the continuing project, and will benefit from the knowledge base provided by this report. We believe the initial stage of collaboration represented in this report has successfully started a process of mutual understanding, helping Chinese researchers to begin evaluating how lessons learned in other countries might translate to China's unique geographic, economic, social, and political contexts.

The triplet repeats of the Sin Nombre hantavirus 5' untranslated region are sufficient in cis for nucleocapsid-mediated translation initiation.

Science.gov (United States)

Mir, Mohammad A; Panganiban, Antonito T

2010-09-01

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

The NS1 Protein from Influenza Virus Stimulates Translation Initiation by Enhancing Ribosome Recruitment to mRNAs.

Science.gov (United States)

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

2017-10-27

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

The translation initiation factor 3 subunit eIF3K interacts with PML and associates with PML nuclear bodies

Energy Technology Data Exchange (ETDEWEB)

Salsman, Jayme; Pinder, Jordan; Tse, Brenda [Department of Pathology, Dalhousie University, P.O. Box 15000, Halifax, Nova Scotia, Canada B3H 4R2 (Canada); Corkery, Dale [Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia (Canada); Dellaire, Graham, E-mail: dellaire@dal.ca [Department of Pathology, Dalhousie University, P.O. Box 15000, Halifax, Nova Scotia, Canada B3H 4R2 (Canada); Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia (Canada)

2013-10-15

The promyelocytic leukemia protein (PML) is a tumor suppressor protein that regulates a variety of important cellular processes, including gene expression, DNA repair and cell fate decisions. Integral to its function is the ability of PML to form nuclear bodies (NBs) that serve as hubs for the interaction and modification of over 90 cellular proteins. There are seven canonical isoforms of PML, which encode diverse C-termini generated by alternative pre-mRNA splicing. Recruitment of specific cellular proteins to PML NBs is mediated by protein–protein interactions with individual PML isoforms. Using a yeast two-hybrid screen employing peptide sequences unique to PML isoform I (PML-I), we identified an interaction with the eukaryotic initiation factor 3 subunit K (eIF3K), and in the process identified a novel eIF3K isoform, which we term eIF3K-2. We further demonstrate that eIF3K and PML interact both in vitro via pull-down assays, as well as in vivo within human cells by co-immunoprecipitation and co-immunofluorescence. In addition, eIF3K isoform 2 (eIF3K-2) colocalizes to PML bodies, particularly those enriched in PML-I, while eIF3K isoform 1 associates poorly with PML NBs. Thus, we report eIF3K as the first known subunit of the eIF3 translation pre-initiation complex to interact directly with the PML protein, and provide data implicating alternative splicing of both PML and eIF3K as a possible regulatory mechanism for eIF3K localization at PML NBs. - Highlights: • The PML-I C-terminus, encoded by exon 9, interacts with translation factor eIF3K. • We identify a novel eIF3K isoform that excludes exon 2 (eIF3K-2). • eIF3K-2 preferentially associates with PML bodies enriched in PML-I vs. PML-IV. • Alternative splicing of eIF3K regulates association with PML bodies.

Quantitative analysis of ribosome–mRNA complexes at different translation stages

Science.gov (United States)

Shirokikh, Nikolay E.; Alkalaeva, Elena Z.; Vassilenko, Konstantin S.; Afonina, Zhanna A.; Alekhina, Olga M.; Kisselev, Lev L.; Spirin, Alexander S.

2010-01-01

Inhibition of primer extension by ribosome–mRNA complexes (toeprinting) is a proven and powerful technique for studying mechanisms of mRNA translation. Here we have assayed an advanced toeprinting approach that employs fluorescently labeled DNA primers, followed by capillary electrophoresis utilizing standard instruments for sequencing and fragment analysis. We demonstrate that this improved technique is not merely fast and cost-effective, but also brings the primer extension inhibition method up to the next level. The electrophoretic pattern of the primer extension reaction can be characterized with a precision unattainable by the common toeprint analysis utilizing radioactive isotopes. This method allows us to detect and quantify stable ribosomal complexes at all stages of translation, including initiation, elongation and termination, generated during the complete translation process in both the in vitro reconstituted translation system and the cell lysate. We also point out the unique advantages of this new methodology, including the ability to assay sites of the ribosomal complex assembly on several mRNA species in the same reaction mixture. PMID:19910372

Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

NARCIS (Netherlands)

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

2008-01-01

OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between

Sepsis and mechnaical ventilation restrain translation initiation in skeletal muscle by inducing AMPK-associated TSC[2] restriction of mTOR signaling in pigs

Science.gov (United States)

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

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.

A Protocol of Japanese-English Translation

OpenAIRE

三浦, 勲夫; MIURA, Isao

1999-01-01

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

Non-unique Product Groups on Two Generators

OpenAIRE

Carter, William Paul

2007-01-01

The main purpose of this paper is to better understand groups that do not have the unique product property. In particular, the goal is to better understand Promislow's example, G, of such a group. In doing so, we will develop methods for generating examples of other sets that do not have the unique product property. With these methods we can show that there exists other distinct 14 element, square, non-unique product sets in G that are not inversions or translations. Also, this paper answers ...

Eukaryotic initiation factor 3 (eIF3) and 5’ mRNA leader sequences as agents of translational regulation in Arabidopsis. Final report

Energy Technology Data Exchange (ETDEWEB)

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

2015-02-04

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

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

Science.gov (United States)

Hashem, Yaser; Frank, Joachim

2018-03-01

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

Typologically robust statistical machine translation : Understanding and exploiting differences and similarities between languages in machine translation

NARCIS (Netherlands)

Daiber, J.

2018-01-01

Machine translation systems often incorporate modeling assumptions motivated by properties of the language pairs they initially target. When such systems are applied to language families with considerably different properties, translation quality can deteriorate. Phrase-based machine translation

Phosphorylation and interactions associated with the control of the Leishmania Poly-A Binding Protein 1 (PABP1) function during translation initiation.

Science.gov (United States)

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

2018-03-23

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

Improvements in Pain Outcomes in a Canadian Pediatric Teaching Hospital Following Implementation of a Multifaceted, Knowledge Translation Initiative

Directory of Open Access Journals (Sweden)

Lisa M Zhu

2012-01-01

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

Shakespeare in translation: a bird’s eye view of problems and perspectives Shakespeare in translation: a bird’s eye view of problems and perspectives

Directory of Open Access Journals (Sweden)

Dirk Delabastita

2008-04-01

Full Text Available The fact that many shelves could be filled with publications on the translation of the Bible and of Shakespeare (but not of, say, Homer, Cervantes, Racine, or Joyce must have to do more with the unique cultural functions Shakespeare and the Scriptures have fulfilled through the centuries than with any concern for the intrinsic difficulties involved in translating them. The fact that many shelves could be filled with publications on the translation of the Bible and of Shakespeare (but not of, say, Homer, Cervantes, Racine, or Joyce must have to do more with the unique cultural functions Shakespeare and the Scriptures have fulfilled through the centuries than with any concern for the intrinsic difficulties involved in translating them.

5'-Terminal AUGs in Escherichia coli mRNAs with Shine-Dalgarno Sequences: Identification and Analysis of Their Roles in Non-Canonical Translation Initiation.

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Heather J Beck

Full Text Available Analysis of the Escherichia coli transcriptome identified a unique subset of messenger RNAs (mRNAs that contain a conventional untranslated leader and Shine-Dalgarno (SD sequence upstream of the gene's start codon while also containing an AUG triplet at the mRNA's 5'- terminus (5'-uAUG. Fusion of the coding sequence specified by the 5'-terminal putative AUG start codon to a lacZ reporter gene, as well as primer extension inhibition assays, reveal that the majority of the 5'-terminal upstream open reading frames (5'-uORFs tested support some level of lacZ translation, indicating that these mRNAs can function both as leaderless and canonical SD-leadered mRNAs. Although some of the uORFs were expressed at low levels, others were expressed at levels close to that of the respective downstream genes and as high as the naturally leaderless cI mRNA of bacteriophage λ. These 5'-terminal uORFs potentially encode peptides of varying lengths, but their functions, if any, are unknown. In an effort to determine whether expression from the 5'-terminal uORFs impact expression of the immediately downstream cistron, we examined expression from the downstream coding sequence after mutations were introduced that inhibit efficient 5'-uORF translation. These mutations were found to affect expression from the downstream cistrons to varying degrees, suggesting that some 5'-uORFs may play roles in downstream regulation. Since the 5'-uAUGs found on these conventionally leadered mRNAs can function to bind ribosomes and initiate translation, this indicates that canonical mRNAs containing 5'-uAUGs should be examined for their potential to function also as leaderless mRNAs.

Pharmacogenetic diversification by alternative translation initiation: background channels to the fore.

Science.gov (United States)

Abbott, G W

2014-02-15

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

Expression of the Eukaryotic Translation Initiation Factors 4E and 2α in Non-Hodgkin’s Lymphomas

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

1999-01-01

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

Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

International Nuclear Information System (INIS)

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

2013-01-01

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

Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

Energy Technology Data Exchange (ETDEWEB)

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

2013-06-01

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

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

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

2017-08-01

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

Existence and uniqueness of entropy solution to initial boundary value problem for the inviscid Burgers equation

CERN Document Server

Zhu, C

2003-01-01

This paper is concerned with the existence and uniqueness of the entropy solution to the initial boundary value problem for the inviscid Burgers equation. To apply the method of vanishing viscosity to study the existence of the entropy solution, we first introduce the initial boundary value problem for the viscous Burgers equation, and as in Evans (1998 Partial Differential Equations (Providence, RI: American Mathematical Society) and Hopf (1950 Commun. Pure Appl. Math. 3 201-30), give the formula of the corresponding viscosity solutions by Hopf-Cole transformation. Secondly, we prove the convergence of the viscosity solution sequences and verify that the limiting function is an entropy solution. Finally, we give an example to show how our main result can be applied to solve the initial boundary value problem for the Burgers equation.

Existence and uniqueness of entropy solution to initial boundary value problem for the inviscid Burgers equation

International Nuclear Information System (INIS)

Zhu, Changjiang; Duan, Renjun

2003-01-01

This paper is concerned with the existence and uniqueness of the entropy solution to the initial boundary value problem for the inviscid Burgers equation. To apply the method of vanishing viscosity to study the existence of the entropy solution, we first introduce the initial boundary value problem for the viscous Burgers equation, and as in Evans (1998 Partial Differential Equations (Providence, RI: American Mathematical Society) and Hopf (1950 Commun. Pure Appl. Math. 3 201-30), give the formula of the corresponding viscosity solutions by Hopf-Cole transformation. Secondly, we prove the convergence of the viscosity solution sequences and verify that the limiting function is an entropy solution. Finally, we give an example to show how our main result can be applied to solve the initial boundary value problem for the Burgers equation

Evidence of Parallel Processing During Translation

DEFF Research Database (Denmark)

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

2014-01-01

conclude that translation is a parallel process and that literal translation is likely to be a universal initial default strategy in translation. This conclusion is strengthened by the fact that all three experiments were relatively naturalistic, due to the combination of remote eye tracking and mixed...

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.

Eukaryotic translation initiation factor 2B-beta (eIF2Bβ), a new class of plant virus resistance gene.

Science.gov (United States)

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

2017-06-01

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

Core competencies in the science and practice of knowledge translation: description of a Canadian strategic training initiative.

Science.gov (United States)

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

2011-12-09

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

The impact of a unique knowledge translation programme implemented in a large multisite paediatric hospital.

Science.gov (United States)

Christensen, Catie; Wessells, David; Byars, Michelle; Marrie, James; Coffman, Shaun; Gates, Erin; Selhorst, Mitch

2017-04-01

Physical therapists (PTs) display positive attitudes toward evidence-based practice (EBP), and implementing it can improve patient outcomes and reduce costs. However, barriers can lead to inconsistent use of EBP. The objectives of this manuscript are to (i) describe the initiation and revisions to a knowledge translation (KT) programme, (ii) assess staff participation in KT, and (iii) evaluate availability, internal use and external dissemination of evidence-based recommendations and research. The KT programme was implemented in a large paediatric hospital employing 66 PTs who provide services in the inpatient, outpatient developmental and sports and orthopaedics settings in 15 locations. The KT programme was initiated 9 years ago but underwent improvements over the past 3 years. Five key revisions included the subdivision of the EBP and Research Coordinator positions by area of practice, increasing the structure of the KT programme, implementing strategies to encourage use of local recommendations, obtaining leadership support to emphasize KT and providing staff education. With the revisions, staff participation in local recommendation development increased from 16.3-68.2%. Research involvement increased from 4.1-50%. The number of local recommendations increased from 1 to 9, and an overall compliance rate of 79% was achieved for the recommendations presented in an algorithm format. External dissemination increased from 1 to 44 for presentations and 0 to 7 for publications. Revisions to a KT programme improved PT engagement in KT activities, increased the availability of local recommendations, encouraged use of EBP and increased external dissemination of information. © 2016 John Wiley & Sons, Ltd.

Modifying chemotherapy response by targeted inhibition of eukaryotic initiation factor 4A

International Nuclear Information System (INIS)

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

2013-01-01

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

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

Core competencies in the science and practice of knowledge translation: description of a Canadian strategic training initiative

Directory of Open Access Journals (Sweden)

Straus Sharon E

2011-12-01

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

Overview of the Inland California Translational Consortium

Science.gov (United States)

Malkas, Linda H.

2017-05-01

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

Eukaryotic translation initiation factor 3 subunit e controls intracellular calcium homeostasis by regulation of cav1.2 surface expression.

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Pawel Buda

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

The Continuing Challenges of Translational Research: Clinician-Scientists’ Perspective

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Shervanthi Homer-Vanniasinkam

2012-01-01

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

Design and Formative Evaluation of the Policy Liaison Initiative: A Long-Term Knowledge Translation Strategy to Encourage and Support the Use of Cochrane Systematic Reviews for Informing

Science.gov (United States)

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

2016-01-01

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

The eukaryotic translation initiation factor 3 subunit E binds to classical swine fever virus NS5A and facilitates viral replication.

Science.gov (United States)

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

2018-02-01

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

Chinese literary works translated into Baba Malay: a bibliographical study

OpenAIRE

Yoong, S. K.; Zainab, A.N.

2002-01-01

Analyses 68 unique titles of Baba translated works published between 1889 and 1950. The titles are held in the libraries of the University of Malaya (UM), Science University Malaysia (USM), National University of Malaysia (UKM), the Dewan Bahasa dan Pustaka (DBP), National University of Singapore (NUS), National Library of Singapore (NLS) and the British Library (BL). The results reveal three periods of active publication of Baba translated works. A total of 18 works were translated before Wo...

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.

Translational Research from an Informatics Perspective

Science.gov (United States)

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

2007-01-01

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

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.

A molecular doorstop ensures a trickle through translational repression.

Science.gov (United States)

Brook, Matthew; Smith, Richard W P; Gray, Nicola K

2012-03-30

Switching mRNA translation off and on is central to regulated gene expression, but what mechanisms moderate the extent of switch-off? Yao et al. describe how basal expression from interferon-gamma-induced transcripts is maintained during mRNA-specific translational repression. This antagonistic mechanism utilizes a truncated RNA-binding factor generated by a unique alternative polyadenylation event. Copyright © 2012 Elsevier Inc. All rights reserved.

Translational Repression in Malaria Sporozoites

Science.gov (United States)

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

2016-01-01

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

Translational repression in malaria sporozoites

Directory of Open Access Journals (Sweden)

Oliver Turque

2016-04-01

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

Gentzler, Edwin. Translation, hypertext, and creativity: Contemporary translation theories. Bristol: Multilingual Matters, 2001. 232 p.

Directory of Open Access Journals (Sweden)

Davi S. Gonçalves

2018-01-01

Full Text Available Contemporary translation theories (Gentzler,2001 provides readers with a thorough historical analysis of how the notion of creativity and autonomy in what regards reading has been transformed – as well as regarding its influence towards the idea of translation. The place occupied by the translator is a place between spaces; a fluid locale where any concreteness has melted. Meaning is thus not graspable or amenable to be tamed; on the contrary, literature is about opening up more space for the wilderness to be (rediscovered. A text is many texts, a hypertext, filled in with narratives that mutually supplement one another, deconstructing and reconstructing meanings; and, within such picture, translation emerges not as an opportunity to resurrect the body of an original text, but as a phantasm of both sameness and uniqueness. What does exist cannot be seen; it is always on the run; meanings surface from liquefied pages, pages that escape our attempt of defining them for good. This is why translation can be taken as metonym: as s/he recreates the original text within the target context, the translator choose to highlight those textual elements that s/he deems relevant – those fragments of the text that have touched and determined his/her reading. The experience of translation, that goes beyond dichotomist standards (e.g. foreign/domestic, equivalent/adapted, etc., is finally taken as a profitable realm for the literary discourse to validate its impalpability. Such shift in the approach towards translation is significant because, even though the process of recreation takes place in every textual practice, tradition has been pressuring translation scholars towards the designing of guidelines and norms that, I dare say, only obstruct the task of translating.

TRADUCCIÓN DE ACRÓNIMOS Y SIGLAS EN TEXTOS MÉDICOS DE CARDIOLOGÍA / Translation of acronyms and initialisms in medical texts on cardiology

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Ana V. Fernández Peraza

2013-01-01

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

The Art of Translation, by Vladimir Nabokov Questions of Reception and of Transmigration in Translation

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Christine Raguet

2017-09-01

Full Text Available The aims of this article are: i to analyze the relations of Vladimir Nabokov as a multilingual author with translation when faced with exile and with the publication of one of his novels in a language in which he could write; ii to explore Nabokov’s attitude towards the translation of one of his books, his desires to be recognized as an author and to polish his style in the new culture-language; iii to present factors like personal and cultural identity, and also financial needs as linked to exile and as significant elements in the translating process; iv to discuss  the impact of rewriting in an author seeking international recognition and in an obvious quest for new aesthetic values. Nabokov is not a unique case, but his situation and reactions are quite representative of the difficulties raised when changing one’s language of composition.

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.

Uniqueness Results for Weak Leray-Hopf Solutions of the Navier-Stokes System with Initial Values in Critical Spaces

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Barker, T.

2018-03-01

The main subject of this paper concerns the establishment of certain classes of initial data, which grant short time uniqueness of the associated weak Leray-Hopf solutions of the three dimensional Navier-Stokes equations. In particular, our main theorem that this holds for any solenodial initial data, with finite L_2(R^3) norm, that also belongs to certain subsets of {it{VMO}}^{-1}(R^3). As a corollary of this, we obtain the same conclusion for any solenodial u0 belonging to L2(R^3)\\cap \\dot{B}^{-1+3/p}_{p,∞}(R^3), for any 3norm is sufficiently small, where 3

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.

Initiation of protein synthesis in bacteria

DEFF Research Database (Denmark)

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

2005-01-01

Valuable information on translation initiation is available from biochemical data and recently solved structures. We present a detailed description of current knowledge about the structure, function, and interactions of the individual components involved in bacterial translation initiation. The f...

Writing under cover: Cristina Campo as translator of John Donne

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Maria Panarello

2009-12-01

Full Text Available The study of Cristina Campo’s translations offers a precious contribution to those of us who are attempting to investigate the unknown area that lies in the shadowy zone between the source text and its translation. Vittoria Guerrini, a rather solitary and reticent figure in 20th-century Italian literature, wrote under several pen names, of which her favourite was Cristina Campo, the masque she chose for her beautiful and intense translations of a small but significant collection of poems by John Donne. This paper aims at exploring Cristina Campo’s attitude towards translation and the unique relationship she established with the poets she translated. John Donne’s translations reflect a singular solidarity displaying points of affinity between two extremely complex personalities. The dialogic rapport abolishes difference in space and time, as well as difference in language, as author and translator testify the same supreme tension towards beauty, truth and perfection. Translation in this perspective is a sacred gesture of mediation.

HIV-1 Replication and the Cellular Eukaryotic Translation Apparatus

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Santiago Guerrero

2015-01-01

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

Euphemism vs explicitness: A corpus-based analysis of translated ...

African Journals Online (AJOL)

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

Evaluation of the "Foundations in Knowledge Translation" training initiative: preparing end users to practice KT.

Science.gov (United States)

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

2018-04-25

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

Translational initiation in Leishmania tarentolae and Phytomonas serpens (Kinetoplastida) is strongly influenced by pre-ATG triplet and its 5´ sequence context

Czech Academy of Sciences Publication Activity Database

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

2006-01-01

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

Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

DEFF Research Database (Denmark)

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

2008-01-01

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

Translating a wicked problem

DEFF Research Database (Denmark)

Tietjen, Anne; Jørgensen, Gertrud

2016-01-01

, place-based and project-oriented process directed at concrete physical outcomes. We frame strategic planning as a translation process where the interaction between human and non-human actors translates a unique, complex and contested situation into an innovated situation. We find that local physical...... on the case of a Danish planning process which was carried out in collaboration with a charitable trust, this paper discusses an emerging strategic planning approach at the municipal level. We use the concept of wicked problems, strategic planning theory and Actor-Network-Theory to study a collaborative...... projects played a major role in this process. First, they acted as a vehicle that assembled planners, politicians and stakeholders to work towards strategic visions across multiple scales. Second and consequently, they stimulated considerable second and third order effects in the form of shared problem...

The mechanism of translation initiation on Aichivirus RNA mediated by a novel type of picornavirus IRES.

Science.gov (United States)

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

2011-08-26

Picornavirus mRNAs contain IRESs that sustain their translation during infection, when host protein synthesis is shut off. The major classes of picornavirus IRESs (Types 1 and 2) have distinct structures and sequences, but initiation on both is determined by their specific interaction with eIF4G. We report here that Aichivirus (AV), a member of the Kobuvirus genus of Picornaviridae, contains an IRES that differs structurally from Type 1 and Type 2 IRESs. Its function similarly involves interaction with eIF4G, but its eIF4G-interacting domain is structurally distinct, although it contains an apical eIF4G-interacting motif similar to that in Type 2 IRESs. Like Type 1 and Type 2 IRESs, AV IRES function is enhanced by pyrimidine tract-binding protein (PTB), but the pattern of PTB's interaction with each of these IRESs is distinct. Unlike all known IRESs, the AV IRES is absolutely dependent on DHX29, a requirement imposed by sequestration of its initiation codon in a stable hairpin.

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.

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.

The antidepressant sertraline inhibits translation initiation by curtailing mammalian target of rapamycin signaling.

Science.gov (United States)

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

2010-04-15

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

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

FRC translation into a compression coil

International Nuclear Information System (INIS)

Chrien, R.E.

1985-01-01

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

A blended knowledge translation initiative to improve colorectal cancer staging [ISRCTN56824239

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Ryan David P

2006-01-01

Full Text Available Abstract Background A significant gap has been documented between best practice and the actual practice of surgery. Our group identified that colorectal cancer staging in Ontario was suboptimal and subsequently developed a knowledge translation strategy using the principles of social marketing and the influence of expert and local opinion leaders for colorectal cancer. Methods/Design Opinion leaders were identified using the Hiss methodology. Hospitals in Ontario were cluster-randomized to one of two intervention arms. Both groups were exposed to a formal continuing medical education session given by the expert opinion leader for colorectal cancer. In the treatment group the local Opinion Leader for colorectal cancer was detailed by the expert opinion leader for colorectal cancer and received a toolkit. Forty-two centres agreed to have the expert opinion leader for colorectal cancer come and give a formal continuing medical education session that lasted between 50 minutes and 4 hours. No centres refused the intervention. These sessions were generally well attended by most surgeons, pathologists and other health care professionals at each centre. In addition all but one of the local opinion leaders for colorectal cancer met with the expert opinion leader for colorectal cancer for the academic detailing session that lasted between 15 and 30 minutes. Discussion We have enacted a unique study that has attempted to induce practice change among surgeons and pathologists using an adapted social marketing model that utilized the influence of both expert and local opinion leaders for colorectal cancer in a large geographic area with diverse practice settings.

