Dabeva, Mariana D.; Post-Beittenmiller, Martha A.; Warner, Jonathan R.
The gene for a yeast ribosomal protein, RPL32, contains a single intron. The product of this gene appears to participate in feedback control of the splicing of the intron from the transcript. This autogenous regulation of splicing provides a striking analogy to the autogenous regulation of translation of ribosomal proteins in Escherichia coli.
Literal translation and liberal translation are two important methods and both play key roles in translation.However,some textbooks say that most translations are literal translations while others maintain most are liberal ones,besides,some others suggest a combination of the two.This paper focuses on the facts that regulate liberal translation.Because of the differences in culture,society,history,geography,and so on,there exists a great difference between Chinese language and English language,which does naturally lead to the liberal translation.
Hera, A; Bures, J
Autogenous vaccines remain a regulatory issue. They are demanded by practising veterinarians and by animal owners and they are quite widely used, mainly in Central European Countries, the Czech Republic, Hungary and Slovak Republic having probably the longest tradition with these products in Central Europe. The scope given in Article 3, Para. 2 (and/or Article 4 for some countries) of Directive 2001/82/EC applies to these products in the Acceding Countries. As these products are exempt from the harmonised regulation at the EU level, they are regulated by individual countries, the regulation varying from practically no regulatory measures in certain countries to a quite complex and demanding regulation in the other countries. Both risks and benefits are related to these products and they shall be taken into account when regulatory measures are considered. The major risks related to veterinary autogenous vaccines relate to possibility of transmission of TSE agents or other viral, bacterial and/or fungal contaminants. As appropriate and well balanced regulation of these products is deemed necessary, considering the risks related to these products, and based on the fact that national regulatory measures could be considered as a trade barrier under certain circumstances, harmonisation of the key issues or legal admission of the nationally based regulatory measures, including movement of these products from the other Member States, shall be laid down in the EU legislation. The veterinary autogenous vaccines complying with basic quality and safety requirements are thus a very useful tool in the animal health and welfare management but their use should be restricted to situations where there is no authorised veterinary medicinal product available and veterinary autogenous vaccines must not be allowed to replace good farming or veterinary practices.
Full Text Available Recent analyses indicate that differences in protein concentrations are only 20%-40% attributable to variable mRNA levels, underlining the importance of posttranscriptional regulation. Generally, protein concentrations depend on the translation rate (which is proportional to the translational activity, TA and the degradation rate. By integrating 12 publicly available large-scale datasets and additional database information of the yeast Saccharomyces cerevisiae, we systematically analyzed five factors contributing to TA: mRNA concentration, ribosome density, ribosome occupancy, the codon adaptation index, and a newly developed "tRNA adaptation index." Our analysis of the functional relationship between the TA and measured protein concentrations suggests that the TA follows Michaelis-Menten kinetics. The calculated TA, together with measured protein concentrations, allowed us to estimate degradation rates for 4,125 proteins under standard conditions. A significant correlation to recently published degradation rates supports our approach. Moreover, based on a newly developed scoring system, we identified and analyzed genes subjected to the posttranscriptional regulation mechanism, translation on demand. Next we applied these findings to publicly available data of protein and mRNA concentrations under four stress conditions. The integration of these measurements allowed us to compare the condition-specific responses at the posttranscriptional level. Our analysis of all 62 proteins that have been measured under all four conditions revealed proteins with very specific posttranscriptional stress response, in contrast to more generic responders, which were nonspecifically regulated under several conditions. The concept of specific and generic responders is known for transcriptional regulation. Here we show that it also holds true at the posttranscriptional level.
Tanenbaum, Marvin E; Stern-Ginossar, Noam; Weissman, Jonathan S; Vale, Ronald D
Passage through mitosis is driven by precisely-timed changes in transcriptional regulation and protein degradation. However, the importance of translational regulation during mitosis remains poorly understood. Here, using ribosome profiling, we find both a global translational repression and identified ~200 mRNAs that undergo specific translational regulation at mitotic entry. In contrast, few changes in mRNA abundance are observed, indicating that regulation of translation is the primary mechanism of modulating protein expression during mitosis. Interestingly, 91% of the mRNAs that undergo gene-specific regulation in mitosis are translationally repressed, rather than activated. One of the most pronounced translationally-repressed genes is Emi1, an inhibitor of the anaphase promoting complex (APC) which is degraded during mitosis. We show that full APC activation requires translational repression of Emi1 in addition to its degradation. These results identify gene-specific translational repression as a means of controlling the mitotic proteome, which may complement post-translational mechanisms for inactivating protein function.
Waite, Christopher; Schumacher, Jörg; Jovanovic, Milija; Bennett, Mark
ABSTRACT The type III secretion system (T3SS) is a principal virulence determinant of the model bacterial plant pathogen Pseudomonas syringae. T3SS effector proteins inhibit plant defense signaling pathways in susceptible hosts and elicit evolved immunity in resistant plants. The extracytoplasmic function sigma factor HrpL coordinates the expression of most T3SS genes. Transcription of hrpL is dependent on sigma-54 and the codependent enhancer binding proteins HrpR and HrpS for hrpL promoter activation. hrpL is oriented adjacently to and divergently from the HrpL-dependent gene hrpJ, sharing an intergenic upstream regulatory region. We show that association of the RNA polymerase (RNAP)-HrpL complex with the hrpJ promoter element imposes negative autogenous control on hrpL transcription in P. syringae pv. tomato DC3000. The hrpL promoter was upregulated in a ΔhrpL mutant and was repressed by plasmid-borne hrpL. In a minimal Escherichia coli background, the activity of HrpL was sufficient to achieve repression of reconstituted hrpL transcription. This repression was relieved if both the HrpL DNA-binding function and the hrp-box sequence of the hrpJ promoter were compromised, implying dependence upon the hrpJ promoter. DNA-bound RNAP-HrpL entirely occluded the HrpRS and partially occluded the integration host factor (IHF) recognition elements of the hrpL promoter in vitro, implicating inhibition of DNA binding by these factors as a cause of negative autogenous control. A modest increase in the HrpL concentration caused hypersecretion of the HrpA1 pilus protein but intracellular accumulation of later T3SS substrates. We argue that negative feedback on HrpL activity fine-tunes expression of the T3SS regulon to minimize the elicitation of plant defenses. PMID:28119474
Wilson, Daniel N; Arenz, Stefan; Beckmann, Roland
As the nascent polypeptide chain is being synthesized, it passes through a tunnel within the large ribosomal subunit. Interaction between the nascent polypeptide chain and the ribosomal tunnel can modulate the translation rate and induce translational stalling to regulate gene expression. In this article, we highlight recent structural insights into how the nascent polypeptide chain, either alone or in cooperation with co-factors, can interact with components of the ribosomal tunnel to regulate translation via inactivating the peptidyltransferase center of the ribosome and inducing ribosome stalling.
Ana B. Castro-Sanz
Full Text Available Plants have developed versatile strategies to deal with the great variety of challenging conditions they are exposed to. Among them, the regulation of translation is a common target to finely modulate gene expression both under biotic and abiotic stress situations. Upon environmental challenges, translation is regulated to reduce the consumption of energy and to selectively synthesize proteins involved in the proper establishment of the tolerance response. In the case of viral infections, the situation is more complex, as viruses have evolved unconventional mechanisms to regulate translation in order to ensure the production of the viral encoded proteins using the plant machinery. Although the final purpose is different, in some cases, both plants and viruses share common mechanisms to modulate translation. In others, the mechanisms leading to the control of translation are viral- or stress-specific. In this paper, we review the different mechanisms involved in the regulation of translation initiation under virus infection and under environmental stress in plants. In addition, we describe the main features within the viral RNAs and the cellular mRNAs that promote their selective translation in plants undergoing biotic and abiotic stress situations.
Qi Xie; Jing Chen; Zengqiang Yuan
The Forkhead box O (FOXO) family transcription factors play critical roles in a series of cellular processes,including the cell cycle,cell death,metabolism,and oxidative stress resistance.FOXO proteins are subject to several posttranslational modifications,which are closely related to their activity.In this paper,we review the post-translational modifications of FOXOs and their biological functions.
Dai, Yanfeng; Newman, Barbara; Moor, Robert
The temporal and spatial translation control of stored mRNA in oocytes is regulated by elements in their 3'-untranslated region (3'-UTR). The MOS 3'-UTR in pig oocytes is both heterogeneous (180, 480, or 530 nucleotides), and it contains multiple U-rich elements and extensive A-rich sequences (CA13CA5CA5CA6). We have examined the role of these potential regulatory elements by fusing wild-type or mutant MOS 3'-UTRs to luciferase mRNA and then injecting these chimeric transcripts into oocytes. We draw six main conclusions. First, the length of the MOS 3'-UTR tightly controls the level of translation of luciferase during oocyte maturation. Second, two U-rich (U5A) elements and the hexanucleotide signal (AAUAAA) are required for translation. Third, mutations, duplications, or relocations of the A-rich sequence reduce or block translation. Fourth, the relative importance of the A-rich and U-rich elements in controlling the level of translation differs. Fifth, none of our MOS 3'-UTR manipulations relieved translational repression before germinal vesicle breakdown. Sixth, all the MOS mRNA variants underwent polyadenylation during maturation. Whereas mutations to the hexanucleotide signal block both polyadenylation and translation, mutations to either the A-rich sequence or the U-rich elements block translation without fully blocking polyadenylation. We conclude that MOS mRNA translation in pig oocytes is subject to a more extensive series of controls than that in lower vertebrates.
Full Text Available Light, a dynamic environmental parameter, is an essential regulator of plant growth and development. Light-regulated transcriptional networks are well documented, whereas light-regulated post-transcriptional regulation has received only limited attention. In this study, dynamics in translation of cytosolic mRNAs were evaluated at the genome-level in Arabidopsis thaliana seedlings grown under a typical light / dark diurnal regime, shifted to darkness at midday and then re-illuminated. One-hour of unanticipated darkness reduced levels of polyribosomes (polysomes by 17% in a manner consistent with inhibition of initiation of translation. This down-regulation of protein synthesis was reversed within 10 minutes of re-illumination. Quantitative comparison of the total cellular population of transcripts (the transcriptome to those associated with one or more 80S ribosome (the translatome identified over 1600 mRNAs that are differentially translated in response to light availability. Unanticipated darkness limited transcription and translation of mRNAs encoding components of the photosynthetic machinery. Many mRNAs encoding proteins associated with the energy demanding process of protein synthesis were stable but sequestered in the dark, in a rapidly reversible manner. A meta-analysis determined these same transcripts were similarly and coordinately regulated in response to changes in oxygen availability. The dark and hypoxia translationally repressed mRNAs lack highly supported candidate RNA-regulatory elements but are characterized by G+C-rich 5’-untranslated regions. We propose that dynamic regulation of the translational status of a subset of cellular mRNAs serves as a general energy conservation mechanism.
Douzou, P; Maurel, P
The polyelectrolyte theory can provide an interpretation of the interdependence of pH, ionic strength, and polyamines one observes in the activity of ribonuclease acting on RNA. According to this theory: (i) A nucleic acid-enzyme complex and the suspending medium may be considered as two phases in equilibrium, even though within limits, the complex is soluble in water. (ii) The enzymatic catalysis is under tight control of the electrostatic potential generated by the system. Consequently, modification in electrostatic potential will induce a concomitant change in activity. (iii) The electrostatic potential can be modified through action on the system of "modulators", either "external" (ionic strength, pH, temperature, etc.) or "internal" (specific ligands, substrates, protein factors, etc.). Similarities between the reaction of ribonuclease (ribonuclease 3'-pyrimidino-oligonucleotidohydrolase; EC 126.96.36.199) and RNA and those observed with highly organized systems catalyzing DNA, RNA, and protein synthesis suggest that the electrostatic potential also provides an important regulatory mechanism in genetic translation. In this view, an essential function of nucleic acids is to provide their enzyme partners with polyanionic microenvironments within which their catalytic activities are controlled by variation in physicochemical parameters, including the proton concentration induced through "modulation" of the local electrostatic potential.
Autogenous deformation of concrete can be defined as the free deformation of sealed concrete at a constant temperature. A number of observed problems with early age cracking of high-performance concretes can be attributed to this phenomenon. During the last 10 years , this has led to an increased...... focus on autogenous deformation both within concrete practice and concrete research. Since 1996 the interest has been significant enough to hold international, yearly conferences entirely devoted to this subject. The papers in this publication were presented at two consecutive half-day sessions...... at the American Concrete Institute’s Fall Convention in Phoenix, Arizona, October 29, 2002. All papers have been reviewed according to ACI rules. This publication, as well as the sessions, was sponsored by ACI committee 236, Material Science of Concrete. The 12 presentations from 8 different countries indicate...
Amruthraj, Brunda; Mishra, H.; Kumaraiah, V.
SUMMARY Ten subjects diagnosed as Psychalgia were taken for study. A multiple baseline design was adapted and clients were subjected to 30 sessions of autogenic training. They were assessed using physiological (EMG and thermal change) and behavioural measures (Visual analogue scale and behavioural symptom checklist). Findings revealed autogenic therapy to be effective in reducing tension headache.
Werner, Achim; Iwasaki, Shintaro; McGourty, Colleen; Medina-Ruiz, Sofia; Teerikorpi, Nia; Fedrigo, Indro; Ingolia, Nicholas T.; Rape, Michael
Metazoan development depends on accurate execution of differentiation programs that allow pluripotent stem cells to adopt specific fates 1. Differentiation requires changes to chromatin architecture and transcriptional networks, yet whether other regulatory events support cell fate determination is less well understood. Here, we have identified the vertebrate-specific ubiquitin ligase CUL3KBTBD8 as an essential regulator of neural crest specification. CUL3KBTBD8 monoubiquitylates NOLC1 and its paralog TCOF1, whose mutation underlies the neurocristopathy Treacher Collins Syndrome 2,3. Ubiquitylation drives formation of a TCOF1-NOLC1 platform that connects RNA polymerase I with ribosome modification enzymes and remodels the translational program of differentiating cells in favor of neural crest specification. We conclude that ubiquitin-dependent regulation of translation is an important feature of cell fate determination. PMID:26399832
Zarai, Yoram; Margaliot, Michael; Tuller, Tamir
Down regulation of mRNA translation is an important problem in various bio-medical domains ranging from developing effective medicines for tumors and for viral diseases to developing attenuated virus strains that can be used for vaccination. Here, we study the problem of down regulation of mRNA translation using a mathematical model called the ribosome flow model (RFM). In the RFM, the mRNA molecule is modeled as a chain of n sites. The flow of ribosomes between consecutive sites is regulated by n + 1 transition rates. Given a set of feasible transition rates, that models the outcome of all possible mutations, we consider the problem of maximally down regulating protein production by altering the rates within this set of feasible rates. Under certain conditions on the feasible set, we show that an optimal solution can be determined efficiently. We also rigorously analyze two special cases of the down regulation optimization problem. Our results suggest that one must focus on the position along the mRNA molecule where the transition rate has the strongest effect on the protein production rate. However, this rate is not necessarily the slowest transition rate along the mRNA molecule. We discuss some of the biological implications of these results. PMID:28120903
Zarai, Yoram; Margaliot, Michael; Tuller, Tamir
Down regulation of mRNA translation is an important problem in various bio-medical domains ranging from developing effective medicines for tumors and for viral diseases to developing attenuated virus strains that can be used for vaccination. Here, we study the problem of down regulation of mRNA translation using a mathematical model called the ribosome flow model (RFM). In the RFM, the mRNA molecule is modeled as a chain of n sites. The flow of ribosomes between consecutive sites is regulated by n + 1 transition rates. Given a set of feasible transition rates, that models the outcome of all possible mutations, we consider the problem of maximally down regulating protein production by altering the rates within this set of feasible rates. Under certain conditions on the feasible set, we show that an optimal solution can be determined efficiently. We also rigorously analyze two special cases of the down regulation optimization problem. Our results suggest that one must focus on the position along the mRNA molecule where the transition rate has the strongest effect on the protein production rate. However, this rate is not necessarily the slowest transition rate along the mRNA molecule. We discuss some of the biological implications of these results.
Satpathy, Shankha; Nabbi, Arash; Riabowol, Karl
The five human ING genes encode at least 15 splicing isoforms, most of which affect cell growth, differentiation and apoptosis through their ability to alter gene expression by epigenetic mechanisms. Since their discovery in 1996, ING proteins have been classified as type II tumour suppressors on the basis of reports describing their down-regulation and mislocalization in a variety of cancer types. In addition to their regulation by transcriptional mechanisms, understanding the range of PTMs (post-translational modifications) of INGs is important in understanding how ING functions are fine-tuned in the physiological setting and how they add to the repertoire of activities affected by the INGs. In the present paper we review the different PTMs that have been reported to occur on INGs. We discuss the PTMs that modulate ING function under normal conditions and in response to a variety of stresses. We also describe the ING PTMs that have been identified by several unbiased MS-based PTM enrichment techniques and subsequent proteomic analysis. Among the ING PTMs identified to date, a subset has been characterized for their biological significance and have been shown to affect processes including subcellular localization, interaction with enzymatic complexes and ING protein half-life. The present review aims to highlight the emerging role of PTMs in regulating ING function and to suggest additional pathways and functions where PTMs may effect ING function.
Full Text Available Recent studies have demonstrated the importance of local protein synthesis for neuronal plasticity. In particular, local mRNA translation through the mammalian target of rapamycin (mTOR has been shown to play a key role in regulating dendrite excitability and modulating long-term synaptic plasticity associated with learning and memory. There is also increased evidence to suggest that intact adult mammalian axons have a functional requirement for local protein synthesis in vivo. Here we show that the translational machinery is present in some myelinated sensory fibers and that active mTOR-dependent pathways participate in maintaining the sensitivity of a subpopulation of fast-conducting nociceptors in vivo. Phosphorylated mTOR together with other downstream components of the translational machinery were localized to a subset of myelinated sensory fibers in rat cutaneous tissue. We then showed with electromyographic studies that the mTOR inhibitor rapamycin reduced the sensitivity of a population of myelinated nociceptors known to be important for the increased mechanical sensitivity that follows injury. Behavioural studies confirmed that local treatment with rapamycin significantly attenuated persistent pain that follows tissue injury, but not acute pain. Specifically, we found that rapamycin blunted the heightened response to mechanical stimulation that develops around a site of injury and reduced the long-term mechanical hypersensitivity that follows partial peripheral nerve damage--a widely used model of chronic pain. Our results show that the sensitivity of a subset of sensory fibers is maintained by ongoing mTOR-mediated local protein synthesis and uncover a novel target for the control of long-term pain states.
Full Text Available Abstract Background In bacteria, the weak correlations at the genome scale between mRNA and protein levels suggest that not all mRNAs are translated with the same efficiency. To experimentally explore mRNA translational level regulation at the systemic level, the detailed translational status (translatome of all mRNAs was measured in the model bacterium Lactococcus lactis in exponential phase growth. Results Results demonstrated that only part of the entire population of each mRNA species was engaged in translation. For transcripts involved in translation, the polysome size reached a maximum of 18 ribosomes. The fraction of mRNA engaged in translation (ribosome occupancy and ribosome density were not constant for all genes. This high degree of variability was analyzed by bioinformatics and statistical modeling in order to identify general rules of translational regulation. For most of the genes, the ribosome density was lower than the maximum value revealing major control of translation by initiation. Gene function was a major translational regulatory determinant. Both ribosome occupancy and ribosome density were particularly high for transcriptional regulators, demonstrating the positive role of translational regulation in the coordination of transcriptional networks. mRNA stability was a negative regulatory factor of ribosome occupancy and ribosome density, suggesting antagonistic regulation of translation and mRNA stability. Furthermore, ribosome occupancy was identified as a key component of intracellular protein levels underlining the importance of translational regulation. Conclusions We have determined, for the first time in a bacterium, the detailed translational status for all mRNAs present in the cell. We have demonstrated experimentally the high diversity of translational states allowing individual gene differentiation and the importance of translation-level regulation in the complex process linking gene expression to protein
Chen, Jin; Choi, Junhong; O'Leary, Seán E; Prabhakar, Arjun; Petrov, Alexey; Grosely, Rosslyn; Puglisi, Elisabetta Viani; Puglisi, Joseph D
Translation of proteins by the ribosome regulates gene expression, with recent results underscoring the importance of translational control. Misregulation of translation underlies many diseases, including cancer and many genetic diseases. Decades of biochemical and structural studies have delineated many of the mechanistic details in prokaryotic translation, and sketched the outlines of eukaryotic translation. However, translation may not proceed linearly through a single mechanistic pathway, but likely involves multiple pathways and branchpoints. The stochastic nature of biological processes would allow different pathways to occur during translation that are biased by the interaction of the ribosome with other translation factors, with many of the steps kinetically controlled. These multiple pathways and branchpoints are potential regulatory nexus, allowing gene expression to be tuned at the translational level. As research focus shifts toward eukaryotic translation, certain themes will be echoed from studies on prokaryotic translation. This review provides a general overview of the dynamic data related to prokaryotic and eukaryotic translation, in particular recent findings with single-molecule methods, complemented by biochemical, kinetic, and structural findings. We will underscore the importance of viewing the process through the viewpoints of regulation, translational control, and heterogeneous pathways.
Cooke, Amy; Prigge, Andrew; Opperman, Laura; Wickens, Marvin
Regulatory complexes formed on mRNAs control translation, stability, and localization. These complexes possess two activities: one that binds RNA and another--the effector--that elicits a biological function. The Pumilio and FBF (PUF) protein family of RNA binding proteins provides a versatile scaffold to design and select proteins with new specificities. Here, the PUF scaffold is used to target translational activation and repression of specific mRNAs, and to induce specific poly(A) addition and removal. To do so, we linked PUF scaffold proteins to a translational activator, GLD2, or a translational repressor, CAF1. The chimeric proteins activate or repress the targeted mRNAs in Xenopus oocytes, and elicit poly(A) addition or removal. The magnitude of translational control relates directly to the affinity of the RNA-protein complex over a 100-fold range of K(d). The chimeric proteins act on both reporter and endogenous mRNAs: an mRNA that normally is deadenylated during oocyte maturation instead receives poly(A) in the presence of an appropriate chimera. The PUF-effector strategy enables the design of proteins that affect translation and stability of specific mRNAs in vivo.
Full Text Available Abstract Background Differential expression of genes can be regulated on many different levels. Most global studies of gene regulation concentrate on transcript level regulation, and very few global analyses of differential translational efficiencies exist. The studies have revealed that in Saccharomyces cerevisiae, Arabidopsis thaliana, and human cell lines translational regulation plays a significant role. Additional species have not been investigated yet. Particularly, until now no global study of translational control with any prokaryotic species was available. Results A global analysis of translational control was performed with two haloarchaeal model species, Halobacterium salinarum and Haloferax volcanii. To identify differentially regulated genes, exponentially growing and stationary phase cells were compared. More than 20% of H. salinarum transcripts are translated with non-average efficiencies. By far the largest group is comprised of genes that are translated with above-average efficiency specifically in exponential phase, including genes for many ribosomal proteins, RNA polymerase subunits, enzymes, and chemotaxis proteins. Translation of 1% of all genes is specifically repressed in either of the two growth phases. For comparison, DNA microarrays were also used to identify differential transcriptional regulation in H. salinarum, and 17% of all genes were found to have non-average transcript levels in exponential versus stationary phase. In H. volcanii, 12% of all genes are translated with non-average efficiencies. The overlap with H. salinarum is negligible. In contrast to H. salinarum, 4.6% of genes have non-average translational efficiency in both growth phases, and thus they might be regulated by other stimuli than growth phase. Conclusion For the first time in any prokaryotic species it was shown that a significant fraction of genes is under differential translational control. Groups of genes with different regulatory patterns
Axelsen, Lene Nygaard; Callø, Kirstine; von Holstein-Rathlou, Niels-Henrik;
expression by transcription and translation is of great importance, the trafficking, channel activity and degradation are also under tight control. The function of connexins can be regulated by several post translational modifications, which affect numerous parameters; including number of channels, open...... probability, single channel conductance or selectivity. The most extensively investigated post translational modifications are phosphorylations, which have been documented in all mammalian connexins. Besides phosphorylations, some connexins are known to be ubiquitinated, SUMOylated, nitrosylated, hydroxylated...
Sucrose can translationally regulate the expression of bZIP11 and four other S-class bZip transcription factors in Arabidopsis thaliana. Sequence encoding 28 amino acids (SC-peptide) in the leader of the bZIP11 is sufficient to mediate sucrose induced translational control. A model proposes that suc
Aleksandra M. Ochnik
Conclusion: The oncogenic transcription factor AIB1 has a novel role in the regulation of polyribosome recruitment and formation of the translational complex. Combinatorial therapies targeting IGF signaling and mRNA translation in AIB1 expressing breast cancers may have clinical benefit and warrants further investigation.
LI; Muyang; (李沐阳); HU; Qirui; (胡其锐); XUAN; Jinsong; (宣劲松); DENG; Daiyong; (邓代永); WENG; Manli; (翁曼丽)
Besides transcription regulation, gene expression is also regulated at translation level. Although translation regulation is mainly mediated by translation initiation, an abundance of evidence shows that the termination phase of translation is also important for gene expression. The expression of λN gene is down regulated at translation level in L24 mutant, however the precise mechanism still remains unknown. We report here that in an L24 mutant strain, the expression of lac-λN and GST-λN is decreased to 25% and 50% of that in wild type T83 strain respectively. Strikingly, the yield of GST-λN fusion protein in L24 mutant can be restored to the level as in T83 wild type strain by changing the two codons upstream λN stop codon. These findings imply that the stop codon and its context are involved in the translation regulation. The possible reason is that the translation termination complex containing L24 mutant ribosome may not dissociate properly in stop code region. This failure of disengagement from mRNA will slow down the process of following ribosomes, and consequently decrease the efficiency of λN gene expression.
The three domains of life – Bacteria, Archaea, and Eukaryotes – can be easily distinguished based on how the genetic information is processed during transcription, translation, and (DNA) replication. Generally, Eukaryotes turned out to employ machineries for these processes that are in their essence
"Translation" is a life narrative about the ways in which cultural histories shape personal stories, and the capacity of the imagination to develop alternative narratives about oneself and the world. It can also be read a way of addressing the effects of what Ato Quayson calls the global process of postcolonializing. Quaysons critical perspective might be used as an interpretive lens for seeing some of the ways in which this autobiographical narrative complicates the jargon of race, cl...
"Translation" is a life narrative about the ways in which cultural histories shape personal stories, and the capacity of the imagination to develop alternative narratives about oneself and the world. It can also be read a way of addressing the effects of what Ato Quayson calls the global process of postcolonializing. Quaysons critical perspective might be used as an interpretive lens for seeing some of the ways in which this autobiographical narrative complicates the jargon of race, class, ...
Fung, To Sing; Liao, Ying; Liu, Ding Xiang
Similar to other viruses, coronavirus infection triggers cellular stress responses in infected host cells. The close association of coronavirus replication with the endoplasmic reticulum (ER) results in the ER stress responses, which impose a challenge to the viruses. Viruses, in turn, have come up with various mechanisms to block or subvert these responses. One of the ER stress responses is inhibition of the global protein synthesis to reduce the amount of unfolded proteins inside the ER lumen. Viruses have evolved the capacity to overcome the protein translation shutoff to ensure viral protein production. Here, we review the strategies exploited by coronavirus to modulate cellular stress response pathways. The involvement of coronavirus-induced stress responses and translational control in viral pathogenesis will also be briefly discussed. PMID:27384577
To Sing Fung
Full Text Available Similar to other viruses, coronavirus infection triggers cellular stress responses in infected host cells. The close association of coronavirus replication with the endoplasmic reticulum (ER results in the ER stress responses, which impose a challenge to the viruses. Viruses, in turn, have come up with various mechanisms to block or subvert these responses. One of the ER stress responses is inhibition of the global protein synthesis to reduce the amount of unfolded proteins inside the ER lumen. Viruses have evolved the capacity to overcome the protein translation shutoff to ensure viral protein production. Here, we review the strategies exploited by coronavirus to modulate cellular stress response pathways. The involvement of coronavirus-induced stress responses and translational control in viral pathogenesis will also be briefly discussed.
Payne, Tom; Hanfrey, Colin; Bishop, Amy L; Michael, Anthony J; Avery, Simon V; Archer, David B
Accumulation of unfolded proteins in the endoplasmic reticulum (ER) causes stress and induces the unfolded protein response (UPR). Genome-wide analysis of translational regulation in response to the UPR-inducing agent dithiothreitol in Saccharomyces cerevisiae is reported. Microarray analysis, confirmed using qRT-PCR, identified transcript-specific translational regulation. Transcripts with functions in ribosomal biogenesis and assembly were translationally repressed. In contrast, mRNAs from known UPR genes, encoding the UPR transcription factor Hac1p, the ER-oxidoreductase Ero1p and the ER-associated protein degradation (ERAD) protein Der1p, were enriched in polysomal fractions, indicating translational up-regulation. Splicing of HAC1 mRNA is shown to be required for efficient ribosomal loading.
Full Text Available African swine fever virus (ASFV, like other complex DNA viruses, deploys a variety of strategies to evade the host's defence systems, such as inflammatory and immune responses and cell death. Here, we analyse the modifications in the translational machinery induced by ASFV. During ASFV infection, eIF4G and eIF4E are phosphorylated (Ser1108 and Ser209, respectively, whereas 4E-BP1 is hyperphosphorylated at early times post infection and hypophosphorylated after 18 h. Indeed, a potent increase in eIF4F assembly is observed in ASFV-infected cells, which is prevented by rapamycin treatment. Phosphorylation of eIF4E, eIF4GI and 4E-BP1 is important to enhance viral protein production, but is not essential for ASFV infection as observed in rapamycin- or CGP57380-treated cells. Nevertheless, eIF4F components are indispensable for ASFV protein synthesis and virus spread, since eIF4E or eIF4G depletion in COS-7 or Vero cells strongly prevents accumulation of viral proteins and decreases virus titre. In addition, eIF4F is not only activated but also redistributed within the viral factories at early times of infection, while eIF4G and eIF4E are surrounding these areas at late times. In fact, other components of translational machinery such as eIF2alpha, eIF3b, eIF4E, eEF2 and ribosomal P protein are enriched in areas surrounding ASFV factories. Notably, the mitochondrial network is polarized in ASFV-infected cells co-localizing with ribosomes. Thus, translation and ATP synthesis seem to be coupled and compartmentalized at the periphery of viral factories. At later times after ASFV infection, polyadenylated mRNAs disappear from the cytoplasm of Vero cells, except within the viral factories. The distribution of these pools of mRNAs is similar to the localization of viral late mRNAs. Therefore, degradation of cellular polyadenylated mRNAs and recruitment of the translation machinery to viral factories may contribute to the inhibition of host protein synthesis
Jonathan P Saxe
Full Text Available Oct4 is a key component of the molecular circuitry which regulates embryonic stem cell proliferation and differentiation. It is essential for maintenance of undifferentiated, pluripotent cell populations, and accomplishes these tasks by binding DNA in multiple heterodimer and homodimer configurations. Very little is known about how formation of these complexes is regulated, or the mechanisms through which Oct4 proteins respond to complex extracellular stimuli which regulate pluripotency. Here, we provide evidence for a phosphorylation-based mechanism which regulates specific Oct4 homodimer conformations. Point mutations of a putative phosphorylation site can specifically abrogate transcriptional activity of a specific homodimer assembly, with little effect on other configurations. Moreover, we performed bioinformatic predictions to identify a subset of Oct4 target genes which may be regulated by this specific assembly, and show that altering Oct4 protein levels affects transcription of Oct4 target genes which are regulated by this assembly but not others. Finally, we identified several signaling pathways which may mediate this phosphorylation and act in combination to regulate Oct4 transcriptional activity and protein stability. These results provide a mechanism for rapid and reversible alteration of Oct4 transactivation potential in response to extracellular signals.