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.

SPEECH ACT OF ILTIFAT AND ITS INDONESIAN TRANSLATION PROBLEMS

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Zaka Al Farisi

2015-01-01

Full Text Available Abstract: Iltifat (shifting speech act is distinctive and considered unique style of Arabic. It has potential errors when it is translated into Indonesian. Therefore, translation of iltifat speech act into another language can be an important issue. The objective of the study is to know translation procedures/techniques and ideology required in dealing with iltifat speech act. This research is directed at translation as a cognitive product of a translator. The data used in the present study were the corpus of Koranic verses that contain iltifat speech act along with their translation. Data analysis typically used descriptive-evaluative method with content analysis model. The data source of this research consisted of the Koran and its translation. The purposive sampling technique was employed, with the sample of the iltifat speech act contained in the Koran. The results showed that more than 60% of iltifat speech act were translated by using literal procedure. The significant number of literal translation of the verses asserts that the Ministry of Religious Affairs tended to use literal method of translation. In other words, the Koran translation made by the Ministry of Religious Affairs tended to be oriented to the source language in dealing with iltifat speech act. The number of the literal procedure used shows a tendency of foreignization ideology. Transitional pronouns contained in the iltifat speech act can be clearly translated when thick translations were used in the form of description in parentheses. In this case, explanation can be a choice in translating iltifat speech act.

Uniqueness of flat spherically symmetric spacelike hypersurfaces admitted by spherically symmetric static spacetimes

Science.gov (United States)

Beig, Robert; Siddiqui, Azad A.

2007-11-01

It is known that spherically symmetric static spacetimes admit a foliation by flat hypersurfaces. Such foliations have explicitly been constructed for some spacetimes, using different approaches, but none of them have proved or even discussed the uniqueness of these foliations. The issue of uniqueness becomes more important due to suitability of flat foliations for studying black hole physics. Here, flat spherically symmetric spacelike hypersurfaces are obtained by a direct method. It is found that spherically symmetric static spacetimes admit flat spherically symmetric hypersurfaces, and that these hypersurfaces are unique up to translation under the timelike Killing vector. This result guarantees the uniqueness of flat spherically symmetric foliations for such spacetimes.

Leucine-rich diet alters the eukaryotic translation initiation factors expression in skeletal muscle of tumour-bearing rats

Directory of Open Access Journals (Sweden)

Mello Maria

2007-03-01

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

Leucine-rich diet alters the eukaryotic translation initiation factors expression in skeletal muscle of tumour-bearing rats

International Nuclear Information System (INIS)

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

2007-01-01

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

Leucine-rich diet alters the eukaryotic translation initiation factors expression in skeletal muscle of tumour-bearing rats

Energy Technology Data Exchange (ETDEWEB)

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

2007-03-06

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

FRC translation into a compression coil

International Nuclear Information System (INIS)

Chrien, R.E.

1986-01-01

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

A universal trend of reduced mRNA stability near the translation-initiation site in prokaryotes and eukaryotes.

Directory of Open Access Journals (Sweden)

Wanjun Gu

2010-02-01

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

Shakespeare in translation: a bird’s eye view of problems and perspectives

Directory of Open Access Journals (Sweden)

Dirk Delabastita

2003-04-01

Full Text Available The fact that many shelves could be filled with publications on the translation of the Bible and of Shakespeare (but not of, say, Homer, Cervantes, Racine, or Joyce must have to do more with the unique cultural functions Shakespeare and the Scriptures have fulfilled through the centuries than with any concern for the intrinsic difficulties involved in translating them.

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…

PRMT1-Mediated Translation Regulation Is a Crucial Vulnerability of Cancer.

Science.gov (United States)

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

2017-09-01

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

Translation of the shallot virus X TGB3 gene depends on non-AUG initiation and leaky scanning.

Science.gov (United States)

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

2015-10-01

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

Some variants of translating Russian realia into the western culture (on the materials of English newspapers

Directory of Open Access Journals (Sweden)

Марина Андреевна Курбакова

2013-12-01

Full Text Available There is no any unique approach to the understanding of the notion “culture-specific vocabulary”. The main techniques used for its translation include transcription, transliteration, loan-translation and mixed methods. The article contains a lot of examples.

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

Leaderless Transcripts and Small Proteins Are Common Features of the Mycobacterial Translational Landscape.

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Scarlet S Shell

2015-11-01

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

Translational control in plant antiviral immunity

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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.

Community-based knowledge translation: unexplored opportunities

Directory of Open Access Journals (Sweden)

Armstrong Rebecca

2011-06-01

Full Text Available Abstract Background Knowledge translation is an interactive process of knowledge exchange between health researchers and knowledge users. Given that the health system is broad in scope, it is important to reflect on how definitions and applications of knowledge translation might differ by setting and focus. Community-based organizations and their practitioners share common characteristics related to their setting, the evidence used in this setting, and anticipated outcomes that are not, in our experience, satisfactorily reflected in current knowledge translation approaches, frameworks, or tools. Discussion Community-based organizations face a distinctive set of challenges and concerns related to engaging in the knowledge translation process, suggesting a unique perspective on knowledge translation in these settings. Specifically, community-based organizations tend to value the process of working in collaboration with multi-sector stakeholders in order to achieve an outcome. A feature of such community-based collaborations is the way in which 'evidence' is conceptualized or defined by these partners, which may in turn influence the degree to which generalizable research evidence in particular is relevant and useful when balanced against more contextually-informed knowledge, such as tacit knowledge. Related to the issues of evidence and context is the desire for local information. For knowledge translation researchers, developing processes to assist community-based organizations to adapt research findings to local circumstances may be the most helpful way to advance decision making in this area. A final characteristic shared by community-based organizations is involvement in advocacy activities, a function that has been virtually ignored in traditional knowledge translation approaches. Summary This commentary is intended to stimulate further discussion in the area of community-based knowledge translation. Knowledge translation, and exchange

Machine translation with minimal reliance on parallel resources

CERN Document Server

Tambouratzis, George; Sofianopoulos, Sokratis

2017-01-01

This book provides a unified view on a new methodology for Machine Translation (MT). This methodology extracts information from widely available resources (extensive monolingual corpora) while only assuming the existence of a very limited parallel corpus, thus having a unique starting point to Statistical Machine Translation (SMT). In this book, a detailed presentation of the methodology principles and system architecture is followed by a series of experiments, where the proposed system is compared to other MT systems using a set of established metrics including BLEU, NIST, Meteor and TER. Additionally, a free-to-use code is available, that allows the creation of new MT systems. The volume is addressed to both language professionals and researchers. Prerequisites for the readers are very limited and include a basic understanding of the machine translation as well as of the basic tools of natural language processing.

Dietary fat and fiber interact to uniquely modify global histone post-translational epigenetic programming in a rat colon cancer progression model.

Science.gov (United States)

Triff, Karen; McLean, Mathew W; Callaway, Evelyn; Goldsby, Jennifer; Ivanov, Ivan; Chapkin, Robert S

2018-04-16

Dietary fermentable fiber generates short-chain fatty acids (SCFA), e.g., butyrate, in the colonic lumen which serves as a chemoprotective histone deacetylase inhibitor and/or as an acetylation substrate for histone acetylases. In addition, n-3 polyunsaturated fatty acids (n-3 PUFA) in fish oil can affect the chromatin landscape by acting as ligands for tumor suppressive nuclear receptors. In an effort to gain insight into the global dimension of post-translational modification of histones (including H3K4me3 and H3K9ac) and clarify the chemoprotective impact of dietary bioactive compounds on transcriptional control in a preclinical model of colon cancer, we generated high-resolution genome-wide RNA (RNA-Seq) and "chromatin-state" (H3K4me3-seq and H3K9ac-seq) maps for intestinal (epithelial colonocytes) crypts in rats treated with a colon carcinogen and fed diets containing bioactive (i) fish oil, (ii) fermentable fiber (a rich source of SCFA), (iii) a combination of fish oil plus pectin or (iv) control, devoid of fish oil or pectin. In general, poor correlation was observed between differentially transcribed (DE) and enriched genes (DERs) at multiple epigenetic levels. The combinatorial diet (fish oil + pectin) uniquely affected transcriptional profiles in the intestinal epithelium, e.g., upregulating lipid catabolism and beta-oxidation associated genes. These genes were linked to activated ligand-dependent nuclear receptors associated with n-3 PUFA and were also correlated with the mitochondrial L-carnitine shuttle and the inhibition of lipogenesis. These findings demonstrate that the chemoprotective fish oil + pectin combination diet uniquely induces global histone state modifications linked to the expression of chemoprotective genes. This article is protected by copyright. All rights reserved. © 2018 UICC.

Translation in cell-free systems

International Nuclear Information System (INIS)

Jagus, R.

1987-01-01

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

AtLa1 protein initiates IRES-dependent translation of WUSCHEL mRNA and regulates the stem cell homeostasis of Arabidopsis in response to environmental hazards.

Science.gov (United States)

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

2015-10-01

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

The translation factors of Drosophila melanogaster.

Science.gov (United States)

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

2017-01-02

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

Recessive Resistance to Plant Viruses: Potential Resistance Genes Beyond Translation Initiation Factors

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Masayoshi Hashimoto

2016-10-01

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

The not-for-profit form and translational research: Kerr revisited?

Directory of Open Access Journals (Sweden)

Joiner Keith A

2005-04-01

Full Text Available Abstract Translational research conducted in academic health centers is confounded by the organizational structure in which the work is performed. Investigators must obtain research funding and appropriate recognition as a part of a research team in a not-for-profit environment which has more readily rewarded basic work, and individual accomplishments. What results is a unique form of conflict of interest, best understood by relating the basic principles underlying the not-for-profit form to the conduct of translational research in the AHC setting.

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

Unique base-initiated depolymerization of limonene-derived polycarbonates

NARCIS (Netherlands)

Li, C.; Sablong, R.J.; van Benthem, R.A.T.M.; Koning, C.E.

2017-01-01

The depolymerization of poly(limonene carbonate) (PLC) initiated by 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) was investigated. The strong organic base TBD was capable of deprotonating the OH-terminated PLC, leading to fast degradation via backbiting reactions at high temperature. An interesting

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...

Translation of SNOMED CT - strategies and description of a pilot project.

Science.gov (United States)

Klein, Gunnar O; Chen, Rong

2009-01-01

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

Trans-acting translational regulatory RNA binding proteins.

Science.gov (United States)

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

2018-05-01

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

Cause for concern? Attitudes towards translation crowdsourcing in professional translators’ blogs

DEFF Research Database (Denmark)

Flanagan, Marian

2016-01-01

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

Suppressed translation as a mechanism of initiation of CASP8 (caspase 8)-dependent apoptosis in autophagy-deficient NSCLC cells under nutrient limitation.

Science.gov (United States)

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

2018-01-01

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

Mitochondrial Respiration Inhibitors Suppress Protein Translation and Hypoxic Signaling via the Hyperphosphorylation and Inactivation of Translation Initiation Factor eIF2α and Elongation Factor eEF2

Science.gov (United States)

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

2011-01-01

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

Genome-Scale Analysis of Translation Elongation with a Ribosome Flow Model

Science.gov (United States)

Meilijson, Isaac; Kupiec, Martin; Ruppin, Eytan

2011-01-01

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

The companion dog as a unique translational model for aging.

Science.gov (United States)

Mazzatenta, Andrea; Carluccio, Augusto; Robbe, Domenico; Giulio, Camillo Di; Cellerino, Alessandro

2017-10-01

The dog is a unique species due to its wide variation among breeds in terms of size, morphology, behaviour and lifespan, coupled with a genetic structure that facilitates the dissection of the genetic architecture that controls these traits. Dogs and humans co-evolved and share recent evolutionary selection processes, such as adaptation to digest starch-rich diets. Many diseases of the dog have a human counterpart, and notably Alzheimer's disease, which is otherwise difficult to model in other organisms. Unlike laboratory animals, companion dogs share the human environment and lifestyle, are exposed to the same pollutants, and are faced with pathogens and infections. Dogs represented a very useful model to understand the relationship between size, insulin-like growth factor-1 genetic variation and lifespan, and have been used to test the effects of dietary restriction and immunotherapy for Alzheimer's disease. Very recently, rapamycin was tested in companion dogs outside the laboratory, and this approach where citizens are involved in research aimed at the benefit of dog welfare might become a game changer in geroscience. Copyright © 2017 Elsevier Ltd. All rights reserved.

Translation of Onomatopoetic Component in Onomastics

Directory of Open Access Journals (Sweden)

Анна Владимировна Соколова

2015-12-01

Full Text Available This article covers the topic of the description of translation strategies of onomatopoetic component of proper names. The term of onomatopoetic proper names is introduced for the first time. The article is the fist work that gives a view of onomatopoetic component in proper names on the material of English proper names, product names, electronic resources, theatre plays and cartoon titles. Onomatopoeia in onomastics is seen form the viewpoint of sociolinguistics. Being an aspect of literary onomastics, onomatopoetic proper names are considered to be a functional and semantic word mark (meaning-creating and text-forming that serves as an individualizing and characteristic device. However examples of onomatopoeia in onomastics are seen not only in imaginative literature but also in advertisements and commercials. Onomatopoetic component is a unique device that allows to verbalize lingvocultural aspects of proper names. These names are pleasant to hear and easy to remember. They help to make up brand names. Translation strategies include two techniques: translator often resorts to borrowings, in other words transliterateration or transcription of the original onomatopoeia, or makes situational equivalents like occasionalisms or oral speech equivalents to render the expressive, stylistic and evaluative components of meaning of such proper names. This article will give an example of both these techniques and deduce the most affective strategies that can be applied to translation of onomatopoetic component of proper names.

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.

On Interactive Teaching Model of Translation Course Based on Wechat

Science.gov (United States)

Lin, Wang

2017-01-01

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

NATIONAL FRAMEWORK FOR THE SUSTAINABILITY OF HEALTH KNOWLEDGE TRANSLATION INITIATIVES IN UGANDA.

Science.gov (United States)

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

2018-01-01

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

Deciphering the Translation Initiation Factor 5A Modification Pathway in Halophilic Archaea

Directory of Open Access Journals (Sweden)

Laurence Prunetti

2016-01-01

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

Integrating Bioethics into Clinical and Translational Science Research: A Roadmap

Science.gov (United States)

Shapiro, Robyn S.; Layde, Peter M.

2008-01-01

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

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....

OOPS, Turning MIT Opencourseware into Chinese: An analysis of a community of practice of global translators

Directory of Open Access Journals (Sweden)

Mimi Miyoung Lee

2007-11-01

Full Text Available An all-volunteer organization called the Opensource Opencourseware Prototype System (OOPS, headquartered in Taiwan, was initially designed to translate open source materials from MIT OpenCourseWare (OCW site into Chinese. Given the recent plethora of open educational resources (OER, such as the OCW, the growing use of such resources by the world community, and the emergence of online global education communities to localize resources such as the OOPS, a key goal of this research was to understand how the OOPS members negotiate meanings and form a collective identity in this cross-continent online community. To help with our explorations and analyses within the OOPS translation community, several core principles from Etienne Wenger’s concept of Communities of Practice (COP guided our analyses, including mutual engagement, joint enterprise, shared repertoire, reification, and overall identity of the community. In this paper, we detail how each of these key components was uniquely manifested within the OOPS. Three issues appeared central to the emergence, success, and challenges of the community such as OOPS: 1 strong, stable, and fairly democratic leadership; 2 participation incentives; and 3 online storytelling or opportunities to share one’s translation successes, struggles, and advice within an asynchronous discussion forum. While an extremely high level of enthusiasm among the OOPS members underpinned the success of the OOPS, discussion continues on issues related to quality control, purpose and scope, and forms of legitimate participation. This study, therefore, provides an initial window into the emergence and functioning of an online global education COP in the OER movement. Future research directions related to online global educational communities are discussed.

International and national initiatives in biobanking.

Science.gov (United States)

Ectors, N

2011-01-01

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

NASA-IGES Translator and Viewer

Science.gov (United States)

Chou, Jin J.; Logan, Michael A.

1995-01-01

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

The Book of Ruth and Song of Songs in the First Hebrew Translation of The Taming of the Shrew

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Kahn Lily

2017-12-01

Full Text Available This article investigates the earliest Hebrew rendition of a Shakespearean comedy, Judah Elkind’s מוסר סוררה musar sorera ‘The Education of the Rebellious Woman’ (The Taming of the Shrew, which was translated directly from the English source text and published in Berditchev in 1892. Elkind’s translation is the only comedy among a small group of pioneering Shakespeare renditions conducted in late nineteenth-century Eastern Europe by adherents of the Jewish Enlightenment movement. It was rooted in a strongly ideological initiative to establish a modern European-style literature in Hebrew and reflecting Jewish cultural values at a time when the language was still primarily a written medium on the cusp of its large-scale revernacularisation in Palestine. The article examines the ways in which Elkind’s employment of a Judaising translation technique drawing heavily on romantic imagery from prominent biblical intertexts, particularly the Book of Ruth and the Song of Songs, affects the Petruchio and Katherine plotline in the target text. Elkind’s use of carefully selected biblical names for the main characters and his conscious insertion of biblical verses well known in Jewish tradition for their romantic connotations serve to transform Petruchio and Katherine into Peretz and Hoglah, the heroes of a distinctly Jewish love story which offers a unique and intriguing perspective on the translation of Shakespearean comedy.

Plant Translation Factors and Virus Resistance

Directory of Open Access Journals (Sweden)

Hélène Sanfaçon

2015-06-01

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

Splicing of goose parvovirus pre-mRNA influences cytoplasmic translation of the processed mRNA

Energy Technology Data Exchange (ETDEWEB)

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

2012-04-25

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

Splicing of goose parvovirus pre-mRNA influences cytoplasmic translation of the processed mRNA

International Nuclear Information System (INIS)

Li, Long; Pintel, David J.

2012-01-01

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

A universal molecular translator for non-nucleic acid targets that enables dynamic DNA assemblies and logic operations.

Science.gov (United States)

Tang, Wei; Hu, Shichao; Wang, Huaming; Zhao, Yan; Li, Na; Liu, Feng

2014-11-28

A universal molecular translator based on the target-triggered DNA strand displacement was developed, which was able to convert various kinds of non-nucleic acid targets into a unique output DNA. This translation strategy was successfully applied in directing dynamic DNA assemblies and in realizing three-input logic gate operations.

Translational physiology: from molecules to public health.

Science.gov (United States)

Seals, Douglas R

2013-07-15

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

ERK 1/2 kinase metabolic pathway is responsible for phosphorylation of translation initiation factor eIF4E during in vitro maturation of pig oocytes

Czech Academy of Sciences Publication Activity Database

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

2008-01-01

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

Activation by insulin and amino acids of signaling components leading to translation initiation in skeletal muscle of neonatal pigs is developmentally regulated.

Science.gov (United States)

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

2007-12-01

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

Genetic Algorithms for Models Optimization for Recognition of Translation Initiation Sites

KAUST Repository

Mora, Arturo Magana

2011-06-01

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

Mapping Translation Technology Research in Translation Studies

DEFF Research Database (Denmark)

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

2017-01-01

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

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.

RNA sequence determinants of a coupled termination-reinitiation strategy for downstream open reading frame translation in Helminthosporium victoriae virus 190S and other victoriviruses (Family Totiviridae).

Science.gov (United States)

Li, Hua; Havens, Wendy M; Nibert, Max L; Ghabrial, Said A

2011-07-01

The genome-length, dicistronic mRNA of the double-stranded RNA fungal virus Helminthosporium victoriae virus 190S (genus Victorivirus, family Totiviridae) contains two long open reading frames (ORFs) that overlap in the tetranucleotide AUGA. Translation of the downstream ORF, which encodes the RNA-dependent RNA polymerase (RdRp), has been proposed to depend on ribosomal reinitiation following termination of the upstream ORF, which encodes the capsid protein. In the current study, we examined the RNA sequence determinants for RdRp translation in this virus and demonstrated that a coupled termination-reinitiation (stop-restart) strategy is indeed used. Signals for termination-reinitiation are found within a 32-nucleotide stretch of RNA immediately upstream of the AUGA motif, including a predicted pseudoknot structure. The close proximity in which this predicted structure is followed by the upstream ORF's stop codon appears to be especially important for promoting translation of the downstream ORF. The normal strong preferences for an AUG start codon and the canonical sequence context to favor translation initiation appear somewhat relaxed for the downstream ORF. Similar sequence motifs and predicted RNA structures in other victoriviruses suggest that they all share a related stop-restart strategy for RdRp translation. Members of the genus Victorivirus thus provide new and unique opportunities for exploring the molecular mechanisms of translational coupling, which remain only partly understood in this and other systems.

A community translational research pilot grants program to facilitate community--academic partnerships: lessons from Colorado's clinical translational science awards.

Science.gov (United States)

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

2012-01-01

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

Africa Centre for Systematic Reviews and Knowledge Translation ...

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

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

Effective knowledge management in translational medicine.

Science.gov (United States)

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

2010-07-19

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

Internal field probing of translating FRCs

International Nuclear Information System (INIS)

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

1984-11-01

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

Effective knowledge management in translational medicine

Directory of Open Access Journals (Sweden)

Khasanova Tatiana

2010-07-01

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

T box riboswitches in Actinobacteria: Translational regulation via novel tRNA interactions

Science.gov (United States)

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

2015-01-01

The T box riboswitch regulates many amino acid-related genes in Gram-positive bacteria. T box riboswitch-mediated gene regulation was shown previously to occur at the level of transcription attenuation via structural rearrangements in the 5′ untranslated (leader) region of the mRNA in response to binding of a specific uncharged tRNA. In this study, a novel group of isoleucyl-tRNA synthetase gene (ileS) T box leader sequences found in organisms of the phylum Actinobacteria was investigated. The Stem I domains of these RNAs lack several highly conserved elements that are essential for interaction with the tRNA ligand in other T box RNAs. Many of these RNAs were predicted to regulate gene expression at the level of translation initiation through tRNA-dependent stabilization of a helix that sequesters a sequence complementary to the Shine–Dalgarno (SD) sequence, thus freeing the SD sequence for ribosome binding and translation initiation. We demonstrated specific binding to the cognate tRNAIle and tRNAIle-dependent structural rearrangements consistent with regulation at the level of translation initiation, providing the first biochemical demonstration, to our knowledge, of translational regulation in a T box riboswitch. PMID:25583497

Report of Committee for JAEA Internationalization Initiative (Translated document)

Energy Technology Data Exchange (ETDEWEB)

NONE

2013-07-15

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

Report of Committee for JAEA Internationalization Initiative (Translated document)

International Nuclear Information System (INIS)

2013-07-01

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

Translating culture: Matthee’s Kringe in ’n bos as a case in point

Directory of Open Access Journals (Sweden)

W. Cloete

2007-07-01

Full Text Available The translation of “cultural identity” in a novel such as “Kringe in ’n bos” contributes towards the definition of a uniquely South African representation of time and space in the global context. When translation is studied as a product of its socio-historical context, the translator is faced with problems of translating ideology and cultural identity in literature. Realia constitute a particular challenge to the translator because, according to the definition, precise equivalents of these words do not exist in other languages, which could cause shifts in the target language text. This article considers the concept of translatability and concludes that, despite the problems encountered, an adequate and satisfactory German translation from the Afrikaans original should be possible. The question of translatability assumes an interesting dimension as the Afrikaans novel was translated into English by the author herself. The privileged position of author-translator granted Matthee a near-perfect understanding of the different layers of meaning and intention of the source text and eliminated the gap between the author and translator. However, one gains the impression that the German translator (Stege resorted to transference as a strategy to avoid translation and it emerges that most instances of definite mistranslations are, indeed, attributable to Stege’s unfamiliarity with the South African context.

Spanish translation Questionnaire of the Developmental Coordination Disorder

Directory of Open Access Journals (Sweden)

Salamanca LM

2012-05-01

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

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...

“De interpretatione recta...”: Early Modern Theories of Translation

Directory of Open Access Journals (Sweden)

Zaharia Oana-Alis

2014-12-01

Full Text Available Translation has been essential to the development of languages and cultures throughout the centuries, particularly in the early modern period when it became a cornerstone of the process of transition from Latin to vernacular productions, in such countries as France, Italy, England and Spain. This process was accompanied by a growing interest in defining the rules and features of the practice of translation. The present article aims to examine the principles that underlay the highly intertextual early modern translation theory by considering its classical sources and development. It focuses on subjects that were constantly reiterated in any discussion about translation: the debate concerning the best methods of translation, the sense-for-sense/ word-for-word dichotomy - a topos that can be traced to the discourse on translation initiated by Cicero and Horace and was further developed by the Church fathers, notably St. Jerome, and eventually inherited by both medieval and Renaissance translators. Furthermore, it looks at the differences and continuities that characterise the medieval and Renaissance discourses on translation with a focus on the transition from the medieval, free manner of translation to the humanist, philological one.

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.

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.

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....

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

Precise control of Si(001) initial oxidation by translational kinetic energy of O2 molecules

International Nuclear Information System (INIS)

Teraoka, Yuden; Yoshigoe, Akitaka

2002-01-01

The influence of translation kinetic energy of incident O 2 molecules on the passive oxidation of the clean Si(001) surface and the partially oxidized-Si(001) surface has been studied by high-resolution photoemission spectroscopy using synchrotron radiation. The incident energy of O 2 molecules was controlled up to 3 eV by a supersonic seeded molecular beam technique. Although two incident energy thresholds (1.0 eV and 2.6 eV) have been determined for the partially oxidized-surface oxidation in accordance with the first-principle calculation, the monotonic increase of oxygen saturation coverage was observed for the clean surface oxidation. The difference is caused by the initial dangling bond termination (Si-H and Si-OH) on the partially oxidized surface. Si-2p and O-1s photoemission spectra measured at representative incident energies showed the incident-energy-induced oxidation at the back bonds of Si dimers and the second-layer (subsurface) Si atoms. Moreover, the low-and high-binding-energy components in the O-1s photoemission spectra were assigned to bridge site oxygen and dangling bond site oxygen for the partially oxidized-surface oxidation. (author)

Surgical Critical Care Initiative

Data.gov (United States)

Federal Laboratory Consortium — The Surgical Critical Care Initiative (SC2i) is a USU research program established in October 2013 to develop, translate, and validate biology-driven critical care....

Public-private partnerships in translational medicine: concepts and practical examples.

Science.gov (United States)

Luijten, Peter R; van Dongen, Guus A M S; Moonen, Chrit T; Storm, Gert; Crommelin, Daan J A

2012-07-20

The way forward in multidisciplinary research according to former NIH's director Elias Zerhouni is to engage in predictive, personalized, preemptive and participatory medicine. For the creation of the optimal innovation climate that would allow for such a strategy, public-private partnerships have been widely proposed as an important instrument. Public-private partnerships have become an important instrument to expedite translational research in medicine. The Netherlands have initiated three large public-private partnerships in the life sciences and health area to facilitate the translation of valuable basic scientific concepts to new products and services in medicine. The focus of these partnerships has been on drug development, improved diagnosis and regenerative medicine. The Dutch model of public-private partnership forms the blueprint of a much larger European initiative called EATRIS. This paper will provide practical examples of public-private partnerships initiated to expedite the translation of new technology for drug development towards the clinic. Three specific technologies are in focus: companion diagnostics using nuclear medicine, the use of ultra high field MRI to generate sensitive surrogate endpoints based on endogenous contrast, and MRI guidance for High Intensity Focused Ultrasound mediated drug delivery. Copyright © 2012 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...

Regulation, initiation, and termination of the cenA and cex transcripts of Cellulomonas fimi

International Nuclear Information System (INIS)

Greenberg, N.M.; Warren, R.A.J.; Kilburn, D.G.; Miller, R.C. Jr.

1987-01-01

The authors characterized the in vivo transcripts of two Cellulomonas fimi genes, which encodes an extracellular endo-β-1,4-glucanase. By Northern blot analysis, cenA mRNA was detected in C. fimi RNA preparations from glycerol- and carboxymethyl cellulose-grown cells but not from glucose-grown cells. In contrast, cex mRNA was detected only in the preparations from carboxymethyl cellulose-grown cells. Therefore, the transcription of these genes is subject to regulation by the carbon source provided to C. fimi. By nuclease SI protection studies with unique 5'-labeled DNA probes and C. fimi RNA isolated in vivo, 5' termini were found 51 and 62 bases before the cenA translational initiation codon and 28 bases before the cex translational initiation codon. S1 mapping with unlabeled DNA probes and C. fimi RNA which had been isolated in vivo but which had been 5' labeled in vitro with guanylyltransferase and [α- 32 P]GTP confirmed that true transcription initiation sites for cenA and cex mRNA had been identified. Comparative analysis of the DNA sequences immediately upstream of the initiation sites of the cenA and cex mRNAs revealed a 30-base-pair region where these two sequences display at least 66% homology. S1 mapping was also used to locate the 3' termini of the cenA and cex transcripts. Three 3' termini were found for cenA messages, whereas only one 3' terminus was identified for cex mRNA. The transcripts of both genes terminate in regions where their corresponding DNA sequences contain inverted repeats

Identification and Evaluation of Medical Translator Mobile Applications Using an Adapted APPLICATIONS Scoring System.

Science.gov (United States)

Khander, Amrin; Farag, Sara; Chen, Katherine T

2017-12-22

With an increasing number of patients requiring translator services, many providers are turning to mobile applications (apps) for assistance. However, there have been no published reviews of medical translator apps. To identify and evaluate medical translator mobile apps using an adapted APPLICATIONS scoring system. A list of apps was identified from the Apple iTunes and Google Play stores, using the search term, "medical translator." Apps not found on two different searches, not in an English-based platform, not used for translation, or not functional after purchase, were excluded. The remaining apps were evaluated using an adapted APPLICATIONS scoring system, which included both objective and subjective criteria. App comprehensiveness was a weighted score defined by the number of non-English languages included in each app relative to the proportion of non-English speakers in the United States. The Apple iTunes and Google Play stores. Medical translator apps identified using the search term "medical translator." Main Outcomes and Measures: Compilation of medical translator apps for provider usage. A total of 524 apps were initially found. After applying the exclusion criteria, 20 (8.2%) apps from the Google Play store and 26 (9.2%) apps from the Apple iTunes store remained for evaluation. The highest scoring apps, Canopy Medical Translator, Universal Doctor Speaker, and Vocre Translate, scored 13.5 out of 18.7 possible points. A large proportion of apps initially found did not function as medical translator apps. Using the APPLICATIONS scoring system, we have identified and evaluated medical translator apps for providers who care for non-English speaking patients.

Fine-tuning translation kinetics selection as the driving force of codon usage bias in the hepatitis A virus capsid.

Science.gov (United States)

Aragonès, Lluís; Guix, Susana; Ribes, Enric; Bosch, Albert; Pintó, Rosa M

2010-03-05

Hepatitis A virus (HAV), the prototype of genus Hepatovirus, has several unique biological characteristics that distinguish it from other members of the Picornaviridae family. Among these, the need for an intact eIF4G factor for the initiation of translation results in an inability to shut down host protein synthesis by a mechanism similar to that of other picornaviruses. Consequently, HAV must inefficiently compete for the cellular translational machinery and this may explain its poor growth in cell culture. In this context of virus/cell competition, HAV has strategically adopted a naturally highly deoptimized codon usage with respect to that of its cellular host. With the aim to optimize its codon usage the virus was adapted to propagate in cells with impaired protein synthesis, in order to make tRNA pools more available for the virus. A significant loss of fitness was the immediate response to the adaptation process that was, however, later on recovered and more associated to a re-deoptimization rather than to an optimization of the codon usage specifically in the capsid coding region. These results exclude translation selection and instead suggest fine-tuning translation kinetics selection as the underlying mechanism of the codon usage bias in this specific genome region. Additionally, the results provide clear evidence of the Red Queen dynamics of evolution since the virus has very much evolved to re-adapt its codon usage to the environmental cellular changing conditions in order to recover the original fitness.

Fine-tuning translation kinetics selection as the driving force of codon usage bias in the hepatitis A virus capsid.

Directory of Open Access Journals (Sweden)

Lluís Aragonès

2010-03-01

Full Text Available Hepatitis A virus (HAV, the prototype of genus Hepatovirus, has several unique biological characteristics that distinguish it from other members of the Picornaviridae family. Among these, the need for an intact eIF4G factor for the initiation of translation results in an inability to shut down host protein synthesis by a mechanism similar to that of other picornaviruses. Consequently, HAV must inefficiently compete for the cellular translational machinery and this may explain its poor growth in cell culture. In this context of virus/cell competition, HAV has strategically adopted a naturally highly deoptimized codon usage with respect to that of its cellular host. With the aim to optimize its codon usage the virus was adapted to propagate in cells with impaired protein synthesis, in order to make tRNA pools more available for the virus. A significant loss of fitness was the immediate response to the adaptation process that was, however, later on recovered and more associated to a re-deoptimization rather than to an optimization of the codon usage specifically in the capsid coding region. These results exclude translation selection and instead suggest fine-tuning translation kinetics selection as the underlying mechanism of the codon usage bias in this specific genome region. Additionally, the results provide clear evidence of the Red Queen dynamics of evolution since the virus has very much evolved to re-adapt its codon usage to the environmental cellular changing conditions in order to recover the original fitness.

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…

Semantic and translation priming from a first language to a second and back: Making sense of the findings

OpenAIRE

Schoonbaert, Sofie; Duyck, Wouter; Brysbaert, Marc; Hartsuiker, Robert

2009-01-01

The present study investigated cross-language priming effects with unique noncognate translation pairs. Unbalanced Dutch (first language [L1])-English (second language [L2]) bilinguals performed a lexical decision task in a masked priming paradigm. The results of two experiments showed significant translation priming from L I to L2 (meisje-GIRL) and from L2 to L I (girl-MEISJE), using two different stimulus onset asynchronies (SOAs) (250 and 100 msec). Although translation priming from L I to...

Non-AUG translation: a new start for protein synthesis in eukaryotes.

Science.gov (United States)

Kearse, Michael G; Wilusz, Jeremy E

2017-09-01

Although it was long thought that eukaryotic translation almost always initiates at an AUG start codon, recent advancements in ribosome footprint mapping have revealed that non-AUG start codons are used at an astonishing frequency. These non-AUG initiation events are not simply errors but instead are used to generate or regulate proteins with key cellular functions; for example, during development or stress. Misregulation of non-AUG initiation events contributes to multiple human diseases, including cancer and neurodegeneration, and modulation of non-AUG usage may represent a novel therapeutic strategy. It is thus becoming increasingly clear that start codon selection is regulated by many trans -acting initiation factors as well as sequence/structural elements within messenger RNAs and that non-AUG translation has a profound impact on cellular states. © 2017 Kearse and Wilusz; Published by Cold Spring Harbor Laboratory Press.

Translation and cultural adaptation of the Aguado Syntax Test (AST) into Brazilian Portuguese.

Science.gov (United States)

Baggio, Gustavo Inheta; Hage, Simone Rocha de Vasconcellos

2017-12-07

To perform the translation and cultural adaptation of the Aguado Syntax Test (AST) into Brazilian Portuguese considering the linguistic and cultural reality of the language. The AST assesses the early morphosyntactic development in children aged 3 to 7 in terms of understanding and expression of various types of structures such as sentences, pronouns, verbal voices, comparisons, prepositions and verbal desinence as to number, mode and tense. The process of translation and cultural adaptation followed four steps: 1) preparation of two translations; 2) synthesis of consensual translations; 3) backtranslation; and 4) verification of equivalence between the initial translations and backtranslations that resulted in the final translated version. The whole process of translation and cultural adaptation revealed the presence of equivalence and reconciliation of the translated items and an almost complete semantic equivalence between the two translations and the absence of consistent translation difficulties. The AST was translated and culturally adapted into Brazilian Portuguese, constituting the first step towards validation and standardization of the test.

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.

Investigating the translation of Earth's inner core

DEFF Research Database (Denmark)

Day, Elizabeth A; Cormier, Vernon F; Geballe, Zachary M

2012-01-01

The Earth’s inner core provides unique insights into processes that are occurring deep within our Earth today, as well as processes that occurred in the past. The seismic structure of the inner core is complex, and is dominated by anisotropic and isotropic differences between the Eastern...... for models of a translating inner core. Additionally, we investigate the structure at the base of the outer core and the inner core boundary by analyzing PKP-Cdiff waves. The search for observable PKP-Cdiff is particularly concentrated in regions that are predicted to be actively freezing and melting...... and Western ‘hemispheres’ of the inner core. Recent geodynamical models suggest that this hemispherical dichotomy can be explained by a fast translation of the inner core. In these models one side of the inner core is freezing, while the other side is melting, leading to the development of different seismic...

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…

Switch from cap- to factorless IRES-dependent 0 and +1 frame translation during cellular stress and dicistrovirus infection.

Directory of Open Access Journals (Sweden)

Qing S Wang

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

PERSONALITY TYPE AND TRANSLATION PERFORMANCE OF PERSIAN TRANSLATOR TRAINEES

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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.

Uniqueness of the Fock quantization of the Gowdy T3 model

International Nuclear Information System (INIS)

Cortez, Jeronimo; Marugan, Guillermo A. Mena; Velhinho, Jose M.

2007-01-01

After its reduction by a gauge-fixing procedure, the family of linearly polarized Gowdy T 3 cosmologies admits a scalar field description whose evolution is governed by a Klein-Gordon type equation in a flat background in 1+1 dimensions with the spatial topology of S 1 , though in the presence of a time-dependent potential. The model is still subject to a homogeneous constraint, which generates S 1 -translations. Recently, a Fock quantization of this scalar field was introduced and shown to be unique under the requirements of unitarity of the dynamics and invariance under the gauge group of S 1 -translations. In this work, we extend and complete this uniqueness result by considering other possible scalar field descriptions, resulting from reasonable field reparametrizations of the induced metric of the reduced model. In the reduced phase space, these alternate descriptions can be obtained by means of a time-dependent scaling of the field, the inverse scaling of its canonical momentum, and the possible addition of a time-dependent, linear contribution of the field to this momentum. Demanding again unitarity of the field dynamics and invariance under the gauge group, we prove that the alternate canonical pairs of fieldlike variables admit a Fock representation if and only if the scaling of the field is constant in time. In this case, there exists essentially a unique Fock representation, provided by the quantization constructed by Corichi, Cortez, and Mena Marugan. In particular, our analysis shows that the scalar field description proposed by Pierri does not admit a Fock quantization with the above unitarity and invariance properties

Eukaryotic translation initiation factor 5A (eIF5A) is essential for HIF-1α activation in hypoxia

Energy Technology Data Exchange (ETDEWEB)

Tariq, Mohammad [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Graduate School of Science and Engineering, Saitama University, 645 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan); Ito, Akihiro, E-mail: akihiro-i@riken.jp [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Japan Agency for Medical Research and Development, AMED-CREST, 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004 (Japan); Ishfaq, Muhammad; Bradshaw, Elliot [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Graduate School of Science and Engineering, Saitama University, 645 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan); Yoshida, Minoru [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Graduate School of Science and Engineering, Saitama University, 645 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan); Japan Agency for Medical Research and Development, AMED-CREST, 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004 (Japan)

2016-02-05

The eukaryotic initiation factor 5A (eIF5A) is an essential protein involved in translation elongation and cell proliferation. eIF5A undergoes several post-translational modifications including hypusination and acetylation. Hypusination is indispensable for the function of eIF5A. On the other hand, the precise function of acetylation remains unknown, but it may render the protein inactive since hypusination blocks acetylation. Here, we report that acetylation of eIF5A increases under hypoxia. During extended hypoxic periods an increase in the level of eIF5A acetylation correlated with a decrease in HIF-1α, suggesting involvement of eIF5A activity in HIF-1α expression under hypoxia. Indeed, suppression of eIF5A by siRNA oligo-mediated knockdown or treatment with GC7, a deoxyhypusine synthase inhibitor, led to significant reduction of HIF-1α activity. Furthermore, knockdown of eIF5A or GC7 treatment reduced tumor spheroid formation with a concomitant decrease in HIF-1α expression. Our results suggest that functional, hypusinated eIF5A is necessary for HIF-1α expression during hypoxia and that eIF5A is an attractive target for cancer therapy. - Highlights: • Hypoxia induces acetylation of eIF5A. • Active eIF5A is necessary for HIF-1α activation in hypoxia. • Active eIF5A is important for tumor spheroid growth.

Eukaryotic translation initiation factor 5A (eIF5A) is essential for HIF-1α activation in hypoxia

International Nuclear Information System (INIS)

Tariq, Mohammad; Ito, Akihiro; Ishfaq, Muhammad; Bradshaw, Elliot; Yoshida, Minoru

2016-01-01

The eukaryotic initiation factor 5A (eIF5A) is an essential protein involved in translation elongation and cell proliferation. eIF5A undergoes several post-translational modifications including hypusination and acetylation. Hypusination is indispensable for the function of eIF5A. On the other hand, the precise function of acetylation remains unknown, but it may render the protein inactive since hypusination blocks acetylation. Here, we report that acetylation of eIF5A increases under hypoxia. During extended hypoxic periods an increase in the level of eIF5A acetylation correlated with a decrease in HIF-1α, suggesting involvement of eIF5A activity in HIF-1α expression under hypoxia. Indeed, suppression of eIF5A by siRNA oligo-mediated knockdown or treatment with GC7, a deoxyhypusine synthase inhibitor, led to significant reduction of HIF-1α activity. Furthermore, knockdown of eIF5A or GC7 treatment reduced tumor spheroid formation with a concomitant decrease in HIF-1α expression. Our results suggest that functional, hypusinated eIF5A is necessary for HIF-1α expression during hypoxia and that eIF5A is an attractive target for cancer therapy. - Highlights: • Hypoxia induces acetylation of eIF5A. • Active eIF5A is necessary for HIF-1α activation in hypoxia. • Active eIF5A is important for tumor spheroid growth.

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

Optimization of translation profiles enhances protein expression and solubility.

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Anne-Katrin Hess

Full Text Available mRNA is translated with a non-uniform speed that actively coordinates co-translational folding of protein domains. Using structure-based homology we identified the structural domains in epoxide hydrolases (EHs and introduced slow-translating codons to delineate the translation of single domains. These changes in translation speed dramatically improved the solubility of two EHs of metagenomic origin in Escherichia coli. Conversely, the importance of transient attenuation for the folding, and consequently solubility, of EH was evidenced with a member of the EH family from Agrobacterium radiobacter, which partitions in the soluble fraction when expressed in E. coli. Synonymous substitutions of codons shaping the slow-transiting regions to fast-translating codons render this protein insoluble. Furthermore, we show that low protein yield can be enhanced by decreasing the free folding energy of the initial 5'-coding region, which can disrupt mRNA secondary structure and enhance ribosomal loading. This study provides direct experimental evidence that mRNA is not a mere messenger for translation of codons into amino acids but bears an additional layer of information for folding, solubility and expression level of the encoded protein. Furthermore, it provides a general frame on how to modulate and fine-tune gene expression of a target protein.

Vortices and polynomials: non-uniqueness of the Adler–Moser polynomials for the Tkachenko equation

International Nuclear Information System (INIS)

Demina, Maria V; Kudryashov, Nikolai A

2012-01-01

Stationary and translating relative equilibria of point vortices in the plane are studied. It is shown that stationary equilibria of any system containing point vortices with arbitrary choice of circulations can be described with the help of the Tkachenko equation. It is also obtained that translating relative equilibria of point vortices with arbitrary circulations can be constructed using a generalization of the Tkachenko equation. Roots of any pair of polynomials solving the Tkachenko equation and the generalized Tkachenko equation are proved to give positions of point vortices in stationary and translating relative equilibria accordingly. These results are valid even if the polynomials in a pair have multiple or common roots. It is obtained that the Adler–Moser polynomial provides non-unique polynomial solutions of the Tkachenko equation. It is shown that the generalized Tkachenko equation possesses polynomial solutions with degrees that are not triangular numbers. (paper)

The Ezrin Metastatic Phenotype Is Associated with the Initiation of Protein Translation

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Joseph W. Briggs

2012-04-01

Full Text Available We previously associated the cytoskeleton linker protein, Ezrin, with the metastatic phenotype of pediatric sarcomas, including osteosarcoma and rhabdomyosarcoma. These studies have suggested that Ezrin contributes to the survival of cancer cells after their arrival at secondary metastatic locations. To better understand this role in metastasis, we undertook two noncandidate analyses of Ezrin function including a microarray subtraction of high-and low-Ezrin-expressing cells and a proteomic approach to identify proteins that bound the N-terminus of Ezrin in tumor lysates. Functional analyses of these data led to a novel and unifying hypothesis that Ezrin contributes to the efficiency of metastasis through regulation of protein translation. In support of this hypothesis, we found Ezrin to be part of the ribonucleoprotein complex to facilitate the expression of complex messenger RNA in cells and to bind with poly A binding protein 1 (PABP1; PABPC1. The relevance of these findings was supported by our identification of Ezrin and components of the translational machinery in pseudopodia of highly metastatic cells during the process of cell invasion. Finally, two small molecule inhibitors recently shown to inhibit the Ezrin metastatic phenotype disrupted the Ezrin/PABP1 association. Taken together, these results provide a novel mechanistic basis by which Ezrin may contribute to metastasis.

Pauses by Student and Professional Translators in Translation Process

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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.

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.

Personalized translational epilepsy research - Novel approaches and future perspectives: Part II: Experimental and translational approaches.