Mazumder, Barsanjit; Li, Xiaoxia; Barik, Sailen
A robust innate immune response is essential to the protection of all vertebrates from infection, but it often comes with the price tag of acute inflammation. If unchecked, a runaway inflammatory response can cause significant tissue damage, resulting in myriad disorders, such as dermatitis, toxicshock, cardiovascular disease, acute pelvic and arthritic inflammatory diseases, and various infections. To prevent such pathologies, cells have evolved mechanisms to rapidly and specifically shut off these beneficial inflammatory activities before they become detrimental. Our review of recent literature, including our own work, reveals that the most dominant and common mechanism is translational silencing, in which specific regulatory proteins or complexes are recruited to cis-acting RNA structures in the untranslated regions of single or multiple mRNAs that code for the inflammatory protein(s). Enhancement of the silencing function may constitute a novel pharmacological approach to prevent immunity-related inflammation. PMID:20304832
Full Text Available mTOR is a central nutrient sensor that signals a cell to grow and proliferate. Through distinct protein complexes it regulates different levels of available cellular energy substrates required for cell growth. One of the important functions of the complex is to maintain available amino acid pool by regulating protein translation. Dysregulation of mTOR pathway leads to aberrant protein translation which manifests into various pathological states. Our review focuses on the role mTOR signaling plays in protein translation and its physiological role. It also throws some light on available data that show translation dysregulation as a cause of pathological complexities like cancer and the available drugs that target the pathway for cancer treatment.
Hess, Douglas T.; Stamler, Jonathan S.
Protein post-translational modification by S-nitrosylation conveys a ubiquitous influence of nitric oxide on signal transduction in eukaryotic cells. The wide functional purview of S-nitrosylation reflects in part the regulation by S-nitrosylation of the principal protein post-translational modifications that play a role in cell signaling, including phosphorylation, acetylation, ubiquitylation and related modifications, palmitoylation, and alternative Cys-based redox modifications. In this mi...
Full Text Available Recently a first genome-wide analysis of translational regulation using prokaryotic species had been performed which revealed that regulation of translational efficiency plays an important role in haloarchaea. In fact, the fractions of genes under differential growth phase-dependent translational control in the two species Halobacterium salinarum and Haloferax volcanii were as high as in eukaryotes. However, nothing is known about the mechanisms of translational regulation in archaea. Therefore, two genes exhibiting opposing directions of regulation were selected to unravel the importance of untranslated regions (UTRs for differential translational control in vivo.Differential translational regulation in exponentially growing versus stationary phase cells was studied by comparing translational efficiencies using a reporter gene system. Translational regulation was not observed when 5'-UTRs or 3'-UTRs alone were fused to the reporter gene. However, their simultaneous presence was sufficient to transfer differential translational control from the native transcript to the reporter transcript. This was true for both directions of translational control. Translational regulation was completely abolished when stem loops in the 5'-UTR were changed by mutagenesis. An "UTR-swap" experiment demonstrated that the direction of translational regulation is encoded in the 3'-UTR, not in the 5'-UTR. While much is known about 5'-UTR-dependent translational control in bacteria, the reported findings provide the first examples that both 5'- and 3'-UTRs are essential and sufficient to drive differential translational regulation in a prokaryote and therefore have to functionally interact in vivo. The current results indicate that 3'-UTR-dependent translational control had already evolved before capping and polyadenylation of transcripts were invented, which are essential for circularization of transcripts in eukaryotes.
β-Secretase, widely known as β-site APP cleaving enzyme 1 (BACE1), is a membrane-associated protease that cleaves amyloid precursor protein (APP) to generate amyloid β-protein (Aβ). As this cleavage is a pathologically relevant event in Alzheimer's disease, BACE1 is considered a viable therapeutic target. BACE1 can be regulated at the transcriptional, post-transcriptional, translational, and post-translational levels. Elucidation of the regulatory pathways of BACE1 is critical, not only for understanding the pathological mechanisms of AD but also developing effective therapeutic strategies to inhibit activity of the protease. This mini-review focuses on the post-translational regulation of BACE1, as modulation at this level is closely associated with both physiological and pathological conditions. Current knowledge on the mechanisms underlying such BACE1 regulation and their implications for therapy are discussed.
Alexanian, Anna; Miller, Bradley; Chesnik, Marla; Mirza, Shama; Sorokin, Andrey
While increased COX2 expression and prostaglandin levels are elevated in human cancers, the mechanisms of COX2 regulation at the post-translational level are unknown. Initial observation that COX2 forms adduct with non-receptor tyrosine kinase FYN, prompted us to study FYN-mediated post-translational regulation of COX2. We found that FYN increased COX2 activity in prostate cancer cells DU145, independent of changes in COX2 or COX1 protein expression levels. We report that FYN phosphorylates h...
Fu, L.; Minden, M D; Benchimol, S
In blast cells obtained from patients with acute myelogenous leukemia, p53 mRNA was present in all the samples examined while the expression of p53 protein was variable from patient to patient. Mutations in the p53 gene are infrequent in this disease and, hence, variable protein expression in the majority of the samples cannot be accounted for by mutation. In this study, we examined the regulation of p53 gene expression in human leukemic blasts and characterized the p53 transcripts in these c...
Gutu, Andrian; Nesbit, April D.; Alverson, Andrew J.; Palmer, Jeffrey D.; Kehoe, David M.
The regulation of photosynthesis is important, yet poorly understood. Our work reveals a previously undescribed form of photosynthesis gene regulation in cyanobacteria that apparently also controls gene expression in plants, including commercially important crops. This finding may provide a unique approach to modifying the environmental responses and developmental programs of agriculturally important species. In addition, translation is a key biological process, and many of its important feat...
Cao, Jicong; Arha, Manish; Sudrik, Chaitanya; Mukherjee, Abhirup; Wu, Xia; Kane, Ravi S
We describe a simple strategy to control mRNA translation in both prokaryotic and eukaryotic cells which relies on a unique protein-RNA interaction. Specifically, we used the Pumilio/FBF (PUF) protein to repress translation by binding in between the ribosome binding site (RBS) and the start codon (in Escherichia coli), or by binding to the 5' untranslated region of target mRNAs (in mammalian cells). The design principle is straightforward, the extent of translational repression can be tuned and the regulator is genetically encoded, enabling the construction of artificial signal cascades. We demonstrate that this approach can also be used to regulate polycistronic mRNAs; such regulation has rarely been achieved in previous reports. Since the regulator used in this study is a modular RNA-binding protein, which can be engineered to target different 8-nucleotide RNA sequences, our strategy could be used in the future to target endogenous mRNAs for regulating metabolic flows and signaling pathways in both prokaryotic and eukaryotic cells.
Sheets, Michael D; Fox, Catherine A; Dowdle, Megan E; Blaser, Susanne Imboden; Chung, Andy; Park, Sookhee
The selective translation of maternal mRNAs encoding cell-fate determinants drives the earliest decisions of embryogenesis that establish the vertebrate body plan. This chapter will discuss studies in Xenopus laevis that provide insights into mechanisms underlying this translational control. Xenopus has been a powerful model organism for many discoveries relevant to the translational control of maternal mRNAs because of the large size of its oocytes and eggs that allow for microinjection of molecules and the relative ease of manipulating the oocyte to egg transition (maturation) and fertilization in culture. Consequently, many key studies have focused on the expression of maternal mRNAs during the oocyte to egg transition (the meiotic cell cycle) and the rapid cell divisions immediately following fertilization. This research has made seminal contributions to our understanding of translational regulatory mechanisms, but while some of the mRNAs under consideration at these stages encode cell-fate determinants, many encode cell cycle regulatory proteins that drive these early cell cycles. In contrast, while maternal mRNAs encoding key developmental (i.e., cell-fate) regulators that function after the first cleavage stages may exploit aspects of these foundational mechanisms, studies reveal that these mRNAs must also rely on distinct and, as of yet, incompletely understood mechanisms. These findings are logical because the functions of such developmental regulatory proteins have requirements distinct from cell cycle regulators, including becoming relevant only after fertilization and then only in specific cells of the embryo. Indeed, key maternal cell-fate determinants must be made available in exquisitely precise amounts (usually low), only at specific times and in specific cells during embryogenesis. To provide an appreciation for the regulation of maternal cell-fate determinant expression, an overview of the maternal phase of Xenopus embryogenesis will be presented
Kirk, M.M.; Kirk, D.L.
In Volvox cultures synchronized by a light-dark cycle, juveniles containing presumptive somatic and reproductive cells are produced during the dark, but their cells do not differentiate until after the lights come on. The pattern of protein synthesis changes rapidly after the lights come on. Action spectra and effects of photosynthesis inhibitors indicate that this protein synthetic change is not simply a consequence of renewed flow of energy from illuminated chloroplasts. Actinomycin, at a level adequate to block the response to heat shock, has virtually no effect on the response of the same cells to light; furthermore, RNAs isolated from unilluminated and illuminated juveniles yield indistinguishable in vitro translation products. The authors conclude, therefore, that this effect of light is exerted almost exclusively at the translational level, generating one of the most striking examples of translational regulation yet described.
Robert J Ihry
Full Text Available Steroid hormones act, through their respective nuclear receptors, to regulate target gene expression. Despite their critical role in development, physiology, and disease, however, it is still unclear how these systemic cues are refined into tissue-specific responses. We identified a mutation in the evolutionarily conserved DEAD box RNA helicase belle/DDX3 that disrupts a subset of responses to the steroid hormone ecdysone during Drosophila melanogaster metamorphosis. We demonstrate that belle directly regulates translation of E74A, an ets transcription factor and critical component of the ecdysone-induced transcriptional cascade. Although E74A mRNA accumulates to abnormally high levels in belle mutant tissues, no E74A protein is detectable, resulting in misregulation of E74A-dependent ecdysone response genes. The accumulation of E74A mRNA in belle mutant salivary glands is a result of auto-regulation, fulfilling a prediction made by Ashburner nearly 40 years ago. In this model, Ashburner postulates that, in addition to regulating secondary response genes, protein products of primary response genes like E74A also inhibit their own ecdysone-induced transcription. Moreover, although ecdysone-triggered transcription of E74A appears to be ubiquitous during metamorphosis, belle-dependent translation of E74A mRNA is spatially restricted. These results demonstrate that translational control plays a critical, and previously unknown, role in refining transcriptional responses to the steroid hormone ecdysone.
Wong, Queenie Wing-Lei; Vaz, Candida; Lee, Qian Yi; Zhao, Tian Yun; Luo, Raymond; Archer, Stuart K; Preiss, Thomas; Tanavde, Vivek; Vardy, Leah A
The presence of multiple variants for many mRNAs is a major contributor to protein diversity. The processing of these variants is tightly controlled in a cell-type specific manner and has a significant impact on gene expression control. Here we investigate the differential translation rates of individual mRNA variants in embryonic stem cells (ESCs) and in ESC derived Neural Precursor Cells (NPCs) using polysome profiling coupled to RNA sequencing. We show that there are a significant number of detectable mRNA variants in ESCs and NPCs and that many of them show variant specific translation rates. This is correlated with differences in the UTRs of the variants with the 5'UTR playing a predominant role. We suggest that mRNA variants that contain alternate UTRs are under different post-transcriptional controls. This is likely due to the presence or absence of miRNA and protein binding sites that regulate translation rate. This highlights the importance of addressing translation rate when using mRNA levels as a read out of protein abundance. Additional analysis shows that many annotated non-coding mRNAs are present on the polysome fractions in ESCs and NPCs. We believe that the use of polysome fractionation coupled to RNA sequencing is a useful method for analysis of the translation state of many different RNAs in the cell.
Queenie Wing-Lei Wong
Full Text Available The presence of multiple variants for many mRNAs is a major contributor to protein diversity. The processing of these variants is tightly controlled in a cell-type specific manner and has a significant impact on gene expression control. Here we investigate the differential translation rates of individual mRNA variants in embryonic stem cells (ESCs and in ESC derived Neural Precursor Cells (NPCs using polysome profiling coupled to RNA sequencing. We show that there are a significant number of detectable mRNA variants in ESCs and NPCs and that many of them show variant specific translation rates. This is correlated with differences in the UTRs of the variants with the 5'UTR playing a predominant role. We suggest that mRNA variants that contain alternate UTRs are under different post-transcriptional controls. This is likely due to the presence or absence of miRNA and protein binding sites that regulate translation rate. This highlights the importance of addressing translation rate when using mRNA levels as a read out of protein abundance. Additional analysis shows that many annotated non-coding mRNAs are present on the polysome fractions in ESCs and NPCs. We believe that the use of polysome fractionation coupled to RNA sequencing is a useful method for analysis of the translation state of many different RNAs in the cell.
Werner, Achim; Iwasaki, Shintaro; McGourty, Colleen A; Medina-Ruiz, Sofia; Teerikorpi, Nia; Fedrigo, Indro; Ingolia, Nicholas T; Rape, Michael
Metazoan development depends on the accurate execution of differentiation programs that allow pluripotent stem cells to adopt specific fates. Differentiation requires changes to chromatin architecture and transcriptional networks, yet whether other regulatory events support cell-fate determination is less well understood. Here we identify the ubiquitin ligase CUL3 in complex with its vertebrate-specific substrate adaptor KBTBD8 (CUL3(KBTBD8)) as an essential regulator of human and Xenopus tropicalis neural crest specification. CUL3(KBTBD8) monoubiquitylates NOLC1 and its paralogue TCOF1, the mutation of which underlies the neurocristopathy Treacher Collins syndrome. Ubiquitylation drives formation of a TCOF1-NOLC1 platform that connects RNA polymerase I with ribosome modification enzymes and remodels the translational program of differentiating cells in favour of neural crest specification. We conclude that ubiquitin-dependent regulation of translation is an important feature of cell-fate determination.
Kopaskie, Karyl S; Ligtenberg, Katherine Given; Schneewind, Olaf
Yersinia enterocolitica type III secretion machines transport YopQ and other Yop effectors into host immune cells. YopD and its chaperone LcrH are essential components of the Yersinia type III pathway, enabling effector translocation into host cells. YopD, LcrH, and YscM1 also regulate yop expression post-transcriptionally in response to environmental signals; however, the molecular mechanisms for this regulation and Yop secretion are unknown. We show here that YopD associates with 30 S ribosomal particles in a manner requiring LcrH. When added to ribosomes, YopD, LcrH, and YscM1 block the translation of yopQ mRNA. We propose a model whereby LcrH-dependent association of YopD with 30 S ribosomal particles enables YscM1 to block yopQ translation unless type III machines are induced to secrete the effector.
Chauvier, Adrien; Picard-Jean, Frédéric; Berger-Dancause, Jean-Christophe; Bastet, Laurène; Naghdi, Mohammad Reza; Dubé, Audrey; Turcotte, Pierre; Perreault, Jonathan; Lafontaine, Daniel A.
On the basis of nascent transcript sequencing, it has been postulated but never demonstrated that transcriptional pausing at translation start sites is important for gene regulation. Here we show that the Escherichia coli thiamin pyrophosphate (TPP) thiC riboswitch contains a regulatory pause site in the translation initiation region that acts as a checkpoint for thiC expression. By biochemically probing nascent transcription complexes halted at defined positions, we find a narrow transcriptional window for metabolite binding, in which the downstream boundary is delimited by the checkpoint. We show that transcription complexes at the regulatory pause site favour the formation of a riboswitch intramolecular lock that strongly prevents TPP binding. In contrast, cotranscriptional metabolite binding increases RNA polymerase pausing and induces Rho-dependent transcription termination at the checkpoint. Early transcriptional pausing may provide a general mechanism, whereby transient transcriptional windows directly coordinate the sensing of environmental cues and bacterial mRNA regulation. PMID:28071751
Alexanian, Anna; Miller, Bradley; Chesnik, Marla; Mirza, Shama; Sorokin, Andrey
While increased COX2 expression and prostaglandin levels are elevated in human cancers, the mechanisms of COX2 regulation at the post-translational level are unknown. Initial observation that COX2 forms adduct with non-receptor tyrosine kinase FYN, prompted us to study FYN-mediated post-translational regulation of COX2. We found that FYN increased COX2 activity in prostate cancer cells DU145, independent of changes in COX2 or COX1 protein expression levels. We report that FYN phosphorylates human COX2 on Tyr 446, and while corresponding phospho-mimetic COX2 mutation promotes COX2 activity, the phosphorylation blocking mutation prevents FYN-mediated increase in COX2 activity.
Onwuli, Donatus O; Beltran-Alvarez, Pedro
Voltage-gated sodium channels are essential proteins in brain physiology, as they generate the sodium currents that initiate neuronal action potentials. Voltage-gated sodium channels expression, localisation and function are regulated by a range of transcriptional and post-translational mechanisms. Here, we review our understanding of regulation of brain voltage-gated sodium channels, in particular SCN1A (NaV1.1), SCN2A (NaV1.2), SCN3A (NaV1.3) and SCN8A (NaV1.6), by transcription factors, by alternative splicing, and by post-translational modifications. Our focus is strongly centred on recent research lines, and newly generated knowledge.
Knight, John R P; Bastide, Amandine; Roobol, Anne; Roobol, Jo; Jackson, Thomas J; Utami, Wahyu; Barrett, David A; Smales, C Mark; Willis, Anne E
Cells respond to external stress conditions by controlling gene expression, a process which occurs rapidly via post-transcriptional regulation at the level of protein synthesis. Global control of translation is mediated by modification of translation factors to allow reprogramming of the translatome and synthesis of specific proteins that are required for stress protection or initiation of apoptosis. In the present study, we have investigated how global protein synthesis rates are regulated upon mild cooling. We demonstrate that although there are changes to the factors that control initiation, including phosphorylation of eukaryotic translation initiation factor 2 (eIF2) on the α-subunit, the reduction in the global translation rate is mediated by regulation of elongation via phosphorylation of eukaryotic elongation factor 2 (eEF2) by its specific kinase, eEF2K (eukaryotic elongation factor 2 kinase). The AMP/ATP ratio increases following cooling, consistent with a reduction in metabolic rates, giving rise to activation of AMPK (5'-AMP-activated protein kinase), which is upstream of eEF2K. However, our data show that the major trigger for activation of eEF2K upon mild cooling is the release of Ca2+ ions from the endoplasmic reticulum (ER) and, importantly, that it is possible to restore protein synthesis rates in cooled cells by inhibition of this pathway at multiple points. As cooling has both therapeutic and industrial applications, our data provide important new insights into how the cellular responses to this stress are regulated, opening up new possibilities to modulate these responses for medical or industrial use at physiological or cooler temperatures.
as a result of multiple adaptations, including AR gene amplification, abnormal AR activation or enhanced steroidogenesis.2 These changes are acquired...AWARD NUMBER: W81XWH-14-1-0209 TITLE: Regulating Prostate Cancer Sensitivity to Chemotherapy through Translational Control of CCAAT Enhancer ... Enhancer Binding Proteins 5a. CONTRACT NUMBER W81XWH-14-1-0209 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) David J. Barakat, Samuel R
Protein synthesis is principally regulated at the initiation stage (rather than during elongation or termination), allowing rapid, reversible and spatial control over gene expression. Progress over recent years in determining the structures and activities of initiation factors, and in mapping their interactions within ribosomal initiation complexes, has significantly advanced our understanding of the complex translation initiation process. These developments have provided a solid foundation f...
Jensen, Ole Mejlhede
Denne afhandling er skrevet med henblik på opnåelse af den danske doktorgrad i teknik, dr.techn. Den vedrører autogene fænomener i cementbaserede materialer – primært deformation og ændring af den relative luftfugtighed (RF). I afhandlingen er det belyst, hvordan betydningen af disse fænomener bl...
Patel, Manish R; Sadiq, Ahad A; Jay-Dixon, Joe; Jirakulaporn, Tanawat; Jacobson, Blake A; Farassati, Faris; Bitterman, Peter B; Kratzke, Robert A
Initiation of protein translation by the 5' mRNA cap is a tightly regulated step in cell growth and proliferation. Aberrant activation of cap-dependent translation is a hallmark of many cancers including non-small cell lung cancer. The canonical signaling mechanisms leading to translation initiation include activation of the Akt/mTOR pathway in response to the presence of nutrients and growth factors. We have previously observed that inhibition of c-jun N-terminal kinase (JNK) leads to inactivation of cap-dependent translation in mesothelioma cells. Since JNK is involved in the genesis of non-small cell lung cancer (NSCLC), we hypothesized that JNK could also be involved in activating cap-dependent translation in NSCLC cells and could represent an alternative pathway regulating translation. In a series of NSCLC cell lines, inhibition of JNK using SP600125 resulted in inhibition of 4E-BP1 phosphorylation and a decrease in formation of the cap-dependent translation complex, eIF4F. Furthermore, we show that JNK-mediated inhibition of translation is independent of mTOR. Our data provide evidence that JNK is involved in the regulation of translation and has potential as a therapeutic target in NSCLC.
Lai, Ming-Chih; Chang, Wen-Cheng; Shieh, Sheau-Yann; Tarn, Woan-Yuh
DDX3 belongs to the DEAD box family of RNA helicases, but the details of its biological function remain largely unclear. Here we show that knockdown of DDX3 expression impedes G(1)/S-phase transition of the cell cycle. To know how DDX3 may act in cell cycle control, we screened for cellular mRNA targets of DDX3. Many of the identified DDX3 targets encoded cell cycle regulators, including G(1)/S-specific cyclin E1. DDX3 depletion specifically downregulates translation of cyclin E1 mRNA. Moreover, our data suggest that DDX3 participates in translation initiation of targeted mRNAs as well as in cell growth control via its RNA helicase activity. Consistent with these findings, we show that in the temperature-sensitive DDX3 mutant hamster cell line tsET24, cyclin E1 expression is downregulated at a nonpermissive temperature that inactivates mutant DDX3. Taken together, our results indicate that DDX3 is critical for translation of cyclin E1 mRNA, which provides an alternative mechanism for regulating cyclin E1 expression during the cell cycle.
Cao, Jicong; Arha, Manish; Sudrik, Chaitanya; Schaffer, David V; Kane, Ravi S
The regulation of gene expression is crucial in diverse areas of biological science, engineering, and medicine. A genetically encoded system based on the RNA binding domain of the Pumilio and FBF (PUF) proteins was developed for the bidirectional regulation (i.e., either upregulation or downregulation) of the translation of a target mRNA. PUF domains serve as designable scaffolds for the recognition of specific RNA elements and the specificity can be easily altered to target any 8-nucleotide RNA sequence. The expression of a reporter could be varied by over 17-fold when using PUF-based activators and repressors. The specificity of the method was established by using wild-type and mutant PUF domains. Furthermore, this method could be used to activate the translation of target mRNA downstream of PUF binding sites in a light-dependent manner. Such specific bidirectional control of mRNA translation could be particularly useful in the fields of synthetic biology, developmental biology, and metabolic engineering.
Full Text Available Circadian clocks coordinate the timing of important biological processes. Interconnected transcriptional and post-translational feedback loops based on a set of clock genes generate and maintain these rhythms with a period of about 24 hours. Many clock proteins undergo circadian cycles of post-translational modifications. Among these modifications, protein phosphorylation plays an important role in regulating activity, stability and intracellular localization of clock components. Several protein kinases were characterized as regulators of the circadian clock. However, the function of protein phosphatases, which balance phosphorylation events, in the mammalian clock mechanism is less well understood. Here, we identify protein phosphatase 1 (PP1 as regulator of period and light-induced resetting of the mammalian circadian clock. Down-regulation of PP1 activity in cells by RNA interference and in vivo by expression of a specific inhibitor in the brain of mice tended to lengthen circadian period. Moreover, reduction of PP1 activity in the brain altered light-mediated clock resetting behavior in mice, enhancing the phase shifts in either direction. At the molecular level, diminished PP1 activity increased nuclear accumulation of the clock component PER2 in neurons. Hence, PP1, may reduce PER2 phosphorylation thereby influencing nuclear localization of this protein. This may at least partially influence period and phase shifting properties of the mammalian circadian clock.
Zach, Lolita; Braunstein, Ilana; Stanhill, Ariel
Initial steps in protein synthesis are highly regulated processes as they define the reading frame of the translation machinery. Eukaryotic translation initiation is a process facilitated by numerous factors (eIFs), aimed to form a “scanning” mechanism toward the initiation codon. Translation initiation of the main open reading frame (ORF) in an mRNA transcript has been reported to be regulated by upstream open reading frames (uORFs) in a manner of re-initiation. This mode of regulation is governed by the phosphorylation status of eIF2α and controlled by cellular stresses. Another mode of translational initiation regulation is leaky scanning, and this regulatory process has not been extensively studied. We have identified arsenite-inducible regulatory particle-associated protein (AIRAP) transcript to be translationally induced during arsenite stress conditions. AIRAP transcript contains a single uORF in a poor-kozak context. AIRAP translation induction is governed by means of leaky scanning and not re-initiation. This induction of AIRAP is solely dependent on eIF1 and the uORF kozak context. We show that eIF1 is phosphorylated under specific conditions that induce protein misfolding and have biochemically characterized this site of phosphorylation. Our data indicate that leaky scanning like re-initiation is responsive to stress conditions and that leaky scanning can induce ORF translation by bypassing poor kozak context of a single uORF transcript. PMID:24898249
Cole, Michael D.; Cowling, Victoria H.
MYC is a potent oncogene that drives unrestrained cell growth and proliferation. Shortly after its discovery as an oncogene, the MYC protein was recognized as a sequence-specific transcription factor. Since that time, MYC oncogene research has focused on the mechanism of MYC-induced transcription and on the identification of MYC transcriptional target genes. Recently, MYC was shown to control protein expression through mRNA translation and to directly regulate DNA replication, thus initiating exciting new areas of oncogene research. PMID:18698328
DDX3 belongs to the DEAD box family of RNA helicases, but the details of its biological function remain largely unclear. Here we show that knockdown of DDX3 expression impedes G1/S-phase transition of the cell cycle. To know how DDX3 may act in cell cycle control, we screened for cellular mRNA targets of DDX3. Many of the identified DDX3 targets encoded cell cycle regulators, including G1/S-specific cyclin E1. DDX3 depletion specifically downregulates translation of cyclin E1 mRNA. Moreover, ...
Huang, Junting; Zamponi, Gerald W
Calcium entry via voltage gated calcium channels mediates a wide range of physiological functions, whereas calcium channel dysregulation has been associated with numerous pathophysiological conditions. There are myriad cell signaling pathways that act on voltage gated calcium channels to fine tune their activities and to regulate their cell surface expression. These regulatory mechanisms include the activation of G protein-coupled receptors and downstream phosphorylation events, and their control over calcium channel trafficking through direct physical interactions. Calcium channels also undergo post-translational modifications that alter both function and density of the channels in the plasma membrane. Here we focus on select aspects of these regulatory mechanisms and highlight recent developments.
Sleeboom-Faulkner, Margaret; Chekar, Choon Key; Faulkner, Alex; Heitmeyer, Carolyn; Marouda, Marina; Rosemann, Achim; Chaisinthop, Nattaka; Chang, Hung-Chieh Jessica; Ely, Adrian; Kato, Masae; Patra, Prasanna K; Su, Yeyang; Sui, Suli; Suzuki, Wakana; Zhang, Xinqing
A very large grey area exists between translational stem cell research and applications that comply with the ideals of randomised control trials and good laboratory and clinical practice and what is often referred to as snake-oil trade. We identify a discrepancy between international research and ethics regulation and the ways in which regulatory instruments in the stem cell field are developed in practice. We examine this discrepancy using the notion of 'national home-keeping', referring to the way governments articulate international standards and regulation with conflicting demands on local players at home. Identifying particular dimensions of regulatory tools - authority, permissions, space and acceleration - as crucial to national home-keeping in Asia, Europe and the USA, we show how local regulation works to enable development of the field, notwithstanding international (i.e. principally 'western') regulation. Triangulating regulation with empirical data and archival research between 2012 and 2015 has helped us to shed light on how countries and organisations adapt and resist internationally dominant regulation through the manipulation of regulatory tools (contingent upon country size, the state's ability to accumulate resources, healthcare demands, established traditions of scientific governance, and economic and scientific ambitions).
Parthasarathy, Ranganath; Subramanian, Shyamsundar; Boder, Eric T; Discher, Dennis E
Display of heterologous proteins on the surface of Saccharomyces cerevisiae is increasingly being exploited for directed evolution because of straightforward cell screens. However, yeast post-translationally modifies proteins in ways that must be factored into library engineering and refinement. Here, we express the extracellular immunoglobulin domain of an ubiquitous mammalian membrane protein, CD47, which is implicated in cancer, immunocompatibility, and motility. CD47 has multiple sites of glycosylation and a core disulfide bond. We assess the effects of both of these post-translational modifications on expression and antibody binding. CD47's extracellular domain is fused to the yeast mating protein Aga2p on the cell wall, and the resulting fusion protein binds several key antibodies, including a conformation-sensitive antibody. Site-by-site mutagenesis of CD47's five N-linked glycosylation sites progressively decreases expression levels on yeast, but folding appears stable. Cysteine mutations disrupt the expected core disulfide, and also decrease protein expression levels, though not to the extent seen with complete deglycosylation. However, with the core disulfide mutants, antibody binding proves to be lower than expected from expression levels and glycosylation is clearly reduced compared to wild-type. The results indicate that glycosylation regulates heterologous display on yeast more than core disulfides do and thus suggest bounds on directed evolution by post-translational processing.
Jojić Boris R.; Leposavić Ljubica M.
Introduction. Autogenic training is a widely recognised psychotherapy technique. The British School of Autogenic Training cites a large list of disorders, states, and changes, where autogenic training may prove to be of help. We wanted to explore the application of autogenic training as a therapy for adjustment disorder in adults. Our sample consisted of a homogeneous group of 35 individuals, with an average age of 39.3±1.6 years, who were diagnosed with adjustment disorder, F 43.2, in accord...
Jojić Boris R.; Leposavić Ljubica M.
INTRODUCTION Autogenic training is a widespread technique used in psychotherapy. The British school of autogenic training cites a large list of diseases, health states, and life changes, in which autogenic training can be of help. We wanted to explore the application of autogenic training as a therapy for adjustment disorder in adolescents. The sample consisted of a homogeneous group of 31 individuals, with an average age of 17.3±0.2 years, who were diagnosed with adjustment disorder, F 43.2,...
Hadziselimovic, Nils; Vukojevic, Vanja; Peter, Fabian; Milnik, Annette; Fastenrath, Matthias; Fenyves, Bank Gabor; Hieber, Petra; Demougin, Philippe; Vogler, Christian; de Quervain, Dominique J-F; Papassotiropoulos, Andreas; Stetak, Attila
A plastic nervous system requires the ability not only to acquire and store but also to forget. Here, we report that musashi (msi-1) is necessary for time-dependent memory loss in C. elegans. Tissue-specific rescue demonstrates that MSI-1 function is necessary in the AVA interneuron. Using RNA-binding protein immunoprecipitation (IP), we found that MSI-1 binds to mRNAs of three subunits of the Arp2/3 actin branching regulator complex in vivo and downregulates ARX-1, ARX-2, and ARX-3 translation upon associative learning. The role of msi-1 in forgetting is also reflected by the persistence of learning-induced GLR-1 synaptic size increase in msi-1 mutants. We demonstrate that memory length is regulated cooperatively through the activation of adducin (add-1) and by the inhibitory effect of msi-1. Thus, a GLR-1/MSI-1/Arp2/3 pathway induces forgetting and represents a novel mechanism of memory decay by linking translational control to the structure of the actin cytoskeleton in neurons.