Science.gov (United States)

Bauer, Sebastian; van Alphen, Natascha; Becker, Albert; Chiocchetti, Andreas; Deichmann, Ralf; Deller, Thomas; Freiman, Thomas; Freitag, Christine M; Gehrig, Johannes; Hermsen, Anke M; Jedlicka, Peter; Kell, Christian; Klein, Karl Martin; Knake, Susanne; Kullmann, Dimitri M; Liebner, Stefan; Norwood, Braxton A; Omigie, Diana; Plate, Karlheinz; Reif, Andreas; Reif, Philipp S; Reiss, Yvonne; Roeper, Jochen; Ronellenfitsch, Michael W; Schorge, Stephanie; Schratt, Gerhard; Schwarzacher, Stephan W; Steinbach, Joachim P; Strzelczyk, Adam; Triesch, Jochen; Wagner, Marlies; Walker, Matthew C; von Wegner, Frederic; Rosenow, Felix

2017-11-01

Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics, and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy. In the context of these advances, the First International Symposium on Personalized Translational Epilepsy Research (1st ISymPTER) was held in Frankfurt on September 8, 2016, to discuss novel approaches and future perspectives for personalized translational research. These included new developments and ideas in a range of experimental and clinical areas such as deep phenotyping, quantitative brain imaging, EEG/MEG-based analysis of network dysfunction, tissue-based translational studies, innate immunity mechanisms, microRNA as treatment targets, functional characterization of genetic variants in human cell models and rodent organotypic slice cultures, personalized treatment approaches for monogenic epilepsies, blood-brain barrier dysfunction, therapeutic focal tissue modification, computational modeling for target and biomarker identification, and cost analysis in (monogenic) disease and its treatment. This report on the meeting proceedings is aimed at stimulating much needed investments of time and resources in personalized translational epilepsy research. This Part II includes the experimental and translational approaches and a discussion of the future perspectives, while the diagnostic methods, EEG network analysis, biomarkers, and personalized treatment approaches were addressed in Part I [1]. Copyright © 2017

tmRNA-mediated trans-translation as the major ribosome rescue system in a bacterial cell

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Hyouta eHimeno

2014-04-01

Full Text Available tmRNA (transfer messenger RNA; also known as 10Sa RNA or SsrA RNA is a small RNA molecule that is conserved among bacteria. It has structural and functional similarities to tRNA: it has an upper half of the tRNA-like structure, its 5’ end is processed by RNase P, it has typical tRNA-specific base modifications, it is aminoacylated with alanine, it binds to EF-Tu after aminoacylation and it enters the ribosome with EF-Tu and GTP. However, tmRNA lacks an anticodon, and instead it has a coding sequence for a short peptide called tag-peptide. An elaborate interplay of actions of tmRNA as both tRNA and mRNA with the help of a tmRNA-binding protein, SmpB, facilitates trans-translation, which produces a single polypeptide from two mRNA molecules. Initially alanyl-tmRNA in complex with EF-Tu and SmpB enters the vacant A-site of the stalled ribosome like aminoacyl-tRNA but without a codon-anticodon interaction, and subsequently truncated mRNA is replaced with the tag-encoding region of tmRNA. During these processes, not only tmRNA but also SmpB structurally and functionally mimics both tRNA and mRNA. Thus trans-translation rescues the stalled ribosome, thereby allowing recycling of the ribosome. Since the tag-peptide serves as a target of AAA+ proteases, the trans-translation products are preferentially degraded so that they do not accumulate in the cell. Although alternative rescue systems have recently been revealed, trans-translation is the only system that universally exists in bacteria. Furthermore, it is unique in that it employs a small RNA and that it prevents accumulation of nonfunctional proteins from truncated mRNA in the cell. It might play the major role in rescuing the stalled translation in the bacterial cell.

The same allele of translation initiation factor 4E mediates resistance against two Potyvirus spp. in Pisum sativum

DEFF Research Database (Denmark)

Bruun-Rasmussen, M.; Møller, I.S.; Tulinius, G.

2007-01-01

to linkage group VI together with other Potyvirus resistances. One of these, sbm1, confers resistance to strains of Pea seedborne mosaic virus and previously has been identified as a mutant allele of the eukaryotic translation initiation factor 4E gene (eIF4E). Sequence comparison of eIF4E from BYMV...... was overcome, and virus from these plants had a codon change causing an Arg to His change at position 116 of the predicted viral genome-linked protein (VPg). Accordingly, plants carrying the wlv resistance gene were infected upon inoculation with BYMV-W derived from cDNA with a His codon at position 116...

Translating gene transfer: a stalled effort.

Science.gov (United States)

Greenberg, Alexandra J; McCormick, Jennifer; Tapia, Carmen J; Windebank, Anthony J

2011-08-01

The journey of gene transfer from laboratory to clinic has been slow and fraught with many challenges and barriers. Despite the development of the initial technology in the early 1970s, a standard clinical treatment involving "gene therapy" remains to be seen. Furthermore, much was written about the technology in the early 1990s, but since then, not much has been written about the journey of gene transfer. The translational path of gene transfer thus far, both pitfalls and successes, can serve as a study not only in navigating ethical and safety concerns, but also in the importance of scientist-public interactions. Here, we examine the translational progress of gene transfer and what can be gleaned from its history. © 2011 Wiley Periodicals, Inc.

Proposal for a telehealth concept in the translational research model.

Science.gov (United States)

Silva, Angélica Baptista; Morel, Carlos Médicis; Moraes, Ilara Hämmerli Sozzi de

2014-04-01

To review the conceptual relationship between telehealth and translational research. Bibliographical search on telehealth was conducted in the Scopus, Cochrane BVS, LILACS and MEDLINE databases to find experiences of telehealth in conjunction with discussion of translational research in health. The search retrieved eight studies based on analysis of models of the five stages of translational research and the multiple strands of public health policy in the context of telehealth in Brazil. The models were applied to telehealth activities concerning the Network of Human Milk Banks, in the Telemedicine University Network. The translational research cycle of human milk collected, stored and distributed presents several integrated telehealth initiatives, such as video conferencing, and software and portals for synthesizing knowledge, composing elements of an information ecosystem, mediated by information and communication technologies in the health system. Telehealth should be composed of a set of activities in a computer mediated network promoting the translation of knowledge between research and health services.

Translating Current Science into Materials for High School via a Scientist-Teacher Partnership

Science.gov (United States)

Brown, Julie C.; Bokor, Julie R.; Crippen, Kent J.; Koroly, Mary Jo

2014-01-01

Scientist-teacher partnerships are a unique form of professional development that can assist teachers in translating current science into classroom instruction by involving them in meaningful collaborations with university researchers. However, few reported models aim to directly alter science teachers' practices by supporting them in the…

Regulation of Translational Efficiency by Disparate 5′-UTRs of PPARγ Splice Variants

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Shawn McClelland

2009-01-01

Full Text Available The PPAR-γ gene encodes for at least 7 unique transcripts due to alternative splicing of five exons in the 5′-untranslated region (UTR. The translated region is encoded by exons 1–6, which are identical in all isoforms. This study investigated the role of the 5′-UTR in regulating the efficiency with which the message is translated to protein. A coupled in vitro transcription-translation assay demonstrated that PPAR-γ1, -γ2, and -γ5 are efficiently translated, whereas PPAR-γ4 and -γ7 are poorly translated. An in vivo reporter gene assay using each 5′-UTR upstream of the firefly luciferase gene showed that the 5′-UTRs for PPAR-γ1, -γ2, and -γ4 enhanced translation, whereas the 5′-UTRs for PPAR-γ5 and -γ7 inhibited translation. Models of RNA secondary structure, obtained by the mfold software, were used to explain the mechanism of regulation by each 5′-UTR. In general, it was found that the translational efficiency was inversely correlated with the stability of the mRNA secondary structure, the presence of base-pairing in the consensus Kozak sequence, the number of start codons in the 5′-UTR, and the length of the 5′-UTR. A better understanding of posttranscriptional regulation of translation will allow modulation of protein levels without altering transcription.

Measurement properties of translated versions of neck-specific questionnaires: a systematic review.

Science.gov (United States)

Schellingerhout, Jasper M; Heymans, Martijn W; Verhagen, Arianne P; de Vet, Henrica C; Koes, Bart W; Terwee, Caroline B

2011-06-06

Several disease-specific questionnaires to measure pain and disability in patients with neck pain have been translated. However, a simple translation of the original version doesn't guarantee similar measurement properties. The objective of this study is to critically appraise the quality of the translation process, cross-cultural validation and the measurement properties of translated versions of neck-specific questionnaires. Bibliographic databases were searched for articles concerning the translation or evaluation of the measurement properties of a translated version of a neck-specific questionnaire. The methodological quality of the selected studies and the results of the measurement properties were critically appraised and rated using the COSMIN checklist and criteria for measurement properties. The search strategy resulted in a total of 3641 unique hits, of which 27 articles, evaluating 6 different questionnaires in 15 different languages, were included in this study. Generally the methodological quality of the translation process is poor and none of the included studies performed a cross-cultural adaptation. A substantial amount of information regarding the measurement properties of translated versions of the different neck-specific questionnaires is lacking. Moreover, the evidence for the quality of measurement properties of the translated versions is mostly limited or assessed in studies of poor methodological quality. Until results from high quality studies are available, we advise to use the Catalan, Dutch, English, Iranian, Korean, Spanish and Turkish version of the NDI, the Chinese version of the NPQ, and the Finnish, German and Italian version of the NPDS. The Greek NDI needs cross-cultural validation and there is no methodologically sound information for the Swedish NDI. For all other languages we advise to translate the original version of the NDI.

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.

Model for bridging the translational "valleys of death" in spinal cord injury research

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Barrable B

2014-04-01

Full Text Available Bill Barrable,1 Nancy Thorogood,1 Vanessa Noonan,1,2 Jocelyn Tomkinson,1 Phalgun Joshi,1 Ken Stephenson,1 John Barclay,1 Katharina Kovacs Burns3 1Rick Hansen Institute, 2Division of Spine, Department of Orthopaedics, University of British Columbia, Vancouver, BC, 3Health Sciences Council, University of Alberta, Edmonton, AB, Canada Abstract: To improve health care outcomes with cost-effective treatments and prevention initiatives, basic health research must be translated into clinical application and studied during implementation, a process commonly referred to as translational research. It is estimated that only 14% of health-related scientific discoveries enter into medical practice and that it takes an average of 17 years for them to do so. The transition from basic research to clinical knowledge and from clinical knowledge to practice or implementation is so fraught with obstacles that these transitions are often referred to as “valleys of death”. The Rick Hansen Institute has developed a unique praxis model for translational research in the field of spinal cord injury (SCI. The praxis model involves three components. The first is a coordinated program strategy of cure, care, consumer engagement, and commercialization. The second is a knowledge cycle that consists of four phases, ie, environmental scanning, knowledge generation and synthesis, knowledge validation, and implementation. The third is the provision of relevant resources and infrastructure to overcome obstacles in the “valleys of death”, ie, funding, clinical research operations, informatics, clinical research and best practice implementation, consumer engagement, collaborative networks, and strategic partnerships. This model, which is to be independently evaluated in 2018 to determine its strengths and limitations, has been used to advance treatments for pressure ulcers in SCI. The Rick Hansen Institute has developed an innovative solution to move knowledge into action by

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

Science.gov (United States)

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

2017-07-01

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

Figurative Language in Malay to English Translation: An Analysis of the 2015 UniMAP VC's Keynote Speech

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Sharmini A.

2018-01-01

Full Text Available Translating figurative language involves more than just replacing the figurative language with its equivalent in the target language. Therefore, it is not surprising for the translation of figurative language to have its own set of challenges. Problems the translator faces in translating the Malay Figurative Language into English include complexities in understanding, interpreting and recreating the Figurative language that are unique in the Source Language (SL culture; which have to be explained and described in Target Language (TL where such practices and customs are non - existent. Secondly, the Source Text (ST figurative language may appear in a variety of types and have a distinct denotative and connotative meaning and reference; most often, it is difficult to find an equivalent which totally matches the original meaning or concept. This particular paper analyses the translation of figurative language extracted from UniMAP's Vice Chancellor Keynote Speech in 2015. Findings reveal that the three categories of figurative language identified were namely idioms, metaphors and similes. Translation strategies used are either not translated, paraphrased or translated with a similar meaning but in different form.

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...

Establishment and Application of a High Throughput Screening System Targeting the Interaction between HCV Internal Ribosome Entry Site and Human Eukaryotic Translation Initiation Factor 3

Directory of Open Access Journals (Sweden)

Yuying Zhu

2017-05-01

Full Text Available Viruses are intracellular obligate parasites and the host cellular machinery is usually recruited for their replication. Human eukaryotic translation initiation factor 3 (eIF3 could be directly recruited by the hepatitis C virus (HCV internal ribosome entry site (IRES to promote the translation of viral proteins. In this study, we establish a fluorescence polarization (FP based high throughput screening (HTS system targeting the interaction between HCV IRES and eIF3. By screening a total of 894 compounds with this HTS system, two compounds (Mucl39526 and NP39 are found to disturb the interaction between HCV IRES and eIF3. And these two compounds are further demonstrated to inhibit the HCV IRES-dependent translation in vitro. Thus, this HTS system is functional to screen the potential HCV replication inhibitors targeting human eIF3, which is helpful to overcome the problem of viral resistance. Surprisingly, one compound HP-3, a kind of oxytocin antagonist, is discovered to significantly enhance the interaction between HCV IRES and eIF3 by this HTS system. HP-3 is demonstrated to directly interact with HCV IRES and promote the HCV IRES-dependent translation both in vitro and in vivo, which strongly suggests that HP-3 has potentials to promote HCV replication. Therefore, this HTS system is also useful to screen the potential HCV replication enhancers, which is meaningful for understanding the viral replication and screening novel antiviral drugs. To our knowledge, this is the first HTS system targeting the interaction between eIF3 and HCV IRES, which could be applied to screen both potential HCV replication inhibitors and enhancers.

Rapid motor learning in the translational vestibulo-ocular reflex

Science.gov (United States)

Zhou, Wu; Weldon, Patrick; Tang, Bingfeng; King, W. M.; Shelhamer, M. J. (Principal Investigator)

2003-01-01

Motor learning was induced in the translational vestibulo-ocular reflex (TVOR) when monkeys were repeatedly subjected to a brief (0.5 sec) head translation while they tried to maintain binocular fixation on a visual target for juice rewards. If the target was world-fixed, the initial eye speed of the TVOR gradually increased; if the target was head-fixed, the initial eye speed of the TVOR gradually decreased. The rate of learning acquisition was very rapid, with a time constant of approximately 100 trials, which was equivalent to or=1 d without any reinforcement, indicating induction of long-term synaptic plasticity. Although the learning generalized to targets with different viewing distances and to head translations with different accelerations, it was highly specific for the particular combination of head motion and evoked eye movement associated with the training. For example, it was specific to the modality of the stimulus (translation vs rotation) and the direction of the evoked eye movement in the training. Furthermore, when one eye was aligned with the heading direction so that it remained motionless during training, learning was not expressed in this eye, but only in the other nonaligned eye. These specificities show that the learning sites are neither in the sensory nor the motor limb of the reflex but in the sensory-motor transformation stage of the reflex. The dependence of the learning on both head motion and evoked eye movement suggests that Hebbian learning may be one of the underlying cellular mechanisms.

Selection of mRNA 5'-untranslated region sequence with high translation efficiency through ribosome display

International Nuclear Information System (INIS)

Mie, Masayasu; Shimizu, Shun; Takahashi, Fumio; Kobatake, Eiry

2008-01-01

The 5'-untranslated region (5'-UTR) of mRNAs functions as a translation enhancer, promoting translation efficiency. Many in vitro translation systems exhibit a reduced efficiency in protein translation due to decreased translation initiation. The use of a 5'-UTR sequence with high translation efficiency greatly enhances protein production in these systems. In this study, we have developed an in vitro selection system that favors 5'-UTRs with high translation efficiency using a ribosome display technique. A 5'-UTR random library, comprised of 5'-UTRs tagged with a His-tag and Renilla luciferase (R-luc) fusion, were in vitro translated in rabbit reticulocytes. By limiting the translation period, only mRNAs with high translation efficiency were translated. During translation, mRNA, ribosome and translated R-luc with His-tag formed ternary complexes. They were collected with translated His-tag using Ni-particles. Extracted mRNA from ternary complex was amplified using RT-PCR and sequenced. Finally, 5'-UTR with high translation efficiency was obtained from random 5'-UTR library

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.

Applying hospital evidence to paramedicine: issues of indirectness, validity and knowledge translation.

Science.gov (United States)

Bigham, Blair; Welsford, Michelle

2015-05-01

The practice of emergency medicine (EM) has been intertwined with emergency medical services (EMS) for more than 40 years. In this commentary, we explore the practice of translating hospital based evidence into the prehospital setting. We will challenge both EMS and EM dogma-bringing hospital care to patients in the field is not always better. In providing examples of therapies championed in hospitals that have failed to translate into the field, we will discuss the unique prehospital environment, and why evidence from the hospital setting cannot necessarily be translated to the prehospital field. Paramedicine is maturing so that the capability now exists to conduct practice-specific research that can inform best practices. Before translation from the hospital environment is implemented, evidence must be evaluated by people with expertise in three domains: critical appraisal, EM, and EMS. Scientific evidence should be assessed for: quality and bias; directness, generalizability, and validity to the EMS population; effect size and anticipated benefit from prehospital application; feasibility (including economic evaluation, human resource availability in the mobile environment); and patient and provider safety.

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

Towards a classification of translation styles based on eye-tracking and keylogging data

Directory of Open Access Journals (Sweden)

Barbara Dragsted & Michael Carl

2013-06-01

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

Making the most of a translator.

Science.gov (United States)

Dannenfeldt, D

1994-01-01

Anaheim Memorial Hospital in California is a trailblazer. It's one of the first hospitals in the nation to use translation software for both supply procurement and claims-related transactions. Initially, it acquired the software to streamline the ordering of supplies by shifting to standard electronic formats. Today, the hospital is using the software to receive electronic remittance advice, and it has plans for other labor-saving applications.

MCT-1 protein interacts with the cap complex and modulates messenger RNA translational profiles

DEFF Research Database (Denmark)

Reinert, Line; Shi, B; Nandi, S

2006-01-01

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

Translational research on advanced therapies

Directory of Open Access Journals (Sweden)

Filippo Belardelli

2011-01-01

Full Text Available Fostering translational research of advanced therapies has become a major priority of both scientific community and national governments. Advanced therapy medicinal products (ATMP are a new medicinal product category comprising gene therapy and cell-based medicinal products as well as tissue engineered medicinal products. ATMP development opens novel avenues for therapeutic approaches in numerous diseases, including cancer and neurodegenerative and cardiovascular diseases. However, there are important bottlenecks for their development due to the complexity of the regulatory framework, the high costs and the needs for good manufacturing practice (GMP facilities and new end-points for clinical experimentation. Thus, a strategic cooperation between different stakeholders (academia, industry and experts in regulatory issues is strongly needed. Recently, a great importance has been given to research infrastructures dedicated to foster translational medicine of advanced therapies. Some ongoing European initiatives in this field are presented and their potential impact is discussed.

Translational research on advanced therapies.

Science.gov (United States)

Belardelli, Filippo; Rizza, Paola; Moretti, Franca; Carella, Cintia; Galli, Maria Cristina; Migliaccio, Giovanni

2011-01-01

Fostering translational research of advanced therapies has become a major priority of both scientific community and national governments. Advanced therapy medicinal products (ATMP) are a new medicinal product category comprising gene therapy and cell-based medicinal products as well as tissue engineered medicinal products. ATMP development opens novel avenues for therapeutic approaches in numerous diseases, including cancer and neurodegenerative and cardiovascular diseases. However, there are important bottlenecks for their development due to the complexity of the regulatory framework, the high costs and the needs for good manufacturing practice (GMP) facilities and new end-points for clinical experimentation. Thus, a strategic cooperation between different stakeholders (academia, industry and experts in regulatory issues) is strongly needed. Recently, a great importance has been given to research infrastructures dedicated to foster translational medicine of advanced therapies. Some ongoing European initiatives in this field are presented and their potential impact is discussed.

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

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…

Translation of a nonpolyadenylated viral RNA is enhanced by binding of viral coat protein or polyadenylation of the RNA.

Science.gov (United States)

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

2001-12-04

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

Mitochondrial translation factors of Trypanosoma brucei: elongation factor-Tu has a unique subdomain that is essential for its function

Czech Academy of Sciences Publication Activity Database

Cristodero, M.; Mani, J.; Oeljeklaus, S.; Aeberhard, L.; Hashimi, Hassan; Ramrath, D.J.F.; Lukeš, Julius; Warscheid, B.; Schneider, A.

2013-01-01

Roč. 90, č. 4 (2013), s. 744-755 ISSN 0950-382X R&D Projects: GA ČR GAP305/12/2261 Institutional support: RVO:60077344 Keywords : mitochondrial translation * Trypanosoma brucei * EF-Tu Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.026, year: 2013

Measurement properties of translated versions of neck-specific questionnaires: a systematic review

Directory of Open Access Journals (Sweden)

de Vet Henrica C

2011-06-01

Full Text Available Abstract Background Several disease-specific questionnaires to measure pain and disability in patients with neck pain have been translated. However, a simple translation of the original version doesn't guarantee similar measurement properties. The objective of this study is to critically appraise the quality of the translation process, cross-cultural validation and the measurement properties of translated versions of neck-specific questionnaires. Methods Bibliographic databases were searched for articles concerning the translation or evaluation of the measurement properties of a translated version of a neck-specific questionnaire. The methodological quality of the selected studies and the results of the measurement properties were critically appraised and rated using the COSMIN checklist and criteria for measurement properties. Results The search strategy resulted in a total of 3641 unique hits, of which 27 articles, evaluating 6 different questionnaires in 15 different languages, were included in this study. Generally the methodological quality of the translation process is poor and none of the included studies performed a cross-cultural adaptation. A substantial amount of information regarding the measurement properties of translated versions of the different neck-specific questionnaires is lacking. Moreover, the evidence for the quality of measurement properties of the translated versions is mostly limited or assessed in studies of poor methodological quality. Conclusions Until results from high quality studies are available, we advise to use the Catalan, Dutch, English, Iranian, Korean, Spanish and Turkish version of the NDI, the Chinese version of the NPQ, and the Finnish, German and Italian version of the NPDS. The Greek NDI needs cross-cultural validation and there is no methodologically sound information for the Swedish NDI. For all other languages we advise to translate the original version of the NDI.

Measurement properties of translated versions of neck-specific questionnaires: a systematic review

Science.gov (United States)

2011-01-01

Background Several disease-specific questionnaires to measure pain and disability in patients with neck pain have been translated. However, a simple translation of the original version doesn't guarantee similar measurement properties. The objective of this study is to critically appraise the quality of the translation process, cross-cultural validation and the measurement properties of translated versions of neck-specific questionnaires. Methods Bibliographic databases were searched for articles concerning the translation or evaluation of the measurement properties of a translated version of a neck-specific questionnaire. The methodological quality of the selected studies and the results of the measurement properties were critically appraised and rated using the COSMIN checklist and criteria for measurement properties. Results The search strategy resulted in a total of 3641 unique hits, of which 27 articles, evaluating 6 different questionnaires in 15 different languages, were included in this study. Generally the methodological quality of the translation process is poor and none of the included studies performed a cross-cultural adaptation. A substantial amount of information regarding the measurement properties of translated versions of the different neck-specific questionnaires is lacking. Moreover, the evidence for the quality of measurement properties of the translated versions is mostly limited or assessed in studies of poor methodological quality. Conclusions Until results from high quality studies are available, we advise to use the Catalan, Dutch, English, Iranian, Korean, Spanish and Turkish version of the NDI, the Chinese version of the NPQ, and the Finnish, German and Italian version of the NPDS. The Greek NDI needs cross-cultural validation and there is no methodologically sound information for the Swedish NDI. For all other languages we advise to translate the original version of the NDI. PMID:21645355

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…

Harnessing the Power of Integrated Mitochondrial Biology and Physiology: A Special Report on the NHLBI Mitochondria in Heart Diseases Initiative.

Science.gov (United States)

Ping, Peipei; Gustafsson, Åsa B; Bers, Don M; Blatter, Lothar A; Cai, Hua; Jahangir, Arshad; Kelly, Daniel; Muoio, Deborah; O'Rourke, Brian; Rabinovitch, Peter; Trayanova, Natalia; Van Eyk, Jennifer; Weiss, James N; Wong, Renee; Schwartz Longacre, Lisa

2015-07-17

Mitochondrial biology is the sum of diverse phenomena from molecular profiles to physiological functions. A mechanistic understanding of mitochondria in disease development, and hence the future prospect of clinical translations, relies on a systems-level integration of expertise from multiple fields of investigation. Upon the successful conclusion of a recent National Institutes of Health, National Heart, Lung, and Blood Institute initiative on integrative mitochondrial biology in cardiovascular diseases, we reflect on the accomplishments made possible by this unique interdisciplinary collaboration effort and exciting new fronts on the study of these remarkable organelles. © 2015 American Heart Association, Inc.

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.

Alternative strategy for steady growth towards high quality translation networks

Energy Technology Data Exchange (ETDEWEB)

Witkam, A P.M.

1983-01-01

This paper points out a rather new and largely unexplored direction. In machine translation (MT), but also in data-base enquiry, advanced word processing and natural language programming systems, the analysis of the source text is the crucial process, responsible for parsing and disambiguation. For this purpose, conventional MT systems initially relied on only grammar and dictionary, the grammar being limited to morphology and syntax. The author points to artificial intelligence as an alternative strategy, leading to knowledge based translation. 12 references.

Using corpora in scientific and technical translation training: resources to identify conventionality and promote creativity

OpenAIRE

Clara Inés López-Rodríguez

2016-01-01

http://dx.doi.org/10.5007/2175-7968.2016v36nesp1p88 Since the first Corpus Use and Learning to Translate (CULT) Conference in Bertinoro (Italy) in 1997, the usefulness of corpora for translators and trainee translators has been highlighted. From an initial approach where translators compiled ad hoc corpora in their hard drive for a subsequent study with lexical analysis software, there emerged a new trend towards the use of the Internet as corpus. In this second approach, the Web is perce...

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.

The Metropolitan Studies Institute at USC Upstate: Translational Research that Drives Community Decision-Making

Science.gov (United States)

Brady, Kathleen

2012-01-01

The Metropolitan Studies Institute (MSI) at the University of South Carolina Upstate (USC Upstate) demonstrates a robust and unique record of community impact through community indicators research and other translational research. The MSI's work drives programmatic priorities and funding decisions, generates revenue, and increases the community's…

Identifying translational science within the triangle of biomedicine.

Science.gov (United States)

Weber, Griffin M

2013-05-24

The National Institutes of Health (NIH) Roadmap places special emphasis on "bench-to-bedside" research, or the "translation" of basic science research into practical clinical applications. The Clinical and Translational Science Awards (CTSA) Consortium is one example of the large investments being made to develop a national infrastructure to support translational science, which involves reducing regulatory burdens, launching new educational initiatives, and forming partnerships between academia and industry. However, while numerous definitions have been suggested for translational science, including the qualitative T1-T4 classification, a consensus has not yet been reached. This makes it challenging to tract the impact of these major policy changes. In this study, we use a bibliometric approach to map PubMed articles onto a graph, called the Triangle of Biomedicine. The corners of the triangle represent research related to animals, cells and molecules, and humans; and, the position of a publication on the graph is based on its topics, as determined by its Medical Subject Headings (MeSH). We define translation as movement of a collection of articles, or the articles that cite those articles, towards the human corner. The Triangle of Biomedicine provides a quantitative way of determining if an individual scientist, research organization, funding agency, or scientific field is producing results that are relevant to clinical medicine. We validate our technique using examples that have been previously described in the literature and by comparing it to prior methods of measuring translational science. The Triangle of Biomedicine is a novel way to identify translational science and track changes over time. This is important to policy makers in evaluating the impact of the large investments being made to accelerate translation. The Triangle of Biomedicine also provides a simple visual way of depicting this impact, which can be far more powerful than numbers alone.

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.

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...

(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 ...

Russian translations for Cochrane.

Science.gov (United States)

Yudina, E V; Ziganshina, L E

2015-01-01

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

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.

Translational nanomedicine: status assessment and opportunities.

Science.gov (United States)

Murday, James S; Siegel, Richard W; Stein, Judith; Wright, J Fraser

2009-09-01

Nano-enabled technologies hold great promise for medicine and health. The rapid progress by the physical sciences/engineering communities in synthesizing nanostructures and characterizing their properties must be rapidly exploited in medicine and health toward reducing mortality rate, morbidity an illness imposes on a patient, disease prevalence, and general societal burden. A National Science Foundation-funded workshop, "Re-Engineering Basic and Clinical Research to Catalyze Translational Nanoscience," was held 16-19 March 2008 at the University of Southern California. Based on that workshop and literature review, this article briefly explores scientific, economic, and societal drivers for nanomedicine initiatives; examines the science, engineering, and medical research needs; succinctly reviews the US federal investment directly germane to medicine and health, with brief mention of the European Union (EU) effort; and presents recommendations to accelerate the translation of nano-enabled technologies from laboratory discovery into clinical practice. An excellent review paper based on the NSF funded workshop "Re-Engineering Basic and Clinical Research to Catalyze Translational Nanoscience" (16-19 March 2008) and extensive literature search, this paper briefly explores the current state and future perspectives of nanomedicine.

Conditions for uniqueness of product representations for separable quantum channels and separable quantum states

International Nuclear Information System (INIS)

Cohen, Scott M.

2014-01-01

We give a sufficient condition that an operator sum representation of a separable quantum channel in terms of product operators is the unique product representation for that channel, and then provide examples of such channels for any number of parties. This result has implications for efforts to determine whether or not a given separable channel can be exactly implemented by local operations and classical communication. By the Choi-Jamiolkowski isomorphism, it also translates to a condition for the uniqueness of product state ensembles representing a given quantum state. These ideas follow from considerations concerning whether or not a subspace spanned by a given set of product operators contains at least one additional product operator

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...

New insights into the interplay between the translation machinery and nonsense-mediated mRNA decay factors.

Science.gov (United States)

Raimondeau, Etienne; Bufton, Joshua C; Schaffitzel, Christiane

2018-06-19

Faulty mRNAs with a premature stop codon (PTC) are recognized and degraded by nonsense-mediated mRNA decay (NMD). Recognition of a nonsense mRNA depends on translation and on the presence of NMD-enhancing or the absence of NMD-inhibiting factors in the 3'-untranslated region. Our review summarizes our current understanding of the molecular function of the conserved NMD factors UPF3B and UPF1, and of the anti-NMD factor Poly(A)-binding protein, and their interactions with ribosomes translating PTC-containing mRNAs. Our recent discovery that UPF3B interferes with human translation termination and enhances ribosome dissociation in vitro , whereas UPF1 is inactive in these assays, suggests a re-interpretation of previous experiments and modification of prevalent NMD models. Moreover, we discuss recent work suggesting new functions of the key NMD factor UPF1 in ribosome recycling, inhibition of translation re-initiation and nascent chain ubiquitylation. These new findings suggest that the interplay of UPF proteins with the translation machinery is more intricate than previously appreciated, and that this interplay quality-controls the efficiency of termination, ribosome recycling and translation re-initiation. © 2018 The Author(s).

(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.

A Unique ISR Program Determines Cellular Responses to Chronic Stress

Czech Academy of Sciences Publication Activity Database

Guan, B.J.; van Hoef, V.; Jobava, R.; Elroy-Stein, O.; Valášek, Leoš Shivaya; Cargnello, M.; Gao, X.H.; Krokowski, D.; Merrick, W.C.; Kimball, S.R.; Komar, A.A.; Koromilas, A.E.; Wynshaw-Boris, A.; Topisirovic, I.; Larsson, O.; Hatzoglou, M.

2017-01-01

Roč. 68, č. 5 (2017), s. 885-900 ISSN 1097-2765 R&D Projects: GA ČR(CZ) GA17-06238S EU Projects: Wellcome Trust(GB) 090812/B/09/A Institutional support: RVO:61388971 Keywords : UNFOLDED PROTEIN RESPONSE * EUKARYOTIC TRANSLATION INITIATION * ENDOPLASMIC-RETICULUM STRESS Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 14.714, year: 2016

Translation of vph mRNA in Streptomyces lividans and Escherichia coli after removal of the 5' untranslated leader.

Science.gov (United States)

Wu, C J; Janssen, G R

1996-10-01

The Streptomyces vinaceus viomycin phosphotransferase (vph) mRNA contains an untranslated leader with a conventional Shine-Dalgarno homology. The vph leader was removed by ligation of the vph coding sequence to the transcriptional start site of a Streptomyces or an Escherichia coli promoter, such that transcription would initiate at the first position of the vph start codon. Analysis of mRNA demonstrated that transcription initiated primarily at the A of the vph AUG translational start codon in both Streptomyces lividans and E. coli; cells expressing the unleadered vph mRNA were resistant to viomycin indicating that the Shine-Dalgarno sequence, or other features contained within the leader, was not necessary for vph translation. Addition of four nucleotides (5'-AUGC-3') onto the 5' end of the unleadered vph mRNA resulted in translation initiation from the vph start codon and the AUG triplet contained within the added sequence. Translational fusions of vph sequence to a Tn5 neo reporter gene indicated that the first 16 codons of vph coding sequence were sufficient to specify the translational start site and reading frame for expression of neomycin resistance in both E. coli and S. lividans.

Class I and II Small Heat Shock Proteins Together with HSP101 Protect Protein Translation Factors during Heat Stress.

Science.gov (United States)

McLoughlin, Fionn; Basha, Eman; Fowler, Mary E; Kim, Minsoo; Bordowitz, Juliana; Katiyar-Agarwal, Surekha; Vierling, Elizabeth

2016-10-01

The ubiquitous small heat shock proteins (sHSPs) are well documented to act in vitro as molecular chaperones to prevent the irreversible aggregation of heat-sensitive proteins. However, the in vivo activities of sHSPs remain unclear. To investigate the two most abundant classes of plant cytosolic sHSPs (class I [CI] and class II [CII]), RNA interference (RNAi) and overexpression lines were created in Arabidopsis (Arabidopsis thaliana) and shown to have reduced and enhanced tolerance, respectively, to extreme heat stress. Affinity purification of CI and CII sHSPs from heat-stressed seedlings recovered eukaryotic translation elongation factor (eEF) 1B (α-, β-, and γ-subunits) and eukaryotic translation initiation factor 4A (three isoforms), although the association with CI sHSPs was stronger and additional proteins involved in translation were recovered with CI sHSPs. eEF1B subunits became partially insoluble during heat stress and, in the CI and CII RNAi lines, showed reduced recovery to the soluble cell fraction after heat stress, which was also dependent on HSP101. Furthermore, after heat stress, CI sHSPs showed increased retention in the insoluble fraction in the CII RNAi line and vice versa. Immunolocalization revealed that both CI and CII sHSPs were present in cytosolic foci, some of which colocalized with HSP101 and with eEF1Bγ and eEF1Bβ. Thus, CI and CII sHSPs have both unique and overlapping functions and act either directly or indirectly to protect specific translation factors in cytosolic stress granules. © 2016 American Society of Plant Biologists. All Rights Reserved.

Parents' Translations of Child Gesture Facilitate Word Learning in Children with Autism, Down Syndrome and Typical Development.

Science.gov (United States)

Dimitrova, Nevena; Özçalışkan, Şeyda; Adamson, Lauren B

2016-01-01

Typically-developing (TD) children frequently refer to objects uniquely in gesture. Parents translate these gestures into words, facilitating children's acquisition of these words (Goldin-Meadow et al. in Dev Sci 10(6):778-785, 2007). We ask whether this pattern holds for children with autism (AU) and with Down syndrome (DS) who show delayed vocabulary development. We observed 23 children with AU, 23 with DS, and 23 TD children with their parents over a year. Children used gestures to indicate objects before labeling them and parents translated their gestures into words. Importantly, children benefited from this input, acquiring more words for the translated gestures than the not translated ones. Results highlight the role contingent parental input to child gesture plays in language development of children with developmental disorders.

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.

Integrated Features by Administering the Support Vector Machine (SVM of Translational Initiations Sites in Alternative Polymorphic Contex

Directory of Open Access Journals (Sweden)

Nurul Arneida Husin

2012-04-01

Full Text Available Many algorithms and methods have been proposed for classification problems in bioinformatics. In this study, the discriminative approach in particular support vector machines (SVM is employed to recognize the studied TIS patterns. The applied discriminative approach is used to learn about some discriminant functions of samples that have been labelled as positive or negative. After learning, the discriminant functions are employed to decide whether a new sample is true or false. In this study, support vector machines (SVM is employed to recognize the patterns for studied translational initiation sites in alternative weak context. The method has been optimized with the best parameters selected; c=100, E=10-6 and ex=2 for non linear kernel function. Results show that with top 5 features and non linear kernel, the best prediction accuracy achieved is 95.8%. J48 algorithm is applied to compare with SVM with top 15 features and the results show a good prediction accuracy of 95.8%. This indicates that the top 5 features selected by the IGR method and that are performed by SVM are sufficient to use in the prediction of TIS in weak contexts.

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.

The Analysis of English and Lithuanian Idioms and the Problems of Their Translation

Directory of Open Access Journals (Sweden)

Jelena Suchanova

2013-12-01

Full Text Available The paper considers the problems associated with comprehension and translation of idioms within the framework of the theory of linguistic relativity and the translation theories. The main statements of these theories used for explaining the difficulties of idioms’ translation from/into the English or Lithuanian language are presented. The considered problems are analysed from various perspectives. Case studies, demonstrating different nomination principles used in English and Lithuanian due to different approaches of the native speakers of these languages to the same objects or ‘pieces’ of reality are provided. The comparative analysis of English and Lithuanian idioms as the most interesting and peculiar expressions of a language, showing its unique character, is performed and the arising difficulties and the available techniques of idioms’ translation are demonstrated, taking into account the main statements of the theories of linguistic relativity and translation. Special attention is paid to idioms, whose main ideas are expressed differently in the considered languages and, therefore, present many difficulties to non-native speakers. The influence of traditions, culture, the environment and other factors on the form and contents of the idioms in each of the considered languages is also shown. The analysis performed demonstrates the effectiveness of the theory of linguistic relativity in explaining the nature and causes of the arising comprehension and translation problems, as well as its possibilities to give a translator a native speaker’s insight and help him\\her avoid some typical errors. The recommendations of how to make a translation of idioms more accurate and authentic by using the appropriate translation techniques are also given.

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.

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.

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...

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.

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.

CCL5 promotes proliferation of MCF-7 cells through mTOR-dependent mRNA translation

International Nuclear Information System (INIS)

Murooka, Thomas T.; Rahbar, Ramtin; Fish, Eleanor N.

2009-01-01

The proliferative capacity of cancer cells is regulated by factors intrinsic to cancer cells and by secreted factors in the microenvironment. Here, we investigated the proto-oncogenic potential of the chemokine receptor, CCR5, in MCF-7 breast cancer cell lines. At physiological levels, CCL5, a ligand for CCR5, enhanced MCF-7.CCR5 proliferation. Treatment with the mTOR inhibitor, rapamycin, inhibited this CCL5-inducible proliferation. Because mTOR directly modulates mRNA translation, we investigated whether CCL5 activation of CCR5 leads to increased translation. CCL5 induced the formation of the eIF4F translation initiation complex through an mTOR-dependent process. Indeed, CCL5 initiated mRNA translation, shown by an increase in high-molecular-weight polysomes. Specifically, we show that CCL5 mediated a rapid up-regulation of protein expression for cyclin D1, c-Myc and Dad-1, without affecting their mRNA levels. Taken together, we describe a mechanism by which CCL5 influences translation of rapamycin-sensitive mRNAs, thereby providing CCR5-positive breast cancer cells with a proliferative advantage.

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....

Uniqueness theorems in linear elasticity

CERN Document Server

Knops, Robin John

1971-01-01

The classical result for uniqueness in elasticity theory is due to Kirchhoff. It states that the standard mixed boundary value problem for a homogeneous isotropic linear elastic material in equilibrium and occupying a bounded three-dimensional region of space possesses at most one solution in the classical sense, provided the Lame and shear moduli, A and J1 respectively, obey the inequalities (3 A + 2 J1) > 0 and J1>O. In linear elastodynamics the analogous result, due to Neumann, is that the initial-mixed boundary value problem possesses at most one solution provided the elastic moduli satisfy the same set of inequalities as in Kirchhoffs theorem. Most standard textbooks on the linear theory of elasticity mention only these two classical criteria for uniqueness and neglect altogether the abundant literature which has appeared since the original publications of Kirchhoff. To remedy this deficiency it seems appropriate to attempt a coherent description ofthe various contributions made to the study of uniquenes...

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.

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.

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

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...

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

Science.gov (United States)

Leppek, Kathrin; Das, Rhiju; Barna, Maria

2018-03-01

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

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....

Development of a mentorship strategy: a knowledge translation case study.

Science.gov (United States)

Straus, Sharon E; Graham, Ian D; Taylor, Mark; Lockyer, Jocelyn

2008-01-01

There are many theories and frameworks for achieving knowledge translation, and the assortment can be confusing to those responsible for planning, evaluation, or policymaking in knowledge translation. A conceptual framework developed by Graham and colleagues provides an approach that builds on the commonalities found in an assessment of planned-action theories. This article describes the application of this knowledge to action framework to a mentorship initiative in academic medicine. Mentorship influences career success but is threatened in academia by increased clinical, research, and administrative demands. A case study review was undertaken of the role of mentors, the experiences of mentors and mentees, and mentorship initiatives in developing and retaining clinician scientists at two universities in Alberta, Canada. This project involved relevant stakeholders including researchers, university administrators, and research funders. The knowledge to action framework was used to develop a strategy for mentorship for clinician researchers. The framework highlights the need to identify and engage stakeholders in the process of knowledge implementation. A series of initiatives were selected and tailored to barriers and facilitators to implementation of the mentorship initiative; strategies for evaluating the knowledge use and its impact on outcomes were developed. The knowledge to action framework can be used to develop a mentorship initiative for clinician researchers. Future work to evaluate the impact of this intervention on recruitment and retention is planned.

Translational Applications of Nanodiamonds: From Biocompatibility to Theranostics

Science.gov (United States)

Moore, Laura Kent

Nanotechnology marks the next phase of development for drug delivery, contrast agents and gene therapy. For these novel systems to achieve success in clinical translation we must see that they are both effective and safe. Diamond nanoparticles, also known as nanodiamonds (NDs), have been gaining popularity as molecular delivery vehicles over the last decade. The uniquely faceted, carbon nanoparticles possess a number of beneficial properties that are being harnessed for applications ranging from small-molecule drug delivery to biomedical imaging and gene therapy. In addition to improving the effectiveness of a variety of therapeutics and contrast agents, initial studies indicate that NDs are biocompatible. In this work we evaluate the translational potential of NDs by demonstrating efficacy in molecular delivery and scrutinizing particle tolerance. Previous work has demonstrated that NDs are effective vehicles for the delivery of anthracycline chemotherapeutics and gadolinium(III) based contrast agents. We have sought to enhance the gains made in both areas through the addition of active targeting. We find that ND-mediated targeted delivery of epirubicin to triple negative breast cancers induces tumor regression and virtually eliminates drug toxicities. Additionally, ND-mediated delivery of the MRI contrast agent ProGlo boosts the per gadolinium relaxivity four fold, eliminates water solubility issues and effectively labels progesterone receptor expressing breast cancer cells. Both strategies open the door to the development of targeted, theranostic constructs based on NDs, capable of treating and labeling breast cancers at the same time. Although we have seen that NDs are effective vehicles for molecular delivery, for any nanoparticle to achieve clinical utility it must be biocompatible. Preliminary research has shown that NDs are non-toxic, however only a fraction of the ND-subtypes have been evaluated. Here we present an in depth analysis of the cellular

Double-diffusive translation of Earth's inner core

Science.gov (United States)

Deguen, R.; Alboussiére, T.; Labrosse, S.

2018-03-01

The hemispherical asymmetry of the inner core has been interpreted as resulting form a high-viscosity mode of inner core convection, consisting in a translation of the inner core. A thermally driven translation, as originally proposed, is unlikely if the currently favoured high values of the thermal conductivity of iron at core conditions are correct. We consider here the possibility that inner core translation results from an unstable compositional gradient, which would develop either because the light elements present in the core become increasingly incompatible as the inner core grows, or because of a possibly positive feedback of the development of the F-layer on inner core convection. Though the magnitude of the destabilising effect of the compositional field is predicted to be similar to or smaller than the stabilising effect of the thermal field, the huge difference between thermal and chemical diffusivities implies that double-diffusive instabilities can still arise even if the net buoyancy increases upward. Using linear stability analysis and numerical simulations, we demonstrate that a translation mode can indeed exist if the compositional field is destabilising, even if the temperature profile is subadiabatic, and irrespectively of the relative magnitudes of the composition and potential temperature gradients. The existence of this double diffusive mode of translation requires that the following conditions are met: (i) the compositional profile within the inner core is destabilising, and remains so for a duration longer than the destabilisation timescale (on the order of 200 My, but strongly dependent on the magnitude of the initial perturbation); and (ii) the inner core viscosity is sufficiently large, the required value being a strongly increasing function of the inner core size (e.g. 1017 Pa.s when the inner core was 200 km in radius, and ≃ 3 × 1021 Pa.s at the current inner core size). If these conditions are met, the predicted inner core

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…

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…

FRC [field-reversed configuration] translation studies on FRX-C/LSM

International Nuclear Information System (INIS)

Rej, D.; Barnes, G.; Baron, M.

1989-01-01

In preparation for upcoming compression-heating experiments, field-reversed configurations (FRCs) have been translated out of the FRX-C/LSM θ-pinch source, and into the 0.4-m-id, 6.7-m-long translation region formerly used on FRX-C/T. Unlike earlier experiments FRCs are generated without magnetic tearing in the larger FRX-C/LSM source (nominal coil id = 0.70 m, length = 2 m); larger, lower-energy-density FRCs are formed: r/sub s/ ≅ 0.17 m, B/sub ext/ ≅ 0.35 T, ≅ 7 /times/ 10 20 m/sup /minus/3/ and T/sub e/ + T/sub i/ ≅ 400 eV. An initial 3-mtorr D 2 pressure is introduced by either static or puff fill. Asymmetric fields from auxiliary end coils (used for non-tearing formation) provide the accelerating force on the FRC, thereby eliminating the need for a conical θ-pinch coil. An important feature is the abrupt 44% decrease in the flux-conserving wall radius at the transition between the θ-pinch and translation region, similar to that in the compressor. In this paper we review a variety of issues addressed by the recent translation experiments: translation dynamics; translation through a modulated magnetic field; stabilization of the n = 2 rotational instability by weak helical quadrupole fields; and confinement properties. Results from internal magnetic field measurements in translating FRCs may be found in a companion paper. 10 refs., 5 figs

Multiple floating metatarsals: a unique injury

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Trikha Vivek

2013-04-01

Full Text Available 【Abstract】Concomitant dislocation of the tar-sometatarsal and metatarsophalangeal joints of foot is an extremely rare injury. Such injuries presenting in a single or adjacent dual rays have been described in few cases previously. We describe such an injury in adjacent three metatarsals of a polytrauma patient. These injuries are likely to be missed in the initial assessment of a polytrauma patient. These patients are at risk of an overlooked diagnosis but the consequences of missing this type of injury may be Vivek Trikha*, Tarun Goyal, Amit K Agarwal quite severe. This case is presented in view of its unique-ness along with possible mechanism of injury, the sequence of reduction and follow-up. Knowledge of such injury and its proper management may be useful to the trauma surgeons. Key words: Metatarsal bones; Metatarsophalangeal joint; Wounds and injuries

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

Science.gov (United States)

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

2011-03-01

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

Plutonium uniqueness

International Nuclear Information System (INIS)

Silver, G.L.