Full Text Available Heat shock transcription factor 1 (HSF1 plays an important role in the cellular response to proteotoxic stresses. Under normal growth conditions HSF1 is repressed as an inactive monomer in part through post-translation modifications that include protein acetylation, sumoylation and phosphorylation. Upon exposure to stress HSF1 homotrimerizes, accumulates in nucleus, binds DNA, becomes hyper-phosphorylated and activates the expression of stress response genes. While HSF1 and the mechanisms that regulate its activity have been studied for over two decades, our understanding of HSF1 regulation remains incomplete. As previous studies have shown that HSF1 and the heat shock response promoter element (HSE are generally structurally conserved from yeast to metazoans, we have made use of the genetically tractable budding yeast as a facile assay system to further understand the mechanisms that regulate human HSF1 through phosphorylation of serine 303. We show that when human HSF1 is expressed in yeast its phosphorylation at S303 is promoted by the MAP-kinase Slt2 independent of a priming event at S307 previously believed to be a prerequisite. Furthermore, we show that phosphorylation at S303 in yeast and mammalian cells occurs independent of GSK3, the kinase primarily thought to be responsible for S303 phosphorylation. Lastly, while previous studies have suggested that S303 phosphorylation represses HSF1-dependent transactivation, we now show that S303 phosphorylation also represses HSF1 multimerization in both yeast and mammalian cells. Taken together, these studies suggest that yeast cells will be a powerful experimental tool for deciphering aspects of human HSF1 regulation by post-translational modifications.
Marsters, P.; Kendall, N.R.; Campbell, B.K.
Differential regulation of LHR in theca cells (TC) and granulosa cells (GC) is important for normal follicular development. Unlike TC, GC only acquire LH-responsiveness during the later stages of antral follicle development. This study tested the hypothesis that differential LH-responsiveness in these two cell types may be due, in part, to shifts in cellular patterns of alternatively spliced LHR mRNA transcripts which may not be obvious from analysis of total LHR gene expression. It also further explored the role of translation inhibition by an LHR binding protein (LHBP), normally associated with the production of endogenous cholesterol. LHR mRNA variation arises as a result of the alternative splicing of two variable deletion sites (VDS) designated 5′ VDS and 3′ VDS, and it was proposed that differences in cell sensitivity to LH may be due in part to variations in the pattern of the mRNA expression of the receptor variants. The outcomes of the present study support a dynamic multi-facetted regulation of LHR during pre-translation. Not only did the ratio between variants change during antral follicle growth and in vitro cell differentiation but also between TC and GC. Regulation could also be linked to LH concentration feedback mechanisms as the absence of LH caused cultured TC to markedly up-regulate amounts of LHR mRNA. In both TC and GC, LHR mRNA was greatly reduced after treatment to block mevalonate production in the de novo cholesterol pathway, adding further support for a regulatory mechanism linked to enriched cellular amounts of mevalonate kinase. PMID:26507944
Jojić Boris R.
Full Text Available INTRODUCTION Autogenic training is a widespread technique used in psychotherapy. The British school of autogenic training cites a large list of diseases, health states, and life changes, in which autogenic training can be of help. We wanted to explore the application of autogenic training as a therapy for adjustment disorder in adolescents. The sample consisted of a homogeneous group of 31 individuals, with an average age of 17.3±0.2 years, who were diagnosed with adjustment disorder, F 43.2, in accordance with ICD 10 search criteria. OBJECTIVE The aim of our work was to figure out the influence of autogenic training on adjustment disorder, through biophysical and biochemical indicators, and to research the efficacy of autogenic training as a therapy for adjustment disorder in adolescents. METHOD We observed adjustment disorder indicators and their changes in three phases, using initial, final, and control values, which we measured immediately before the beginning, immediately after the completion, and six months after the completion, of the practical course in autogenic training. We measured systolic and diastolic arterial blood pressure, brachial pulse rates, cortisol levels in plasma, cholesterol levels in blood, as well as glucose concentrations. During that period, autogenic training was employed as the sole therapy. RESULTS The study confirmed our preliminary assumptions. The measurements we performed showed that arterial blood pressure, pulse rates, cholesterol and cortisol concentrations, after the application of autogenic training among adolescents suffering from adjustment disorder, were lower than the initial values. They remained lower even six months after the completion of the practical course in autogenic training. CONCLUSION We concluded that autogenic training significantly decreases the values of physiological indicators of adjustment disorder, diminishes the effects of stress in an individual, and eases the adaptation of
Susor, Andrej; Jelínková, Lucie; Karabínová, Pavla; Torner, Helmut; Tomek, Wolfgang; Kovárová, Hana; Kubelka, Michal
The binding of mRNAs to ribosomes is mediated by the protein complex eIF4F in conjunction with eIF4B (eukaryotic initiation factor 4F and 4B). EIF4F is a three subunit complex consisting of eIF4A (RNA helicase), eIF4E (mRNA cap binding protein), and eIF4G (bridging protein). The crucial role is played by eIF4E, which directly binds the 5'-cap structure of the mRNA and facilitates the recruitment to the mRNA of other translation factors and the 40S ribosomal subunit. EIF4E binding to mRNA and to other initiation factors is regulated on several levels, including its phosphorylation on Ser-209, and association with its regulatory protein 4E-binding protein (4E-BP1). In this study we document that both the translation initiation factor eIF4E and its regulator 4E-BP1 become dephosphorylated in the early stage porcine zygotes already 8 hr post-activation. Similarly, the activities of ERK1/2 MAP and Mnk1 kinases, which are both involved in eIF4E phosphorylation, gradually decrease during this period with the timing similar to that of eIF4E dephosphorylation. The formation of an active eIF4F complex is also diminished after 9-15 hr post-activation, although substantial amounts of this complex have been detected also 24 hr post-activation (2-cell stage). The overall protein synthesis in the parthenotes decreases gradually from 12 hr post-activation reaching a minimum after 48 hr (4-cell stage). Although the translation is gradually decreasing during early preimplantation development, the eIF4F complex, which is temporarily formed, might be a premise for the translation of a small subset of mRNAs at this period of development.
Feng JIN; Guoxin ZHANG; Xiaoqing LUO; Chuhan ZHANG
Magnesia Concrete is a kind of expansive con-crete used in Chinese hydraulic engineering more and more widely. To evaluate the effects of autogenous expan-sion on the stresses of arch dams, a simple model of auto-genous expansion for Magnesia Concrete in dam engineering is presented. This model is based on three assumptions: 1) the total amount of autogenous expan-sion of Magnesia Concrete is related only to the properties of materials and mixing of concrete; 2) the autogenous expansion of Magnesia Concrete is irreversible due to the irreversibility of hydration reaction of Magnesia in the concrete; 3) the autogenous expansion strain rates of Magnesia Concrete bear a relation between temperature and residual Magnesia per unit volume of concrete. The model is verified by some experimental data of autogen-ous expansion of Magnesia Concrete and field-measured data of an arch dam in China. Embedded into finite ele-ment arch dam simulation software, this model is employed to simulate the effects of autogenous expansion of Magnesia Concrete in hydraulic engineering.
Lu, T.; Koenders, E.A.B.
In this paper, a conceptual model for analyzing the plastic part of autogenous deformation of cement paste based on the Arrhenius rate theory will be presented. The autogenous deformation will be calculated from the elastic deformations with inclusion of creep. Different kinds of cement paste with a
David G Hendrickson
Full Text Available MicroRNAs (miRNAs regulate gene expression posttranscriptionally by interfering with a target mRNA's translation, stability, or both. We sought to dissect the respective contributions of translational inhibition and mRNA decay to microRNA regulation. We identified direct targets of a specific miRNA, miR-124, by virtue of their association with Argonaute proteins, core components of miRNA effector complexes, in response to miR-124 transfection in human tissue culture cells. In parallel, we assessed mRNA levels and obtained translation profiles using a novel global approach to analyze polysomes separated on sucrose gradients. Analysis of translation profiles for approximately 8,000 genes in these proliferative human cells revealed that basic features of translation are similar to those previously observed in rapidly growing Saccharomyces cerevisiae. For approximately 600 mRNAs specifically recruited to Argonaute proteins by miR-124, we found reductions in both the mRNA abundance and inferred translation rate spanning a large dynamic range. The changes in mRNA levels of these miR-124 targets were larger than the changes in translation, with average decreases of 35% and 12%, respectively. Further, there was no identifiable subgroup of mRNA targets for which the translational response was dominant. Both ribosome occupancy (the fraction of a given gene's transcripts associated with ribosomes and ribosome density (the average number of ribosomes bound per unit length of coding sequence were selectively reduced for hundreds of miR-124 targets by the presence of miR-124. Changes in protein abundance inferred from the observed changes in mRNA abundance and translation profiles closely matched changes directly determined by Western analysis for 11 of 12 proteins, suggesting that our assays captured most of miR-124-mediated regulation. These results suggest that miRNAs inhibit translation initiation or stimulate ribosome drop-off preferentially near the
Li, Chen; Ge, Ling-ling; Li, Peng-peng; Wang, Yue; Dai, Juan-juan; Sun, Ming-xia; Huang, Li; Shen, Zhi-qiang; Hu, Xiao-chun; Ishag, Hassan; Mao, Xiang
Japanese encephalitis virus is one of the most common causes for epidemic viral encephalitis in humans and animals. Herein we demonstrated that cellular helicase DDX3 is involved in JEV replication. DDX3 knockdown inhibits JEV replication. The helicase activity of DDX3 is crucial for JEV replication. GST-pulldown and co-immunoprecipitation experiments demonstrated that DDX3 could interact with JEV non-structural proteins 3 and 5. Co-immunoprecipitation and confocal microscopy analysis confirmed that DDX3 interacts and colocalizes with these viral proteins and viral RNA during the infection. We determined that DDX3 binds to JEV 5' and 3' un-translated regions. We used a JEV-replicon system to demonstrate that DDX3 positively regulates viral RNA translation, which might affect viral RNA replication at the late stage of virus infection. Collectively, we identified that DDX3 is necessary for JEV infection, suggesting that DDX3 might be a novel target to design new antiviral agents against JEV or other flavivirus infections.
Castaño, Aurora; Ruiz, Leticia; Hernández, Carmen
Pelargonium line pattern virus (PLPV), a proposed member of a prospective genus (Pelarspovirus) within family Tombusviridae, has a positive-sense, single-stranded genomic RNA. According to previous predictions, it contains six open reading frames (ORFs) potentially encoding proteins of 27 (p27), 13 (p13), 87 (p87), 7 (p7), 6 (p6), and 37 kDa (p37). Using a variety of techniques we demonstrate that all predicted ORFs are functional, with the exception of (p13) and (p6). We also characterize a previously unidentified ORF which encodes a 9.7 kDa protein (p9.7) that is essential for viral movement. Furthermore, we present evidence that the single subgenomic RNA (sgRNA) produced by the virus directs synthesis of p7, p9.7 and p37. Remarkably, the translation of these totally unrelated proteins is coordinated via leaky-scanning. This mechanism seems to be favoured by the poor translation context of the start codon of ORF(p7), the non-AUG weak initiation codon of ORF(p9.7) and the lack of additional AUG codons in any reading frame preceding ORF(p37). The results also suggest that precise regulation of protein production from the sgRNA is critical for virus viability. Altogether, the data supports the notion that PLPV belongs to a new genus of plant viruses.
David J Leslie
Full Text Available Bacteria can arrest their own growth and proliferation upon nutrient depletion and under various stressful conditions to ensure their survival. However, the molecular mechanisms responsible for suppressing growth and arresting the cell cycle under such conditions remain incompletely understood. Here, we identify post-transcriptional mechanisms that help enforce a cell-cycle arrest in Caulobacter crescentus following nutrient limitation and during entry into stationary phase by limiting the accumulation of DnaA, the conserved replication initiator protein. DnaA is rapidly degraded by the Lon protease following nutrient limitation. However, the rate of DnaA degradation is not significantly altered by changes in nutrient availability. Instead, we demonstrate that decreased nutrient availability downregulates dnaA translation by a mechanism involving the 5' untranslated leader region of the dnaA transcript; Lon-dependent proteolysis of DnaA then outpaces synthesis, leading to the elimination of DnaA and the arrest of DNA replication. Our results demonstrate how regulated translation and constitutive degradation provide cells a means of precisely and rapidly modulating the concentration of key regulatory proteins in response to environmental inputs.
Van Lehn, Reid C; Zhang, Bin; Miller, Thomas F
The canonical mechanism for multispanning membrane protein topogenesis suggests that protein topology is established during cotranslational membrane integration. However, this mechanism is inconsistent with the behavior of EmrE, a dual-topology protein for which the mutation of positively charged loop residues, even close to the C-terminus, leads to dramatic shifts in its topology. We use coarse-grained simulations to investigate the Sec-facilitated membrane integration of EmrE and its mutants on realistic biological timescales. This work reveals a mechanism for regulating membrane-protein topogenesis, in which initially misintegrated configurations of the proteins undergo post-translational annealing to reach fully integrated multispanning topologies. The energetic barriers associated with this post-translational annealing process enforce kinetic pathways that dictate the topology of the fully integrated proteins. The proposed mechanism agrees well with the experimentally observed features of EmrE topogenesis and provides a range of experimentally testable predictions regarding the effect of translocon mutations on membrane protein topogenesis.
Full Text Available B-cell lymphoma 2 protein (BCL-2 is one of the more widely investigated anti-apoptotic protein in mammals, and its levels are critical for protecting from programmed cell death. We report here that the cellular content of BCL-2 is regulated at post-translational level along the autophagy/lysosome pathways in organotypic cultures of post-natal mouse cerebellar cortex. Specifically this mechanism appears to be effective in the cerebellar granule cells (CGCs that are known to undergo massive programmed cell death (apoptosis during post-natal maturation. By the use of specific agonists/antagonist of calcium channels at the endoplasmic reticulum it was possible to understand the pivotal role of calcium release from intracellular stores in CGC neuroprotection. The more general significance of these findings is supported by a very recent study Niemann-Pick transgenic mice.
Full Text Available Nucleoplasmin (Npm is an abundant histone chaperone in vertebrate oocytes and embryos. During embryogenesis, regulation of Npm histone binding is critical for its function in storing and releasing maternal histones to establish and maintain the zygotic epigenome. Here, we demonstrate that Xenopus laevis Npm post-translational modifications (PTMs specific to the oocyte and egg promote either histone deposition or sequestration, respectively. Mass spectrometry and Npm phosphomimetic mutations used in chromatin assembly assays identified hyperphosphorylation on the N-terminal tail as a critical regulator for sequestration. C-terminal tail phosphorylation and PRMT5-catalyzed arginine methylation enhance nucleosome assembly by promoting histone interaction with the second acidic tract of Npm. Electron microscopy reconstructions of Npm and TTLL4 activity toward the C-terminal tail demonstrate that oocyte- and egg-specific PTMs cause Npm conformational changes. Our results reveal that PTMs regulate Npm chaperoning activity by modulating Npm conformation and Npm-histone interaction, leading to histone sequestration in the egg.
Lin Xu; Li Yang; Hai Huang
Leaf morphogenesis requires the establishment of adaxial-abaxial polarity after primordium initiation from the shoot apical meristem (SAM). Several families of transcription factors are known to play critical roles in promoting adaxial or abaxial leaf fate. Recently, post-transcriptional gene silencing pathways have been shown to regulate the establishment of leaf polarity, providing novel and exciting insights into leaf development. For example, microRNAs (miR165/166)and a trans-acting siRNA (TAS3-derived tasiR-ARF) have been shown to repress the expression of several key transcription factor genes. In addition, yet another level of regulation, post-translational regulation, has been revealed recently by studies on the role of the 26S proteasome in leaf polarity. Although our understanding regarding the molecular mechanisms underlying establishment of adaxial-abaxial polarity has greatly improved, there is still much that remains elusive.This review aims to discuss recent progress, as well as the remaining questions, regarding the molecular mechanisms underlying leaf polarity formation.
John R. Sinnamon; Kevin Czaplinski
Localized translation and the requisite trafficking of the mRNA template play significant roles in the nervous system including the establishment of dendrites and axons,axon path-finding,and synaptic plasticity.We provide a brief review on the regulation of localizing mRNA in mammalian neurons through critical posttranslational modifications of the factors involved.These examples highlight the relationship between mRNA trafficking and the translational regulation of trafficked mRNAs and provide insight into how extracellular signals target these events during signal transduction.
Robert H Jenkins
Full Text Available Transforming growth factor-β(1 (TGF-β(1 regulates cellular proliferation, differentiation, migration, and survival. The human TGF-β(1 transcript is inherently poorly translated, and translational activation has been documented in relation to several stimuli. In this paper, we have sought to identify in cis regulatory elements within the TGF-β(1 5'Untranslated Region (5'UTR. In silico analysis predicted formation of stable secondary structure in a G/C-rich element between nucleotides +77 to +106, and demonstrated that this element is highly conserved across species. Circular dichroism spectroscopy confirmed the presence of secondary structure in this region. The proximal 5'UTR was inhibitory to translation in reporter gene experiments, and mutation of the secondary structure motif increased translational efficiency. Translational regulation of TGF-β(1 mRNA is linked to altered binding of YB-1 protein to its 5'UTR. Immunoprecipitation-RT-qPCR demonstrated a high basal association of YB-1 with TGF-β(1 mRNA. However, mutation of the secondary structure motif did not prevent interaction of YB-1 with the 5'UTR, suggesting that YB-1 binds to this region due to its G/C-rich composition, rather than a specific, sequence-dependent, binding site. These data identify a highly conserved element within the TGF-β(1 5'UTR that forms stable secondary structure, and is responsible for the inherent low translation efficiency of this cytokine.
Full Text Available The peroxisome proliferator-activated receptor gamma (PPARγ regulates osteoblast and osteoclast differentiation, and is the molecular target of thiazolidinediones (TZDs, insulin sensitizers that enhance glucose utilization and adipocyte differentiation. However, clinical use of TZDs has been limited by side effects including a higher risk of fractures and bone loss. Here we demonstrate that the same post-translational modifications at S112 and S273, which influence PPARγ pro-adipocytic and insulin sensitizing activities, also determine PPARγ osteoblastic (pS112 and osteoclastic (pS273 activities. Treatment of either hyperglycemic or normoglycemic animals with SR10171, an inverse agonist that blocks pS273 but not pS112, increased trabecular and cortical bone while normalizing metabolic parameters. Additionally, SR10171 treatment modulated osteocyte, osteoblast, and osteoclast activities, and decreased marrow adiposity. These data demonstrate that regulation of bone mass and energy metabolism shares similar mechanisms suggesting that one pharmacologic agent could be developed to treat both diabetes and metabolic bone disease.
Full Text Available The present study sought to investigate the probable link between Iranian English translation studies students’ metacognitive awareness, self-regulation, and gender. Furthermore, the role of educational level of translation students in metacognitive awareness and self-regulation was explored. For the purpose of the study, a sample of 230 M.A and B.A senior English translation students comprised the participants of the research. They were asked to complete two questionnaires of Metacognitive Awareness Inventory (MAI and Self-regulation Trait (SRT.The Metacognitive Awareness Inventory (MAI was developed by Schraw and Dennison (1994 and consists of 52 statements. It measures two components of metacognition: metacognitive knowledge and metacognitive regulation. Metacognitive knowledge comprises three subscales: Declarative knowledge, Procedural knowledge, and Conditional knowledge. Metacognitive regulation consists of five subscales: Planning, Information management, Monitoring, Debugging, and Evaluation. The self-regulation trait (SRT questionnaire was designed by O'Neil and Herl (1998. It was developed based on Zimmerman's self –regulation model. It consists of 32 Likert-scale questions. The scale seeks to measure metacognition and motivation dimensions. Each dimension comprises two sub-scales. Meta-cognition covers the constructs of planning and self-monitoring, and motivation contains effort and self-efficacy. Independent samples t-tests were run to investigate the role of gender and educational level in the level of translation students’ metacognitive awareness and self-regulation. The results of t-test demonstrated that there are not any differences between male and female translation students regarding metacognitive awareness and self-regulation. It was also found that there is a negative significant impact of educational level on total metacognitive awareness, and some components of metacognitive awareness: declarative knowledge
Full Text Available 17223959 Translational mini-review series on Toll-like receptors: networks regulate...ol. 2007 Feb;147(2):199-207. (.png) (.svg) (.html) (.csml) Show Translational mini-review series on Toll-like receptors: network... immunity. PubmedID 17223959 Title Translational mini-review series on Toll-like receptors: networks regulat
Reshetnikov, M M
The efficiency of specific psychophysiological preparation--autogenic training--to parachute jumps was measured in two groups of cadets (test subjects and controls). Hetero- and autogenic training was carried out according to a scheme specially developed for this type of activity. The study of questionnaires and physiological data demonstrated that the specific psychophysiological preparation by means of autogenic training for a certain type of activity helped to develop active self-control over one's own state and emotions, alleviated tension, arrested adverse neurotic manifestations (sleep disturbances, depression, anxiety), contributed to the feeling of confidence in the successful completion of the jump and promoted positive tuning towards subsequent jumps.
Full Text Available The transcription factor Nrf2 is the master regulator of a cellular defense mechanism against environmental insults. The Nrf2-mediated antioxidant response is accomplished by the transcription of a battery of genes that encode phase II detoxifying enzymes, xenobiotic transporters, and antioxidants. Coordinated expression of these genes is critical in protecting cells from toxic and carcinogenic insults and in maintaining cellular redox homeostasis. Activation of the Nrf2 pathway is primarily controlled by Kelch-like ECH-associated protein 1 (Keap1, which is a molecular switch that turns on or off the Nrf2 signaling pathway according to intracellular redox conditions. Here we report our finding of a novel Nrf2 suppressor ectodermal-neural cortex 1 (ENC1, which is a BTB-Kelch protein and belongs to the same family as Keap1. Transient expression of ENC1 reduced steady-state levels of Nrf2 and its downstream gene expression. Although ENC1 interacted with Keap1 indirectly, the ENC1-mediated down-regulation of Nrf2 was independent of Keap1. The negative effect of ENC1 on Nrf2 was not due to a change in the stability of Nrf2 because neither proteasomal nor lysosomal inhibitors had any effects. Overexpression of ENC1 did not result in a change in the level of Nrf2 mRNA, rather, it caused a decrease in the rate of Nrf2 protein synthesis. These results demonstrate that ENC1 functions as a negative regulator of Nrf2 through suppressing Nrf2 protein translation, which adds another level of complexity in controlling the Nrf2 signaling pathway.
Laberge, Remi-Martin; Sun, Yu; Orjalo, Arturo V; Patil, Christopher K; Freund, Adam; Zhou, Lili; Curran, Samuel C; Davalos, Albert R; Wilson-Edell, Kathleen A; Liu, Su; Limbad, Chandani; Demaria, Marco; Li, Patrick; Hubbard, Gene B; Ikeno, Yuji; Javors, Martin; Desprez, Pierre-Yves; Benz, Christopher C; Kapahi, Pankaj; Nelson, Peter S; Campisi, Judith
The TOR (target of rapamycin) kinase limits longevity by poorly understood mechanisms. Rapamycin suppresses the mammalian TORC1 complex, which regulates translation, and extends lifespan in diverse species, including mice. We show that rapamycin selectively blunts the pro-inflammatory phenotype of s
Qu, Xiaoling; Afelik, Solomon; Jensen, Jan Nygaard
protein stabilization in the normal mouse pancreas explants. We conclude that the mutually exclusive expression pattern of Ngn3/Hes1 proteins in the mammalian pancreas is partially controlled through Notch-mediated post-translational regulation and we demonstrate that the formation of insulin...
Cruz, Lissette A; Vedula, Pavan; Gutierrez, Natasha; Shah, Neel; Rodriguez, Steven; Ayee, Brian; Davis, Justin; Rodriguez, Alexis J
Regulating adherens junction complex assembly/disassembly is critical to maintaining epithelial homeostasis in healthy epithelial tissues. Consequently, adherens junction structure and function is often perturbed in clinically advanced tumors of epithelial origin. Some of the most studied factors driving adherens junction complex perturbation in epithelial cancers are transcriptional and epigenetic down-regulation of E-cadherin expression. However, numerous reports demonstrate that post-translational regulatory mechanisms such as endocytosis also regulate early phases of epithelial-mesenchymal transition and metastatic progression. In already assembled healthy epithelia, E-cadherin endocytosis recycles cadherin-catenin complexes to regulate the number of mature adherens junctions found at cell-cell contact sites. However, following de novo epithelial cell-cell contact, endocytosis negatively regulates adherens junction assembly by removing E-cadherin from the cell surface. By contrast, following de novo epithelial cell-cell contact, spatially localized β-actin translation drives cytoskeletal remodeling and consequently E-cadherin clustering at cell-cell contact sites and therefore positively regulates adherens junction assembly. In this report we demonstrate that dynamin-mediated endocytosis and β-actin translation-dependent cadherin-catenin complex anchoring oppose each other following epithelial cell-cell contact. Consequently, the final extent of adherens junction assembly depends on which of these processes is dominant following epithelial cell-cell contact. We expressed β-actin transcripts impaired in their ability to properly localize monomer synthesis (Δ3'UTR) in MDCK cells to perturb actin filament remodeling and anchoring, and demonstrate the resulting defect in adherens junction structure and function is rescued by inhibiting dynamin mediated endocytosis. Therefore, we demonstrate balancing spatially regulated β-actin translation and dynamin
Zakershahrak, Mehrsa; Moshari, Amirabbas; Vatanpour, Mehdi; Khalilak, Zohreh; Jalali Ara, Afsoon
Autogenous tooth transplantation (ATT) is a simple and reasonable choice for replacing the missing teeth when a proper donor tooth is available. This report presents a case of successful ATT of a maxillary right third molar for replacement of mandibular right second molar with a concomitant endodontic-periodontal disease. The mandibular second molar was believed to be hopeless due to a severe damage to coronal tooth structure, inappropriate root canal treatment and apical radiolucency. After extraction of mandibular second molar and maxillary third molar (the donor), the tooth was re-implanted into the extracted socket of second molar site. Root canal therapy was then performed. After 3 years, clinical and radiographic examinations revealed satisfying results, with no signs and symptoms. The patient is asymptomatic and the transplanted tooth is still functional with no signs of marginal periodontal pathosis. Radiographies showed bone regeneration in the site of previous extensive periapical lesion, normal periodontal ligament with no signs of root resorption. PMID:28179939
Wang, Yu-Chieh; Peterson, Suzanne E; Loring, Jeanne F
Post-translational modifications (PTMs) are known to be essential mechanisms used by eukaryotic cells to diversify their protein functions and dynamically coordinate their signaling networks. Defects in PTMs have been linked to numerous developmental disorders and human diseases, highlighting the importance of PTMs in maintaining normal cellular states. Human pluripotent stem cells (hPSCs), including embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), are capable of self-renewal and differentiation into a variety of functional somatic cells; these cells hold a great promise for the advancement of biomedical research and clinical therapy. The mechanisms underlying cellular pluripotency in human cells have been extensively explored in the past decade. In addition to the vast amount of knowledge obtained from the genetic and transcriptional research in hPSCs, there is a rapidly growing interest in the stem cell biology field to examine pluripotency at the protein and PTM level. This review addresses recent progress toward understanding the role of PTMs (glycosylation, phosphorylation, acetylation and methylation) in the regulation of cellular pluripotency.
Full Text Available The perception of reactive oxygen species (ROS has evolved over the past decade from agents of cellular damage to secondary messengers which modify signaling proteins in physiology and the disease state (e.g. cancer. New protein targets of specific oxidation are rapidly being identified. One emerging class of redox modification occurs to the thiol side chain of cysteine residues which can produce multiple chemically-distinct alterations to the protein (e.g. sulfenic/sulfinic/sulfonic acid, disulfides. These post-translational modifications (PTM are shown to affect the protein structure and function. Because redox-sensitive proteins can traffic between subcellular compartments that have different redox environments, cysteine oxidation enables a spatio-temporal control to signaling. Understanding ramifications of these oxidative modifications to the functions of signaling proteins is crucial for understanding cellular regulation as well as for informed-drug discovery process. The effects of EGFR oxidation of Cys797 on inhibitor pharmacology are presented to illustrate the principle. Taken together, cysteine redox PTM can impact both cell biology and drug pharmacology.
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.
von Arnim, Albrecht G. [Univ. of Tennessee, Knoxville, TN (United States)
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.
Newton, Derek C; Bevan, Sian C; Choi, Stephen; Robb, G Brett; Millar, Adam; Wang, Yang; Marsden, Philip A
Expression of the neuronal nitric-oxide synthase (nNOS) mRNA is subject to complex cell-specific transcriptional regulation, which is mediated by alternative promoters. Unexpectedly, we identified a 89-nucleotide alternatively spliced exon located in the 5'-untranslated region between exon 1 variants and a common exon 2 that contains the translational initiation codon. Alternative splicing events that do not affect the open reading frame are distinctly uncommon in mammals; therefore, we assessed its functional relevance. Transient transfection of reporter RNAs performed in a variety of cell types revealed that this alternatively spliced exon acts as a potent translational repressor. Stably transfected cell lines confirmed that the alternatively spliced exon inhibited translation of the native nNOS open reading frame. Reverse transcription-PCR and RNase protection assays indicated that nNOS mRNAs containing this exon are common and expressed in both a promoter-specific and tissue-restricted fashion. Mutational analysis identified the functional cis-element within this novel exon, and a secondary structure prediction revealed that it forms a putative stem-loop. RNA electrophoretic mobility shift assay techniques revealed that a specific cytoplasmic RNA-binding complex interacts with this motif. Hence, a unique splicing event within a 5'-untranslated region is demonstrated to introduce a translational control element. This represents a newer model for the translational control of a mammalian mRNA.
Full Text Available Mature Drosophila sperm are highly polarized cells--on one side is a nearly 2 mm long flagellar tail that comprises most of the cell, while on the other is the sperm head, which carries the gamete's genetic information. The polarization of the sperm cells commences after meiosis is complete and the 64-cell spermatid cyst begins the process of differentiation. The spermatid nuclei cluster to one side of the cyst, while the flagellar axonemes grows from the other. The elongating spermatid bundles are also polarized with respect to the main axis of the testis; the sperm heads are always oriented basally, while the growing tails extend apically. This orientation within the testes is important for transferring the mature sperm into the seminal vesicles. We show here that orienting cyst polarization with respect to the main axis of the testis depends upon atypical Protein Kinase C (aPKC, a factor implicated in polarity decisions in many different biological contexts. When apkc activity is compromised in the male germline, the direction of cyst polarization within this organ is randomized. Significantly, the mechanisms used to spatially restrict apkc activity to the apical side of the spermatid cyst are different from the canonical cross-regulatory interactions between this kinase and other cell polarity proteins that normally orchestrate polarization. We show that the asymmetric accumulation of aPKC protein in the cyst depends on an mRNA localization pathway that is regulated by the Drosophila CPEB protein Orb2. orb2 is required to properly localize and activate the translation of apkc mRNAs in polarizing spermatid cysts. We also show that orb2 functions not only in orienting cyst polarization with respect to the apical-basal axis of the testis, but also in the process of polarization itself. One of the orb2 targets in this process is its own mRNA. Moreover, the proper execution of this orb2 autoregulatory pathway depends upon apkc.