1984-01-01

A standard is suggested against which the putative uniqueness of plutonium may be tested. It is common folklore that plutonium is unique among the chemical elements because its four common oxidation states can coexist in the same solution. Whether this putative uniqueness appears only during transit to equilibrium, or only at equilibrium, or all of the time, is not generally made clear. But while the folklore may contain some truth, it cannot be put to test until some measure of 'uniqueness' is agreed upon so that quantitative comparisons are possible. One way of measuring uniqueness is as the magnitude of the product of the mole fractions of the element at equilibrium. A 'coexistence index' is defined and discussed. (author)

Molecular mechanism and structure of Trigger Factor bound to the translating ribosome

Science.gov (United States)

Merz, Frieder; Boehringer, Daniel; Schaffitzel, Christiane; Preissler, Steffen; Hoffmann, Anja; Maier, Timm; Rutkowska, Anna; Lozza, Jasmin; Ban, Nenad; Bukau, Bernd; Deuerling, Elke

2008-01-01

Ribosome-associated chaperone Trigger Factor (TF) initiates folding of newly synthesized proteins in bacteria. Here, we pinpoint by site-specific crosslinking the sequence of molecular interactions of Escherichia coli TF and nascent chains during translation. Furthermore, we provide the first full-length structure of TF associated with ribosome–nascent chain complexes by using cryo-electron microscopy. In its active state, TF arches over the ribosomal exit tunnel accepting nascent chains in a protective void. The growing nascent chain initially follows a predefined path through the entire interior of TF in an unfolded conformation, and even after folding into a domain it remains accommodated inside the protective cavity of ribosome-bound TF. The adaptability to accept nascent chains of different length and folding states may explain how TF is able to assist co-translational folding of all kinds of nascent polypeptides during ongoing synthesis. Moreover, we suggest a model of how TF's chaperoning function can be coordinated with the co-translational processing and membrane targeting of nascent polypeptides by other ribosome-associated factors. PMID:18497744

tRNA-like structure regulates translation of Brome mosaic virus RNA.

Science.gov (United States)

Barends, Sharief; Rudinger-Thirion, Joëlle; Florentz, Catherine; Giegé, Richard; Pleij, Cornelis W A; Kraal, Barend

2004-04-01

For various groups of plant viruses, the genomic RNAs end with a tRNA-like structure (TLS) instead of the 3' poly(A) tail of common mRNAs. The actual function of these TLSs has long been enigmatic. Recently, however, it became clear that for turnip yellow mosaic virus, a tymovirus, the valylated TLS(TYMV) of the single genomic RNA functions as a bait for host ribosomes and directs them to the internal initiation site of translation (with N-terminal valine) of the second open reading frame for the polyprotein. This discovery prompted us to investigate whether the much larger TLSs of a different genus of viruses have a comparable function in translation. Brome mosaic virus (BMV), a bromovirus, has a tripartite RNA genome with a subgenomic RNA4 for coat protein expression. All four RNAs carry a highly conserved and bulky 3' TLS(BMV) (about 200 nucleotides) with determinants for tyrosylation. We discovered TLS(BMV)-catalyzed self-tyrosylation of the tyrosyl-tRNA synthetase but could not clearly detect tyrosine incorporation into any virus-encoded protein. We established that BMV proteins do not need TLS(BMV) tyrosylation for their initiation. However, disruption of the TLSs strongly reduced the translation of genomic RNA1, RNA2, and less strongly, RNA3, whereas coat protein expression from RNA4 remained unaffected. This aberrant translation could be partially restored by providing the TLS(BMV) in trans. Intriguingly, a subdomain of the TLS(BMV) could even almost fully restore translation to the original pattern. We discuss here a model with a central and dominant role for the TLS(BMV) during the BMV infection cycle.

The local translation of a top-down football-based initiative for health

DEFF Research Database (Denmark)

Bennike, Søren; Ottesen, Laila

and document analysis. 4 cases have been conducted resulting in a cross-case synthesis. The data has been coded and condensed with pre-existing codes directing the coding in a hermeneutic deductive way (Creswell, 2007). The findings conclude that the implementation is heavily influenced by the unique...

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.

MD-CTS: An integrated terminology reference of clinical and translational medicine

Directory of Open Access Journals (Sweden)

Will Ray

2016-01-01

Full Text Available New vocabularies are rapidly evolving in the literature relative to the practice of clinical medicine and translational research. To provide integrated access to new terms, we developed a mobile and desktop online reference—Marshfield Dictionary of Clinical and Translational Science (MD-CTS. It is the first public resource that comprehensively integrates Wiktionary (word definition, BioPortal (ontology, Wiki (image reference, and Medline abstract (word usage information. MD-CTS is accessible at http://spellchecker.mfldclin.edu/. The website provides a broadened capacity for the wider clinical and translational science community to keep pace with newly emerging scientific vocabulary. An initial evaluation using 63 randomly selected biomedical words suggests that online references generally provided better coverage (73%-95% than paper-based dictionaries (57–71%.

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.

Breaking the language barrier: machine assisted diagnosis using the medical speech translator.

Science.gov (United States)

Starlander, Marianne; Bouillon, Pierrette; Rayner, Manny; Chatzichrisafis, Nikos; Hockey, Beth Ann; Isahara, Hitoshi; Kanzaki, Kyoko; Nakao, Yukie; Santaholma, Marianne

2005-01-01

In this paper, we describe and evaluate an Open Source medical speech translation system (MedSLT) intended for safety-critical applications. The aim of this system is to eliminate the language barriers in emergency situation. It translates spoken questions from English into French, Japanese and Finnish in three medical subdomains (headache, chest pain and abdominal pain), using a vocabulary of about 250-400 words per sub-domain. The architecture is a compromise between fixed-phrase translation on one hand and complex linguistically-based systems on the other. Recognition is guided by a Context Free Grammar Language Model compiled from a general unification grammar, automatically specialised for the domain. We present an evaluation of this initial prototype that shows the advantages of this grammar-based approach for this particular translation task in term of both reliability and use.

A Writer's Thoughts on Translation and Always Living in Translation.

Science.gov (United States)

Agosin, Marjorie; Jones, Robin

2000-01-01

Discusses how it feels to be a poet who writes in Spanish and has her work translated, examining the author's immigration experiences and noting the translator's contributions in making her work accessible across languages, borders, and cultures. Explains that writing in Spanish is a gesture of survival, and translation allows her memories to…

Translation, cultural adaptation and validation of the Diabetes Attitudes Scale - third version into Brazilian Portuguese 1

Science.gov (United States)

Vieira, Gisele de Lacerda Chaves; Pagano, Adriana Silvino; Reis, Ilka Afonso; Rodrigues, Júlia Santos Nunes; Torres, Heloísa de Carvalho

2018-01-01

ABSTRACT Objective: to perform the translation, adaptation and validation of the Diabetes Attitudes Scale - third version instrument into Brazilian Portuguese. Methods: methodological study carried out in six stages: initial translation, synthesis of the initial translation, back-translation, evaluation of the translated version by the Committee of Judges (27 Linguists and 29 health professionals), pre-test and validation. The pre-test and validation (test-retest) steps included 22 and 120 health professionals, respectively. The Content Validity Index, the analyses of internal consistency and reproducibility were performed using the R statistical program. Results: in the content validation, the instrument presented good acceptance among the Judges with a mean Content Validity Index of 0.94. The scale presented acceptable internal consistency (Cronbach’s alpha = 0.60), while the correlation of the total score at the test and retest moments was considered high (Polychoric Correlation Coefficient = 0.86). The Intra-class Correlation Coefficient, for the total score, presented a value of 0.65. Conclusion: the Brazilian version of the instrument (Escala de Atitudes dos Profissionais em relação ao Diabetes Mellitus) was considered valid and reliable for application by health professionals in Brazil. PMID:29319739

Lost in translation?: Comparing three Scandinavian translations of the Beliefs about Medicines Questionnaire.

Science.gov (United States)

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

2014-08-01

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? 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. 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 completely different meaning. Some dissimilarities reflect different cultural beliefs about medicines. When translating questionnaires, bilingual researchers should scrutinize translations across similar languages to address content validity across different countries and languages. Our findings are of relevance to other BMQ translations in non-English countries, as direct comparisons between different translations might not be reliable or valid. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Identification of Plasmodium falciparum translation initiation eIF2β subunit: direct interaction with Protein Phosphatase type 1

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Géraldine eTellier

2016-05-01

Full Text Available Protein phosphatase 1 (PP1c is one of the main phosphatases whose function is shaped by many regulators to confer a specific location and a selective function for this enzyme. Here, we report that eukaryotic initiation factor 2 of P. falciparum (PfeIF2β is an interactor of PfPP1c. Sequence analysis of PfeIF2 revealed a deletion of 111 amino acids when compared to its human counterpart and the presence of two potential binding motifs to PfPP1 (29FGEKKK34, 103KVAW106. As expected, we showed that PfeIF2 binds PfeIF2 and PfeIF5, confirming its canonical interaction with partners of the translation complex. Studies of the PfeIF2-PfPP1 interaction using wild-type, single and double mutated versions of PfeIF2β revealed that both binding motifs are critical. We next showed that PfeIF2 is able to induce Germinal Vesicle BreakDown (GVBD when expressed in Xenopus oocytes, an indicator of its capacity to regulate PP1. Only combined mutations of both binding motifs abolished the interaction with PP1 and the induction of GVBD. In P. falciparum, although the locus is accessible for genetic manipulation, PfeIF2 seems to play an essential role in intraerythrocytic cycle as no viable knockout parasites were detectable. Interestingly, as for PfPP1, the subcellular fractionation of P. falciparum localized PfeIF2β in cytoplasm and nuclear extracts, suggesting a potential effect on PfPP1 in both compartments and raising the question of a non-canonical function of PfeIf2 in the nucleus. Hence, the role played by PfeIF2 in blood stage parasites could occur at multiple levels involving the binding to proteins of the translational complex and to PfPP1.

Externalization and recognition by macrophages of large subunit of eukaryotic translation initiation factor 3 in apoptotic cells

International Nuclear Information System (INIS)

Nakai, Yuji; Shiratsuchi, Akiko; Manaka, Junko; Nakayama, Hiroshi; Takio, Koji; Zhang Jianting; Suganuma, Tatsuo; Nakanishi, Yoshinobu

2005-01-01

We previously isolated a monoclonal antibody named PH2 that inhibits phosphatidylserine-mediated phagocytosis of apoptotic cells by macrophages [C. Fujii, A. Shiratsuchi, J. Manaka, S. Yonehara, Y. Nakanishi. Cell Death Differ. 8 (2001) 1113-1122]. We report here the identification of the cognate antigen. A protein bound by PH2 in Western blotting was identified as the 170-kDa subunit of eukaryotic translation initiation factor 3 (eIF3 p170/eIF3a). When eIF3a was expressed in a culture cell line as a protein fused to green fluorescence protein, the fusion protein was detected at the cell surface only after the induction of apoptosis. The same phenomenon was seen when the localization of endogenous eIF3a was determined using anti-eIF3a antibody, and eIF3a seemed to be partially degraded during apoptosis. Furthermore, bacterially expressed N-terminal half of eIF3a fused to glutathione S-transferase bound to the surface of macrophages and inhibited phagocytosis of apoptotic cells by macrophages when it was added to phagocytosis reactions. These results collectively suggest that eIF3a translocates to the cell surface upon apoptosis, probably after partial degradation, and bridges apoptotic cells and macrophages to enhance phagocytosis

Ribosome Profiling Reveals Pervasive Translation Outside of Annotated Protein-Coding Genes

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Nicholas T. Ingolia

2014-09-01

Full Text Available Ribosome profiling suggests that ribosomes occupy many regions of the transcriptome thought to be noncoding, including 5′ UTRs and long noncoding RNAs (lncRNAs. Apparent ribosome footprints outside of protein-coding regions raise the possibility of artifacts unrelated to translation, particularly when they occupy multiple, overlapping open reading frames (ORFs. Here, we show hallmarks of translation in these footprints: copurification with the large ribosomal subunit, response to drugs targeting elongation, trinucleotide periodicity, and initiation at early AUGs. We develop a metric for distinguishing between 80S footprints and nonribosomal sources using footprint size distributions, which validates the vast majority of footprints outside of coding regions. We present evidence for polypeptide production beyond annotated genes, including the induction of immune responses following human cytomegalovirus (HCMV infection. Translation is pervasive on cytosolic transcripts outside of conserved reading frames, and direct detection of this expanded universe of translated products enables efforts at understanding how cells manage and exploit its consequences.

Translation of dipeptide repeat proteins from the C9ORF72 expanded repeat is associated with cellular stress.

Science.gov (United States)

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

2018-08-01

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

Combat Wound Initiative program.

Science.gov (United States)

Stojadinovic, Alexander; Elster, Eric; Potter, Benjamin K; Davis, Thomas A; Tadaki, Doug K; Brown, Trevor S; Ahlers, Stephen; Attinger, Christopher E; Andersen, Romney C; Burris, David; Centeno, Jose; Champion, Hunter; Crumbley, David R; Denobile, John; Duga, Michael; Dunne, James R; Eberhardt, John; Ennis, William J; Forsberg, Jonathan A; Hawksworth, Jason; Helling, Thomas S; Lazarus, Gerald S; Milner, Stephen M; Mullick, Florabel G; Owner, Christopher R; Pasquina, Paul F; Patel, Chirag R; Peoples, George E; Nissan, Aviram; Ring, Michael; Sandberg, Glenn D; Schaden, Wolfgang; Schultz, Gregory S; Scofield, Tom; Shawen, Scott B; Sheppard, Forest R; Stannard, James P; Weina, Peter J; Zenilman, Jonathan M

2010-07-01

The Combat Wound Initiative (CWI) program is a collaborative, multidisciplinary, and interservice public-private partnership that provides personalized, state-of-the-art, and complex wound care via targeted clinical and translational research. The CWI uses a bench-to-bedside approach to translational research, including the rapid development of a human extracorporeal shock wave therapy (ESWT) study in complex wounds after establishing the potential efficacy, biologic mechanisms, and safety of this treatment modality in a murine model. Additional clinical trials include the prospective use of clinical data, serum and wound biomarkers, and wound gene expression profiles to predict wound healing/failure and additional clinical patient outcomes following combat-related trauma. These clinical research data are analyzed using machine-based learning algorithms to develop predictive treatment models to guide clinical decision-making. Future CWI directions include additional clinical trials and study centers and the refinement and deployment of our genetically driven, personalized medicine initiative to provide patient-specific care across multiple medical disciplines, with an emphasis on combat casualty care.

Using corpora in scientific and technical translation training: resources to identify conventionality and promote creativity

Directory of Open Access Journals (Sweden)

Clara Inés López-Rodríguez

2016-06-01

Full Text Available Since the first Corpus Use and Learning to Translate (CULT Conference in Bertinoro (Italy in 1997, the usefulness of corpora for translators and trainee translators has been highlighted. From an initial approach where translators compiled ad hoc corpora in their hard drive for a subsequent study with lexical analysis software, there emerged a new trend towards the use of the Internet as corpus. In this second approach, the Web is perceived as a huge corpus which is accessed by means of online tools which produce monolingual wordlists and concordances from texts available from the Internet or pre-existing corpora, or by means of bilingual or multilingual concordancers displaying aligned texts from international institutions' parallel corpora. Bilingual concordancers and translation memories are widely used by translators and trainee translators because of the immediate translation solutions they offer, but these tools can restrain creativity by offering conventional solutions and eliminating layout and multimodal elements in texts. The aim of this article is to describe the exploitation of quality corpora in a scientific and technical translation course, focusing on texts on health translated from English into Spanish, and on terminological variation as a reflection of creativity in language.

When Visions for City Planning and Development are Translated into Practice

DEFF Research Database (Denmark)

Zapata Campos, Maria José; Zapata, Patrik

The ‘knowing-doing’ gaps between policy goals and their outcome when implemented is of increasing concern both in practice and in research. This paper explores how the visions of a sustainable development and the corresponding planning are translated into practice; what aspects of visions and plans...... of the waste-pickers now are formally employed, and new housing for the informal settlement’s residents. The analysis is based on interviews, observations, workshop participations and document analysis; gathered from 2009 until 2012. It combines action net theory with the sociology of translation...... as theoretical framework. Despite the initial compliance to the program (funded and initially led by international aid organizations), local actors enacted a myriad of small acts of defiance and resistance that, without abruptly contesting the project, shaped it to better fit local needs; a) first by municipal...

From Translation to Organization to International Business: an Academic No Man’s Land

Directory of Open Access Journals (Sweden)

José Lambert

2016-08-01

Full Text Available Universities claim to represent a crucial component in the contemporary world of knowledge, which involves a given degree of self-criticism and the redefinition of a few priorities. The recognition of new departments, such as Translation Studies (TS is obviously part of this historical movement of self-criticism, and TS itself reflects similar processes in its own history, or rather prehistory. Although TS claims to have integrated Globalization and the new international world into its academic program, exactly how it will combine its initial self-definitions (built around translator training with academic definitions (What is translation? How can past and present translation phenomena be accounted for? How do language policies, multilingualism, media discourse or communities, not to mention ranking, fit into all this? is its challenge for the coming years. Without excluding topics from the initial moments of the new discipline (such as training or nation-state interaction, we propose to explore and exploit what can be learned from organization by making use of the contemporary business world (in this case the international car industry, which is a No Man’s Land within the coalescing traditions of the new discipline. And in this little-known world, fundamental new insights are waiting to be gathered.

From Translation to Organization to International Business: an Academic No Man’s Land

Directory of Open Access Journals (Sweden)

José Lambert

2016-05-01

Full Text Available Universities claim to represent a crucial component in the contemporary world of knowledge, which involves a given degree of self-criticism and the redefinition of a few priorities. The recognition of new departments, such as Translation Studies (TS is obviously part of this historical movement of self-criticism, and TS itself reflects similar processes in its own history, or rather prehistory. Although TS claims to have integrated Globalization and the new international world into its academic program, exactly how it will combine its initial self-definitions (built around translator training with academic definitions (What is translation? How can past and present translation phenomena be accounted for? How do language policies, multilingualism, media discourse or communities, not to mention ranking, fit into all this? is its challenge for the coming years. Without excluding topics from the initial moments of the new discipline (such as training or nation-state interaction, we propose to explore and exploit what can be learned from organization by making use of the contemporary business world (in this case the international car industry, which is a No Man’s Land within the coalescing traditions of the new discipline. And in this little-known world,  fundamental new insights are waiting to be gathered.

Translating Gene Transfer: A Stalled Effort

OpenAIRE

Greenberg, Alexandra J.; McCormick, Jennifer; Tapia, Carmen J.; Windebank, Anthony J.

2011-01-01

The journey of gene transfer from laboratory to clinic has been slow and fraught with many challenges and barriers. Despite the development of the initial technology in the early 1970s, a standard clinical treatment involving “gene therapy” remains to be seen. Furthermore, much was written about the technology in the early 1990s, but since then, not much has been written about the journey of gene transfer. The translational path of gene transfer thus far, both pitfalls and successes, can serv...

Programmed cell death in the leaves of the Arabidopsis spontaneous necrotic spots (sns-D mutant correlates with increased expression of the eukaryotic translation initiation factor eIF4B2

Directory of Open Access Journals (Sweden)

Gwenael M.D.J.-M. Gaussand

2011-04-01

Full Text Available From a pool of transgenic Arabidopsis (Arabidopsis thaliana plants harboring an activator T-DNA construct, one mutant was identified that developed spontaneous necrotic spots (sns-D on the rosette leaves under aseptic conditions. The sns-D mutation is dominant and homozygous plants are embryo lethal. The mutant produced smaller rosettes with a different number of stomata than the wild-type. DNA fragmentation in the nuclei of cells in the necrotic spots and a significant increase of caspase-3 and caspase-6 like activities in sns-D leaf extracts indicated that the sns-D mutation caused programmed cell death (PCD. The integration of the activator T-DNA caused an increase of the expression level of At1g13020, which encodes the eukaryotic translation initiation factor eIF4B2. The expression level of eIF4B2 was positively correlated with the severity of sns-D mutant phenotype. Overexpression of the eIF4B2 cDNA mimicked phenotypic traits of the sns-D mutant indicating that the sns-D mutant phenotype is indeed caused by activation tagging of eIF4B2. Thus, incorrect regulation of translation initiation may result in PCD.

Translation Methods Applied in Translating Quotations in “the Secret” by Rhonda

OpenAIRE

FEBRIANTI, VICKY

2014-01-01

Keywords: Translation Methods, The Secret, Quotations.Translation helps human to get information written in any language evenwhen it is written in foreign languages. Therefore translation happens in printed media. Books have been popular printed media. The Secret written by Rhonda Byrne is a popular self-help book which has been translated into 50 languages including Indonesian (“The Secret”, n.d., para.5-6).This study is meant to find out the translation methods applied in The Secret. The wr...

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

Inhibition of tumor cell growth by Sigma1 ligand mediated translational repression

International Nuclear Information System (INIS)

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

2012-01-01

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

Why Translation Is Difficult

DEFF Research Database (Denmark)

Carl, Michael; Schaeffer, Moritz Jonas

2017-01-01

The paper develops a definition of translation literality that is based on the syntactic and semantic similarity of the source and the target texts. We provide theoretical and empirical evidence that absolute literal translations are easy to produce. Based on a multilingual corpus of alternative...... translations we investigate the effects of cross-lingual syntactic and semantic distance on translation production times and find that non-literality makes from-scratch translation and post-editing difficult. We show that statistical machine translation systems encounter even more difficulties with non-literality....

Cultural Context and Translation

Institute of Scientific and Technical Information of China (English)

张敏

2009-01-01

cultural context plays an important role in translation. Because translation is a cross-culture activity, the culture context that influ-ences translating is consisted of both the culture contexts of source language and target language. This article firstly analyzes the concept of context and cultural context, then according to the procedure of translating classifies cultural context into two stages and talks about how they respectively influence translating.

Gender issues in translation

OpenAIRE

ERGASHEVA G.I.

2015-01-01

The following research is done regarding gender in translation dealing specifically with the issue of the translators’ gender identity and its effect on their translations, as well as on how gender itself is translated and produced. We will try to clarify what gender is, how gender manifests itself in the system of language, and what problems translators encounter when translating or producing gender-related materials

Socorro Students Translate NRAO Web Pages Into Spanish

Science.gov (United States)

2002-07-01

Six Socorro High School students are spending their summer working at the National Radio Astronomy Observatory (NRAO) on a unique project that gives them experience in language translation, World Wide Web design, and technical communication. Under the project, called "Un puente a los cielos," the students are translating many of NRAO's Web pages on astronomy into Spanish. "These students are using their bilingual skills to help us make basic information about astronomy and radio telescopes available to the Spanish-speaking community," said Kristy Dyer, who works at NRAO as a National Science Foundation postdoctoral fellow and who developed the project and obtained funding for it from the National Aeronautics and Space Administration. The students are: Daniel Acosta, 16; Rossellys Amarante, 15; Sandra Cano, 16; Joel Gonzalez, 16; Angelica Hernandez, 16; and Cecilia Lopez, 16. The translation project, a joint effort of NRAO and the NM Tech physics department, also includes Zammaya Moreno, a teacher from Ecuador, Robyn Harrison, NRAO's education officer, and NRAO computer specialist Allan Poindexter. The students are translating NRAO Web pages aimed at the general public. These pages cover the basics of radio astronomy and frequently-asked questions about NRAO and the scientific research done with NRAO's telescopes. "Writing about science for non-technical audiences has to be done carefully. Scientific concepts must be presented in terms that are understandable to non-scientists but also that remain scientifically accurate," Dyer said. "When translating this type of writing from one language to another, we need to preserve both the understandability and the accuracy," she added. For that reason, Dyer recruited 14 Spanish-speaking astronomers from Argentina, Mexico and the U.S. to help verify the scientific accuracy of the Spanish translations. The astronomers will review the translations. The project is giving the students a broad range of experience. "They are

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...

Machine Translation

Indian Academy of Sciences (India)

Research Mt System Example: The 'Janus' Translating Phone Project. The Janus ... based on laptops, and simultaneous translation of two speakers in a dialogue. For more ..... The current focus in MT research is on using machine learning.

Opposite responses of rabbit and human globin mRNAs to translational inhibition by cap analogues

International Nuclear Information System (INIS)

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

1987-01-01

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

Human uniqueness-self-interest and social cooperation.