Jovanovic, G; Dworkin, J; Model, P
Escherichia coli sigma54-dependent phage shock protein operon (pspA to -E) transcription is under the control of PspF, a constitutively active activator. Sigma70-dependent transcription of pspF is under autogenous control by wild-type PspF but not by a DNA-binding mutant, PspF deltaHTH. Negative autoregulation of PspF is continual and not affected by stimuli, like f1 pIV, that induce the pspA to -E operon. PspF production is independent of PspA (the negative regulator of the pspA to -E operon...
Chang, K S; Lee, S H; Hwang, S B; Park, K Y
Arginine decarboxylase (ADC; EC 188.8.131.52) is a key enzyme in polyamine biosynthesis in plants. We characterized a carnation genomic clone, gDcADC8, in which the deduced polypeptide of ADC was 725 amino acids with a molecular mass of 77.7 kDa. The unusually long 5'-UTR that contained a short upstream open reading frame (uORF) of seven amino acids (MQKSLHI) was predicted to form an extensive secondary structure (free energy of approximately -117 kcal mol-1) using the Zuker m-fold algorithm. The result that an ADC antibody detected two bands of 45 and 33 kDa in a petal extract suggested the full length of the 78 kDa polypeptide precursor converted into two polypeptides in the processing reaction. To investigate the role of the transcript leader in translation, in vitro transcription/translation reactions with various constructs of deletion and mutation were performed using wheat germ extract. The ADC transcript leader affected positively downstream translation in both wheatgerm extract and primary transformant overexpressing ADC gene. It was demonstrated that heptapeptide (8.6 kDa) encoded by the ADC uORF was synthesized in vitro. Both uORF peptide, and the synthetic heptapeptide MQKSLHI of the uORF, repressed the translation of downstream ORF. Mutation of the uORF ATG codon alleviated the inhibitory effect. ORF translation was not affected by either a frame-shift mutation in uORF or a random peptide. To our knowledge, this is the first report to provide evidence that a uORF may inhibit the translation of a downstream ORF, not only in cis but also in trans, and that the leader sequence of the ADC gene is important for efficient translation.
Full Text Available Spinocerebellar ataxia type 2 (SCA2 is an autosomal dominant disorder with progressive degeneration of cerebellar Purkinje cells (PCs and other neurons caused by expansion of a glutamine (Q tract in the ATXN2 protein. We generated BAC transgenic lines in which the full-length human ATXN2 gene was transcribed using its endogenous regulatory machinery. Mice with the ATXN2 BAC transgene with an expanded CAG repeat (BAC-Q72 developed a progressive cellular and motor phenotype, whereas BAC mice expressing wild-type human ATXN2 (BAC-Q22 were indistinguishable from control mice. Expression analysis of laser-capture microdissected (LCM fractions and regional expression confirmed that the BAC transgene was expressed in PCs and in other neuronal groups such as granule cells (GCs and neurons in deep cerebellar nuclei as well as in spinal cord. Transcriptome analysis by deep RNA-sequencing revealed that BAC-Q72 mice had progressive changes in steady-state levels of specific mRNAs including Rgs8, one of the earliest down-regulated transcripts in the Pcp2-ATXN2[Q127] mouse line. Consistent with LCM analysis, transcriptome changes analyzed by deep RNA-sequencing were not restricted to PCs, but were also seen in transcripts enriched in GCs such as Neurod1. BAC-Q72, but not BAC-Q22 mice had reduced Rgs8 mRNA levels and even more severely reduced steady-state protein levels. Using RNA immunoprecipitation we showed that ATXN2 interacted selectively with RGS8 mRNA. This interaction was impaired when ATXN2 harbored an expanded polyglutamine. Mutant ATXN2 also reduced RGS8 expression in an in vitro coupled translation assay when compared with equal expression of wild-type ATXN2-Q22. Reduced abundance of Rgs8 in Pcp2-ATXN2[Q127] and BAC-Q72 mice supports our observations of a hyper-excitable mGluR1-ITPR1 signaling axis in SCA2, as RGS proteins are linked to attenuating mGluR1 signaling.
Full Text Available Reductive stress leads to the loss of disulfide bond formation and induces the unfolded protein response of the endoplasmic reticulum (UPRER, necessary to regain proteostasis in the compartment. Here we show that peroxide accumulation during reductive stress attenuates UPRER amplitude by altering translation without any discernible effect on transcription. Through a comprehensive genetic screen in Saccharomyces cerevisiae, we identify modulators of reductive stress-induced UPRER and demonstrate that oxidative quality control (OQC genes modulate this cellular response in the presence of chronic but not acute reductive stress. Using a combination of microarray and relative quantitative proteomics, we uncover a non-canonical translation attenuation mechanism that acts in a bipartite manner to selectively downregulate highly expressed proteins, decoupling the cell’s transcriptional and translational response during reductive ER stress. Finally, we demonstrate that PERK, a canonical translation attenuator in higher eukaryotes, helps in bypassing a ROS-dependent, non-canonical mode of translation attenuation.
Chen, Hong; Hao, Yuqing; Wang, Lijing; Jia, Dongwei [Gene Research Center, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Ruan, Yuanyuan, E-mail: firstname.lastname@example.org [Gene Research Center, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Gu, Jianxin [Gene Research Center, Shanghai Medical College, Fudan University, Shanghai 200032 (China)
Highlights: Black-Right-Pointing-Pointer Sodium arsenite down-regulates the protein expression level of XIAP in HCC. Black-Right-Pointing-Pointer Sodium arsenite inhibits the de novo XIAP synthesis and its IRES activity. Black-Right-Pointing-Pointer Sodium arsenite decreases XIAP stability and promotes its proteasomal degradation. Black-Right-Pointing-Pointer Overexpression of XIAP attenuates the pro-apoptotic effect of sodium arsenite. -- Abstract: X-linked inhibitor of apoptosis protein (XIAP) is a member of the inhibitors of apoptosis protein (IAP) family, and has been reported to exhibit elevated expression levels in hepatocellular carcinoma (HCC) and promote cell survival, metastasis and tumor recurrence. Targeting XIAP has proven effective for the inhibition of cancer cell proliferation and restoration of cancer cell chemosensitivity. Arsenic (or sodium arsenite) is a potent anti-tumor agent used to treat patients with acute promyelocytic leukemia (APL). Additionally, arsenic induces cell growth inhibition, cell cycle arrest and apoptosis in human HCC cells. In this study, we identified XIAP as a target for sodium arsenite-induced cytotoxicity in HCC. The exposure of HCC cell lines to sodium arsenite resulted in inhibition of XIAP expression in both a dose- and time-dependent manner. Sodium arsenite blocked the de novo XIAP synthesis and the activity of its internal ribosome entry site (IRES) element. Moreover, treatment with sodium arsenite decreased the protein stability of XIAP and induced its ubiquitin-proteasomal degradation. Overexpression of XIAP attenuated the pro-apoptotic effect of sodium arsenite in HCC. Taken together, our data demonstrate that sodium arsenite suppresses XIAP expression via translational and post-translational mechanisms in HCC.
Weston, Andrew; Sommerville, John
The DEAD-box RNA helicase Xp54 is an integral component of the messenger ribonucleoprotein (mRNP) particles of Xenopus oocytes. In oocytes, several abundant proteins bind pre-mRNA transcripts to modulate nuclear export, RNA stability and translational fate. Of these, Xp54, the mRNA-masking protein FRGY2 and its activating protein kinase CK2α, bind to nascent transcripts on chromosome loops, whereas an Xp54-associated factor, RapA/B, binds to the mRNP complex in the cytoplasm. Over-expression, mutation and knockdown experiments indicate that Xp54 functions to change the conformation of mRNP complexes, displacing one subset of proteins to accommodate another. The sequence of Xp54 is highly conserved in a wide spectrum of organisms. Like Xp54, Drosophila Me31B and Caenorhabditis CGH-1 are required for proper meiotic development, apparently by regulating the translational activation of stored mRNPs and also for sorting certain mRNPs into germplasm-containing structures. Studies on yeast Dhh1 and mammalian rck/p54 have revealed a key role for these helicases in mRNA degradation and in earlier remodelling of mRNP for entry into translation, storage or decay pathways. The versatility of Xp54 and related helicases in modulating the metabolism of mRNAs at all stages of their lifetimes marks them out as key regulators of post-transcriptional gene expression. PMID:16769775
Park, Seung Kuk; Jeong, Sunjoo
Gene expression is regulated at multiple steps, such as transcription, splicing, export, degradation and translation. Considering diverse roles of SR proteins, we determined whether the tumor-related splicing factor SRSF3 regulates the expression of the tumor-suppressor protein, PDCD4, at multiple steps. As we have reported previously, knockdown of SRSF3 increased the PDCD4 protein level in SW480 colon cancer cells. More interestingly, here we showed that the alternative splicing and the nuclear export of minor isoforms of pdcd4 mRNA were repressed by SRSF3, but the translation step was unaffected. In contrast, only the translation step of the major isoform of pdcd4 mRNA was repressed by SRSF3. Therefore, overexpression of SRSF3 might be relevant to the repression of all isoforms of PDCD4 protein levels in most types of cancer cell. We propose that SRSF3 could act as a coordinator of the expression of PDCD4 protein via two mechanisms on two alternatively spliced mRNA isoforms.
Vučićević, Dubravka; Gehre, Maja; Dhamija, Sonam; Friis-Hansen, Lennart; Meierhofer, David; Sauer, Sascha; Ørom, Ulf Andersson
Long non-coding RNAs are important regulators of gene expression and signaling pathways. The expression of long ncRNAs is dysregulated in cancer and other diseases. The identification and characterization of long ncRNAs is often challenging due to their low expression level and localization to chromatin. Here, we identify a functional long ncRNA, PARROT (Proliferation Associated RNA and Regulator Of Translation) transcribed by RNA polymerase II and expressed at a relatively high level in a number of cell lines. The PARROT long ncRNA is associated with proliferation in both transformed and normal cell lines. We characterize the long ncRNA PARROT as an upstream regulator of c-Myc affecting cellular proliferation and translation using RNA sequencing and mass spectrometry following depletion of the long ncRNA. PARROT is repressed during senescence of human mammary epithelial cells and overexpressed in some cancers, suggesting an important association with proliferation through regulation of c-Myc. With this study, we add to the knowledge of cytoplasmic functional long ncRNAs and extent the long ncRNA-Myc regulatory network in transformed and normal cells. PMID:27129154
Carlson, B.; Kim, W.; Piliouras, A.
ABSTRACT Autogenic processes are inherent processes in sediment transport that influence landscape building and leave distinct signatures in the sedimentary record. It is of great interest to understand autogenic processes in order to decouple internal processes from external controls, such as tectonics or climate change. Here we present results from a series of delta-building experiments to determine the variability of the fluviodeltaic autogenic timescale in response to varying basin water depth. This internal timescale was measured as the time that is required for the delta topset to be reworked through a full cycle of storage and release of sediment. The topset aggrades by fluvial sedimentation until it reaches a maximum slope, at which point a large amount of sediment starts to release, typically resulting in strong channelization. This is followed by a period of avulsions, lateral migration, and backfilling of channels on the topset. These storage and release events are repeated. We used time-lapse images to track shoreline positions and observe changes in progradation rate. The changes in topset topography were also used to determine storage and release duration. The experimental results indicate that the autogenic timescales generally increase with increasing basin water depth. These observations may be explained by the amount of time required to build a lobe with an area large enough to trigger a switch from a lobe-building release event to a backfilling storage event. Individual lobes show a similar surface area regardless of basin depth in the experiments. Deeper basin depth simply requires a larger volume to be filled within this area, thus more time to complete one autogenic process. However, when channel depth is significantly smaller than basin depth, e.g., in very deep basins, stochastic variability in sediment transport and channel lateral mobility outweighs the autogenic cyclicity. This study suggests that internal dynamics and its stratigraphic
Full Text Available PUF proteins are post-transcriptional regulators that bind to the 3′ UTRs of mRNA transcripts. Herein, we show how a yeast PUF protein, Puf3p, responds to glucose availability to switch the fate of its bound transcripts that encode proteins required for mitochondrial biogenesis. Upon glucose depletion, Puf3p becomes heavily phosphorylated within its N-terminal region of low complexity, associates with polysomes, and promotes translation of its target mRNAs. Such nutrient-responsive phosphorylation toggles the activity of Puf3p to promote either degradation or translation of these mRNAs according to the needs of the cell. Moreover, activation of translation of pre-existing mRNAs might enable rapid adjustment to environmental changes without the need for de novo transcription. Strikingly, a Puf3p phosphomutant no longer promotes translation but becomes trapped in intracellular foci in an mRNA-dependent manner. Our findings suggest that the inability to properly resolve Puf3p-containing RNA-protein granules via a phosphorylation-based mechanism might be toxic to a cell.
Bunnik, Evelien M; Le Roch, Karine G
During the asexual replication cycle of the malaria parasite Plasmodium falciparum, the RNA-binding protein PfAlba1 binds and stabilizes a subset of transcripts for translation at a later time point.Please see related Research article: http://www.genomebiology.com/2015/16/1/212.
Gingold, Hila; Tehler, Disa; Christoffersen, Nanna R;
and their corresponding tRNAs, and in multicellularity genes and their tRNAs, suggesting the existence of transcriptional programs coordinating tRNA supply and demand. Hence, we describe the existence of two distinct translation programs that operate during proliferation and differentiation....
Molon, Barbara; Viola, Antonella; Bronte, Vincenzo
We described a novel tumor-associated immunosuppressive mechanism based on post-translational modifications of chemokines by reactive nitrogen species (RNS). To overcome tumor immunosuppressive hindrances, we designed and developed a new drug, AT38, that inhibits RNS generation at the tumor site. Combinatorial approaches with AT38 boost the effectiveness of cancer immunotherapy protocols.
Thandapani, Palaniraja; Song, Jingwen; Gandin, Valentina; Cai, Yutian; Rouleau, Samuel G; Garant, Jean-Michel; Boisvert, Francois-Michel; Yu, Zhenbao; Perreault, Jean-Pierre; Topisirovic, Ivan; Richard, Stéphane
G-quadruplexes (G4) are extremely stable secondary structures forming stacks of guanine tetrads. DNA G4 structures have been extensively studied, however, less is known about G4 motifs in mRNAs, especially in their coding sequences. Herein, we show that Aven stimulates the mRNA translation of the mixed lineage leukemia (MLL) proto-oncogene in an arginine methylation-dependent manner. The Aven RGG/RG motif bound G4 structures within the coding regions of the MLL1 and MLL4 mRNAs increasing their polysomal association and translation, resulting in the induction of transcription of leukemic genes. The DHX36 RNA helicase associated with the Aven complex and was required for optimal translation of G4 mRNAs. Depletion of Aven led to a decrease in synthesis of MLL1 and MLL4 proteins resulting in reduced proliferation of leukemic cells. These findings identify an Aven-centered complex that stimulates the translation of G4 harboring mRNAs, thereby promoting survival of leukemic cells.
Voß, Björn; Maass, Dirk; Beyer, Peter
Phytoene synthase (PSY) catalyzes the highly regulated, frequently rate-limiting synthesis of the first biosynthetically formed carotene. While PSY constitutes a small gene family in most plant taxa, the Brassicaceae, including Arabidopsis (Arabidopsis thaliana), predominantly possess a single PSY gene. This monogenic situation is compensated by the differential expression of two alternative splice variants (ASV), which differ in length and in the exon/intron retention of their 5′UTRs. ASV1 contains a long 5′UTR (untranslated region) and is involved in developmentally regulated carotenoid formation, such as during deetiolation. ASV2 contains a short 5′UTR and is preferentially induced when an immediate increase in the carotenoid pathway flux is required, such as under salt stress or upon sudden light intensity changes. We show that the long 5′UTR of ASV1 is capable of attenuating the translational activity in response to high carotenoid pathway fluxes. This function resides in a defined 5′UTR stretch with two predicted interconvertible RNA conformations, as known from riboswitches, which might act as a flux sensor. The translation-inhibitory structure is absent from the short 5′UTR of ASV2 allowing to bypass translational inhibition under conditions requiring rapidly increased pathway fluxes. The mechanism is not found in the rice (Oryza sativa) PSY1 5′UTR, consistent with the prevalence of transcriptional control mechanisms in taxa with multiple PSY genes. The translational control mechanism identified is interpreted in terms of flux adjustments needed in response to retrograde signals stemming from intermediates of the plastid-localized carotenoid biosynthesis pathway. PMID:27729470
Lura, Pietro; Jensen, Ole Mejlhede
Volumetric measurement of autogenous strain is frequently performed by placing the fresh cement paste in a rubber membrane submerged in water. The volume change of the cement paste is measured by the amount of water displaced by the submerged sample. Volumetric and linear measurements of autogenous...... of the volumetric method. Water absorption is driven by a lowering of the water activity in the cement paste due to dissolved salts in the pore fluid and to self-desiccation. From the moment of casting, significant water uptake was registered in all experiments. This water uptake influenced the volumetric...... on the same cement pastes....
Lura, Pietro; Jensen, Ole Mejlhede
Volumetric measurement of autogenous strain is frequently performed by placing the fresh cement paste in a rubber membrane submerged in water. The volume change of the cement paste is measured by the amount of water displaced by the submerged sample. Volumetric and linear measurements of autogenous...... of the volumetric method. Water absorption is driven by a lowering of the water activity in the cement paste due to dissolved salts in the pore fluid and to self-desiccation. From the moment of casting, significant water uptake was registered in all experiments. This water uptake influenced the volumetric...... on the same cement pastes....
Full Text Available RD21-like proteases are ubiquitous, plant-specific papain-like proteases typified by carrying a C-terminal granulin domain. RD21-like proteases are involved in immunity and associated with senescence and various types of biotic and abiotic stresses. Here, we interrogated Arabidopsis RD21 regulation and trafficking by site-directed mutagenesis, agroinfiltration, western blotting, protease activity profiling and protein degradation. Using an introduced N-glycan sensor, deglycosylation experiments and glyco-engineered N. benthamiana plants, we show that RD21 passes through the Golgi where it becomes fucosylated. Our studies demonstrate that RD21 is regulated at three post-translational levels. Prodomain removal is not blocked in the catalytic Cys mutant, indicating that RD21 is activated by a proteolytic cascade. However, RD21 activation in Arabidopsis does not require vacuolar processing enzymes (VPEs or aleurain-like protease AALP. In contrast, granulin domain removal requires the catalytic Cys and His residues and is therefore autocatalytic. Furthermore, SDS can (re-activate latent RD21 in Arabidopsis leaf extracts, indicating the existence of a third layer of post-translational regulation, possibly mediated by endogenous inhibitors. RD21 causes a dominant protease activity in Arabidopsis leaf extracts, responsible for SDS-induced proteome degradation.
Pedraza, Neus; Ortiz, Raúl; Cornadó, Alba; Llobet, Artur; Aldea, Martí; Gallego, Carme
Local regulation of protein synthesis allows a neuron to rapidly alter the proteome in response to synaptic signals, an essential mechanism in synaptic plasticity that is altered in many neurological diseases. Synthesis of many synaptic proteins is under local control and much of this regulation occurs through structures termed RNA granules. KIS is a protein kinase that associates with stathmin, a modulator of the tubulin cytoskeleton. Furthermore, KIS is found in RNA granules and stimulates translation driven by the β-actin 3'UTR in neurites. Here we explore the physiological and molecular mechanisms underlying the action of KIS on hippocampal synaptic plasticity in mice. KIS downregulation compromises spine development, alters actin dynamics, and reduces postsynaptic responsiveness. The absence of KIS results in a significant decrease of protein levels of PSD-95, a postsynaptic scaffolding protein, and the AMPAR subunits GluR1 and GluR2 in a CPEB3-dependent manner. Underlying its role in spine maturation, KIS is able to suppress the spine developmental defects caused by CPEB3 overexpression. Moreover, either by direct or indirect mechanisms, KIS counteracts the inhibitory activity of CPEB3 on the GluR2 3'UTR at both mRNA translation and polyadenylation levels. Our study provides insights into the mechanisms that mediate dendritic spine morphogenesis and functional synaptic maturation, and suggests KIS as a link regulating spine cytoskeleton and postsynaptic activity in memory formation.
Smith, Jennifer A; Schmechel, Stephen C; Williams, Bryan R G; Silverman, Robert H; Schiff, Leslie A
Cellular translation is inhibited following infection with most strains of reovirus, but the mechanisms responsible for this phenomenon remain to be elucidated. The extent of host shutoff varies in a strain-dependent manner; infection with the majority of strains leads to strong host shutoff, while infection with strain Dearing results in minimal inhibition of cellular translation. A genetic study with reassortant viruses and subsequent biochemical analyses led to the hypothesis that the interferon-induced, double-stranded RNA-activated protein kinase, PKR, is responsible for reovirus-induced host shutoff. To directly determine whether PKR is responsible for reovirus-induced host shutoff, we used a panel of reovirus strains and mouse embryo fibroblasts derived from knockout mice. This approach revealed that PKR contributes to but is not wholly responsible for reovirus-induced host shutoff. Studies with cells lacking RNase L, the endoribonuclease component of the interferon-regulated 2',5'-oligoadenylate synthetase-RNase L system, demonstrated that RNase L also down-regulates cellular protein synthesis in reovirus-infected cells. In many viral systems, PKR and RNase L have well-characterized antiviral functions. An analysis of reovirus replication in cells lacking these molecules indicated that, while they contributed to host shutoff, neither PKR nor RNase L exerted an antiviral effect on reovirus growth. In fact, some strains of reovirus replicated more efficiently in the presence of PKR and RNase L than in their absence. Data presented in this report illustrate that the inhibition of cellular translation following reovirus infection is complex and involves multiple interferon-regulated gene products. In addition, our results suggest that reovirus has evolved effective mechanisms to avoid the actions of the interferon-stimulated antiviral pathways that include PKR and RNase L and may even benefit from their expression.
Chowdhury, N.; Wessel, R.A.
How should we conceive of regulation in the European context? This paper attempts to answer this by developing multilevel regulation as a theoretical concept. The basic aim of the paper is to explore the difference and convergence between regulation and governance and develop multilevel governance a
Full Text Available If we want to encompass adequately the wide-ranging field of human translation, it is necessary to include in translation studies (TS the concept of translator awareness (or translator consciousness, for that matter. However, this is more easily said than done, because this concept does not easily lend itself to definition, let alone to measurement, e. g., by investigating translator behaviour. To put it bluntly: Translator awareness is a fuzzy concept. Like many obviously difficult-to-define concepts, with which dialogue in TS is burdened, translator awareness lacks an articulated theory within which different forms of translator behaviour can be convincingly related to, or distinguished from, one another. Hence, TS has so far not tackled, at least not systematically, the issue of translator awareness. If we want to encompass adequately the wide-ranging field of human translation, it is necessary to include in translation studies (TS the concept of translator awareness (or translator consciousness, for that matter. However, this is more easily said than done, because this concept does not easily lend itself to definition, let alone to measurement, e. g., by investigating translator behaviour. To put it bluntly: Translator awareness is a fuzzy concept. Like many obviously difficult-to-define concepts, with which dialogue in TS is burdened, translator awareness lacks an articulated theory within which different forms of translator behaviour can be convincingly related to, or distinguished from, one another. Hence, TS has so far not tackled, at least not systematically, the issue of translator awareness.
@@ 1 Introduction Recent years have witnessed a significant growth of corpora heat. One of the many fields where corpora have a growing impact is translation, both at a descriptive and a practical level. Chesterman pointed out that the focus of Translation Studies shifted from translation itself to translators, from regulative to descriptive studies, from philosophical to empirical studies (Chesterman, 1998).
Laursen, Lisbeth Schmidt; Chan, Colin W; ffrench-Constant, Charles
Myelination in the central nervous system provides a unique example of how cells establish asymmetry. The myelinating cell, the oligodendrocyte, extends processes to and wraps multiple axons of different diameter, keeping the number of wraps proportional to the axon diameter. Local regulation...... translation of a key sheath protein, myelin basic protein (MBP), by reversing the inhibitory effect of the mRNA 3′UTR. During oligodendrocyte differentiation and myelination α6β1-integrin interacts with hnRNP-K, an mRNA-binding protein, which binds to MBP mRNA and translocates from the nucleus to the myelin...
Jing Zhang; Shannon N Tessier; Kyle K Biggar; Cheng-Wei Wu; Fabien Pifferi; Martine Perret; Kenneth B Storey
The gray mouse lemur (Microcebus murinus) is one of few primate species that is able to enter daily torpor or prolonged hibernation in response to environmental stresses. With an emerg-ing significance to human health research, lemurs present an optimal model for exploring molecular adaptations that regulate primate hypometabolism. A fundamental challenge is how to effectively regulate energy expensive cellular processes (e.g., transcription and translation) during transitions to/from torpor without disrupting cellular homeostasis. One such regulatory mechanism is reversi-ble posttranslational modification of selected protein targets that offers fine cellular control without the energetic burden. This study investigates the role of phosphorylation and/or acetylation in reg-ulating key factors involved in energy homeostasis (AMP-activated protein kinase, or AMPK, sig-naling pathway), mRNA translation (eukaryotic initiation factor 2a or eIF2a, eukaryotic initiation factor 4E or eIF4E, and initiation factor 4E binding protein or 4EBP), and gene transcription (his-tone H3) in six tissues of torpid and aroused gray mouse lemurs. Our results indicated selective tissue-specific changes of these regulatory proteins. The relative level of Thr172-phosphorylated AMPKa was significantly elevated in the heart but reduced in brown adipose tissue during daily torpor, as compared to the aroused lemurs, implicating the regulation of AMPK activity during daily torpor in these tissues. Interestingly, the levels of the phosphorylated eIFs were largely unal-tered between aroused and torpid animals. Phosphorylation and acetylation of histone H3 were examined as a marker for transcriptional regulation. Compared to the aroused lemurs, level of Ser10-phosphorylated histone H3 decreased significantly in white adipose tissue during torpor, sug-gesting global suppression of gene transcription. However, a significant increase in acetyl-histone H3 in the heart of torpid lemurs indicated a
Dunne, Matthew; Leicht, Stefan; Krichel, Boris; Thompson, Andrew; Gómez-Torres, Natalia; Garde, Sonia; Narbad, Arjan; Mayer, Melinda J.
Bacteriophages produce endolysins, which lyse the bacterial host cell to release newly produced virions. The timing of lysis is regulated and is thought to involve the activation of a molecular switch. We present a crystal structure of the activated endolysin CTP1L that targets Clostridium tyrobutyricum, consisting of a complex between the full-length protein and an N-terminally truncated C-terminal cell wall binding domain (CBD). The truncated CBD is produced through an internal translation start site within the endolysin gene. Mutants affecting the internal translation site change the oligomeric state of the endolysin and reduce lytic activity. The activity can be modulated by reconstitution of the full-length endolysin-CBD complex with free CBD. The same oligomerization mechanism applies to the CD27L endolysin that targets Clostridium difficile and the CS74L endolysin that targets Clostridium sporogenes. When the CTP1L endolysin gene is introduced into the commensal bacterium Lactococcus lactis, the truncated CBD is also produced, showing that the alternative start codon can be used in other bacterial species. The identification of a translational switch affecting oligomerization presented here has implications for the design of effective endolysins for the treatment of bacterial infections. PMID:26683375
David B. Kamadjaja
Full Text Available Background: The gold standard treatment to replace missing tooth is dental implants, however, in certain cases, such as in young patients its placement is contraindicated. Autogenous tooth transplantation, which has been widely done in Scandinavian countries for many years, may become a good alternative to overcome this problem. Purpose: This article attempted to provide information about the indication, treatment planning, surgical technique and the successful result of autogenous tooth transplantation. Case: A fifteen year old male patient presented with large caries and periapical disease of his lower left first molar, which was partially erupted and the roots was not fully formed in radiograph. Case management: Autogenous tooth transplantation procedure was performed consisting of extraction of #36, odontectomy of #38 followed by its implantation to socket #36 and fixation of the transplanted tooth to the adjacent teeth. Post operative evaluation was done on regular basis within 18 months period. There was no complaint, the tooth was clinically stable and no evidence of periodontal problem. Serial radiographs showed healing of alveolar bone and periodontal tissue, and the complete root formation was evident by 18 months post operatively. Conclusion: Autogenous tooth transplantation is a potential alternative to replace extracted tooth. Provided that the case be properly planned and operation carefully performed, successful result of this treatment can be achieved.
Tian, Qian; Jensen, Ole Mejlhede
A reliable technique to quantify autogenous strain is a prerequisite to numerical modeling in stress calculations for high performance concrete. The introducing of a special kind of corrugated tube mould helps to transforming volume strain measurement into liner strain measurement in horizontal...
Concrete is a brittle composite cementitious material that easily fractures under tensile loading. Microcracks can appear throughout the concrete prior to application of any load because of temperature-induced strain and autogenous and drying shrinkage. There is no doubt that these cracks provide pr
...-constantan or chromelalumel—and a potentiometer shall be used for all temperature measurements. (3) Syringe...) Temperature control. Each autotransformer shall be so adjusted that the temperature at the neck, mid-section... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Autogenous-ignition temperature test....
Savija, B.; Schlangen, E.
An experimental study of the influence of autogeneous healing on chloride ingress in cracked concrete is presented. In the study, two concrete mixtures (a Portland cement mix and a blast furnace slag mix), two healing regimes (submerged and fog room regime), two cracking ages (14 and 28 days), and m
Lura, Pietro; Jensen, Ole Mejlhede; Weiss, Jason
technique allows identification of microcracks while avoiding artefacts induced by unwanted restraint, drying, or temperature variations during sample preparation. Small cylindrical samples of cement paste are cast with steel rods of different diameters in their centre. The rods restrain the autogenous...
This review of controlled outcome research on Autogenic Training complements the literature by pooling narrative and quantitative approaches, by including only studies with experimental controls, by integrating the English and German literature, and by adding research findings published since the last review. Whereas previous reviews have already reported positive effects of Autogenic Training for migraine, insomnia, and test anxiety, additional supportive findings for angina pectoris, asthma, childbirth, eczema, hypertension, infertility, Raynaud's disease, and recovery from myocardial infarction are discussed here. The impact of protocol variations on outcome is described, and the specificity of Autogenic Training relative to other stress management techniques is highlighted. Quantitative findings suggested that Autogenic Training was associated with medium-sized pre- to posttreatment effects ranging from d = .43 for biological indices of change to d = .58 for psychological and behavioral indices thus matching effect sizes for other biobehavioral treatment techniques like biofeedback and muscular relaxation. Length of treatment did not affect clinical outcome. The discussion emphasizes how narrative and quantitative strategies complement one another.
Labbe, Elise L.