Science.gov (United States)

Okada, Daijiro; Bingham, Paul M

2008-07-21

Humans are unique among all species of terrestrial history in both ecological dominance and individual properties. Many, or perhaps all, of the unique elements of this nonpareil status can be plausibly interpreted as evolutionary and strategic elements and consequences of the unprecedented intensity and scale of our social cooperation. Convincing explanation of this unique human social adaptation remains a central, unmet challenge to the scientific enterprise. We develop a hypothesis for the ancestral origin of expanded cooperative social behavior. Specifically, we present a game theoretic analysis demonstrating that a specific pattern of expanded social cooperation between conspecific individuals with conflicts of interest (including non-kin) can be strategically viable, but only in animals that possess a highly unusual capacity for conspecific violence (credible threat) having very specific properties that dramatically reduce the costs of coercive violence. The resulting reduced costs allow preemptive or compensated coercion to be an instantaneously self-interested behavior under diverse circumstances rather than in rare, idiosyncratic circumstances as in actors (animals) who do not have access to inexpensive coercive threat. Humans are apparently unique among terrestrial organisms in having evolved conspecific coercive capabilities that fulfill these stringent requirements. Thus, our results support the proposal that access to a novel capacity for projection of coercive threat might represent the essential initiating event for the evolution of a human-like pattern of social cooperation and the subsequent evolution of the diverse features of human uniqueness. Empirical evidence indicates that these constraints were, in fact, met only in our evolutionary lineage. The logic for the emergence of uniquely human cooperation suggested by our analysis apparently accounts simply for the human fossil record.

Translating Proper Nouns: A Case Study on English Translation of Hafez's Lyrics

Science.gov (United States)

Shirinzadeh, Seyed Alireza; Mahadi, Tengku Sepora Tengku

2014-01-01

Proper nouns are regarded so simple that they might be taken for granted in translation explorations. Some may believe that they should not be translated in transmitting source texts to target texts. But, it is not the case; if one looks at present translations, he will notice that different strategies might be applied for translating proper…

Conversational Implicatures in English Plays and Their Persian Translations: A Norm-governed Study

Directory of Open Access Journals (Sweden)

Zahra Hassani Laharomi

2013-09-01

Full Text Available The present study attempted to describe in full detail the status of implicature translation in two 20-year time periods before and after Iran Islamic Revolution to provide a clear picture of the strategies applied by translators in the two eras and, as its main objective, to shed light on the translational norms of this linguistic element. To this end, it first sought to elaborate on the reasons and the ways they emerge in conversations. Accordingly, identifying the implicatures arose due to the violation of Grice’s (1975 four maxims of conversation, the researcher separately categorized the translations of the implicatures based on Desilla’s (2009 classification. As the last phase of the study, the strategies for implicature translation were thoroughly scrutinized with the hope to determine the dominant norms of implicature translation in light of Toury’s (1995 notion of initial norm. Based on the results obtained from both pre- and post-revolution data, preservation was revealed to be the most frequent strategy in both eras, attesting to the significance of the adequacy of implicature translation; modification and explicitation were the second and the third most frequent strategies respectively. However, the frequency of modification and explicitation increased in the post-revolution translations. It seems that the trend of the norm of implicature translation moves toward acceptability.

Translation and Quality Management

DEFF Research Database (Denmark)

Petersen, Margrethe

1996-01-01

theory which would seem likely to be of interest in this connection and section 2. gives a linguist's introduction to the part of the area of quality management which I consider relevant for present purposes. Section 3. is devoted to the case study of a small translation firm which has been certified......The aim of this article is to consider the issue of quality in translation. Specifically, the question under consideration is whether quality assurance in relation to translation is feasible and, if so, what some of the implications for translation theory, translation practice and the teaching...... of translation would be. To provide a backdrop against which the issue may be discussed, I present an overview of the two areas which seem most likely to hold potential answers, viz., that of translation theory and that of quality management. Section 1. gives a brief outline of some contributions to translation...

Translation-Memory (TM) Research

DEFF Research Database (Denmark)

Schjoldager, Anne Gram; Christensen, Tina Paulsen

2010-01-01

to be representative of the research field as a whole. Our analysis suggests that, while considerable knowledge is available about the technical side of TMs, more research is needed to understand how translators interact with TM technology and how TMs influence translators' cognitive translation processes.......  It is no exaggeration to say that the advent of translation-memory (TM) systems in the translation profession has led to drastic changes in translators' processes and workflow, and yet, though many professional translators nowadays depend on some form of TM system, this has not been the object...... of much research. Our paper attempts to find out what we know about the nature, applications and influences of TM technology, including translators' interaction with TMs, and also how we know it. An essential part of the analysis is based on a selection of empirical TM studies, which we assume...

Translation modalities: an investigation of the translated short story “Dez de dezembro”

Directory of Open Access Journals (Sweden)

Clara Peron da Silva Guedes

2017-05-01

Full Text Available During the translation process translators adopt linguistic strategies in order to make decisions that help to render a translated text suitable to the target language and culture. The translation modalities proposed by Aubert (105-10 constitute a tool that enables one to identify some of these strategies. In addition, they permit to measure the level of linguistic differentiation between a source text and a target text verifying the distance or the proximity of the target text to the linguistic and cultural issues of the source text. Thus, this paper aims to investigate the translation modalities in the short story “Dez de dezembro” (Saunders 204-38, a translation of the short story “Tenth of December” (Saunders 215-51. For quantifying the translation modalities in the translated text the noun phrases from the source text were selected and their counterparts in the target text were classified and annotated within Notepad++ software. The most recurrent translation modalities in the corpus were Literal Translation and Transposition, categories considered intermediate ones in the rank proposed by Aubert (105-10. Therefore, a relation of equivalence can be established between the target and the source texts.

Discourse Analysis in Translator Training

OpenAIRE

Gülfidan Ayvaz

2015-01-01

Translator training enables students to gain experience in both linguistic parameters and translation practice. Discourse Analysis is one of the strategies that lead to a better translation process and quality in translation. In that regard, this study aims to present DA as a translation strategy for translation practice and a useful tool for translator training. The relationship between DA and Translator Training is not widely studied. Therefore this study aims to define DA and how it can be...

Translation Competence and Translation Performance: Lexical, Syntactic and Textual Patterns in Student Translations of a Specialized EU Genre

Science.gov (United States)

Karoly, Adrienn

2012-01-01

This paper reports the findings of a study aiming to reveal the recurring patterns of lexical, syntactic and textual errors in student translations of a specialized EU genre from English into Hungarian. By comparing the student translations to the official translation of the text, this article uncovers the most frequent errors that students made…

How Italian dialect poets translate themselves and how they translate other poets

Directory of Open Access Journals (Sweden)

Edoardo Zuccato

2017-07-01

Full Text Available Part one of this essay discusses the way most contemporary Italian dialect poets translate themselves into Italian. Part two of the essay examines examples of poetry translation into dialect made by some of the same contemporary authors. A comparison between the style of the self-translations, which is mainly lyrical, and the variety of styles of the translations from other poets, shows that each choice is an intentional strategy rather than a missed opportunity for a more creative self-translation, as some scholars have argued.

Translation Memory and Computer Assisted Translation Tool for Medieval Texts

Directory of Open Access Journals (Sweden)

Törcsvári Attila

2013-05-01

Full Text Available Translation memories (TMs, as part of Computer Assisted Translation (CAT tools, support translators reusing portions of formerly translated text. Fencing books are good candidates for using TMs due to the high number of repeated terms. Medieval texts suffer a number of drawbacks that make hard even “simple” rewording to the modern version of the same language. The analyzed difficulties are: lack of systematic spelling, unusual word orders and typos in the original. A hypothesis is made and verified that even simple modernization increases legibility and it is feasible, also it is worthwhile to apply translation memories due to the numerous and even extremely long repeated terms. Therefore, methods and algorithms are presented 1. for automated transcription of medieval texts (when a limited training set is available, and 2. collection of repeated patterns. The efficiency of the algorithms is analyzed for recall and precision.

Who translates the translation? (Retraduire les héros marginaux d'Alan Moore

Directory of Open Access Journals (Sweden)

Alice RAY

2016-11-01

Full Text Available The retranslation phenomenon is essential to the translation process. It is considered as the logical progression of this process which allows the translated literary work to regenerate in a restless cultural and language space. To a lesser extent, we can observe the same phenomenon in the translation of comics. However, this specific translation requires other competencies and a translating approach somehow different from the ones required to translate fiction literature, especially because of the presence of the visual system of drawings which is strongly bound to its own culture and the endless mutations it goes through. The comic book Watchmen (Les Gardiens, in the first French translation by Alan Moore and Dave Gibbons, is known in the whole world as the comic which had not only remodeled the vision we had of super-heroes, but had also given the comic books another voice. Watchmen was published between 1986 and 1987 in the United States and translated in French from 1987 to 1988. Fifteen years after this first translation by Jean-Patrick Manchette, Panini publishing decided to retranslate this famous comic in 2007. However, if the reviews of the first translation were laudatory, the retranslation did not enjoy a great reception from the readers or from the reviewers. This paper proposes a comparative analysis of both these translations and of their original version as well as an experiment on the readers, comic books readers or not, in order to establish why the first translation was a success and the retranslation a failure. Thus, we could withdraw the elements which allow us to understand the reception of comic translation.

Translation techniques for distributed-shared memory programming models

Energy Technology Data Exchange (ETDEWEB)

Fuller, Douglas James [Iowa State Univ., Ames, IA (United States)

2005-01-01

The high performance computing community has experienced an explosive improvement in distributed-shared memory hardware. Driven by increasing real-world problem complexity, this explosion has ushered in vast numbers of new systems. Each new system presents new challenges to programmers and application developers. Part of the challenge is adapting to new architectures with new performance characteristics. Different vendors release systems with widely varying architectures that perform differently in different situations. Furthermore, since vendors need only provide a single performance number (total MFLOPS, typically for a single benchmark), they only have strong incentive initially to optimize the API of their choice. Consequently, only a fraction of the available APIs are well optimized on most systems. This causes issues porting and writing maintainable software, let alone issues for programmers burdened with mastering each new API as it is released. Also, programmers wishing to use a certain machine must choose their API based on the underlying hardware instead of the application. This thesis argues that a flexible, extensible translator for distributed-shared memory APIs can help address some of these issues. For example, a translator might take as input code in one API and output an equivalent program in another. Such a translator could provide instant porting for applications to new systems that do not support the application's library or language natively. While open-source APIs are abundant, they do not perform optimally everywhere. A translator would also allow performance testing using a single base code translated to a number of different APIs. Most significantly, this type of translator frees programmers to select the most appropriate API for a given application based on the application (and developer) itself instead of the underlying hardware.

Uniqueness of Gibbs measure for Potts model with countable set of spin values

International Nuclear Information System (INIS)

Ganikhodjaev, N.N.; Rozikov, U.A.

2004-11-01

We consider a nearest-neighbor Potts model with countable spin values 0,1,..., and non zero external field, on a Cayley tree of order k (with k+1 neighbors). We study translation-invariant 'splitting' Gibbs measures. We reduce the problem to the description of the solutions of some infinite system of equations. For any k≥1 and any fixed probability measure ν with ν(i)>0 on the set of all non negative integer numbers Φ={0,1,...} we show that the set of translation-invariant splitting Gibbs measures contains at most one point, independently on parameters of the Potts model with countable set of spin values on Cayley tree. Also we give a full description of the class of measures ν on Φ such that wit respect to each element of this class our infinite system of equations has unique solution {a i =1,2,...}, where a is an element of (0,1). (author)

A new spin on research translation: the Boston Consensus Conference on Human Biomonitoring.

Science.gov (United States)

Nelson, Jessica W; Scammell, Madeleine Kangsen; Altman, Rebecca Gasior; Webster, Thomas F; Ozonoff, David M

2009-04-01

Translating research to make it more understandable and effective (research translation) has been declared a priority in environmental health but does not always include communication to the public or residents of communities affected by environmental hazards. Their unique perspectives are also commonly missing from discussions about science and technology policy. The consensus conference process, developed in Denmark, offers a way to address this gap. The Boston Consensus Conference on Human Biomonitoring, held in Boston, Massachusetts, in the fall of 2006, was designed to educate and elicit input from 15 Boston-area residents on the scientifically complex topic of human biomonitoring for environmental chemicals. This lay panel considered the many ethical, legal, and scientific issues surrounding biomonitoring and prepared a report expressing their views. The lay panel's findings provide a distinct and important voice on the expanding use of biomonitoring. In some cases, such as a call for opt-in reporting of biomonitoring results to study participants, they mirror recommendations raised elsewhere. Other conclusions have not been heard previously, including the recommendation that an individual's results should be statutorily exempted from the medical record unless permission is granted, and the opportunity to use biomonitoring data to stimulate green chemistry. The consensus conference model addresses both aspects of a broader conception of research translation: engaging the public in scientific questions, and bringing their unique perspectives to bear on public health research, practice, and policy. In this specific application, a lay panel's recommendations on biomonitoring surveillance, communication, and ethics have practical implications for the conduct of biomonitoring studies and surveillance programs.

Determinants of translation ambiguity

Science.gov (United States)

Degani, Tamar; Prior, Anat; Eddington, Chelsea M.; Arêas da Luz Fontes, Ana B.; Tokowicz, Natasha

2016-01-01

Ambiguity in translation is highly prevalent, and has consequences for second-language learning and for bilingual lexical processing. To better understand this phenomenon, the current study compared the determinants of translation ambiguity across four sets of translation norms from English to Spanish, Dutch, German and Hebrew. The number of translations an English word received was correlated across these different languages, and was also correlated with the number of senses the word has in English, demonstrating that translation ambiguity is partially determined by within-language semantic ambiguity. For semantically-ambiguous English words, the probability of the different translations in Spanish and Hebrew was predicted by the meaning-dominance structure in English, beyond the influence of other lexical and semantic factors, for bilinguals translating from their L1, and translating from their L2. These findings are consistent with models postulating direct access to meaning from L2 words for moderately-proficient bilinguals. PMID:27882188

Models of Interinstitutional Partnerships between Research Intensive Universities and Minority Serving Institutions (MSI) across the Clinical Translational Science Award (CTSA) Consortium

Science.gov (United States)

Fair, Alecia; Norris, Keith; Verbalis, Joseph G.; Poland, Russell; Bernard, Gordon; Stephens, David S.; Dubinett, Steven M.; Imperato‐McGinley, Julianne; Dottin, Robert P.; Pulley, Jill; West, Andrew; Brown, Arleen; Mellman, Thomas A.

2013-01-01

Abstract Health disparities are an immense challenge to American society. Clinical and Translational Science Awards (CTSAs) housed within the National Center for Advancing Translational Science (NCATS) are designed to accelerate the translation of experimental findings into clinically meaningful practices and bring new therapies to the doorsteps of all patients. Research Centers at Minority Institutions (RCMI) program at the National Institute on Minority Health and Health Disparities (NIMHD) are designed to build capacity for biomedical research and training at minority serving institutions. The CTSA created a mechanism fostering formal collaborations between research intensive universities and minority serving institutions (MSI) supported by the RCMI program. These consortium‐level collaborations activate unique translational research approaches to reduce health disparities with credence to each academic institutions history and unique characteristics. Five formal partnerships between research intensive universities and MSI have formed as a result of the CTSA and RCMI programs. These partnerships present a multifocal approach; shifting cultural change and consciousness toward addressing health disparities, and training the next generation of minority scientists. This collaborative model is based on the respective strengths and contributions of the partnering institutions, allowing bidirectional interchange and leveraging NIH and institutional investments providing measurable benchmarks toward the elimination of health disparities. PMID:24119157

Linguistic Levels of Translation: A Generic Exploration of Translation Difficulties in Literary Textual Corpus

Directory of Open Access Journals (Sweden)

Magda Madkour

2016-11-01

Full Text Available This case study research was based on a generic exploration of the translation problems that graduate students face in literary translation. Literary translation is fundamental to translation programs at higher education due to the upsurge that has occurred in publishing classical and modern literary works from various cultures. However, literary texts have special characteristics that make the process of transferring them from one language into another a daunting task. Translating literary texts is difficult even for professional translators because misinterpreting the messages of the source texts can lead to distorting the aesthetic aspects of the literary work. Students need to learn various linguistic levels of literary translation as well as strategies and methods of translation. Learning the linguistics levels of translation necessitates providing adequate training that is based on enhancing students’ cognitive abilities. Cognitive-based translation training helps students learn the procedures of solving the problems of translating sound and literary devices. Cognitive approaches are relevant to the translation process since cognition implies mental activities that students can use to understand and synthesize the literary text, and reconstruct it creatively. Therefore, the current study aimed at examining the relationship between cognitive teaching methodologies and students’ performance in literary translation. To examine this relationship, qualitative and quantitative data was collected from graduate students at the College of Languages and Translation at Imam Mohammed bin Saud Islamic University (IMAMU University, Riyadh, Saudi Arabia. In addition, corpus data was gathered from authentic literary texts including, novels, short stories, and poetry, to investigate the effect of linguistic analysis and cognitive strategies on the quality of literary translation. Quantitative data was analyzed using the Statistical Package for the

An analysis of machine translation and speech synthesis in speech-to-speech translation system

OpenAIRE

Hashimoto, K.; Yamagishi, J.; Byrne, W.; King, S.; Tokuda, K.

2011-01-01

This paper provides an analysis of the impacts of machine translation and speech synthesis on speech-to-speech translation systems. The speech-to-speech translation system consists of three components: speech recognition, machine translation and speech synthesis. Many techniques for integration of speech recognition and machine translation have been proposed. However, speech synthesis has not yet been considered. Therefore, in this paper, we focus on machine translation and speech synthesis, ...

A sensitive mass spectrometric method for hypothesis-driven detection of peptide post-translational modifications: multiple reaction monitoring-initiated detection and sequencing (MIDAS).

Science.gov (United States)

Unwin, Richard D; Griffiths, John R; Whetton, Anthony D

2009-01-01

The application of a targeted mass spectrometric workflow to the sensitive identification of post-translational modifications is described. This protocol employs multiple reaction monitoring (MRM) to search for all putative peptides specifically modified in a target protein. Positive MRMs trigger an MS/MS experiment to confirm the nature and site of the modification. This approach, termed MIDAS (MRM-initiated detection and sequencing), is more sensitive than approaches using neutral loss scanning or precursor ion scanning methodologies, due to a more efficient use of duty cycle along with a decreased background signal associated with MRM. We describe the use of MIDAS for the identification of phosphorylation, with a typical experiment taking just a couple of hours from obtaining a peptide sample. With minor modifications, the MIDAS method can be applied to other protein modifications or unmodified peptides can be used as a MIDAS target.

Alternative translation initiation of Caveolin-2 desensitizes insulin signaling through dephosphorylation of insulin receptor by PTP1B and causes insulin resistance.

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Kwon, Hayeong; Jang, Donghwan; Choi, Moonjeong; Lee, Jaewoong; Jeong, Kyuho; Pak, Yunbae

2018-06-01

Insulin resistance, defined as attenuated sensitivity responding to insulin, impairs insulin action. Direct causes and molecular mechanisms of insulin resistance have thus far remained elusive. Here we show that alternative translation initiation (ATI) of Caveolin-2 (Cav-2) regulates insulin sensitivity. Cav-2β isoform yielded by ATI desensitizes insulin receptor (IR) via dephosphorylation by protein-tyrosine phosphatase 1B (PTP1B), and subsequent endocytosis and lysosomal degradation of IR, causing insulin resistance. Blockage of Cav-2 ATI protects against insulin resistance by preventing Cav-2β-PTP1B-directed IR desensitization, thereby normalizing insulin sensitivity and glucose uptake. Our findings show that Cav-2β is a negative regulator of IR signaling, and identify a mechanism causing insulin resistance through control of insulin sensitivity via Cav-2 ATI. Copyright © 2018 Elsevier B.V. All rights reserved.

Fast and frugal trees: translating population-based pharmacogenomics to medication prioritization

NARCIS (Netherlands)

Rooij, T. van; Roederer, M.; Wareham, H.T.; Rooij, I.J.E.I. van; McLeod, H.L.; Marsh, S.

2015-01-01

Aim: Fast and frugal decision trees (FFTs) can simplify clinical decision making by providing a heuristic approach to contextual guidance. We wanted to use FFTs for pharmacogenomic knowledge translation at point-of-care. Materials & Methods: The Pharmacogenomics for Every Nation Initiative (PGENI),

Translation Meets Cognitive Science: The Imprint of Translation on Cognitive Processing

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Rojo, Ana

2015-01-01

Translation has long played a role in linguistic and literary studies research. More recently, the theoretical and methodological concerns of process research have given translation an additional role in cognitive science. The interest in the cognitive aspects of translation has led scholars to turn to disciplines such as cognitive linguistics,…

Audiovisual Translation:A Critical Review on Sino-western Perspectives of Film Subtitle Translation

OpenAIRE

Junchen Zhang

2018-01-01

The paper argues the development of audiovisual translation (mainly focuses on the strand of film subtitle translation) in the West and China. Firstly, the paper discusses film translation from the perspective of the West and critically reviews the achievements produced by western researchers. Secondly, the paper analyzes film translation from Chinese perspective and outlines its change and development in Mainland China. Thirdly, some major issues exited in film translation such as cultural p...

Hepatitis C virus translation preferentially depends on active RNA replication.

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Helene Minyi Liu

Full Text Available Hepatitis C virus (HCV RNA initiates its replication on a detergent-resistant membrane structure derived from the endoplasmic reticulum (ER in the HCV replicon cells. By performing a pulse-chase study of BrU-labeled HCV RNA, we found that the newly-synthesized HCV RNA traveled along the anterograde-membrane traffic and moved away from the ER. Presumably, the RNA moved to the site of translation or virion assembly in the later steps of viral life cycle. In this study, we further addressed how HCV RNA translation was regulated by HCV RNA trafficking. When the movement of HCV RNA from the site of RNA synthesis to the Golgi complex was blocked by nocodazole, an inhibitor of ER-Golgi transport, HCV protein translation was surprisingly enhanced, suggesting that the translation of viral proteins occurred near the site of RNA synthesis. We also found that the translation of HCV proteins was dependent on active RNA synthesis: inhibition of viral RNA synthesis by an NS5B inhibitor resulted in decreased HCV viral protein synthesis even when the total amount of intracellular HCV RNA remained unchanged. Furthermore, the translation activity of the replication-defective HCV replicons or viral RNA with an NS5B mutation was greatly reduced as compared to that of the corresponding wildtype RNA. By performing live cell labeling of newly synthesized HCV RNA and proteins, we further showed that the newly synthesized HCV proteins colocalized with the newly synthesized viral RNA, suggesting that HCV RNA replication and protein translation take place at or near the same site. Our findings together indicate that the translation of HCV RNA is coupled to RNA replication and that the both processes may occur at the same subcellular membrane compartments, which we term the replicasome.

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

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Leppek, Kathrin; Das, Rhiju; Barna, Maria

2017-01-01

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

TRANSLATING BLACKNESS: A CHALLENGE TO TRANSLATION STUDIES IN CONTEMPORANEITY

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Maria Aparecida Andrade Salgueiro

2014-07-01

Full Text Available The present article presents aspects of a work in progress about both African-American and Afro-Brazilian Literatures as well as Translation Studies. As it makes observations about how blackness has been translated in different contexts and geographical spaces, it calls the reader’s attention to power relations, processes of colonial and post-colonial identity construction, the rising of literary canons, cultural hegemony and globalization, demystifying spaces and showing translation as an activity that does not take place in a neutral space, but, for sure, inside social and political concrete situations.

Word reading and translation in bilinguals: The impact of formal and informal translation expertise

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Adolfo M. García

2014-11-01

Full Text Available Studies on bilingual word reading and translation have examined the effects of lexical variables (e.g., concreteness, cognate status by comparing groups of non-translators with varying levels of L2 proficiency. However, little attention has been paid to another relevant factor: translation expertise (TI. To explore this issue, we administered word reading and translation tasks to two groups of non-translators possessing different levels of informal TI (Experiment 1, and to three groups of bilinguals possessing different levels of translation training (Experiment 2. Reaction-time recordings showed that in all groups reading was faster than translation and unaffected by concreteness and cognate effects. Conversely, in both experiments, all groups translated concrete and cognate words faster than abstract and non-cognate words, respectively. Notably, an advantage of backward over forward translation was observed only for low-proficiency non-translators (in Experiment 1. Also, in Experiment 2, the modifications induced by translation expertise were more marked in the early than in the late stages of training and practice. The results suggest that TI contributes to modulating inter-equivalent connections in bilingual memory.

What is a translator?

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Martha Pulido

2016-08-01

Full Text Available I copied the title from Foucault’s text, "Qu'est-ce qu'un auteur" in Dits et écrits [1969], Paris, Gallimard, 1994, that I read in French, then in English in Donald F. Bouchard’s and Sherry Simon’s translation, and finally in Spanish in Yturbe Corina’s translation, and applied for the translator some of the analysis that Foucault presents to define the author. Foucault suggests that if we cannot define an author, at least we can see where their function is reflected. My purpose in this paper is to present those surfaces where the function of the translator is reflected or where it can be revealed, and to analyse the categories that could lead us to the elaboration of a suitable definition of a Translator. I dare already give a compound noun for the translator: Translator-Function.

What is a translator?

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Martha Martha Pulido

2016-05-01

Full Text Available I copied the title from Foucault’s text, "Qu'est-ce qu'un auteur" in Dits et écrits [1969], Paris, Gallimard, 1994, that I read in French, then in English in Donald F. Bouchard’s and Sherry Simon’s translation, and finally in Spanish in Yturbe Corina’s translation, and applied for the translator some of the analysis that Foucault presents to define the author. Foucault suggests that if we cannot define an author, at least we can see where their function is reflected. My purpose in this paper is to present those surfaces where the function of the translator is reflected or where it can be revealed, and to analyse the categories that could lead us to the elaboration of a suitable definition of a Translator. I dare already give a compound noun for the translator: Translator-Function.

Using corpora in scientific and technical translation training: resources to identify conventionality and promote creativity

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Clara Inés López-Rodríguez

2016-04-01

Full Text Available http://dx.doi.org/10.5007/2175-7968.2016v36nesp1p88 Since the first Corpus Use and Learning to Translate (CULT Conference in Bertinoro (Italy in 1997, the usefulness of corpora for translators and trainee translators has been highlighted. From an initial approach where translators compiled ad hoc corpora in their hard drive for a subsequent study with lexical analysis software, there emerged a new trend towards the use of the Internet as corpus. In this second approach, the Web is perceived as a huge corpus which is accessed by means of online tools which produce monolingual wordlists and concordances from texts available from the Internet or pre-existing corpora, or by means of bilingual or multilingual concordancers displaying aligned texts from international institutions' parallel corpora. Bilingual concordancers and translation memories are widely used by translators and trainee translators because of the immediate translation solutions they offer, but these tools can restrain creativity by offering conventional solutions and eliminating layout and multimodal elements in texts. The aim of this article is to describe the exploitation of quality corpora in a scientific and technical translation course, focusing on texts on health translated from English into Spanish, and on terminological variation as a reflection of creativity in language.

Learning by Translating: A Contrastive Methodology for ESP Learning and Translation

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Sara Laviosa

2015-11-01

Full Text Available Over the last few years applied linguists have explored the possibility of integrating the insights of second language acquisition theories, contrastive analysis, foreign language teaching methodologies, and translation studies with a view to enhancing current communicative models and techniques for L2 teaching and translator training (see for example Sewell and Higgins 1996; Laviosa-Braithwaite 1997; Campbell 1998; Malmkjær 1998; Laviosa 2000; Colina 2002. We intend to make a contribution to this interdisciplinary orientation by putting forward a translation-based methodology for learning ESP vocabulary and grammar through real life mediating communicative activities. With particular reference to the translation task itself, we endeavour to provide teachers of English for special purposes and translator trainers with a methodology for guiding their students in producing, to the best of their abilities, a target text which meets the quality criteria of terminological accuracy and stylistic fluency, and is also effective in terms of the communicative situation it is intended for. After outlining the rationale and main theoretical approaches underpinning our work, we will illustrate our methodology for learning ESP vocabulary and translation skills from a contrastive perspective, as in our book Learning by Translating (Laviosa and Cleverton 2003.

Structural and Functional Diversity of Plant Virus 3′-Cap-Independent Translation Enhancers (3′-CITEs

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Verónica Truniger

2017-11-01

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

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

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

2017-01-01

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

Unique factors rural Veterans' Affairs hospitals face when implementing health care-associated infection prevention initiatives.

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Harrod, Molly; Manojlovich, Milisa; Kowalski, Christine P; Saint, Sanjay; Krein, Sarah L

2014-01-01

Health care-associated infection (HAI) is costly to hospitals and potentially life-threatening to patients. Numerous infection prevention programs have been implemented in hospitals across the United States. Yet, little is known about infection prevention practices and implementation in rural hospitals. The purpose of this study was to understand the infection prevention practices used by rural Veterans' Affairs (VA) hospitals and the unique factors they face in implementing these practices. This study used a sequential, mixed methods approach. Survey data to identify the HAI prevention practices used by rural VA hospitals were collected, analyzed, and used to inform the development of a semistructured interview guide. Phone interviews were conducted followed by site visits to rural VA hospitals. We found that most rural VA hospitals were using key recommended infection prevention practices. Nonetheless, a number of challenges with practice implementation were identified. The 3 most prominent themes were: (1) lack of human capital including staff with HAI expertise; (2) having to cultivate needed resources; and (3) operating as a system within a system. Rural VA hospitals are providing key infection prevention services to ensure a safe environment for the veterans they serve. However, certain factors, such as staff expertise, limited resources, and local context impacted how and when these practices were used. The creative use of more accessible alternative resources as well as greater flexibility in implementing HAI-related initiatives may be important strategies to further improve delivery of these important services by rural VA hospitals. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Translation and Intertextuality

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Mohammad Rahimi

2015-09-01

Full Text Available This study is intends to describe and Presents a new theory of translation based on the "Intertextuality" unlike the Translation theories that presented to date, what all are based on the principle of "Equivalence". Our theory is based on the examples of Arabic poetry translated into Persian poetry. The major findings of this study show that the Intertextuality can serve as a link between the original text and the target. it can also interact with other texts is the translation result in the target language, Whtich is the book of poetic eloquence is addressed and was mentioned Literary robbery.

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

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Jan Mani

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

Specific Increase of Protein Levels by Enhancing Translation Using Antisense Oligonucleotides Targeting Upstream Open Frames.

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Liang, Xue-Hai; Shen, Wen; Crooke, Stanley T

2017-01-01

A number of diseases are caused by low levels of key proteins; therefore, increasing the amount of specific proteins in human bodies is of therapeutic interest. Protein expression is downregulated by some structural or sequence elements present in the 5' UTR of mRNAs, such as upstream open reading frames (uORF). Translation initiation from uORF(s) reduces translation from the downstream primary ORF encoding the main protein product in the same mRNA, leading to a less efficient protein expression. Therefore, it is possible to use antisense oligonucleotides (ASOs) to specifically inhibit translation of the uORF by base-pairing with the uAUG region of the mRNA, redirecting translation machinery to initiate from the primary AUG site. Here we review the recent findings that translation of specific mRNAs can be enhanced using ASOs targeting uORF regions. Appropriately designed and optimized ASOs are highly specific, and they act in a sequence- and position-dependent manner, with very minor off-target effects. Protein levels can be increased using this approach in different types of human and mouse cells, and, importantly, also in mice. Since uORFs are present in around half of human mRNAs, the uORF-targeting ASOs may thus have valuable potential as research tools and as therapeutics to increase the levels of proteins for a variety of genes.

Sound Effects in Translation

DEFF Research Database (Denmark)

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

2013-01-01

On the basis of a pilot study using speech recognition (SR) software, this paper attempts to illustrate the benefits of adopting an interdisciplinary approach in translator training. It shows how the collaboration between phoneticians, translators and interpreters can (1) advance research, (2) have......), Translog was employed to measure task times. The quality of the products was assessed by three experienced translators, and the number and types of misrecognitions were identified by a phonetician. Results indicate that SR translation provides a potentially useful supplement to written translation...

Translation Training in the Jordanian Context: Curriculum Evaluation in Translator Education

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Mahasneh, Anjad

2013-01-01

This study aims at drawing a clear picture of translator training in Jordan through the evaluation of translation programs at the Master's level. The framework of the Context, Input, Process, and Product components of the CIPP evaluation model developed by Daniel Stufflebeam in 1971 was used to evaluate the three translation Master's programs at…

The Interface of Clinical Decision-Making With Study Protocols for Knowledge Translation From a Walking Recovery Trial.

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Hershberg, Julie A; Rose, Dorian K; Tilson, Julie K; Brutsch, Bettina; Correa, Anita; Gallichio, Joann; McLeod, Molly; Moore, Craig; Wu, Sam; Duncan, Pamela W; Behrman, Andrea L

2017-01-01

Despite efforts to translate knowledge into clinical practice, barriers often arise in adapting the strict protocols of a randomized, controlled trial (RCT) to the individual patient. The Locomotor Experience Applied Post-Stroke (LEAPS) RCT demonstrated equal effectiveness of 2 intervention protocols for walking recovery poststroke; both protocols were more effective than usual care physical therapy. The purpose of this article was to provide knowledge-translation tools to facilitate implementation of the LEAPS RCT protocols into clinical practice. Participants from 2 of the trial's intervention arms: (1) early Locomotor Training Program (LTP) and (2) Home Exercise Program (HEP) were chosen for case presentation. The two cases illustrate how the protocols are used in synergy with individual patient presentations and clinical expertise. Decision algorithms and guidelines for progression represent the interface between implementation of an RCT standardized intervention protocol and clinical decision-making. In each case, the participant presents with a distinct clinical challenge that the therapist addresses by integrating the participant's unique presentation with the therapist's expertise while maintaining fidelity to the LEAPS protocol. Both participants progressed through an increasingly challenging intervention despite their own unique presentation. Decision algorithms and exercise progression for the LTP and HEP protocols facilitate translation of the RCT protocol to the real world of clinical practice. The two case examples to facilitate translation of the LEAPS RCT into clinical practice by enhancing understanding of the protocols, their progression, and their application to individual participants.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A147).

Inhibition of Ribosome Recruitment Induces Stress Granule Formation Independently of Eukaryotic Initiation Factor 2α Phosphorylation

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

2006-01-01

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

Inhibition of ribosome recruitment induces stress granule formation independently of eukaryotic initiation factor 2alpha phosphorylation.

Science.gov (United States)

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

2006-10-01

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

Measuring Difficulty in English-Chinese Translation: Towards a General Model of Translation Difficulty

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Sun, Sanjun

2012-01-01

Accurate assessment of a text's level of translation difficulty is critical for translator training and accreditation, translation research, and the language industry as well. Traditionally, people rely on their general impression to gauge a text's translation difficulty level. If the evaluation process is to be more effective and the…

Translator-computer interaction in action

DEFF Research Database (Denmark)

Bundgaard, Kristine; Christensen, Tina Paulsen; Schjoldager, Anne

2016-01-01

perspective, this paper investigates the relationship between machines and humans in the field of translation, analysing a CAT process in which machine-translation (MT) technology was integrated into a translation-memory (TM) suite. After a review of empirical research into the impact of CAT tools......Though we lack empirically-based knowledge of the impact of computer-aided translation (CAT) tools on translation processes, it is generally agreed that all professional translators are now involved in some kind of translator-computer interaction (TCI), using O’Brien’s (2012) term. Taking a TCI......, the study indicates that the tool helps the translator conform to project and customer requirements....

Computer-aided translation tools

DEFF Research Database (Denmark)

Christensen, Tina Paulsen; Schjoldager, Anne

2016-01-01

in Denmark is rather high in general, but limited in the case of machine translation (MT) tools: While most TSPs use translation-memory (TM) software, often in combination with a terminology management system (TMS), only very few have implemented MT, which is criticised for its low quality output, especially......The paper reports on a questionnaire survey from 2013 of the uptake and use of computer-aided translation (CAT) tools by Danish translation service providers (TSPs) and discusses how these tools appear to have impacted on the Danish translation industry. According to our results, the uptake...

Modeling timelines for translational science in cancer; the impact of technological maturation.

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Laura M McNamee

Full Text Available This work examines translational science in cancer based on theories of innovation that posit a relationship between the maturation of technologies and their capacity to generate successful products. We examined the growth of technologies associated with 138 anticancer drugs using an analytical model that identifies the point of initiation of exponential growth and the point at which growth slows as the technology becomes established. Approval of targeted and biological products corresponded with technological maturation, with first approval averaging 14 years after the established point and 44 years after initiation of associated technologies. The lag in cancer drug approvals after the increases in cancer funding and dramatic scientific advances of the 1970s thus reflects predictable timelines of technology maturation. Analytical models of technological maturation may be used for technological forecasting to guide more efficient translation of scientific discoveries into cures.

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 role of PKA in the translational response to heat stress in Saccharomyces cerevisiae.

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Carla E Barraza

Full Text Available Cellular responses to stress stem from a variety of different mechanisms, including translation arrest and relocation of the translationally repressed mRNAs to ribonucleoprotein particles like stress granules (SGs and processing bodies (PBs. Here, we examine the role of PKA in the S. cerevisiae heat shock response. Under mild heat stress Tpk3 aggregates and promotes aggregation of eIF4G, Pab1 and eIF4E, whereas severe heat stress leads to the formation of PBs and SGs that contain both Tpk2 and Tpk3 and a larger 48S translation initiation complex. Deletion of TPK2 or TPK3 impacts upon the translational response to heat stress of several mRNAs including CYC1, HSP42, HSP30 and ENO2. TPK2 deletion leads to a robust translational arrest, an increase in SGs/PBs aggregation and translational hypersensitivity to heat stress, whereas TPK3 deletion represses SGs/PBs formation, translational arrest and response for the analyzed mRNAs. Therefore, this work provides evidence indicating that Tpk2 and Tpk3 have opposing roles in translational adaptation during heat stress, and highlight how the same signaling pathway can be regulated to generate strikingly distinct physiological outputs.

Translation goes to the movies

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Cronin, Michael

2008-01-01

This highly accessible introduction to translation theory, written by a leading author in the field, uses the genre of film to bring the main themes in translation to life. Through analyzing films as diverse as the Marx Brothers' A Night at the Opera, The Star Wars Trilogies and Lost in Translation, the reader is encouraged to think about both issues and problems of translation as they are played out on the screen and issues of filmic representation through examining the translation dimension of specific films. In highlighting how translation has featured in both mainstream commercial and arthouse films over the years, Cronin shows how translation has been a concern of filmmakers dealing with questions of culture, identity, conflict and representation. This book is a lively and accessible text for translation theory courses and offers a new and largely unexplored approach to topics of identity and representation on screen. Translation Goes to the Movies will be of interest to those on translation studies...

Clinical translation of autologous cell-based tissue engineering techniques as Class III therapeutics in China: Taking cartilage tissue engineering as an example

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Wei Zhang

2014-04-01

Full Text Available Autologous cell-based tissue engineering (TE techniques have been clinically approved for approximately 4 years in China, since the first cartilage TE technique was approved for clinical use by the Zhejiang Health Bureau. TE techniques offer a promising alternative to traditional transplantation surgery, and are different from those for transplanted tissues (biologics or pharmaceutical, the clinical translational procedures are unique and multitasked, and the requirements may differ from those of the target tissues. Thus, the translational procedure is still unfamiliar to most researchers and needs further improvement. This perspectives paper describes the key guidelines and regulations involved in the current translational process, and shares our translational experiences in cartilage TE to provide an example of autologous cell-based TE translation in China. Finally, we discuss the scientific and social challenges and provide some suggestions for future improvements.

Mutation of a Nicotiana tabacum L. eukaryotic translation-initiation factor gene reduces susceptibility to a resistance-breaking strain of Potato Virus Y.

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Takakura, Yoshimitsu; Udagawa, Hisashi; Shinjo, Akira; Koga, Kazuharu

2018-04-06

Eukaryotic translation-initiation factors eIF4E and eIF(iso)4E in plants play key roles in infection by potyviruses and other plant RNA viruses. Mutations in the genes encoding these factors reduce susceptibility to the viruses, and are the basis of several recessive virus-resistance genes widely used in plant breeding. Because virus variants occasionally break such resistance, the molecular basis for this process must be elucidated. Although deletion mutants of eIF4E1-S of tobacco (Nicotiana tabacum L.) resist Potato virus Y (PVY; the type member of the genus Potyvirus), resistance-breaking strains of PVY threaten tobacco production worldwide. Here, we used RNA interference technology to knock down tobacco eIF4E2-S and eIF4E2-T genes or eIF(iso)4E-S and eIF(iso)4E-T genes. Transgenic plants with reduced transcript levels of both eIF(iso)4E-S and eIF(iso)4E-T showed reduced susceptibility to a resistance-breaking PVY strain with a K105E mutation in the viral genome-associated protein (VPg). By screening a population of chemically-induced mutants of eIF(iso)4E-S and eIF(iso)4E-T, we showed that plants with a nonsense mutation in eIF(iso)4E-T, but not eIF(iso)4E-S, showed reduced susceptibility to the resistance-breaking PVY strain. In a yeast two-hybrid assay, VPg of the resistance-breaking strain, but not wild-type PVY, physically interacted with the eIF(iso)4E-T protein. Thus, eIF4E1-S is required for infection by PVY, but eIF(iso)4E-T is required for infection by the resistance-breaking strain. Our study provides the first evidence for the involvement of a host eukaryotic translation-initiation factor in the infection cycle of a resistance-breaking virus strain. The eIF(iso)4E-T mutants will be useful in tobacco breeding to introduce resistance against resistance-breaking PVY strains. This article is protected by copyright. All rights reserved. © 2018 BSPP and John Wiley & Sons Ltd.

Signals Involved in Regulation of Hepatitis C Virus RNA Genome Translation and Replication

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Michael Niepmann

2018-03-01

Full Text Available Hepatitis C virus (HCV preferentially replicates in the human liver and frequently causes chronic infection, often leading to cirrhosis and liver cancer. HCV is an enveloped virus classified in the genus Hepacivirus in the family Flaviviridae and has a single-stranded RNA genome of positive orientation. The HCV RNA genome is translated and replicated in the cytoplasm. Translation is controlled by the Internal Ribosome Entry Site (IRES in the 5′ untranslated region (5′ UTR, while also downstream elements like the cis-replication element (CRE in the coding region and the 3′ UTR are involved in translation regulation. The cis-elements controlling replication of the viral RNA genome are located mainly in the 5′- and 3′-UTRs at the genome ends but also in the protein coding region, and in part these signals overlap with the signals controlling RNA translation. Many long-range RNA–RNA interactions (LRIs are predicted between different regions of the HCV RNA genome, and several such LRIs are actually involved in HCV translation and replication regulation. A number of RNA cis-elements recruit cellular RNA-binding proteins that are involved in the regulation of HCV translation and replication. In addition, the liver-specific microRNA-122 (miR-122 binds to two target sites at the 5′ end of the viral RNA genome as well as to at least three additional target sites in the coding region and the 3′ UTR. It is involved in the regulation of HCV RNA stability, translation and replication, thereby largely contributing to the hepatotropism of HCV. However, we are still far from completely understanding all interactions that regulate HCV RNA genome translation, stability, replication and encapsidation. In particular, many conclusions on the function of cis-elements in HCV replication have been obtained using full-length HCV genomes or near-full-length replicon systems. These include both genome ends, making it difficult to decide if a cis-element in

Signals Involved in Regulation of Hepatitis C Virus RNA Genome Translation and Replication.

Science.gov (United States)

Niepmann, Michael; Shalamova, Lyudmila A; Gerresheim, Gesche K; Rossbach, Oliver

2018-01-01

Hepatitis C virus (HCV) preferentially replicates in the human liver and frequently causes chronic infection, often leading to cirrhosis and liver cancer. HCV is an enveloped virus classified in the genus Hepacivirus in the family Flaviviridae and has a single-stranded RNA genome of positive orientation. The HCV RNA genome is translated and replicated in the cytoplasm. Translation is controlled by the Internal Ribosome Entry Site (IRES) in the 5' untranslated region (5' UTR), while also downstream elements like the cis -replication element (CRE) in the coding region and the 3' UTR are involved in translation regulation. The cis -elements controlling replication of the viral RNA genome are located mainly in the 5'- and 3'-UTRs at the genome ends but also in the protein coding region, and in part these signals overlap with the signals controlling RNA translation. Many long-range RNA-RNA interactions (LRIs) are predicted between different regions of the HCV RNA genome, and several such LRIs are actually involved in HCV translation and replication regulation. A number of RNA cis -elements recruit cellular RNA-binding proteins that are involved in the regulation of HCV translation and replication. In addition, the liver-specific microRNA-122 (miR-122) binds to two target sites at the 5' end of the viral RNA genome as well as to at least three additional target sites in the coding region and the 3' UTR. It is involved in the regulation of HCV RNA stability, translation and replication, thereby largely contributing to the hepatotropism of HCV. However, we are still far from completely understanding all interactions that regulate HCV RNA genome translation, stability, replication and encapsidation. In particular, many conclusions on the function of cis -elements in HCV replication have been obtained using full-length HCV genomes or near-full-length replicon systems. These include both genome ends, making it difficult to decide if a cis -element in question acts on HCV

Nat1 promotes translation of specific proteins that induce differentiation of mouse embryonic stem cells.

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

2017-01-10

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

Translation and adaptation of the Competencias Esenciales en Salud Pública para los recursos humanos en salud 1

Science.gov (United States)

de Almeida, Maria de Lourdes; Peres, Aida Maris; Ferreira, Maria Manuela Frederico; Mantovani, Maria de Fátima

2017-01-01

ABSTRACT Objective: to perform the translation and cultural adaptation of the document named Marco Regional de Competencias Esenciales en Salud Pública para los Recursos Humanos en Salud de la Región de las Américas (Regional Framework of Core Competencies in Public Health for Health Human Resources in the Region of Americas) from Spanish to Brazilian Portuguese. Method: a methodological study comprising the following phases: authorization for translation; initial translation; synthesis of translations and consensus; back-translation and formation of an expert committee. Result: in the translation of domain names, there was no difference in 66.7% (N = 4); in the translation of domain description and competencies there were divergences in 100% of them (N = 6, N = 56). A consensus of more than 80% was obtained in the translation and improvement in the expert committee by the change of words and expressions for approximation of meanings to the Brazilian context. Conclusion: the translated and adapted document has the potential of application in research, and use in the practice of collective/public health care in Brazil. PMID:28591302

Jungmann's translation of Paradise Lost

OpenAIRE

Janů, Karel

2014-01-01

This thesis examines Josef Jungmann's translation of John Milton's Paradise Lost. Josef Jungmann was one of the leading figures of the Czech National Revival and translated Milton 's poem between the years 1800 and 1804. The thesis covers Jungmann's theoretical model of translation and presents Jungmann's motives for translation of Milton's epic poem. The paper also describes the aims Jungmann had with his translation and whether he has achieved them. The reception Jungmann's translation rece...