Compared autogenic feedback training with a waiting-list control group as a treatment for children (N=28) with migraine headaches. Children in the treatment condition were significantly improved at the end of treatment and at one-month and six-month follow-up. No improvement was found for the children in the control condition. (BH)
Cho, Seok Keun; Ryu, Moon Young; Shah, Pratik; Poulsen, Christian Peter; Yang, Seong Wook
Post-translational modifications (PTMs) of proteins are essential to increase the functional diversity of the proteome. By adding chemical groups to proteins, or degrading entire proteins by phosphorylation, glycosylation, ubiquitination, neddylation, acetylation, lipidation, and proteolysis, the complexity of the proteome increases, and this then influences most biological processes. Although small RNAs are crucial regulatory elements for gene expression in most eukaryotes, PTMs of small RNA microprocessor and RNA silencing components have not been extensively investigated in plants. To date, several studies have shown that the proteolytic regulation of AGOs is important for host-pathogen interactions. DRB4 is regulated by the ubiquitin-proteasome system, and the degradation of HYL1 is modulated by a de-etiolation repressor, COP1, and an unknown cytoplasmic protease. Here, we discuss current findings on the PTMs of microprocessor and RNA silencing components in plants. PMID:27440184
Mita, Toshinari; Mayanagi, Taira; Ichijo, Hiroshi; Fukumoto, Kentaro; Otsuka, Kotaro; Sakai, Akio; Sobue, Kenji
n-3 PUFAs are essential for neuronal development and brain function. However, the molecular mechanisms underlying their biological effects remain unclear. Here we examined the mechanistic action of docosahexaenoic acid (DHA), the most abundant n-3 polyunsaturated fatty acids in the brain. We found that DHA treatment of cortical neurons resulted in enhanced axon outgrowth that was due to increased axon elongation rates. DHA-mediated axon outgrowth was accompanied by the translational up-regulation of Tau and collapsin response mediator protein 2 (CRMP2), two important axon-related proteins, and the activation of Akt and p70 S6 kinase. Consistent with these findings, rapamycin, a potent inhibitor of mammalian target of rapamycin (mTOR), prevented DHA-mediated axon outgrowth and up-regulation of Tau and CRMP2. In addition, DHA-dependent activation of the Akt-mTOR-S6K pathway enhanced 5'-terminal oligopyrimidine tract-dependent translation of Tau and CRMP2. Therefore, our results revealed an important role for the Akt-mTOR-S6K pathway in DHA-mediated neuronal development.
Wu, J; Miller, B L
The Stunted protein (StuAp) is a member of a family of transcription factors that regulate fungal development and cell cycle progression. Regulated stuA gene expression is required for correct cell pattern formation during asexual reproduction (conidiation) and for initiation of the sexual reproductive cycle in Aspergillus nidulans. Transcriptional initiation from two different promoters yields overlapping mRNAs (stuA alpha and stuAbeta) that upon translation yield the same protein. Here we show that multiple regulatory mechanisms interact to control (i) developmental competence-dependent expression of both transcripts and (ii) induction-dependent expression of stuA alpha, but not stuAbeta, by the conidiation-specific Bristle (BrlAp) transcriptional activator. Quantitative levels of both mRNAs are further modulated by (i) an activator(s) located at a far-upstream upstream activation sequence, (ii) feedback regulation by StuAp, and (iii) positive translational regulation that requires the peptide product of a micro-open reading frame unique to the stuA alpha mRNA 5' untranslated region. Gradients in stuA alpha expression were most important for correct cell and tissue type development. Threshold requirements were as follows: metula-phialide differentiation < ascosporogenesis < cleistothecial shell-Hülle cell differentiation. Altered stuA expression affected conidiophore morphology and conidial yields quantitatively but did not alter the temporal development of cell types or conidiophore density. By contrast, the sexual cycle showed both temporal delay and quantitative reduction in the number of cleistothecial initials but normal morphogenesis of tissue types.
Michael J Shipston
Full Text Available Mechanisms that control surface expression and/or activity of large conductance calcium-activated potassium (BK channels are important determinants of their (pathophysiological function. Indeed, BK channel dysfunction is associated with major human disorders ranging from epilepsy to hypertension and obesity. S-acylation (S-palmitoylation represents a major reversible, post-translational modification controlling the properties and function of many proteins including ion channels. Recent evidence reveals that both pore-forming and regulatory subunits of BK channels are S-acylated and control channel trafficking and regulation by AGC-family protein kinases. The pore-forming α-subunit is S-acylated at two distinct sites within the N- and C-terminus, each site being regulated by different palmitoyl acyl transferases (zDHHCs and acyl thioesterases. (APTs. S-acylation of the N-terminus controls channel trafficking and surface expression whereas S-acylation of the C-terminal domain determines regulation of channel activity by AGC-family protein kinases. S-acylation of the regulatory β4-subunit controls ER exit and surface expression of BK channels but does not affect ion channel kinetics at the plasma membrane. Furthermore, a significant number of previously identified BK-channel interacting proteins have been shown, or are predicted to be, S-acylated. Thus, the BK channel multi-molecular signalling complex may be dynamically regulated by this fundamental post-translational modification and thus S-acylation likely represents an important determinant of BK channel physiology in health and disease.
Chatterjee, Sangeeta; Panda, Amaresh C; Berwal, Sunil K; Sreejith, R K; Ritvika, Charu; Seshadri, Vasudevan; Pal, Jayanta K
The human heme-regulated eIF2α kinase, also called the human heme-regulated inhibitor (hHRI) is significantly up-regulated particularly at the level of translation during stress. In this report we show that during lead-stress, the regulation of hHRI mRNA translation is mediated through its 5'-untranslated region (UTR) that interacts with specific trans-acting factors. Further, vimentin has been identified as one of the trans-acting factors that contribute to this regulation.
Jack, Samantha C; Chan, Shiu-Wan
We have previously shown that translation from the HCV IRES is up-regulated by patho/physiological doses of H(2)O(2) but is still sensitive to the inhibitory effect of phospho-eIF2α in hepatocytes. In this study using wild type and 'knockout' mouse embryonic fibroblasts (MEFs), we showed that two of the eIF2α kinases, PERK and GCN2, were not responsible for translational regulation under physiological and a higher apoptotic doses of H(2)O(2) (100 μM). However, a differential translational response was observed at a lower apoptotic dose of H(2)O(2) (50 μM) between Perk+/+ and Perk-/- MEFs but not that between Gcn2+/+ and Gcn2-/- MEFs, suggesting that PERK may play a role in translational up-regulation under oxidative stress. Our results also suggest that PERK mediates such an effect via an eIF2-independent pathway. This is in contrast to the canonical role of PERK on translational inhibition under stress conditions via phosphorylation of eIF2α. When tested for the role of PERK and GCN2 on basal translation from the HCV IRES under non-stressed condition, we found that basal translation from the HCV IRES was also favoured in the presence of PERK or GCN2 in MEFs over that of cap-dependent translation and was favoured in the presence of GCN2 but not PERK in Huh-7 cells. These results suggest that PERK and GCN2 also have a functional role on regulating translation under non-stressed conditions, apart from their long established roles as stress kinases.
Saffran, Holly A; Read, G Sullivan; Smiley, James R
The herpes simplex virus (HSV) virion host shutoff protein (vhs) encoded by gene UL41 is an mRNA-specific RNase that triggers accelerated degradation of host and viral mRNAs in infected cells. We report here that vhs is also able to modulate reporter gene expression without greatly altering the levels of the target mRNA in transient-transfection assays conducted in HeLa cells. We monitored the effects of vhs on a panel of bicistronic reporter constructs bearing a variety of internal ribosome entry sites (IRESs) located between two test cistrons. As expected, vhs inhibited the expression of the 5' cistrons of all of these constructs; however, the response of the 3' cistron varied with the IRES: expression driven from the wild-type EMCV IRES was strongly suppressed, while expression controlled by a mutant EMCV IRES and the cellular ApaF1, BiP, and DAP5 IRES elements was strongly activated. In addition, several HSV type 1 (HSV-1) 5' untranslated region (5' UTR) sequences also served as positive vhs response elements in this assay. IRES activation was also observed in 293 and HepG2 cells, but no such response was observed in Vero cells. Mutational analysis has yet to uncouple the ability of vhs to activate 3' cistron expression from its shutoff activity. Remarkably, repression of 5' cistron expression could be observed under conditions where the levels of the reporter RNA were not correspondingly reduced. These data provide strong evidence that vhs can modulate gene expression at the level of translation and that it is able to activate cap-independent translation through specific cis-acting elements.
Kunze, Michael M; Benz, Fabienne; Brauß, Thilo F; Lampe, Sebastian; Weigand, Julia E; Braun, Johannes; Richter, Florian M; Wittig, Ilka; Brüne, Bernhard; Schmid, Tobias
Translation is an energy-intensive process and tightly regulated. Generally, translation is initiated in a cap-dependent manner. Under stress conditions, typically found within the tumor microenvironment in association with e.g. nutrient deprivation or hypoxia, cap-dependent translation decreases, and alternative modes of translation initiation become more important. Specifically, internal ribosome entry sites (IRES) facilitate translation of specific mRNAs under otherwise translation-inhibitory conditions. This mechanism is controlled by IRES trans-acting factors (ITAF), i.e. by RNA-binding proteins, which interact with and determine the activity of selected IRESs. We aimed at characterizing the translational regulation of the IL-33 decoy receptor sST2, which was enhanced by fibroblast growth factor 2 (FGF2). We identified and verified an IRES within the 5'UTR of sST2. Furthermore, we found that MEK/ERK signaling contributes to FGF2-induced, sST2-IRES activation and translation. Determination of the sST2-5'UTR structure by in-line probing followed by deletion analyses identified 23 nucleotides within the sST2-5'UTR to be required for optimal IRES activity. Finally, we show that the RNA-binding protein heterogeneous ribonucleoprotein A1 (hnRNP A1) binds to the sST2-5'UTR, acts as an ITAF, and thus controls the activity of the sST2-IRES and consequently sST2 translation. Specifically, FGF2 enhances nuclear-cytoplasmic translocation of hnRNP A1, which requires intact MEK/ERK activity. In summary, we provide evidence that the sST2-5'UTR contains an IRES element, which is activated by a MEK/ERK-dependent increase in cytoplasmic localization of hnRNP A1 in response to FGF2, enhancing the translation of sST2.
Rofey, Dana L; McMakin, Dana L; Shaw, Daniel; Dahl, Ronald E
Self-regulation-the ability to manage motivations, emotions, physiological sensations, and behavior to meet internal and external demands of the environment-is critical to health and development. Adolescence represents a dynamic period of change in both the demand and capacity for self-regulation. As teens mature and become more autonomous, they are confronted with decisions in determining where they spend their time, what they eat, when they go to bed, and how they prioritize and pursue various social, academic, and recreational goals. We highlight opportunities to improve self-regulatory capacities and related health outcomes during this important developmental window. In particular, we focus on emotion regulation, sleep regulation, and weight regulation as three separate but synergistic self-regulatory systems that may provide unique opportunities for intervention to optimize health outcomes. To this end, we begin by describing developmental changes that occur in emotion, sleep and weight regulatory systems during the transitional period of adolescence, as well as how these changes can lead to profound and enduring health consequences. Next, we describe emerging evidence that indicates complex and synergistic interactions among these regulatory systems during adolescence. Last, we end with possible prevention and intervention efforts that capitalize on the interactions among these three regulatory domains.
Full Text Available Neuronal activity results in long lasting changes in synaptic structure and function by regulating mRNA translation in dendrites. These activity dependent events yield the synthesis of proteins known to be important for synaptic modifications and diverse forms of synaptic plasticity. Worthy of note, there is accumulating evidence that the eukaryotic Elongation Factor 2 Kinase (eEF2K/eukaryotic Elongation Factor 2 (eEF2 pathway may be strongly involved in this process. Upon activation, eEF2K phosphorylates and thereby inhibits eEF2, resulting in a dramatic reduction of mRNA translation. eEF2K is activated by elevated levels of calcium and binding of Calmodulin (CaM, hence its alternative name calcium/CaM-dependent protein kinase III (CaMKIII. In dendrites, this process depends on glutamate signaling and N-methyl-D-aspartate receptor (NMDAR activation. Interestingly, it has been shown that eEF2K can be activated in dendrites by the metabotropic glutamate receptor (mGluR 1/5 signaling, as well. Therefore, neuronal activity can induce local proteomic changes at the postsynapse by altering eEF2K activity. Well-established targets of eEF2K in dendrites include Brain-derived neurotrophic factor (BDNF, activity-regulated cytoskeletal-associated protein (Arc, the alpha subunit of calcium/CaM-dependent protein kinase II (αCaMKII, and Microtubule-associated protein 1B (MAP1B, all of which have well-known functions in different forms of synaptic plasticity.In this review we will give an overview of the involvement of the eEF2K/eEF2 pathway at dendrites in regulating the translation of dendritic mRNA in the context of altered NMDAR- and neuronal activity, and diverse forms of synaptic plasticity, such as metabotropic glutamate receptor-dependent-long-term depression (mGluR-LTD. For this, we draw on studies carried out both in vitro and in vivo.
Tsuchiya, Naoto [Biochemistry Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Nakagama, Hitoshi, E-mail: email@example.com [Biochemistry Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Early Oncogenesis Research Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan)
Post-transcriptional regulation of gene expression by microRNA (miRNA) has recently attracted major interest in relation to its involvement in cancer development. miRNA is a member of small non-coding RNA, consists of 22-24 nucleotides and regulates expression of target mRNA species in a post-transcriptional manner by being incorporated with RNA-induced silencing complex (RISC). Staphylococcal nuclease homology domain containing 1 (SND1), a component of RISC, is frequently up-regulated in human colon cancers and also chemically induced colon cancers in animals. We here showed that SDN1 is involved in miRNA-mediated gene suppression and overexpression of SND1 in colon cancer cells causes down-regulation of APC without altering APC mRNA levels. As for the miRNA expression profile in human colon cancer, miR-34a was among the list of down-regulated miRNA. Expression of miR-34a is tightly regulated by p53, and ectopic expression of miR-34a in colon cancer cells causes remarkable reduction of cell proliferation and induces senescence-like phenotypes. MiR-34a also participates in the positive feedback loop of the p53 tumor suppressor network. This circuitry mechanism for p53 activation is of interest in understanding the tumor suppressive function of miR-34a in colon carcinogenesis. miRNA should also be considered as novel anti-cancer agents in tumor suppressive therapeutic applications.
Laberge, Remi-Martin; Sun, Yu; Orjalo, Arturo V.; Patil, Christopher K.; Freund, Adam; Zhou, Lili; Curran, Samuel C.; Davalos, Albert R.; Wilson-Edell, Kathleen A.; Liu, Su; Limbad, Chandani; Demaria, Marco; Li, Patrick; Hubbard, Gene B.; Ikeno, Yuji; Javors, Martin; Desprez, Pierre-Yves; Benz, Christopher C.; Kapahi, Pankaj; Nelson, Peter S.; Campisi, Judith
The TOR (target of rapamycin) kinase limits longevity by poorly understood mechanisms. Rapamycin suppresses the mammalian TORC1 complex, which regulates translation, and extends lifespan in diverse species, including mice. We show that rapamycin selectively blunts the pro-inflammatory phenotype of senescent cells. Cellular senescence suppresses cancer by preventing cell proliferation. However, as senescent cells accumulate with age, the senescence-associated secretory phenotype (SASP) can disrupt tissues and contribute to age-related pathologies, including cancer. MTOR inhibition suppressed the secretion of inflammatory cytokines by senescent cells. Rapamycin reduced IL6 and other cytokine mRNA levels, but selectively suppressed translation of the membrane-bound cytokine IL1A. Reduced IL1A diminished NF-κB transcriptional activity, which controls much of the SASP; exogenous IL1A restored IL6 secretion to rapamycin-treated cells. Importantly, rapamycin suppressed the ability of senescent fibroblasts to stimulate prostate tumour growth in mice. Thus, rapamycin might ameliorate age-related pathologies, including late-life cancer, by suppressing senescence-associated inflammation. PMID:26147250
Bandiera, Lucia; Pasini, Alice; Pasotti, Lorenzo; Zucca, Susanna; Mazzini, Giuliano; Magni, Paolo; Giordano, Emanuele; Furini, Simone
The small number of molecules, unevenly distributed within an isogenic cell population, makes gene expression a noisy process, and strategies have evolved to deal with this variability in protein concentration and to limit its impact on cellular behaviors. As translational efficiency has a major impact on biological noise, a possible strategy to control noise is to regulate gene expression processes at the post-transcriptional level. In this study, fluctuations in the concentration of a green fluorescent protein were compared, at the single cell level, upon transformation of an isogenic bacterial cell population with synthetic gene circuits implementing either a transcriptional or a post-transcriptional control of gene expression. Experimental measurements showed that protein variability is lower under post-transcriptional control, when the same average protein concentrations are compared. This effect is well reproduced by stochastic simulations, supporting the hypothesis that noise reduction is due to the control mechanism acting on the efficiency of translation. Similar strategies are likely to play a role in noise reduction in natural systems and to be useful for controlling noise in synthetic biology applications.
Proud Christopher G
Full Text Available Abstract Background Activation of human resting T lymphocytes results in an immediate increase in protein synthesis. The increase in protein synthesis after 16–24 h has been linked to the increased protein levels of translation initiation factors. However, the regulation of protein synthesis during the early onset of T cell activation has not been studied in great detail. We studied the regulation of protein synthesis after 1 h of activation using αCD3 antibody to stimulate the T cell receptor and αCD28 antibody to provide the co-stimulus. Results Activation of the T cells with both antibodies led to a sustained increase in the rate of protein synthesis. The activities and/or phosphorylation states of several translation factors were studied during the first hour of stimulation with αCD3 and αCD28 to explore the mechanism underlying the activation of protein synthesis. The initial increase in protein synthesis was accompanied by activation of the guanine nucleotide exchange factor, eukaryotic initiation factor (eIF 2B, and of p70 S6 kinase and by dephosphorylation of eukaryotic elongation factor (eEF 2. Similar signal transduction pathways, as assessed using signal transduction inhibitors, are involved in the regulation of protein synthesis, eIF2B activity and p70 S6 kinase activity. A new finding was that the p38 MAPK α/β pathway was involved in the regulation of overall protein synthesis in primary T cells. Unexpectedly, no changes were detected in the phosphorylation state of the cap-binding protein eIF4E and the eIF4E-binding protein 4E-BP1, or the formation of the cap-binding complex eIF4F. Conclusions Both eIF2B and p70 S6 kinase play important roles in the regulation of protein synthesis during the early onset of T cell activation.
B. Schumacher (Björn); A. Gartner (Anton)
textabstractThe tumor suppressor p53 is a central player in apoptosis induction in response to oncogenic stimuli and DNA damage. As activation of p53 has been suggested as a prime strategy for future tumor therapy, inhibition of negative regulators of p53 activity would be a similarly desirable stra
Nida, Eugene A.
The necessity for stylistic appropriateness in translation as well as correct content is discussed. To acquire this skill, translators must be trained in stylistics through close examination of their own language and must have practice in translating for different audiences at different levels. (PMJ)
Full Text Available Aurora-A, a centrosomal serine-threonine kinase, orchestrates several key aspects of cell division. However, the regulatory pathways for the protein stability and kinase activity of Aurora-A are still not completely understood. In this study, PUM2, an RNA-binding protein, is identified as a novel substrate and interacting protein of Aurora-A. Overexpression of the PUM2 mutant which fails to interact with Aurora-A, and depletion of PUM2 result in a decrease in the amount of Aurora-A. PUM2 physically binds to the D-box of Aurora-A, which is recognized by APC/C(Cdh1. Overexpression of PUM2 prevents ubiquitination and enhances the protein stability of Aurora-A, suggesting that PUM2 protects Aurora-A from APC/C(Cdh1-mediated degradation. Moreover, association of PUM2 with Aurora-A not only makes Aurora-A more stable but also enhances the kinase activity of Aurora-A. Our study suggests that PUM2 plays two different but important roles during cell cycle progression. In interphase, PUM2 localizes in cytoplasm and plays as translational repressor through its RNA binding domain. However, in mitosis, PUM2 physically associates with Aurora-A to ensure enough active Aurora-A at centrosomes for mitotic entry. This is the first time to reveal the moonlight role of PUM2 in mitosis.
Juan Carlos Begara-Morales
Full Text Available Nitric oxide (NO is a biological messenger that orchestrates a plethora of plant functions, mainly through post-translational modifications (PTMs such as S-nitrosylation or tyrosine nitration. In plants, hundreds of proteins have been identified as potential targets of these NO-PTMs under physiological and stress conditions indicating the relevance of NO in plant-signaling mechanisms. Among these NO protein targets, there are different antioxidant enzymes involved in the control of reactive oxygen species (ROS, such as H2O2, which is also a signal molecule. This highlights the close relationship between ROS/NO signaling pathways. The major plant antioxidant enzymes, including catalase, superoxide dismutases (SODs peroxiredoxins (Prx and all the enzymatic components of the ascorbate-glutathione (Asa-GSH cycle, have been shown to be modulated to different degrees by NO-PTMs. This mini-review will update the recent knowledge concerning the interaction of NO with these antioxidant enzymes, with a special focus on the components of the Asa-GSH cycle and their physiological relevance.
Rodriguez-Furlán, Cecilia; Miranda, Giovanna; Reggiardo, Martín; Hicks, Glenn R; Norambuena, Lorena
Plant growth regulators (PGRs) have become an integral part of agricultural and horticultural practices. Accordingly, there is an increased demand for new and cost-effective products. Nevertheless, the market is limited by insufficient innovation. In this context chemical genomics has gained increasing attention as a powerful approach addressing specific traits. Here is described the successful implementation of a highly specific, sensitive and efficient high throughput screening approach using Arabidopsis as a model. Using a combination of techniques, 10,000 diverse compounds were screened and evaluated for several important plant growth traits including root and leaf growth. The phenotype-based selection allowed the compilation of a collection of putative Arabidopsis growth regulators with a broad range of activities and specificities. A subset was selected for evaluating their bioactivity in agronomically valuable plants. Their validation as growth regulators in commercial species such as tomato, lettuce, carrot, maize and turfgrasses reinforced the success of the screening in Arabidopsis and indicated that small molecules activity can be efficiently translated to commercial species. Therefore, the chemical genomics approach in Arabidopsis is a promising field that can be incorporated in PGR discovery programs and has a great potential to develop new products that can be efficiently used in crops.
Rudiuk, Sergii; Saito, Hirohide; Hara, Tomoaki; Inoue, Tan; Yoshikawa, Kenichi; Baigl, Damien
AzoTAB, a photosensitive azobenzene cationic surfactant, which phototriggers translation activity through light-regulated condensation of mRNA, is added to a translation solution containing several mRNAs, which can be selectively silenced by specific small RNAs. We find that gene silencing by small RNAs remains functional regardless of AzoTAB concentration and UV illumination. In the absence of UV, the translation of all genes present in the medium is partially to fully inhibited depending on AzoTAB concentration. In contrast, the application of a short UV stimulus (365 nm for 1.5 min) results in the selective photoactivation of genes that are not silenced by small RNA. These results show that light-regulated condensation by AzoTAB works as a sequence-independent series photoswitch added to parallel sequence-specific regulation by small RNAs.
Kang, Ji-Youn; Chang, Hoon-Sang; Hwang,Yun-Chan; Hwang, In-Nam; Oh, Won-Mann; LEE, Bin-Na
The autogenous tooth transplantation is an alternative treatment replacing a missing tooth when a suitable donor tooth is available. It is also a successful treatment option to save significant amount of time and cost comparing implants or conventional prosthetics. These cases, which required single tooth extraction due to deep caries and severe periodontal disease, could have good results by transplanting non-functional but sound donor tooth to the extraction site.
Full Text Available Activation of the mammalian Notch receptor after ligand binding relies on a succession of events including metalloprotease-cleavage, endocytosis, monoubiquitination, and eventually processing by the gamma-secretase, giving rise to a soluble, transcriptionally active molecule. The Notch1 receptor was proposed to be monoubiquitinated before its gamma-secretase cleavage; the targeted lysine has been localized to its submembrane domain. Investigating how this step might be regulated by a deubiquitinase (DUB activity will provide new insight for understanding Notch receptor activation and downstream signaling. An immunofluorescence-based screening of an shRNA library allowed us to identify eIF3f, previously known as one of the subunits of the translation initiation factor eIF3, as a DUB targeting the activated Notch receptor. We show that eIF3f has an intrinsic DUB activity. Knocking down eIF3f leads to an accumulation of monoubiquitinated forms of activated Notch, an effect counteracted by murine WT eIF3f but not by a catalytically inactive mutant. We also show that eIF3f is recruited to activated Notch on endocytic vesicles by the putative E3 ubiquitin ligase Deltex1, which serves as a bridging factor. Finally, catalytically inactive forms of eIF3f as well as shRNAs targeting eIF3f repress Notch activation in a coculture assay, showing that eIF3f is a new positive regulator of the Notch pathway. Our results support two new and provocative conclusions: (1 The activated form of Notch needs to be deubiquitinated before being processed by the gamma-secretase activity and entering the nucleus, where it fulfills its transcriptional function. (2 The enzyme accounting for this deubiquitinase activity is eIF3f, known so far as a translation initiation factor. These data improve our knowledge of Notch signaling but also open new avenues of research on the Zomes family and the translation initiation factors.
Full Text Available What exactly does (or should translation from one language into another try to do? Attempt to convey to readers of the target language (the language into which one is translating something of the strangeness, difference and historicity of the original in the source language (the language from which one is translating? Or must translation try to bridge the gap between source and target language, by rendering the original in a thoroughly contemporary style and diction, as if this were a work being written now for the first time? And related to these the further questions: how closely should a translation render the genre, language, metre, style and content of the original? How far can a translation depart from the original without ceasing to be a translation – in other words, where is one to situate the border between “translation”, “version” and “adaptation”?
Young, Sara K; Baird, Thomas D; Wek, Ronald C
In the integrated stress response, phosphorylation of eIF2α (eIF2α-P) reduces protein synthesis while concomitantly promoting preferential translation of specific transcripts associated with stress adaptation. Translation of the glutamyl-prolyl-tRNA synthetase gene EPRS is enhanced in response to eIF2α-P. To identify the underlying mechanism of translation control, we employed biochemical approaches to determine the regulatory features by which upstream ORFs (uORFs) direct downstream translation control and expression of the EPRS coding region. Our findings reveal that translation of two inhibitory uORFs encoded by noncanonical CUG and UUG initiation codons in the EPRS mRNA 5'-leader serve to dampen levels of translation initiation at the EPRS coding region. By a mechanism suggested to involve increased translation initiation stringency during stress-induced eIF2α-P, we observed facilitated ribosome bypass of these uORFs, allowing for increased translation of the EPRS coding region. Importantly, EPRS protein expression is enhanced through this preferential translation mechanism in response to multiple known activators of eIF2α-P and likely serves to facilitate stress adaptation in response to a variety of cellular stresses. The rules presented here for the regulated ribosome bypass of noncanonical initiation codons in the EPRS 5'-leader add complexity into the nature of uORF-mediated translation control mechanisms during eIF2α-P and additionally illustrate the roles that previously unexamined uORFs with noncanonical initiation codons can play in modulating gene expression.
Hu, Jing; Straub, Jonathan; Xiao, Dong; Singh, Shivendra V; Yang, Hsin-Sheng; Sonenberg, Nahum; Vatsyayan, Jaya
Phenethyl isothiocyanate (PEITC), a constituent of many edible cruciferous vegetables, exerts significant protection against chemically induced cancer in animal models and inhibits growth of cancer cells in culture and in vivo by causing cell cycle arrest and apoptosis induction. In this study, we report a novel response to PEITC involving the regulation of translation initiation at pharmacologically achievable concentrations. Treatment of human colorectal cancer HCT-116 cells and human prostate cancer PC-3 cells, but not a normal prostate epithelial cell line (PrEC), with PEITC caused an increase in expression of the eukaryotic translation initiation factor 4E (eIF4E) binding protein (4E-BP1) and inhibition of 4E-BP1 phosphorylation. Results from pull-down assay using 7-methyl-GTP Sepharose 4B beads indicated that PEITC treatment reduced cap-bound eIF4E, confirming that increased 4E-BP1 expression and inhibition of 4E-BP1 phosphorylation indeed reduced the availability of eIF4E for translation initiation. Accordingly, results from in vivo translation using luciferase reporter assay indicated that PEITC treatment inhibited cap-dependent translation, in particular the translation of mRNA with secondary structure (stem-loop structure). Ectopic expression of eIF4E prevented PEITC-induced translation inhibition and conferred significant protection against PEITC-induced apoptosis. These results indicate that PEITC modulates availability of eIF4E for translation initiation leading to inhibition of cap-dependent translation. The present study also suggests that inhibition of cap-dependent translation may be an important mechanism in PEITC-induced apoptosis.
Full Text Available The mammalian circadian clock influences most aspects of physiology and behavior through the transcriptional control of a wide variety of genes, mostly in a tissue-specific manner. About 20 clock-controlled genes (CCGs oscillate in virtually all mammalian tissues and are generally considered as core clock components. One of them is Ubiquitin-Specific Protease 2 (Usp2, whose status remains controversial, as it may be a cogwheel regulating the stability or activity of core cogwheels or an output effector. We report here that Usp2 is a clock output effector related to bodily Ca2+ homeostasis, a feature that is conserved across evolution. Drosophila with a whole-body knockdown of the orthologue of Usp2, CG14619 (dUsp2-kd, predominantly die during pupation but are rescued by dietary Ca2+ supplementation. Usp2-KO mice show hyperabsorption of dietary Ca2+ in small intestine, likely due to strong overexpression of the membrane scaffold protein NHERF4, a regulator of the Ca2+ channel TRPV6 mediating dietary Ca2+ uptake. In this tissue, USP2-45 is found in membrane fractions and negatively regulates NHERF4 protein abundance in a rhythmic manner at the protein level. In clock mutant animals (Cry1/Cry2-dKO, rhythmic USP2-45 expression is lost, as well as the one of NHERF4, confirming the inverse relationship between USP2-45 and NHERF4 protein levels. Finally, USP2-45 interacts in vitro with NHERF4 and endogenous Clathrin Heavy Chain. Taken together these data prompt us to define USP2-45 as the first clock output effector acting at the post-translational level at cell membranes and possibly regulating membrane permeability of Ca2+.
Full Text Available P2X receptor channels mediate fast excitatory signaling by ATP and play major roles in sensory transduction, neuro-immune communication and inflammatory response. P2X receptors constitute a gene family of calcium-permeable ATP-gated cation channels therefore the regulation of P2X signaling is critical for both membrane potential and intracellular calcium homeostasis. Phosphoinositides (PIPn are anionic signaling phospholipids that act as functional regulators of many types of ion channels. Direct PIPn binding was demonstrated for several ligand- or voltage-gated ion channels, however no generic motif emerged to accurately predict lipid-protein binding sites. This review presents what is currently known about the modulation of the different P2X subtypes by phospholipids and about critical determinants underlying their sensitivity to PIPn levels in the plasma membrane.All functional mammalian P2X subtypes tested, with the notable exception of P2X5, have been shown to be positively modulated by PIPn, i.e. homomeric P2X1, P2X2, P2X3, P2X4, and P2X7, as well as heteromeric P2X1/5 and P2X2/3 receptors. Based on various results reported on the aforementioned subtypes including mutagenesis of the prototypical PIPn-sensitive P2X4 and PIPn-insensitive P2X5 receptor subtypes, an increasing amount of functional, biochemical and structural evidence converges on the modulatory role of a short polybasic domain located in the proximal C-terminus of P2X subunits. This linear motif, semi-conserved in the P2X family, seems necessary and sufficient for encoding direct modulation of ATP-gated channels by PIPn. Furthermore, the physiological impact of the regulation of ionotropic purinergic responses by phospholipids on pain pathways was recently revealed in the context of native crosstalks between phospholipase C-linked metabotropic receptors and P2X receptor channels in DRG sensory neurons and microglia.
Full Text Available Tel2, a protein conserved from yeast to vertebrates, is an essential regulator of diverse cellular processes including telomere maintenance, DNA damage checkpoints, DNA repair, biological clocks, and cell signaling. The Drosophila Tel2 protein is produced as a translational fusion with EpsinR, a Clathrin adapter that facilitates vesicle trafficking between the Golgi and endosomes. EpsinR and Tel2 are encoded by a Drosophila gene called lqfR. lqfR is required for viability, and its specific roles include cell growth, proliferation, and planar cell polarity. We find that all of these functions of lqfR are attributed entirely to Tel2, not EpsinR. In addition, we find that Drosophila LqfR/Tel2 is a component of one or more protein complexes that contain E-cadherin and Armadillo. Moreover, Tel2 modulates E-cadherin and Armadillo cellular dynamics. We propose that at least one of the functions of Drosophila Tel2 is regulation of Wingless signaling.
Lyon, David; Castillejo, Maria Angeles; Mehmeti-Tershani, Vlora; Staudinger, Christiana; Kleemaier, Christoph; Wienkoop, Stefanie
Climate change in conjunction with population growth necessitates a systems biology approach to characterize plant drought acclimation as well as a more thorough understanding of the molecular mechanisms of stress recovery. Plants are exposed to a continuously changing environment. Extremes such as several weeks of drought are followed by rain. This requires a molecular plasticity of the plant enabling drought acclimation and the necessity of deacclimation processes for recovery and continuous growth.During drought stress and subsequent recovery, the metabolome and proteome are regulated through a sequence of molecular processes including synthesis and degradation and molecular interaction networks are part of this regulatory process. In order to study this complex regulatory network, a comprehensive analysis is presented for the first time, investigating protein turnover and regulatory classes of proteins and metabolites during a stress recovery scenario in the model legume Medicago truncatula The data give novel insights into the molecular capacity and differential processes required for acclimation and deacclimation of severe drought stressed plants.Functional cluster and network analyses unraveled independent regulatory mechanisms for stress and recovery with different dynamic phases that during the course of recovery define the plants deacclimation from stress. The combination of relative abundance levels and turnover analysis revealed an early transition phase that seems key for recovery initiation through water resupply and is independent from renutrition. Thus, a first indication for a metabolite and protein-based load capacity was observed necessary for the recovery from drought, an important but thus far ignored possible feature toward tolerance. The data indicate that apart from the plants molecular stress response mechanisms, plasticity may be related to the nutritional status of the plant prior to stress initiation. A new perspective and possible new
In French universities, only one out of two students is successful in his/her first year. The change of the working rhythm and the importance of self-regulated learning (relying on metacognition) can to a large extent explain these dramatic rates. Metacognition, as the process of being aware of one's own cognition and activity implies…
In French universities, only one out of two students is successful in his/her first year. The change of the working rhythm and the importance of self-regulated learning (relying on metacognition) can to a large extent explain these dramatic rates. Metacognition, as the process of being aware of one's own cognition and activity implies awareness…
Acid invertase (EC 184.108.40.206) is one of the key enzymes involved in the carbohydrate sink-organ development and the sink strength modulation in crops. The experiment conducted with 'Starkrimson' apple (Malus domestica Borkh) fruit showed that, during the fruit development, the activity of acid invertase gradually declined concomitantly with the progressive accumulation of fructose, glucose and sucrose, while Western blotting assay of acid invertase detected a 30 ku peptide of which the immuno-signal intensity increased during the fruit development. The immuno-localization via immunogold electron microscopy showed that, on the one hand, acid invertase was mainly located on the flesh cell wall with numbers of the immunosignals present in the vacuole at the late stage of fruit development; and on the other hand, the amount of acid invertase increased during fruit development, which was consistent with the results of Western blotting. The in vivo pre-incubation of fruit discs with soluble sugars showed that the activity of extractible acid invertase was inhibited by fructose or glucose, while Western blotting did not detect any changes in apparent quantity of the enzyme nor other peptides than 30 ku one. So it is considered that fructose and glucose induced the post-translational or translocational inhibitory regulation of acid invertase in developing apple fruit. The mechanism of the post-translational inhibition was shown different from both the two previously reported ones that proposed either the inhibition by hexose products in the in vitro chemical reaction equilibrium system or the inhibition by the proteinaceous inhibitors. It was hypothesized that fructose and glucose might induce acid invertase inhibition by modulating the expression of some inhibition-related genes or some structural modification of acid invertase.
Giangregorio, Nicola; Tonazzi, Annamaria; Console, Lara; Indiveri, Cesare
The carnitine/acylcarnitine transporter (CACT; SLC25A20) mediates an antiport reaction allowing entry of acyl moieties in the form of acylcarnitines into the mitochondrial matrix and exit of free carnitine. The transport function of CACT is crucial for the β-oxidation pathway. In this work, it has been found that CACT is partially acetylated in rat liver mitochondria as demonstrated by anti-acetyl-lys antibody immunostaining. Acetylation was reversed by the deacetylase Sirtuin 3 in the presence of NAD(+). After treatment of the mitochondrial extract with the deacetylase, the CACT activity, assayed in proteoliposomes, increased. The half-saturation constant of the CACT was not influenced, while the V max was increased by deacetylation. Sirtuin 3 was not able to deacetylate the CACT when incubation was performed in intact mitoplasts, indicating that the acetylation sites are located in the mitochondrial matrix. Prediction on the localization of acetylated residues by bioinformatics correlates well with the experimental data. Recombinant CACT treated with acetyl-CoA was partially acetylated by non-enzymatic mechanism with a corresponding decrease of transport activity. The experimental data indicate that acetylation of CACT inhibits its transport activity, and thus may contribute to the regulation of the mitochondrial β-oxidation pathway.
Millonigg, Sophia; Minasaki, Ryuji; Nousch, Marco; Novak, Jakub; Eckmann, Christian R
To avoid organ dysfunction as a consequence of tissue diminution or tumorous growth, a tight balance between cell proliferation and differentiation is maintained in metazoans. However, cell-intrinsic gene expression mechanisms controlling adult tissue homeostasis remain poorly understood. By focusing on the adult Caenorhabditis elegans reproductive tissue, we show that translational activation of mRNAs is a fundamental mechanism to maintain tissue homeostasis. Our genetic experiments identified the Trf4/5-type cytoplasmic poly(A) polymerase (cytoPAP) GLD-4 and its enzymatic activator GLS-1 to perform a dual role in regulating the size of the proliferative zone. Consistent with a ubiquitous expression of GLD-4 cytoPAP in proliferative germ cells, its genetic activity is required to maintain a robust proliferative adult germ cell pool, presumably by regulating many mRNA targets encoding proliferation-promoting factors. Based on translational reporters and endogenous protein expression analyses, we found that gld-4 activity promotes GLP-1/Notch receptor expression, an essential factor of continued germ cell proliferation. RNA-protein interaction assays documented also a physical association of the GLD-4/GLS-1 cytoPAP complex with glp-1 mRNA, and ribosomal fractionation studies established that GLD-4 cytoPAP activity facilitates translational efficiency of glp-1 mRNA. Moreover, we found that in proliferative cells the differentiation-promoting factor, GLD-2 cytoPAP, is translationally repressed by the stem cell factor and PUF-type RNA-binding protein, FBF. This suggests that cytoPAP-mediated translational activation of proliferation-promoting factors, paired with PUF-mediated translational repression of differentiation factors, forms a translational control circuit that expands the proliferative germ cell pool. Our additional genetic experiments uncovered that the GLD-4/GLS-1 cytoPAP complex promotes also differentiation, forming a redundant translational circuit with
Full Text Available To avoid organ dysfunction as a consequence of tissue diminution or tumorous growth, a tight balance between cell proliferation and differentiation is maintained in metazoans. However, cell-intrinsic gene expression mechanisms controlling adult tissue homeostasis remain poorly understood. By focusing on the adult Caenorhabditis elegans reproductive tissue, we show that translational activation of mRNAs is a fundamental mechanism to maintain tissue homeostasis. Our genetic experiments identified the Trf4/5-type cytoplasmic poly(A polymerase (cytoPAP GLD-4 and its enzymatic activator GLS-1 to perform a dual role in regulating the size of the proliferative zone. Consistent with a ubiquitous expression of GLD-4 cytoPAP in proliferative germ cells, its genetic activity is required to maintain a robust proliferative adult germ cell pool, presumably by regulating many mRNA targets encoding proliferation-promoting factors. Based on translational reporters and endogenous protein expression analyses, we found that gld-4 activity promotes GLP-1/Notch receptor expression, an essential factor of continued germ cell proliferation. RNA-protein interaction assays documented also a physical association of the GLD-4/GLS-1 cytoPAP complex with glp-1 mRNA, and ribosomal fractionation studies established that GLD-4 cytoPAP activity facilitates translational efficiency of glp-1 mRNA. Moreover, we found that in proliferative cells the differentiation-promoting factor, GLD-2 cytoPAP, is translationally repressed by the stem cell factor and PUF-type RNA-binding protein, FBF. This suggests that cytoPAP-mediated translational activation of proliferation-promoting factors, paired with PUF-mediated translational repression of differentiation factors, forms a translational control circuit that expands the proliferative germ cell pool. Our additional genetic experiments uncovered that the GLD-4/GLS-1 cytoPAP complex promotes also differentiation, forming a redundant
Papoulas, Ophelia; Monzo, Kathryn F; Cantin, Greg T; Ruse, Cristian; Yates, John R; Ryu, Young Hee; Sisson, John C
The molecular mechanisms driving the conserved metazoan developmental shift referred to as the mid-blastula transition (MBT) remain mysterious. Typically, cleavage divisions give way to longer asynchronous cell cycles with the acquisition of a gap phase. In Drosophila, rapid synchronous nuclear divisions must pause at the MBT to allow the formation of a cellular blastoderm through a special form of cytokinesis termed cellularization. Drosophila Fragile X mental retardation protein (dFMRP; FMR1), a transcript-specific translational regulator, is required for cellularization. The role of FMRP has been most extensively studied in the nervous system because the loss of FMRP activity in neurons causes the misexpression of specific mRNAs required for synaptic plasticity, resulting in mental retardation and autism in humans. Here, we show that in the early embryo dFMRP associates specifically with Caprin, another transcript-specific translational regulator implicated in synaptic plasticity, and with eIF4G, a key regulator of translational initiation. dFMRP and Caprin collaborate to control the cell cycle at the MBT by directly mediating the normal repression of maternal Cyclin B mRNA and the activation of zygotic frühstart mRNA. These findings identify two new targets of dFMRP regulation and implicate conserved translational regulatory mechanisms in processes as diverse as learning, memory and early embryonic development.
Cvitanich, Cristina; Judelson, Howard S.
of the Puf family of translational regulators. The protein showed up to 51% amino acid identity to other Puf proteins within its 353-amino-acid RNA-binding domain. Little similarity extended beyond this region, as noted for other members of the family. Expression of M90 was measured by using RNA blots...
Kim, Kyoung Mi; Cho, Hana [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of); Kim, Yoon Ki, E-mail: firstname.lastname@example.org [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of)
Highlights: Black-Right-Pointing-Pointer CDKN1A mRNA is a bona fide NMD substrate. Black-Right-Pointing-Pointer The uORF of CDKN1A mRNA is efficiently translated. Black-Right-Pointing-Pointer Translation of downstream main ORF is negatively regulated by translation of uORF in CDKN1A mRNA. -- Abstract: The first round of translation occurs on mRNAs bound by nuclear cap-binding complex (CBC), which is composed of nuclear cap-binding protein 80 and 20 (CBP80/20). During this round of translation, aberrant mRNAs are recognized and downregulated in abundance by nonsense-mediated mRNA decay (NMD), which is one of the mRNA quality control mechanisms. Here, our microarray analysis reveals that the level of cyclin-dependent kinase inhibitor 1A (CDKN1A; also known as Waf1/p21) mRNAs increases in cells depleted of cellular NMD factors. Intriguingly, CDKN1A mRNA contains an upstream open reading frame (uORF), which is a NMD-inducing feature. Using chimeric reporter constructs, we find that the uORF of CDKN1A mRNA negatively modulates translation of the main downstream ORF. These findings provide biological insights into the possible role of NMD in diverse biological pathways mediated by CDKN1A.
Lura, Pietro; Jensen, Ole Mejlhede; van Breugel, Klaas
In this paper, various mechanisms Suggested to cause autogenous shrinkage are presented. The mechanisms are evaluated from the point of view of their soundness and applicability to quantitative modeling of autogenous shrinkage. The capillary tension approach is advantageous, because it has a soun...
Jensen, Ole Mejlhede; Hansen, Per Freiesleben
This paper deals with autogenous deformation and autogenous relative humidity change (RH change) in hardening cement paste. Theoretical considerations and experimental data are presented, which elucidate the influence of temperature on these properties. This is an important subject in the control...
Liu, Jianyu; Stevens, Payton D; Eshleman, Nichole E; Gao, Tianyan
Protein translation initiation is a tightly controlled process responding to nutrient availability and mitogen stimulation. Serving as one of the most important negative regulators of protein translation, 4E binding protein 1 (4E-BP1) binds to translation initiation factor 4E and inhibits cap-dependent translation in a phosphorylation-dependent manner. Although it has been demonstrated previously that the phosphorylation of 4E-BP1 is controlled by mammalian target of rapamycin in the mammalian target of rapamycin complex 1, the mechanism underlying the dephosphorylation of 4E-BP1 remains elusive. Here, we report the identification of PPM1G as the phosphatase of 4E-BP1. A coimmunoprecipitation experiment reveals that PPM1G binds to 4E-BP1 in cells and that purified PPM1G dephosphorylates 4E-BP1 in vitro. Knockdown of PPM1G in 293E and colon cancer HCT116 cells results in an increase in the phosphorylation of 4E-BP1 at both the Thr-37/46 and Ser-65 sites. Furthermore, the time course of 4E-BP1 dephosphorylation induced by amino acid starvation or mammalian target of rapamycin inhibition is slowed down significantly in PPM1G knockdown cells. Functionally, the amount of 4E-BP1 bound to the cap-dependent translation initiation complex is decreased when the expression of PPM1G is depleted. As a result, the rate of cap-dependent translation, cell size, and protein content are increased in PPM1G knockdown cells. Taken together, our study has identified protein phosphatase PPM1G as a novel regulator of cap-dependent protein translation by negatively controlling the phosphorylation of 4E-BP1.
Bernateck, M; Becker, M; Schwake, C
BACKGROUND: In contrast to psychological interventions the usefulness of acupuncture as an adjuvant therapy in rheumatoid arthritis (RA) has not yet been demonstrated. OBJECTIVE: The efficacy of auricular electroacupuncture (EA) was directly compared with autogenic training (AT). METHODS: Patients...
Kuroda, Hiroshi; Sugiura, Masahiro
The chloroplast psbB operon includes five genes encoding photosystem II and cytochrome b 6 /f complex components. The psbN gene is located on the opposite strand. PsbN is localized in the thylakoid and is present even in the dark, although its level increases upon illumination and then decreases. However, the translation mechanism of the psbN mRNA remains unclear. Using an in vitro translation system from tobacco chloroplasts and a green fluorescent protein as a reporter protein, we show that translation occurs from a tobacco primary psbN 5'-UTR of 47 nucleotides (nt). Unlike many other chloroplast 5'-UTRs, the psbN 5'-UTR has two processing sites, at -39 and -24 upstream from the initiation site. Processing at -39 enhanced the translation rate fivefold. In contrast, processing at -24 did not affect the translation rate. These observations suggest that the two distinct processing events regulate, at least in part, the level of PsbN during development. The psbN 5'-UTR has no Shine-Dalgarno (SD)-like sequence. In vitro translation assays with excess amounts of the psbN 5'-UTR or with deleted psbN 5'-UTR sequences demonstrated that protein factors are required for translation and that their binding site is an 18 nt sequence in the 5'-UTR. Mobility shift assays using 10 other chloroplast 5'-UTRs suggested that common or similar proteins are involved in translation of a set of mRNAs lacking SD-like sequences.
Whitney, John C; Whitfield, Gregory B; Marmont, Lindsey S; Yip, Patrick; Neculai, A Mirela; Lobsanov, Yuri D; Robinson, Howard; Ohman, Dennis E; Howell, P Lynne
Pseudomonas aeruginosa is an opportunistic human pathogen that secretes the exopolysaccharide alginate during infection of the respiratory tract of individuals afflicted with cystic fibrosis and chronic obstructive pulmonary disease. Among the proteins required for alginate production, Alg44 has been identified as an inner membrane protein whose bis-(3',5')-cyclic dimeric guanosine monophosphate (c-di-GMP) binding activity post-translationally regulates alginate secretion. In this study, we report the 1.8 Å crystal structure of the cytoplasmic region of Alg44 in complex with dimeric self-intercalated c-di-GMP and characterize its dinucleotide-binding site using mutational analysis. The structure shows that the c-di-GMP binding region of Alg44 adopts a PilZ domain fold with a dimerization mode not previously observed for this family of proteins. Calorimetric binding analysis of residues in the c-di-GMP binding site demonstrate that mutation of Arg-17 and Arg-95 alters the binding stoichiometry between c-di-GMP and Alg44 from 2:1 to 1:1. Introduction of these mutant alleles on the P. aeruginosa chromosome show that the residues required for binding of dimeric c-di-GMP in vitro are also required for efficient alginate production in vivo. These results suggest that the dimeric form of c-di-GMP represents the biologically active signaling molecule needed for the secretion of an important virulence factor produced by P. aeruginosa.
Menichelli, Elena; Wu, Joann; Campbell, Zachary T; Wickens, Marvin; Williamson, James R
Caenorhabditis elegans CPB-1 (cytoplasmic polyadenylation element binding protein homolog-1) and FBF (fem-3 mRNA binding factor) are evolutionary conserved regulators of mRNA translation that belong to the CPEB (cytoplasmic polyadenylation element binding) and PUF (Pumilio and FBF) protein families, respectively. In hermaphrodite worms, CPB-1 and FBF control key steps during germline development, including stem cell maintenance and sex determination. While CPB-1 and FBF are known to interact, the molecular basis and function of the CPB-1⋅FBF complex are not known. The surface of CPB-1 that interacts with FBF was localized using in vivo and in vitro methods to a 10-residue region at the N-terminus of the protein and these residues are present in the FBF-binding protein GLD-3 (germline development defective-3). PUF proteins are characterized by the presence of eight α-helical repeats (PUF repeats) arranged side by side in an elongated structure. Critical residues for CPB-1 binding are found in the extended loop that connects PUF repeats 7 and 8. The same FBF residues also mediate binding to GLD-3, indicating a conserved binding mode between different protein partners. CPB-1 binding was competitive with GLD-3, suggestive of mutual exclusivity in vivo. RNA binding measurements demonstrated that CPB-1 alters the affinity of FBF for specific RNA sequences, implying a functional model where the coregulatory protein CPB-1 modulates FBF target selection.
Full Text Available Expansion of CAG repeats, which code for the disease-causing polyglutamine protein, is a common feature in polyglutamine diseases. RNA-mediated mechanisms that contribute to neuropathology in polyglutamine diseases are important. RNA-toxicity describes a phenomenon by which the mutant CAG repeat RNA recruits RNA-binding proteins, thereby leading to aberrant function. For example the MID1 protein binds to mutant huntingtin (HTT RNA, which is linked to Huntington’s disease (HD, at its CAG repeat region and induces protein synthesis of mutant protein. But is this mechanism specific to HD or is it a common mechanism in CAG repeat expansion disorders? To answer this question, we have analysed the interaction between MID1 and three other CAG repeat mRNAs, Ataxin2 (ATXN2, Ataxin3 (ATXN3, and Ataxin7 (ATXN7, that all differ in the sequence flanking the CAG repeat. We show that ATXN2, ATXN3 and ATXN7 bind to MID1 in a CAG repeat length-dependent manner. Furthermore, we show that functionally, in line with what we have previously observed for HTT, the binding of MID1 to ATXN2, ATXN3 and ATXN7 mRNA induces protein synthesis in a repeat length-dependent manner. Our data suggest that regulation of protein translation by the MID1 complex is a common mechanism for CAG repeat containing mRNAs.
Reinhold, Robert; Bareth, Bettina; Balleininger, Martina; Wissel, Mirjam; Rehling, Peter; Mick, David U
Defects in mitochondrial energy metabolism lead to severe human disorders, mainly affecting tissues especially dependent on oxidative phosphorylation, such as muscle and brain. Leigh Syndrome describes a severe encephalomyopathy in infancy, frequently caused by mutations in SURF1. SURF1, termed Shy1 in Saccharomyces cerevisiae, is a conserved assembly factor for the terminal enzyme of the respiratory chain, cytochrome c oxidase. Although the molecular function of SURF1/Shy1 is still enigmatic, loss of function leads to cytochrome c oxidase deficiency and reduced expression of the central subunit Cox1 in yeast. Here, we provide insights into the molecular mechanisms leading to disease through missense mutations in codons of the most conserved amino acids in SURF1. Mutations affecting G(124) do not compromise import of the SURF1 precursor protein but lead to fast turnover of the mature protein within the mitochondria. Interestingly, an Y(274)D exchange neither affects stability nor localization of the protein. Instead, SURF1(Y274D) accumulates in a 200 kDa cytochrome c oxidase assembly intermediate. Using yeast as a model, we demonstrate that the corresponding Shy1(Y344D) is able to overcome the stage where cytochrome c oxidase assembly links to the feedback regulation of mitochondrial Cox1 expression. However, Shy1(Y344D) impairs the assembly at later steps, most apparent at low temperature and exhibits a dominant-negative phenotype upon overexpression. Thus, exchanging the conserved tyrosine (Y(344)) with aspartate in yeast uncouples translational regulation of Cox1 from cytochrome c oxidase assembly and provides evidence for the dual functionality of Shy1.
Manuel R. Abuín
Full Text Available Autogenic therapy emerges from the "autogenic training" method created by Schultz, and its development incorporates different therapeutic methods based on a psychophysiological approach. All these methods promote homeostatic self-regulatory brain processes. The aims of this paper are to describe and analyse the autogenic methods, the psychophysiological and neurophysiological processes involved, and their effective applications in both health and clinical fields. For these purposes, beside reviewing the earlier work by Schultz and Luthe, an electronic search of literature was conducted in order to find relevant contributions on these topics. Results show a big development of autogenic methods until the 80s, with an enormous amount of applications and studies on the psychophysiological and neurophysiological changes related to the practice of autogenic training. However, their expansion during the last 25 years has been much lower in comparison with other methods such as mindfulness and hypnosis. Possible causes are discussed and new challenges are suggested
sidney Shapiro, an American-born translator famous for his translation of Chinese literary works, received the Lifetime Achievement Award in Translation by the Translators Association of China on December 2, 2010.
Stacey L Lehman
Full Text Available Multiple transcripts encode for the cell cycle inhibitor p21(Cip1. These transcripts produce identical proteins but differ in their 5' untranslated regions (UTRs. Although several stresses that induce p21 have been characterized, the mechanisms regulating the individual transcript variants and their functional significance are unknown. Here we demonstrate through (35S labeling, luciferase reporter assays, and polysome transcript profiling that activation of the Integrated Stress Response (ISR kinase GCN2 selectively upregulates the translation of a p21 transcript variant containing 5' upstream open reading frames (uORFs through phosphorylation of the eukaryotic translation initiation factor eIF2α. Mutational analysis reveals that the uORFs suppress translation under basal conditions, but promote translation under stress. Functionally, ablation of p21 ameliorates G1/S arrest and reduces cell survival in response to GCN2 activation. These findings uncover a novel mechanism of p21 post-transcriptional regulation, offer functional significance for the existence of multiple p21 transcripts, and support a key role for GCN2 in regulating the cell cycle under stress.
@@In the management of traumatic skull defect, the classical treatment has usually been adopted, i.e.,primary debridement and secondary repair of bone defect, especially in cases of open lacerated skull fracture. 1 In general, the use of prosthetic material in repair is often not so satisfactory either in China or abroad. Decalcificated human dentin matrix (DHDM)has been used in autogenous repair of traumatic skull defect in primary operation and a good curative effect has been gained since the time from September 1996 to March 1998. Clinical results and CT scanning observation are reported in the following.
Sharp, D.J.; Armstrong, P.S.; Panitz, J.K.G.
A solid electrolytic capacitor is described having a solid electrolyte comprising manganese dioxide dispersed in an aromatic polyamide capable of further cure to form polyimide linkages, the solid electrolyte being disposed between a first electrode made of valve metal covered by an anodic oxide film and a second electrode opposite the first electrode. The electrolyte autogenously produces water, oxygen, and hydroxyl groups which act as healing substances and is not itself produced pyrolytically. Reduction of the manganese dioxide and the water molecules released by formation of imide linkages result in substantially improved self-healing of anodic dielectric layer defects. 2 figs.
Cowings, Patricia S.; Toscano, William B.; Kamiya, Joe; Miller, Neal E.; Pickering, Thomas G.
NASA has identified cardiovascular deconditioning as a serious biomedical problem associated with long-duration exposure to microgravity in space. High priority has been given to the development of countermeasures for this disorder and the resulting orthostatic intolerance experienced by crewmembers upon their return to the 1g norm of Earth. The present study was designed to examine the feasibility of training human subjects to control their own cardiovascular responses to gravitational stimulation (i.e., a tilt table). Using an operant conditioning procedure, Autogenic-Feedback Training (AFT), we would determine if subjects could learn to increase their own blood pressure voluntarily.
Susor, Andrej; Jansova, Denisa; Cerna, Renata; Danylevska, Anna; Anger, Martin; Toralova, Tereza; Malik, Radek; Supolikova, Jaroslava; Cook, Matthew S; Oh, Jeong Su; Kubelka, Michal
The fully grown mammalian oocyte is transcriptionally quiescent and utilizes only transcripts synthesized and stored during early development. However, we find that an abundant RNA population is retained in the oocyte nucleus and contains specific mRNAs important for meiotic progression. Here we show that during the first meiotic division, shortly after nuclear envelope breakdown, translational hotspots develop in the chromosomal area and in a region that was previously surrounded the nucleus. These distinct translational hotspots are separated by endoplasmic reticulum and Lamin, and disappear following polar body extrusion. Chromosomal translational hotspots are controlled by the activity of the mTOR-eIF4F pathway. Here we reveal a mechanism that-following the resumption of meiosis-controls the temporal and spatial translation of a specific set of transcripts required for normal spindle assembly, chromosome alignment and segregation.
Susor, Andrej; Jansova, Denisa; Cerna, Renata; Danylevska, Anna; Anger, Martin; Toralova, Tereza; Malik, Radek; Supolikova, Jaroslava; Cook, Matthew S.; Oh, Jeong Su; Kubelka, Michal
The fully grown mammalian oocyte is transcriptionally quiescent and utilizes only transcripts synthesized and stored during early development. However, we find that an abundant RNA population is retained in the oocyte nucleus and contains specific mRNAs important for meiotic progression. Here we show that during the first meiotic division, shortly after nuclear envelope breakdown, translational hotspots develop in the chromosomal area and in a region that was previously surrounded the nucleus. These distinct translational hotspots are separated by endoplasmic reticulum and Lamin, and disappear following polar body extrusion. Chromosomal translational hotspots are controlled by the activity of the mTOR–eIF4F pathway. Here we reveal a mechanism that—following the resumption of meiosis—controls the temporal and spatial translation of a specific set of transcripts required for normal spindle assembly, chromosome alignment and segregation. PMID:25629602
With the great development of technology, translation technology exerts great influence on human translators because during their translation process, they may use many computer-aided translation tools, such as TRADOS, Snowman, WordFisher and etc. However, they always misunderstand the concept of computer-aided translation, so this thesis managed to providedetails about some translation technology and human translators' strengths so as to help them improve the productivity and the quality of theirtranslation works effectively and efficiently.
美国著名翻译理论家尤金·奈达说 :“翻译即译意 (Translating m eans translating m eaning)。”就实质而言 ,翻译即译意。就是把一种语言表达的意义用另一种语言表达出来。翻译分理解与表达两个步骤。理解是翻译的基础 ,表达直接决定译文的成败与优劣 ,两者缺一不可
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....
As a kind of ancillary translation tool, Machine Translation has been paid increasing attention to and received different kinds of study by a great deal of researchers and scholars for a long time. To know the definition of Machine Translation and to analyse its benefits and problems are significant for translators in order to make good use of Machine Translation, and helpful to develop and consummate Machine Translation Systems in the future.
Grabowska Anna D
Full Text Available Abstract Background Many bacterial extracytoplasmic proteins are stabilized by intramolecular disulfide bridges that are formed post-translationally between their cysteine residues. This protein modification plays an important role in bacterial pathogenesis, and is facilitated by the Dsb (disulfide bond family of the redox proteins. These proteins function in two parallel pathways in the periplasmic space: an oxidation pathway and an isomerization pathway. The Dsb oxidative pathway in Campylobacter jejuni is more complex than the one in the laboratory E. coli K-12 strain. Results In the C. jejuni 81-176 genome, the dsb genes of the oxidative pathway are arranged in three transcriptional units: dsbA2-dsbB-astA, dsbA1 and dba-dsbI. Their transcription responds to an environmental stimulus - iron availability - and is regulated in a Fur-dependent manner. Fur involvement in dsb gene regulation was proven by a reporter gene study in a C. jejuni wild type strain and its isogenic fur mutant. An electrophoretic mobility shift assay (EMSA confirmed that analyzed genes are members of the Fur regulon but each of them is regulated by a disparate mechanism, and both the iron-free and the iron-complexed Fur are able to bind in vitro to the C. jejuni promoter regions. This study led to identification of a new iron- and Fur-regulated promoter that drives dsbA1 gene expression in an indirect way. Moreover, the present work documents that synthesis of DsbI oxidoreductase is controlled by the mechanism of translational coupling. The importance of a secondary dba-dsbI mRNA structure for dsbI mRNA translation was verified by estimating individual dsbI gene expression from its own promoter. Conclusions The present work shows that iron concentration is a significant factor in dsb gene transcription. These results support the concept that iron concentration - also through its influence on dsb gene expression - might control the abundance of extracytoplasmic proteins
Ingram, Brian J.; Pol, Vilas G.; Cronauer, Donald C.; Ramanathan, Muruganathan
In one preferred embodiment, a photocatalyst for conversion of carbon dioxide and water to a hydrocarbon and oxygen comprises at least one nanoparticulate metal or metal oxide material that is substantially free of a carbon coating, prepared by heating a metal-containing precursor compound in a sealed reactor under a pressure autogenically generated by dissociation of the precursor material in the sealed reactor at a temperature of at least about 600.degree. C. to form a nanoparticulate carbon-coated metal or metal oxide material, and subsequently substantially removing the carbon coating. The precursor material comprises a solid, solvent-free salt comprising a metal ion and at least one thermally decomposable carbon- and oxygen-containing counter-ion, and the metal of the salt is selected from the group consisting of Mn, Ti, Sn, V, Fe, Zn, Zr, Mo, Nb, W, Eu, La, Ce, In, and Si.
DING Qingjun; TIAN Yaogang; WANG Fazhou; ZHANG Feng; HU Shuguang
The characteristic of autogenous shrinkage ( AS ) and its effect on high strength lightweight aggregate concrete (HSLAC) were studied. The experimental results show that the main shrinkage of high strength concrete is AS and the amount of cement can affect the AS of HSLAC remarkably. At the early stage the AS of HSLAC is lower than that of high strength normal concrete, but it has a large growth at the later stage. The AS of high strength normal concrete becomes stable at 90d age, but HSLAC still has a high AS growth. It is found that adjusting the volume rate of lightweight aggregate, mixing with a proper dosage of fly ash and raising the water saturation degree of lightweight aggregate can markedly reduce the AS rate of HSLAC.
Full Text Available Translation initiation and activity of eukaryotic initiation factor-alpha (eIF2α, the rate-limiting step of translation initiation, is often overactivated in malignant cells. Here, we investigated the regulation and role of eIF2α 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 eIF2α, through the induction of protein kinase C delta (PKCδ and PKR, but not other eIF2α kinases, such as GCN2 and PERK in APL (NB4 and AML cells (HL60, U937, and THP-1. Inhibition of eIF2α reduced the expression of cellular proteins that are involved in apoptosis (DAP5/p97, cell cycle (p21Waf1/Cip1, differentiation (TG2 and induced those regulating proliferation (c-myc and survival (p70S6K. PI3K/Akt/mTOR pathway is involved in regulation of eIF2α through PKCδ/PKR axis. PKCδ and p-eIF2α protein expression levels revealed a significant association between the reduced levels of PKCδ (P=0.0378 and peIF2 (P=0.0041 and relapses in AML patients (n=47. In conclusion, our study provides the first evidence that PKCδ regulates/inhibits eIF2α through induction of PKR in AML cells and reveals a novel signaling mechanism regulating translation initiation.
Shaheen, Zachary R; Naatz, Aaron; Corbett, John A
Encephalomyocarditis virus (EMCV) infection of macrophages results in the expression of a number of inflammatory and antiviral genes, including inducible NO synthase (iNOS) and cyclooxygenase (COX)-2. EMCV-induced macrophage activation has been shown to require the presence of CCR5 and the activation of PI3K-dependent signaling cascades. The purpose of this study was to determine the role of PI3K in regulating the macrophage responses to EMCV. We show that PI3K regulates EMCV-stimulated iNOS and COX-2 expression by two independent mechanisms. In response to EMCV infection, Akt is activated and regulates the translation of iNOS and COX-2 through the mammalian target of rapamycin complex (mTORC)1. The activation of mTORC1 during EMCV infection is CCR5-dependent and appears to function in a manner that promotes the translation of iNOS and COX-2. CCR5-dependent mTORC1 activation functions as an antiviral response, as mTORC1 inhibition increases the expression of EMCV polymerase. PI3K also regulates the transcriptional induction of iNOS and COX-2 in response to EMCV infection by a mechanism that is independent of Akt and mTORC1 regulation. These findings indicate that macrophage expression of the inflammatory genes iNOS and COX-2 occurs via PI3K- and Akt-dependent translational control of mTORC1 and PI3K-dependent, Akt-independent transcriptional control.
Zismanov, Victoria; Chichkov, Victor; Colangelo, Veronica; Jamet, Solène; Wang, Shuo; Syme, Alasdair; Koromilas, Antonis E; Crist, Colin
Regeneration of adult tissues depends on somatic stem cells that remain quiescent yet are primed to enter a differentiation program. The molecular pathways that prevent activation of these cells are not well understood. Using mouse skeletal muscle stem cells as a model, we show that a general repression of translation, mediated by the phosphorylation of translation initiation factor eIF2α at serine 51 (P-eIF2α), is required to maintain the quiescent state. Skeletal muscle stem cells unable to phosphorylate eIF2α exit quiescence, activate the myogenic program, and differentiate, but do not self-renew. P-eIF2α ensures in part the robust translational silencing of accumulating mRNAs that is needed to prevent the activation of muscle stem cells. Additionally, P-eIF2α-dependent translation of mRNAs regulated by upstream open reading frames (uORFs) contributes to the molecular signature of stemness. Pharmacological inhibition of eIF2α dephosphorylation enhances skeletal muscle stem cell self-renewal and regenerative capacity.
Velásquez, Celestino; Cheng, Erdong; Shuda, Masahiro; Lee-Oesterreich, Paula J; Pogge von Strandmann, Lisa; Gritsenko, Marina A; Jacobs, Jon M; Moore, Patrick S; Chang, Yuan
Mammalian target of rapamycin (mTOR)-directed eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) phosphorylation promotes cap-dependent translation and tumorigenesis. During mitosis, cyclin-dependent kinase 1 (CDK1) substitutes for mTOR and fully phosphorylates 4E-BP1 at canonical sites (T37, T46, S65, and T70) and the noncanonical S83 site, resulting in a mitosis-specific hyperphosphorylated δ isoform. Colocalization studies with a phospho-S83 specific antibody indicate that 4E-BP1 S83 phosphorylation accumulates at centrosomes during prophase, peaks at metaphase, and decreases through telophase. Although S83 phosphorylation of 4E-BP1 does not affect general cap-dependent translation, expression of an alanine substitution mutant 4E-BP1.S83A partially reverses rodent cell transformation induced by Merkel cell polyomavirus small T antigen viral oncoprotein. In contrast to inhibitory mTOR 4E-BP1 phosphorylation, these findings suggest that mitotic CDK1-directed phosphorylation of δ-4E-BP1 may yield a gain of function, distinct from translation regulation, that may be important in tumorigenesis and mitotic centrosome function.
Sucrose dependent translational dynamics Gene expression is regulated at several different levels starting from chromatin remodeling and transcription in the nucleus to translation and post-translational modifications in the cytosol. Depending on the gene and circumstances, different regulatory mech
Liu, Jinfeng; Henao-Mejia, Jorge; Liu, Hao; Zhao, Yingren; He, Johnny J
Nuclear export and translation of HIV-1 RNA are two important posttranscriptional events for HIV-1 gene expression and replication. HIV-1 Rev functions to export unspliced and incompletely spliced HIV-1 RNA from the nucleus to the cytoplasm; it requires interaction with several cellular cofactors such as Sam68, eIF5A, hRIP, and DDX3. Meanwhile, some studies have also implicated Rev and some of its cofactors such as Sam68 in HIV-1 RNA translation. Thus, in this study, we aimed to characterize the potential function of all these four Rev cofactors in HIV-1 RNA translation. Ectopic expression, siRNA knockdown, and trans-complementation assays confirmed that all these cofactors were very important for HIV-1 gene expression and production through Rev and, accordingly, Rev-dependent reporter gene expression. Importantly, these studies revealed for the first time that each of these cofactors also regulated Rev-independent reporter gene expression. To directly determine the roles of these cofactors in HIV-1 RNA translation, we designed and synthesized a full-length capped HIV-1 RNA in vitro, transfected it into cells to bypass the RNA nuclear export step, and determined HIV-1 Gag expression from the cytoplasmic RNA in the cells that had ectopically expressed or siRNA knocked down cofactors. Gag expression was found to closely correlate with the expression levels of all these cofactors. Furthermore, we took advantage of a HIV-1 internal ribosomal entry site (IRES)-based bicistronic reporter gene assay and determined the effects of these cofactors on cap-independent IRES-mediated HIV-1 translation. The results showed that DDX3, eIF5A, and hRIP enhanced HIV-1 IRES-mediated translation, whereas Sam68 did not. Taken together, these results show that HIV-1 Rev cofactors Sam68, eIF5A, hRIP, and DDX3 also function in the translation of HIV-1 RNA and suggest that the regulatory mechanisms of HIV-1 RNA translation are likely different among these cofactors.
Bernateck, M.; Becker, M.; Schwacke, C.
BACKGROUND: In contrast to psychological interventions the usefulness of acupuncture as an adjuvant therapy in rheumatoid arthritis (RA) has not yet been demonstrated. OBJECTIVE: The efficacy of auricular electroacupuncture (EA) was directly compared with autogenic training (AT). METHODS: Patients...
The article presented peculiarities of applying the method of autogenic training in the correction of eating disorders. Described stages of correction work with desadaptive eating behavior. Author makes accent on the rules self-assembly formula intentions.
Li, Mi; Pehar, Mariana; Liu, Yan; Bhattacharyya, Anita; Zhang, Su-Chun; O'Riordan, Kenneth J; Burger, Corinna; D'Adamio, Luciano; Puglielli, Luigi
p44 is a short isoform of the tumor suppressor protein p53 that is regulated in an age-dependent manner. When overexpressed in the mouse, it causes a progeroid phenotype that includes premature cognitive decline, synaptic defects, and hyperphosphorylation of tau. The hyperphosphorylation of tau has recently been linked to the ability of p44 to regulate transcription of relevant tau kinases. Here, we report that the amyloid precursor protein (APP) intracellular domain (AICD), which results from the processing of the APP, regulates translation of p44 through a cap-independent mechanism that requires direct binding to the second internal ribosome entry site (IRES) of the p53 mRNA. We also report that AICD associates with nucleolin, an already known IRES-specific trans-acting factor that binds with p53 IRES elements and regulates translation of p53 isoforms. The potential biological impact of our findings was assessed in a mouse model of Alzheimer's disease. In conclusion, our study reveals a novel aspect of AICD and p53/p44 biology and provides a possible molecular link between APP, p44, and tau.
Full Text Available Synthesis and assembly of the mitochondrial oxidative phosphorylation (OXPHOS system requires genes located both in the nuclear and mitochondrial genomes, but how gene expression is coordinated between these two compartments is not fully understood. One level of control is through regulated expression mitochondrial ribosomal proteins and other factors required for mitochondrial translation and OXPHOS assembly, which are all products of nuclear genes that are subsequently imported into mitochondria. Interestingly, this cadre of genes in budding yeast has in common a 3'-UTR element that is bound by the Pumilio family protein, Puf3p, and is coordinately regulated under many conditions, including during the yeast metabolic cycle. Multiple functions have been assigned to Puf3p, including promoting mRNA degradation, localizing nucleus-encoded mitochondrial transcripts to the outer mitochondrial membrane, and facilitating mitochondria-cytoskeletal interactions and motility. Here we show that Puf3p has a general repressive effect on mitochondrial OXPHOS abundance, translation, and respiration that does not involve changes in overall mitochondrial biogenesis and largely independent of TORC1-mitochondrial signaling. We also identified the cytoplasmic translation factor Slf1p as yeast metabolic cycle-regulated gene that is repressed by Puf3p at the post-transcriptional level and promotes respiration and extension of yeast chronological life span when over-expressed. Altogether, these results should facilitate future studies on which of the many functions of Puf3p is most relevant for regulating mitochondrial gene expression and the role of nuclear-mitochondrial communication in aging and longevity.
钱济先; 宋胜云; 马保安; 范清宇
Objective: To investigate changes of Ca2+ activated potassium channels (KCa) in autogenous vein grafts. Methods: Contraction of venous ring was measured by means of perfusion in vitro. The intimal rabbits proliferation of vascular and proliferation of cultured smooth muscle cells(vascular smooth muscle cells, VSMCs)were observed by the means of computerised image analysis and MTT method respectively. Furthermore, whole cell mode of patch clamp was used to record KCa of VSMCs isolated from autogenous vein grafts. Results: One week after transplantation there were no significant differences of contraction and intimal relative thickness between autogenous vein grafts and control. Contraction and intimal relative thickness of autogenous vein graft were significantly increased 2 weeks after transplantation (P<0.05, n=8 vs control), and they was more enhanced 4 weeks after vein transplantation (P<0.01, n=8 vs control).TEA(blocker of Ca2+ activated potassium channels)increased MTT A490 nm value of VSMCs from femoral vein in a dose dependent manner(P<0.05, n=8). KCa current density was significantly attenuated in VSMCs from autogenous vein grafts (1-4) week after transplantation(P<0.05, n=5).Conclusion: KCa is inhibited in autogenous vein graft, which account for vasospasm and intimal proliferation.
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...
Jendresen, Christian Bille; Martinussen, Jan; Kilstrup, Mogens
Purine nucleotides are either synthesized de novo from 5-phosphoribosyl-1-pyrophosphate (PRPP) or salvaged from the environment. In Lactococcus lactis, transcription of the de novo synthesis operons, purCSQLF and purDEK, has genetically been shown to be activated by the PurR protein when bound to......-related functions. Of special interest is the presence of PurBox motifs in rrn promoters, suggesting a novel connection between nucleotide availability and the translational machinery........ This suggests that binding of the PurR protein to the PurBox takes over the role of the -35 sequence. The study has expanded the PurR regulon to include promoters in nucleotide metabolism, C(1) compound metabolism, phosphonate transport, pyrophosphatase activity, (p)ppGpp metabolism, and translation...
M Harms, J.; Wilson, D. N.; Schluenzen, F.; Connell, S. R.; Stachelhaus, T.; Zaborowska, Z.; Spahn, C. M. T.; Fucini, P.
The thiopeptide class of antibiotics targets the GTPase-associated center (GAC) of the ribosome to inhibit translation factor function. Using X-ray crystallography, we have determined the binding sites of thiostrepton (Thio), nosiheptide (Nosi), and micrococcin (Micro), on the Deinococcus radiodurans large ribosomal subunit. The thiopeptides, by binding within a cleft located between the ribosomal protein L11 and helices 43 and 44 of the 23S rRNA, overlap with the position of domain V of EF-G...
Michel, Kelly; Zhao, Tianna; Karl, Molly; Lewis, Katherine; Fyffe-Maricich, Sharyl L
Successful myelin repair in the adult CNS requires the robust and timely production of myelin proteins to generate new myelin sheaths. The underlying regulatory mechanisms and complex molecular basis of myelin regeneration, however, remain poorly understood. Here, we investigate the role of ERK MAP kinase signaling in this process. Conditional deletion of Erk2 from cells of the oligodendrocyte lineage resulted in delayed remyelination following demyelinating injury to the adult mouse corpus callosum. The delayed repair occurred as a result of a specific deficit in the translation of the major myelin protein, MBP. In the absence of ERK2, activation of the ribosomal protein S6 kinase (p70S6K) and its downstream target, ribosomal protein S6 (S6RP), was impaired at a critical time when premyelinating oligodendrocytes were transitioning to mature cells capable of generating new myelin sheaths. Thus, we have described an important link between the ERK MAP kinase signaling cascade and the translational machinery specifically in remyelinating oligodendrocytes in vivo. These results suggest an important role for ERK2 in the translational control of MBP, a myelin protein that appears critical for ensuring the timely generation of new myelin sheaths following demyelinating injury in the adult CNS.
Velásquez, Celestino; Cheng, Erdong; Shuda, Masahiro; Lee-Oesterreich, Paula J.; Pogge von Strandmann, Lisa; Gritsenko, Marina A.; Jacobs, Jon M.; Moore, Patrick S.; Chang, Yuan
mTOR-directed 4E-BP1 phosphorylation promotes cap-dependent translation and tumorigen-esis. During mitosis, CDK1 substitutes for mTOR and fully phosphorylates 4E-BP1 at canoni-cal as well a non-canonical S83 site resulting in a mitosis-specific hyperphosphorylated δ isoform. Colocalization studies with a phospho-S83 specific antibody indicate that 4E-BP1 S83 phosphorylation accumulates at centrosomes during prophase, peaks at metaphase, and decreases through telophase. While S83 phosphorylation of 4E-BP1 does not affect in vitro cap-dependent translation, nor eIF4G/4E-BP1 cap-binding, expression of an alanine substitution mutant 4E-BP1.S83A partially reverses rodent cell transformation induced by Merkel cell polyomavirus (MCV) small T (sT) antigen viral oncoprotein. In contrast to inhibitory mTOR 4E-BP1 phosphorylation, these findings suggest that mitotic CDK1-directed phosphorylation of δ-4E-BP1 may yield a gain-of-function, distinct from translation regulation, that may be important in tumorigenesis and mitotic centrosome function.
Fennis, J.P.M.; Stoelinga, P.J.W.; Merkx, M.A.T.; Jansen, J.A.
An animal study is presented, evaluating a method of mandibular reconstruction using a poly(D,Llactide) (PDLLA) scaffold. Six goats underwent a continuity resection of the mandibular angle. The defect was bridged with a preshaped PDLLA scaffold, filled with an autogenous particulate bone graft from
Europe thinks in many languages and Europe is a land of translation. Translation is a means of transmitting culture, a means of making it available to others and an invitation to share. It is a cement which binds Europe together.
The International Federation of Translators will hold its largest ever world congress in China on the eve of 2008 Olympic Games china’ s position as a powerhouse of the translation industry is to be cemented,
Sergio Bolaños Cuéllar
Full Text Available The advance in cultural-oriented perspectives in Translation Studies has sometimes played down the text linguistic nature of translation. A pilot study in teaching translation was carried out to make students aware of the text linguistic character of translating and help them to improve their translation skills, particularly with an emphasis on self-awareness and self-correcting strategies. The theoretical background is provided by the Dynamic Translation Model (2004, 2005 proposed by the author, with relevant and important contributions taken from Genettes (1982 transtextuality phenomena (hypertext, hypotext, metatext, paratext, intertext and House and Kaspers (1981 pragmatic modality markers (downgraders, upgraders. The key conceptual role of equivalence as a defining feature of translation is also dealt with. The textual relationship between Source Language Text (slt is deemed to be pivotal for performing translation and correction tasks in the classroom. Finally, results of the pilot study are discussed and some conclusions are drawn.
van den Bergh, J P; ten Bruggenkate, C M; Krekeler, G; Tuinzing, D B
Insufficient bone height in the posterior area of the maxilla, due to expansion of the maxillary sinus and atrophic reduction of the alveolar process of the maxilla, represents a contra-indication for insertion of dental implants. This anatomic problem can, in many cases, be solved by augmentation of the floor of the maxillary sinus. This surgical technique was introduced by Tatum. The so-called top hinge door method creates a new floor of the maxillary sinus at a more cranial level. Underneath this new floor the existing space is filled with a bone graft. Implantation in the alveolar process with increased bone height allows insertion of dental implants. This sinus grafting technique was used in the present study. In total, 62 sinusfloor elevations were performed with cancellous iliac bone grafts in 42 patients. In those 62 augmented sinuses, 161 ITI screw type implants were inserted. The follow-up was 1-6 years after implantation. In 2 cases infections occurred. One implant needed an extended integration time. No implants were lost. The ITI solid screw implant appears to be a suitable implant following sinusfloor elevation operations, due to its rough surface, its shape and the size of the thread. The sinusfloor elevation procedure with autogenous cancellous bone graft appears to be a valuable and reliable pre-implantological procedure, provided a proper pre-operative investigation and careful surgery are performed. This procedure allows dental implant placement with a high success rate.
Stetter, Friedhelm; Kupper, Sirko
Autogenic training (AT) is a self-relaxation procedure by which a psychophysiological determined relaxation response is elicited. A meta-analysis was performed to evaluate the clinical effectiveness of AT. Seventy-three controlled outcome studies were found (published 1952-99). Sixty studies (35 randomized controlled trials [RCT]) qualified for inclusion in the meta-analysis. Medium-to-large effect sizes (ES) occurred for pre-post comparisons of disease-specific AT-effects, with the RCTs showing larger ES. When AT was compared to real control conditions, medium ES were found. Comparisons of AT versus other psychological treatment mostly resulted in no effects or small negative ES. This pattern of results was stable at follow-up. Unspecific AT-effects (i.e., effects on mood, cognitive performance, quality of life, and physiological variables) tended to be even larger than main effects. Separate meta-analyses for different disorders revealed a significant reduction of the heterogeneity of ES. Positive effects (medium range) of AT and of AT versus control in the meta-analysis of at least 3 studies were found for tension headache/migraine, mild-to-moderate essential hypertension, coronary heart disease, asthma bronchiale, somatoform pain disorder (unspecified type), Raynaud's disease, anxiety disorders, mild-to-moderate depression/dysthymia, and functional sleep disorders.
Full Text Available The underlying changes in heart coherence that are associated with reported EEG changes in response to meditation have been explored. We measured EEG and heart rate variability (HRV before and during autogenic meditation. Fourteen subjects participated in the study. Heart coherence scores were significantly increased during meditation compared to the baseline. We found near significant decrease in high beta absolute power, increase in alpha relative power and significant increases in lower(alpha and higher(above beta band coherence during 3 minute epochs of heart coherent meditation compared to 3 minute epochs of heart noncoherence at baseline. The coherence and relative power increase in alpha band and absolute power decrease in high beta band could reflect relaxation state during the heart coherent meditation. The coherence increase in the higher(above beta band could reflect cortico-cortical local integration and thereby affect cognitive reorganization, simultaneously with relaxation. Further research is still needed for a confirmation of heart coherence as a simple window for the meditative state.
Full Text Available Soil-dwelling Streptomyces bacteria such as S. coelicolor have to constantly adapt to the nitrogen (N availability in their habitat. Thus, strict transcriptional and post-translational control of the N-assimilation is fundamental for survival of this species. GlnR is a global response regulator that controls transcription of the genes related to the N-assimilation in S. coelicolor and other members of the Actinomycetales. GlnR represents an atypical orphan response regulator that is not activated by the phosphorylation of the conserved aspartate residue (Asp 50. We have applied transcriptional analysis, LC-MS/MS analysis and electrophoretic mobility shift assays (EMSAs to understand the regulation of GlnR in S. coelicolor M145. The expression of glnR and GlnR-target genes was revisited under four different N-defined conditions and a complex N-rich condition. Although, the expression of selected GlnR-target genes was strongly responsive to changing N-concentrations, the glnR expression itself was independent of the N-availability. Using LC-MS/MSanalysis we demonstrated that GlnR was post-translationally modified. The post-translational modifications of GlnR comprise phosphorylation of the serine/threonine residues and acetylation of lysine residues. In the complex N-rich medium GlnR was phosphorylated on six serine/ threonine residues and acetylated on one lysine residue. Under defined N-excess conditions only two phosphorylated residues were detected whereas under defined N-limiting conditions no phosphorylation was observed. GlnR phosphorylation is thus clearly correlated with N-rich conditions. Furthermore, GlnR was acetylated on four lysine residues independently of the N-concentration in the defined media and on only one lysine residue in the complex N-rich medium. Using EMSAs we demonstrated that phosphorylation inhibited the binding of GlnR to its targets genes, whereas acetylation had little influence on the formation of GlnR-DNA complex
@@ Dispute over the method of literal translation and that of free translation had a long history in China, in East Jin Dynasty Daoan(道安314-385),a well-known monk, was the representative of those who firmly advocated literal translation.Since he feared that free translation might not be true to the original, he advocated strict literal translation so as to preserve the true features.Works under his direction were typical of word-for-word translation, in which no alteration was made except accidental changes in word order.
Patricia L Graham
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.
Surdina, A V; Rassokhin, T I; Golovin, A V; Spiridonova, V A; Kraal, B; Kopylov, A M
In E. coli cells ribosomal small subunit biogenesis is regulated by RNA-protein interactions involving protein S7. S7 initiates the subunit assembly interacting with 16S rRNA. During shift-down of rRNA synthesis level, free S7 inhibits self-translation by interacting with 96 nucleotides long specific region of streptomycin (str) mRNA between cistrons S12 and S7 (intercistron). Many bacteria do not have the extended intercistron challenging development of specific approaches for searching putative mRNA regulatory regions, which are able to interact with proteins. The paper describes application of SERF approach (Selection of Random RNA Fragments) to reveal regulatory regions of str mRNA. Set of random DNA fragments has been generated from str operon by random hydrolysis and then transcribed into RNA; the fragments being able to bind protein S7 (serfamers) have been selected by iterative rounds. S7 binds to single serfamer, 109 nucleotide long (RNA109), derived from the intercistron. After multiple copying and selection, the intercistronic mutant (RNA109) has been isolated; it has enhanced affinity to S7. RNA109 binds to the protein better than authentic intercistronic str mRNA; apparent dissociation constants are 26 +/- 5 and 60 +/- 8 nM, respectively. Location of S7 binding site on the mRNA, as well as putative mode of regulation of coupled translation of S12 and S7 cistrons have been hypothesized.
Yu, Cuiping; Luo, Chaochao; Qu, Bo; Khudhair, Nagam; Gu, Xinyu; Zang, Yanli; Wang, Chunmei; Zhang, Na; Li, Qingzhang; Gao, Xuejun
14-3-3γ, an isoform of the 14-3-3 protein family, was proved to be a positive regulator of mTOR pathway. Here, we analyzed the function of 14-3-3γ in protein synthesis using bovine mammary epithelial cells (BMECs). We found that 14-3-3γ interacted with eIF1AX and RPS7 by 14-3-3γ coimmunoprecipitation (CoIP) and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight (MALDI-TOF/TOF) peptide mass fingerprinting analysis. These interactions of 14-3-3γ with eIF1AX and RPS7 were further confirmed by colocalization and fluorescence resonance energy transfer (FRET) analysis. We also found that methionine could promote protein synthesis and trigger the protein expression levels of 14-3-3γ, eIF1AX and RPS7. Analysis of overexpression and inhibition of 14-3-3γ confirmed that it positively affected the protein expression levels of eIF1AX, RPS7, Stat5 and mTOR pathway to promote protein synthesis and cell proliferation in BMECs. We further showed that overexpression of eIF1AX and RPS7 also triggered protein translation and cell proliferation. From these results, we conclude that molecular network including eIF1AX, RPS7, and 14-3-3γ regulates protein translation and cell proliferation in BMECs.
Full Text Available Obsessive-compulsive disorder (OCD is a clinically heterogeneous condition. Although structural brain alterations have been consistently reported in OCD, their interaction with particular clinical subtypes deserves further examination. Among other approaches, a two-group classification in patients with autogenous and reactive obsessions has been proposed. The purpose of the present study was to assess, by means of a voxel-based morphometry analysis, the putative brain structural correlates of this classification scheme in OCD patients. Ninety-five OCD patients and 95 healthy controls were recruited. Patients were divided into autogenous (n = 30 and reactive (n = 65 sub-groups. A structural magnetic resonance image was acquired for each participant and pre-processed with SPM8 software to obtain a volume-modulated gray matter map. Whole-brain and voxel-wise comparisons between the study groups were then performed. In comparison to the autogenous group, reactive patients showed larger gray matter volumes in the right Rolandic operculum. When compared to healthy controls, reactive patients showed larger volumes in the putamen (bilaterally, while autogenous patients showed a smaller left anterior temporal lobe. Also in comparison to healthy controls, the right middle temporal gyrus was smaller in both patient subgroups. Our results suggest that autogenous and reactive obsessions depend on partially dissimilar neural substrates. Our findings provide some neurobiological support for this classification scheme and contribute to unraveling the neurobiological basis of clinical heterogeneity in OCD.
Limaye, Ajay B. S.; Lamb, Michael P.
Terraces eroded into sediment (alluvial) and bedrock (strath) preserve an important history of river activity. River terraces are thought to form when a river switches from a period of slow vertical incision and valley widening to fast vertical incision and terrace abandonment. Consequently, terraces are often interpreted to reflect changing external drivers including tectonics, sea level, and climate. In contrast, the intrinsic unsteadiness of lateral migration in rivers may generate terraces even under constant rates of vertical incision without external forcing. To explore this mechanism, we simulate landscape evolution by a vertically incising, meandering river and isolate the age and geometry of autogenic river terraces. Modeled autogenic terraces form for a wide range of lateral and vertical incision rates and are often paired and longitudinally extensive for intermediate ratios of vertical-to-lateral erosion rate. Autogenic terraces have a characteristic reoccurrence time that scales with the time for relief generation. There is a preservation bias against older terraces due to reworking of previously visited parts of the valley. Evolving, spatial differences in bank strength between bedrock and sediment reduce terrace formation frequency and length, favor pairing, and can explain sublinear terrace margins at valley boundaries. Age differences and geometries for modeled autogenic terraces are consistent, in cases, with natural terraces and overlap with metrics commonly attributed to terrace formation due to climate change. We suggest a new phase space of terrace properties that may allow differentiation of autogenic terraces from terraces formed by external drivers.
Full Text Available Eshcerichia coli mazEF is a stress-induced toxin-antitoxin module mediating cell death and requiring a quorum-sensing (QS extracellular death factor (EDF, the pentapeptide NNWNN. Here we uncovered several distinct molecular mechanisms involved in its generation from the zwf mRNA encoding glucose-6-phosphate dehydrogenase. In particular, we show that, under stress conditions, the endoribonuclease MazF cleaves specific ACA sites, thereby generating a leaderless zwf mRNA which is truncated 30 codons after the EDF-encoding region. Since the nascent ribosome peptide exit tunnel can accommodate up to 40 amino acids, this arrangement allows the localization of the EDF residues inside the tunnel when the ribosome is stalled at the truncation site. Moreover, ribosome stalling activates the trans-translation system, which provides a means for the involvement of ClpPX in EDF generation. Furthermore, the trans-translation is described as a regulatory system that attenuated the generation of EDF, leading to low levels of EDF in the single cell. Therefore, the threshold EDF molecule concentration required is achieved only by the whole population, as expected for QS.
Moriyama, Tetsuji; Tanaka, Shu; Nakayama, Yasumune; Fukumoto, Masahiro; Tsujimura, Kenji; Yamada, Kohji; Bamba, Takeshi; Yoneda, Yoshihiro; Fukusaki, Eiichiro; Oka, Masahiro
Transaldolase 1 (TALDO1) is a rate-limiting enzyme involved in the pentose phosphate pathway, which is traditionally thought to occur in the cytoplasm. In this study, we found that the gene TALDO1 has two translational initiation sites, generating two isoforms that differ by the presence of the first 10 N-terminal amino acids. Notably, the long and short isoforms were differentially localised to the cell nucleus and cytoplasm, respectively. Pull-down and in vitro transport assays showed that the long isoform, unlike the short one, binds to importin α and is actively transported into the nucleus in an importin α/β-dependent manner, demonstrating that the 10 N-terminal amino acids are essential for its nuclear localisation. Additionally, we found that these two isoforms can form homo- and/or hetero-dimers with different localisation dynamics. A metabolite analysis revealed that the subcellular localisation of TALDO1 is not crucial for its activity in the pentose phosphate pathway. However, the expression of these two isoforms differentially affected the levels of various metabolites, including components of the tricarboxylic acid cycle, nucleotides, and sugars. These results demonstrate that the nucleocytoplasmic distribution of TALDO1, modulated via alternative translational initiation and dimer formation, plays an important role in a wide range of metabolic networks. PMID:27703206
Full Text Available 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 artistic translation focuses on reactions, judging the quality of an artistic translation work is one of the most difficult things one can do. We end up having a score of complexity and humanity for each one of the mentioned techniques: Literal translation would be the closest thing we have to the machines world and artistic translation would be the closest thing we have to the purely human world. By creating these classifications and studying the subtleties of each one of them, we are adding degrees of quality to our courses and to translation as a professional field. The main contribution of this paper is then the formalization of such a piece of knowledge. We, however, also lay the foundations for studies of this type.
Snoeck, D.; Jensen, Ole Mejlhede; De Belie, N.
Fly ash and blast-furnace slag containing binders are frequently used in the construction industry and it is important to know the extent of autogenous shrinkage and its (ideal) mitigation by superabsorbent polymers in these systems as a function of their age. In this paper, the autogenous shrink...
Jensen, Thomas; Schou, Søren; Gundersen, Hans Jørgen G;
OBJECTIVES: The objective was to test the hypotheses: (i) no differences in bone-to-implant contact formation, and (ii) no differences between the use of autogenous mandibular or iliac bone grafts, when autogenous bone, Bio-Oss mixed with autogenous bone, or Bio-Oss is used as graft for the maxil...
Park, Eun Jung; Woo, Seon Min; Min, Kyoung-Jin; Kwon, Taeg Kyu
Melatonin (N-acetyl-5-methoxytryptamine) has recently gained attention as an anticancer agent and for combined cancer therapy. In this study, we investigated the underlying molecular mechanisms of the effects of melatonin on cancer cell death. Treatment with melatonin induced apoptosis and upregulated the expression of the pro-apoptotic protein Bcl-2-interacting mediator of cell death (Bim) in renal cancer Caki cells. Furthermore, downregulation of Bim expression by siRNA markedly reduced melatonin-mediated apoptosis. Melatonin increased Bim mRNA expression through the induction of Sp1 and E2F1 expression and transcriptional activity. We found that melatonin also modulated Bim protein stability through the inhibition of proteasome activity. However, melatonin-induced Bim upregulation was independent of melatonin's antioxidant properties and the melatonin receptor. Taken together, our results suggest that melatonin induces apoptosis through the upregulation of Bim expression at the transcriptional level and at the post-translational level.
Pedrolli, Danielle; Langer, Simone; Hobl, Birgit; Schwarz, Julia; Hashimoto, Masayuki; Mack, Matthias
FMN riboswitches are genetic elements that, in many bacteria, control genes responsible for biosynthesis and/or transport of riboflavin (vitamin B2 ). We report that the Escherichia coli ribB FMN riboswitch controls expression of the essential gene ribB coding for the riboflavin biosynthetic enzyme 3,4-dihydroxy-2-butanone-4-phosphate synthase (RibB; EC 220.127.116.11). Our data show that the E. coli ribB FMN riboswitch is unusual because it operates at the transcriptional and also at the translational level. Expression of ribB is negatively affected by FMN and by the FMN analog roseoflavin mononucleotide, which is synthesized enzymatically from roseoflavin and ATP. Consequently, in addition to flavoenzymes, the E. coli ribB FMN riboswitch constitutes a target for the antibiotic roseoflavin produced by Streptomyces davawensis.
Full Text Available Alzheimer's disease (AD is the main cause of dementia in our increasingly aging population. The debilitating cognitive and behavioral symptoms characteristic of AD make it an extremely distressing illness for patients and carers. Although drugs have been developed to treat AD symptoms and to slow disease progression, there is currently no cure. The incidence of AD is predicted to increase to over one hundred million by 2050, placing a heavy burden on communities and economies, and making the development of effective therapies an urgent priority. Two proteins are thought to have major contributory roles in AD: the microtubule associated protein tau, also known as MAPT; and the amyloid-beta peptide (A-beta, a cleavage product of amyloid precursor protein (APP. Oxidative stress is also implicated in AD pathology from an early stage. By targeting eIF4A, an RNA helicase involved in translation initiation, the synthesis of APP and tau, but not neuroprotective proteins, can be simultaneously and specifically reduced, representing a novel avenue for AD intervention. We also show that protection from oxidative stress is increased upon eIF4A inhibition. We demonstrate that the reduction of these proteins is not due to changes in mRNA levels or increased protein degradation, but is a consequence of translational repression conferred by inhibition of the helicase activity of eIF4A. Inhibition of eIF4A selectively and simultaneously modulates the synthesis of proteins involved in Alzheimer's disease: reducing A-beta and tau synthesis, while increasing proteins predicted to be neuroprotective.
Calcine and mill kaolin were used under agreeable technological conditions to generate matakaolin (MK). The autogenous shrinkage performance of high performance concrete added with MK was researched. It is shown that MK has an effective inhibitory action to early autogenous shrinkage of cement concrete, and the inhibitory action increases with the increase of MK. The autogenous shrinkage values from 24 hours after placement to 56 days are all higher than those of the contrasted concrete, among which, the value of the concrete with 5% MK is the highest. But the total shrinkage values in 56 days are all less than those of the contrasted test pieces. The total contraction after 24 h of placement decreases as the increase of MK, moreover,it is greatly less than that of the contrasted ones.
Studier, F. William (Stony Brook, NY); Dubendorff, John W. (Sound Beach, NY)
This invention relates to the cloning and expression of autogenes encoding RNA polymerases of T7 and T7-like bacteriophages, in which the RNA polymerase gene is transcribed from a promoter which is recognized by the encoded RNA polymerase. Cloning of T7 autogenes was achieved by reducing the activity of the RNA polymerase sufficiently to permit host cell growth. T7 RNA polymerase activity was controlled by combining two independent methods: lac-repression of the recombinant lac operator-T7 promoter in the autogene and inhibition of the polymerase by T7 lysozyme. Expression systems for producing the RNA polymerases of T7 and other T7-like bacteriophages, and expression systems for producing selected gene products are described, as well as other related materials and methods.
Studier, F. William (Stony Brook, NY); Dubendorff, John W. (Sound Beach, NY)
This invention relates to the cloning and expression of autogenes encoding RNA polymerases of T7 and T7-like bacteriophages, in which the RNA polymerase gene is transcribed from a promoter which is recognized by the encoded RNA polymerase. Cloning of T7 autogenes was achieved by reducing the activity of the RNA polymerase sufficiently to permit host cell growth. T7 RNA polymerase activity was controlled by combining two independent methods: lac-repression of the recombinant lac operator-T7 promoter in the autogene and inhibition of the polymerase by T7 lysozyme. Expression systems for producing the RNA polymerases of T7 and other T7-like bacteriophages, and expression systems for producing selected gene products are described, as well as other related materials and methods.
Studier, F.W.; Dubendorff, J.W.
This invention relates to the cloning and expression of autogenes encoding RNA polymerases of T7 and T7-like bacteriophages, in which the RNA polymerase gene is transcribed from a promoter which is recognized by the encoded RNA polymerase. Cloning of T7 autogenes was achieved by reducing the activity of the RNA polymerase sufficiently to permit host cell growth. T7 RNA polymerase activity was controlled by combining two independent methods: lac-repression of the recombinant lac operator-T7 promoter in the autogene and inhibition of the polymerase by T7 lysozyme. Expression systems for producing the RNA polymerases of T7 and other T7-like bacteriophages, and expression systems for producing selected gene products are described, as well as other related materials and methods. 12 figs.
Studier, F.W.; Dubendorff, J.W.
This invention relates to the cloning and expression of autogenes encoding RNA polymerases of T7 and T7-like bacteriophages, in which the RNA polymerase gene is transcribed from a promoter which is recognized by the encoded RNA polymerase. Cloning of T7 autogenes was achieved by reducing the activity of the RNA polymerase sufficiently to permit host cell growth. T7 RNA polymerase activity was controlled by combining two independent methods: lac-repression of the recombinant lac operator-T7 promoter in the autogene and inhibition of the polymerase by T7 lysozyme. Expression systems for producing the RNA polymerases of T7 and other T7-like bacteriophages, and expression systems for producing selected gene products are described, as well as other related materials and methods. 12 figs.
Haith, Linwood R; Stair-Buchmann, Megan E; Ackerman, Bruce H; Herder, Diane; Reigart, Cynthia L; Stoering, Marla; Guilday, Robert E; Patton, Mary Lou; Ross, Kerry M
An ongoing objective of burn research is to evaluate wound dressings and develop new treatments to expedite wound healing. This was a single-center, prospective, randomized, controlled study to evaluate the effectiveness of Aquacel Ag as a dressing for autogenous skin donor sites compared with Xeroform. We hypothesized that donor sites treated with Aquacel Ag would heal faster. Patients were considered for enrollment if they required skin grafting with two donor sites >100 cm at least 2 inches apart. Dressings were observed daily starting on post-op day #2 until discharge and then weekly in the outpatient burn clinic. Assessments evaluated pain, infection, and reapplication. Photographs were taken on post-op day #2, upon "90% re-epithelialization," and at post-op day #30-45. Scar assessments and blinded photographic reviews were completed to assess cosmetic healing. Twenty-nine patients completed the study. Re-epithelialization occurred faster with Xeroform (15.2 days vs. 17.6 days). Daily pain scores were higher with Xeroform (6.72 vs. 5.68) and Aquacel Ag needed to be replaced more often (1.72 times vs. 0.10 times). Three patients developed donor site infections with Aquacel Ag. Scar scores between the donor sites were not statistically significant. The blinded photo review concluded that Xeroform had a better cosmetic outcome (24 vs. 10%). Although patients complained of more pain with Xeroform, it demonstrated shorter healing times and better cosmetic outcomes. Aquacel Ag needed to be replaced more often and represented the only three donor site infections.
Jônatas Caldeira Esteves
Full Text Available From a biological standpoint, the best material for reconstruction of bone defects is the autogenous bone graft. However, as tissue healing is affected under diabetic conditions, major changes might take place in the revascularization, incorporation, replacement and remodeling phases of the grafted area. The purpose of this study was to assess the bone healing process in surgical wounds prepared in tibiae of diabetic rats and filled with autogenous bone. Forty male rats (Rattus norvegicus albinus, Wistar were randomly assigned to receive an endovenous injection (penile vein of either citrate buffer solution (Group 1 - control; n=20 or streptozotocin dissolved in citrate buffer solution (35 mg/kg to induce diabetes (Group 2 - diabetic; n=20. After determination of glycemia, the animals were anesthetized and the anterolateral regions of the tibiae of both limbs were shaved, antisepsis was performed and longitudinal incisions were made in each limb. The tibiae were exposed and two 2mm-diameter surgical cavities were prepared: one in the right limb, filled with particulate autogenous bone and the other in the left limb, filled with blood clot. The animals were euthanized at 10 and 30 postoperative days. The anatomic pieces were obtained, submitted to laboratory processing and sections were stained by hematoxylin and eosin and Masson's Trichrome for histomorphologic and histometric analyses. In both groups, the wounds filled with autogenous bone graft showed better results than those filled with blood clot. The control group showed higher new bone formation in wounds filled with autogenous bone graft at 30 days than the diabetic group, but without statistical significance. It may be concluded that, in general, the new bone formation occurred with autogenous graft was quantitatively similar between control and diabetic groups and qualitatively better in the control group.
There are select instances where autogenous tooth transplantation should be considered as part of the overall management of the developing occlusion in the child patient. These circumstances occur when there are missing mandibular premolars in Class II malocclusions with good faces, unevenly distributed agenesis, missing or lost incisors, and ectopic teeth. The purposes of this paper were to educate pediatric dentists about the autogenous tooth transplantation technique, its success, its potential advantages and disadvantages and to report on three cases treated with autogenesis tooth transplantation.
Nozick, J H; Farnsworth, P; Montefusco, C M; Parsonnet, V; Ruigrok, T J; Zimmerman, A N
The morphological and functional effects of calcium-free and calcium-containing solutions on canine jugular vein intima were examined under conditions which closely resemble those techniques currently employed in peripheral vascular and aortocoronary bypass surgery. Veins that had been exposed only to calcium-containing solutions remained patent for the duration of the experimental period. Vein perfusion with a calcium-free solution, however, resulted in disruption of the jugular vein intima once calcium ions were reintroduced. Autogenous as a femoral arterial graft became thrombosed within 60 minutes. It is therefore suggested that vein grafts of autogenous origin be irrigated with calcium-containing solutions to prevent intimal damage and thrombosis.
Pánek, Josef; Kolár, Michal; Vohradský, Jirí; Shivaya Valásek, Leos
There are several key mechanisms regulating eukaryotic gene expression at the level of protein synthesis. Interestingly, the least explored mechanisms of translational control are those that involve the translating ribosome per se, mediated for example via predicted interactions between the ribosomal RNAs (rRNAs) and mRNAs. Here, we took advantage of robustly growing large-scale data sets of mRNA sequences for numerous organisms, solved ribosomal structures and computational power to computationally explore the mRNA-rRNA complementarity that is statistically significant across the species. Our predictions reveal highly specific sequence complementarity of 18S rRNA sequences with mRNA 5' untranslated regions (UTRs) forming a well-defined 3D pattern on the rRNA sequence of the 40S subunit. Broader evolutionary conservation of this pattern may imply that 5' UTRs of eukaryotic mRNAs, which have already emerged from the mRNA-binding channel, may contact several complementary spots on 18S rRNA situated near the exit of the mRNA binding channel and on the middle-to-lower body of the solvent-exposed 40S ribosome including its left foot. We discuss physiological significance of this structurally conserved pattern and, in the context of previously published experimental results, propose that it modulates scanning of the 40S subunit through 5' UTRs of mRNAs.
Kaito, Chikara; Saito, Yuki; Nagano, Gentaro; Ikuo, Mariko; Omae, Yosuke; Hanada, Yuichi; Han, Xiao; Kuwahara-Arai, Kyoko; Hishinuma, Tomomi; Baba, Tadashi; Ito, Teruyo; Hiramatsu, Keiichi; Sekimizu, Kazuhisa
The F region downstream of the mecI gene in the SCCmec element in hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) contains two bidirectionally overlapping open reading frames (ORFs), the fudoh ORF and the psm-mec ORF. The psm-mec ORF encodes a cytolysin, phenol-soluble modulin (PSM)-mec. Transformation of the F region into the Newman strain, which is a methicillin-sensitive S. aureus (MSSA) strain, or into the MW2 (USA400) and FRP3757 (USA300) strains, which are community-acquired MRSA (CA-MRSA) strains that lack the F region, attenuated their virulence in a mouse systemic infection model. Introducing the F region to these strains suppressed colony-spreading activity and PSMα production, and promoted biofilm formation. By producing mutations into the psm-mec ORF, we revealed that (i) both the transcription and translation products of the psm-mec ORF suppressed colony-spreading activity and promoted biofilm formation; and (ii) the transcription product of the psm-mec ORF, but not its translation product, decreased PSMα production. These findings suggest that both the psm-mec transcript, acting as a regulatory RNA, and the PSM-mec protein encoded by the gene on the mobile genetic element SCCmec regulate the virulence of Staphylococcus aureus.
Full Text Available The F region downstream of the mecI gene in the SCCmec element in hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA contains two bidirectionally overlapping open reading frames (ORFs, the fudoh ORF and the psm-mec ORF. The psm-mec ORF encodes a cytolysin, phenol-soluble modulin (PSM-mec. Transformation of the F region into the Newman strain, which is a methicillin-sensitive S. aureus (MSSA strain, or into the MW2 (USA400 and FRP3757 (USA300 strains, which are community-acquired MRSA (CA-MRSA strains that lack the F region, attenuated their virulence in a mouse systemic infection model. Introducing the F region to these strains suppressed colony-spreading activity and PSMα production, and promoted biofilm formation. By producing mutations into the psm-mec ORF, we revealed that (i both the transcription and translation products of the psm-mec ORF suppressed colony-spreading activity and promoted biofilm formation; and (ii the transcription product of the psm-mec ORF, but not its translation product, decreased PSMα production. These findings suggest that both the psm-mec transcript, acting as a regulatory RNA, and the PSM-mec protein encoded by the gene on the mobile genetic element SCCmec regulate the virulence of Staphylococcus aureus.
Boysen, Anders; Møller-Jensen, Jakob; Kallipolitis, Birgitte H.;
. Furthermore, in previous work most of the potential target genes have been shown to be repressed by FNR through an undetermined mechanism. Collectively, our results provide insight into the mechanism by which FNR negatively regulates genes such as sodA, sodB, cydDC, and metE, thereby demonstrating...
were collected by centrifugation and lysed by sonication in the presence of a cocktail of protease inhibitors. Lysates were cleared by centrifugation...Cherukuri P, Li H, Yuan Z, et al. (2008) Reciprocal intraepithelial interactions between TP63 and hedgehog signaling regulate quiescence and activation of
Rasmussen, Kirsten Wølch; Schjoldager, Anne
out by specialised revisers, but by staff translators, who revise the work of colleagues and freelancers on an ad hoc basis. Corrections are mostly given in a peer-to-peer fashion, though the work of freelancers and inexperienced in-house translators is often revised in an authoritative (nonnegotiable......) way. Most respondents and interviewees are worried about increasing pressures on the translation market, which, combined with customers’ general lack of understanding of the translation process, mean that systematic, all-encompassing quality assurance is rarely financially viable....
Kramer, Philip A.; Duan, Jicheng; Qian, Wei-Jun; Marcinek, David J.
Mitochondrial oxidative stress is a common feature of skeletal myopathies across multiple conditions; however, the mechanism by which it contributes to skeletal muscle dysfunction remains controversial. Oxidative damage to proteins, lipids, and DNA has received the most attention, yet an important role for reversible redox post-translational modifications (PTMs) in pathophysiology is emerging. The possibility that these PTMs can exert dynamic control of muscle function implicates them as a mechanism contributing to skeletal muscle dysfunction in chronic disease. Herein, we discuss the significance of thiol-based redox dependent modifications to mitochondrial, myofibrillar and excitation-contraction (EC) coupling proteins with an emphasis on how these changes could alter skeletal muscle performance under chronically stressed conditions. A major barrier to a better mechanistic understanding of the role of reversible redox PTMs in muscle function is the technical challenges associated with accurately measuring the changes of site-specific redox PTMs. Here we will critically review current approaches with an emphasis on sample preparation artifacts, quantitation, and specificity. Despite these challenges, the ability to accurately quantify reversible redox PTMs is critical to understanding the mechanisms by which mitochondrial oxidative stress contributes to skeletal muscle dysfunction in chronic diseases.
Spiridonova, V A; Rozhdestvensky, T S; Kopylov, A M
A study of the ability of His6-tagged ribosomal protein S7 of Thermus thermophilus to interact with the truncated S12-S7 intercistronic region of str mRNA of Escherichia coli has been described. A minimal S7 binding mRNA fragment is a part of the composite hairpin, with the termination codon of the S12 cistron on one side and the initiation codon of the next S7 cistron on the other. It has a length in the range of 63-103 nucleotides. The 63 nucleotide mRNA fragment, which corresponds to a putative S7 binding site, binds very poorly with S7. Tight RNA structure models, which behave as integral systems and link the S7 binding site with the translational regulation region of the hairpin, are suggested. This observation provides more insight into the mechanism of S7-directed autogenous control of translational coupling of str mRNA.
Full Text Available The aim of this paper is to trace the contemporary perceptions/definitions of the translator and translation in Turkey where the translation profession is not a legally regulated profession. (Invisibility of the translator and the scope of his/her expertise are widely debated issues among both the scholars/students of translation and the various players in the world of translation. Although translation is no longer being defined as a mere linguistic activity, reductionist views of translation that equate translation to ‘know’ing a foreign language still continues to prevail. What accompanies the said reductionist view is the claim that a translator can not translate ‘all the texts’ in different fields of expertise, at least not as successfully as the ‘real’ experts of the field who also know a foreign language such as engineer-translators or lawyer-translators who know English. However, recent developments concerning legal translation in plurilingual settings evidence a completely different understanding of translation and the identity/expertise of the translator. In such settings, translators work together with the drafters of the legal texts and are responsible for the source legal texts as well as the target ones, broadening the scope of the ‘expertise’ of the translator in an unprecedented way. In the light of the implications of the said transformation of the identity of the legal translator, this paper argues that the identity/definition of the translator/translation needs to be reconsidered and the results should be reflected onto the translator training programs with the aim of helping students of translation (redefine their identity as real ‘experts’ of the translation field and contributing to the transformation of the perception of translation and the translator.
The research described in this final report focused on the influence of stress agents on protein synthesis in crop plants (primarily soybean). Investigations into the `heat shock` (HS) stress mediated changes in transcriptional and translocational regulation of protein synthesis coupled with studies on anaerobic water deficit and other stress mediated alterations in protein synthesis in plants provided the basis of the research. Understanding of the HS gene expression and function(s) of the HSPs may clarify regulatory mechanisms operative in development. Since the reproductive systems of plants if often very temperature sensitive, it may be that the system could be manipulated to provide greater thermotolerance.
Kim, Young-Kyun; Kim, Su-Gwan; Bae, Ji-Hyun; Um, In-Woong; Oh, Ji-Su; Jeong, Kyung-In
Recently, techniques have been reported that involve the preparation of extracted teeth from patients used as particulated bone graft materials for bone graft purposes. For implant placement and bone graft, autogenous teeth bone graft materials were used in 15 patients, and clinically excellent results were obtained. In histological examination, favorable bony healing by osteoconduction was observed.
Stavropoulos, Andreas; Sima, Catalin; Sima, Andrea;
OBJECTIVES: The aim was to evaluate histologically the outcome of a bioglass and autogenous bone (at 1 : 1 ratio) composite implantation for transalveolar sinus augmentation. METHODS: In 31 patients, during implant installation ca. 4 months after sinus augmentation, biopsies were harvested throug...
Full Text Available Objectives. (1 Evaluate safety of autogenous engineered septal neocartilage grafts and (2 compare properties of implanted grafts versus controls. Study Design. Prospective, basic science. Setting. Research laboratory. Methods. Constructs were fabricated from septal cartilage and then cultured in vitro or implanted on the nasal dorsum as autogenous grafts for 30 or 60 days. Rabbits were monitored for local and systemic complications. Histological, biochemical, and biomechanical properties of constructs were evaluated. Results. No serious complications were observed. Implanted constructs contained more DNA (P<0.01 and less sGAG perDNA (P<0.05 when compared with in vitro controls. Confined compressive aggregate moduli were also higher in implanted constructs (P<0.05 and increased with longer in vivo incubation time (P<0.01. Implanted constructs displayed resorption rates of 20–45 percent. Calcium deposition in implanted constructs was observe. Conclusion. Autogenous engineered septal cartilage grafts were well tolerated. As seen in experiments with athymic mice, implanted constructs accumulated more DNA and less sGAG when compared with in vitro controls. Confined compressive aggregate moduli were higher in implanted constructs. Implanted constructs displayed resorption rates similar to previously published studies using autogenous implants of native cartilage.
Huang, Ke; Liu, PengFei; Li, Xiang; Chen, ShuBin; Wang, LiHui; Qin, Li; Su, ZhengHui; Huang, WenHao; Liu, Juli; Jia, Bei; Liu, Jie; Cai, JingLei; Pei, DuanQing; Pan, GuangJin
The breakthrough development of induced pluripotent stem cells (iPSCs) raises the prospect of patient-specific treatment for many diseases through the replacement of affected cells. However, whether iPSC-derived functional cell lineages generate a deleterious immune response upon auto-transplantation remains unclear. In this study, we differentiated five human iPSC lines from skin fibroblasts and urine cells into neural progenitor cells (NPCs) and analyzed their immunogenicity. Through co-culture with autogenous peripheral blood mononuclear cells (PBMCs), we showed that both somatic cells and iPSC-derived NPCs do not stimulate significant autogenous PBMC proliferation. However, a significant immune reaction was detected when these cells were co-cultured with allogenous PBMCs. Furthermore, no significant expression of perforin or granzyme B was detected following stimulation of autogenous immune effector cells (CD3(+)CD8(-) T cells, CD3(+)CD8(+) T cells or CD3(-)CD56(+) NK cells) by NPCs in both PBMC and T cell co-culture systems. These results suggest that human iPSC-derived NPCs may not initiate an immune response in autogenous transplants, and thus set a base for further preclinical evaluation of human iPSCs.
Lindeboom, R.E.F.; Ding, L.; Weijma, J.; Plugge, C.M.; Lier, van J.B.
Autogenerative high pressure digestion (AHPD) provides an integrated biogas upgrading technology, capable of producing biogas with a CH4 content exceeding 95% at pressures up to 90 bar. Hydrolysis is generally regarded as the rate-limiting step in the anaerobic digestion of complex organic matter, g
The report deals with experimental measurement of autogenous shrinkage of Ducorit S5R according to the test method ASTM C 1698-09. This test method measures the bulk strain of a sealed cementitious specimen, at constant temperature and not subjected to external forces, from the time of final...
Jade PY Ho
Full Text Available We present a case of chronic acromioclavicular joint dislocation (Rockwood type 5 in which the choice of acromioclavicular reconstruction using autogenous semitendinosus tendon graft was made due to its superiority in anatomical reconstruction of the coracoclavicular ligaments, and the impact of postoperative rehabilitation on the recovery of this patient. We also discuss the rationale behind this.
Raghoebar, GM; Batenburg, RHK; Vissink, A; Reintsema, H
Purpose: This study evaluated the applicability of intraorally harvested autogenous bone grafts for the augmentation of the narrow maxillary alveolar ridge to enable insertion of implants for single tooth replacement. Materials and Methods: Local defects of the anterior maxilla were reconstructed in
Karl Ravet; Brigitte Touraine; Sun A. Kim; Francoise Cellier; Sébastien Thomine; Mary Lou Guerinot; Jean-Francois Briat; Frédéric Gaymard
Ferritins are major players in plant iron homeostasis. Surprisingly, their overexpression in transgenic plants led only to a moderate increase in seed iron content, suggesting the existence of control checkpoints for iron loading and storage in seeds. This work reports the identification of two of these checkpoints. First, measurement of seed metal con-tent during fruit development in Arabidopsis thaliana reveals a similar dynamic of loading for Fe, Mn, Cu, and Zn. The step controlling metal loading into the seed occurs by the regulation of transport from the hull to the seed. Second, metal loading and ferritin abundance were monitored in different genetic backgrounds affected in vacuolar iron transport (AtVIT1, AtNRAMP3, AtNRAMP4) or plastid iron storage (AtFER1 to 4). This approach revealed (1) a post-translational reg-ulation of ferritin accumulation in seeds, and (2) that ferritin stability depends on the balance of iron allocation between vacuoles and plastids. Thus, the success of ferritin overexpression strategies for iron biofortification, a promising approach to reduce iron-deficiency anemia in developing countries, would strongly benefit from the identification and engineering of mechanisms enabling the translocation of high amounts of iron into seed plastids.
Esquivel, Rianne N; Pohlschroder, Mechthild
In many bacteria and archaea, type IV pili facilitate surface adhesion, the initial step in biofilm formation. Haloferax volcanii has a specific set of adhesion pilins (PilA1-A6) that, although diverse, contain an absolutely conserved signal peptide hydrophobic (H) domain. Data presented here demonstrate that these pilins (PilA1-A6) also play an important role in regulating flagella-dependent motility, which allows cells to rapidly transition between planktonic and sessile states. Cells lacking adhesion pilins exhibit a severe motility defect, however, expression of any one of the adhesion pilins in trans can rescue the motility and adhesion. Conversely, while deleting pilB3-C3, genes required for PilA pilus biosynthesis, results in cells lacking pili and having an adhesion defect, it does not affect motility, indicating that motility regulation requires the presence of pilins, but not assembled pili. Mutagenesis studies revealed that the pilin-dependent motility regulatory mechanism does not require the diverse C-terminal region of the PilA pilins but specifically involves the conserved H-domain. This novel post-translational regulatory mechanism, which employs components that promote biofilm formation to inhibit motility, can provide a rapid response to changing environmental conditions. A model for this regulatory mechanism, which may also be present in other prokaryotes, is discussed.
Liu Chang; Li Shuai; Dai Xiaoyan; Ma Ji; Wan Junhu; Jiang Hao; Wang Peng; Liu Zhaoli; Zhang Hongquan
Polycomb repression complex 2 ( PRC2 ) component EZH2 tri-methylates H3 K27 and exerts ep-igenetic repression on target gene expression. EZH2-mediated epigenetic control of RNA polymerase II(Pol II) transcribed coding gene transcription has been well established. However, little is known about EZH2-mediated epigenetic regulation of RNA polymerase III( Pol III) transcription. Here we present a paradigm that EZH2 is in-volved in the repression of Pol III transcription via interaction with transcriptional factor complex IIIC ( TFIIIC ) . EZH2 and H3K27 me3 cooccupy the promoter of tRNATyr, 5S rRNA and 7SL RNA genes. Depletion of EZH2 or inhibition of EZH2 methyl transferase activity led to upregulation of Pol III target gene transcription. EZH2-media-ted repression of Pol III transcribed gene expression requires presence of SUZ12 . SUZ12 was able to interact with TFIIIC complex and knockdown of SUZ12 decreased occupancy of EZH2 and H3 K27 me3 at the promoter of Pol III target genes. Our findings pointed out a previously unidentified role of PRC2 complex in suppressing transcription of Pol III transcribed non-translated RNA genes, putting Pol III on a new layer of epigenetic regulation.
Gallego, C; Garí, E; Colomina, N; Herrero, E; Aldea, M
Nutrients are among the most important trophic factors in all organisms. When deprived of essential nutrients, yeast cells use accumulated reserves to complete the current cycle and arrest in the following G1 phase. We show here that the Cln3 cyclin, which has a key role in the timely activation of SBF (Swi4-Swi6)- and MBF (Mbp1-Swi6)-dependent promoters in late G1, is down-regulated rapidly at a post-transcriptional level in cells deprived of the nitrogen source. In addition to the fact that Cln3 is degraded faster by ubiquitin-dependent mechanisms, we have found that translation of the CLN3 mRNA is repressed approximately 8-fold under nitrogen deprivation conditions. As a consequence, both SBF- and MBF-dependent expression is strongly down-regulated. Mainly because of their transcriptional dependence on SBF, and perhaps with the contribution of similar post-transcriptional mechanisms to those found for Cln3, the G1 cyclins Cln1 and 2 become undetectable in starved cells. The complete loss of Cln cyclins and the sustained presence of the Clb-cyclin kinase inhibitor Sic1 in starved cells may provide the molecular basis for the G1 arrest caused by nitrogen deprivation.
Bansal, Sorav; Aiken, Alex
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.
Lambert, Jr., F. J.
A study on autogenous welding of Type 309 thin stainless steel sheet was made after experiencing cracking difficulties on several commercial heats. A relationship exists between the sum of the phosphorus plus sulfur, the ferrite control of the weld metal, and the crack sensitivity of autogenously made welds. A new simple weld test for thin-gage sheet is utilized for studying the susceptibility to cracking. A chemistry modification is suggested to alleviate possible weld cracking when autogenously welding this grade. The principles of crack sensitivity prediction could apply to other austenitic stainless steel types where chemistry limits are such that ferrite is possible.
Full Text Available Prader-Willi Syndrome (PWS, a maternally imprinted disorder and leading cause of obesity, is characterised by insatiable appetite, poor muscle development, cognitive impairment, endocrine disturbance, short stature and osteoporosis. A number of causative loci have been located within the imprinted Prader-Willi Critical Region (PWCR, including a set of small non-translated nucleolar RNA's (snoRNA. Recently, micro-deletions in humans identified the snoRNA Snord116 as a critical contributor to the development of PWS exhibiting many of the classical symptoms of PWS. Here we show that loss of the PWCR which includes Snord116 in mice leads to a reduced bone mass phenotype, similar to that observed in humans. Consistent with reduced stature in PWS, PWCR KO mice showed delayed skeletal development, with shorter femurs and vertebrae, reduced bone size and mass in both sexes. The reduction in bone mass in PWCR KO mice was associated with deficiencies in cortical bone volume and cortical mineral apposition rate, with no change in cancellous bone. Importantly, while the length difference was corrected in aged mice, consistent with continued growth in rodents, reduced cortical bone formation was still evident, indicating continued osteoblastic suppression by loss of PWCR expression in skeletally mature mice. Interestingly, deletion of this region included deletion of the exclusively brain expressed Snord116 cluster and resulted in an upregulation in expression of both NPY and POMC mRNA in the arcuate nucleus. Importantly, the selective deletion of the PWCR only in NPY expressing neurons replicated the bone phenotype of PWCR KO mice. Taken together, PWCR deletion in mice, and specifically in NPY neurons, recapitulates the short stature and low BMD and aspects of the hormonal imbalance of PWS individuals. Moreover, it demonstrates for the first time, that a region encoding non-translated RNAs, expressed solely within the brain, can regulate bone mass in health
The human YB-1 cold shock domain : structural, dynamical and binding properties of the central nucleic acid binding domain of the human Y-box protein YB-1, a transcription and translation regulating protein
Kloks, Cathelijne Petra Anne Marie
Y-box proteins are a highly conserved group of proteins present in bacteria, plants and animals. They are essential in regulating transcription and translation and the coupling between theses two processes. Their central domain, the so-called cold shock domain (CSD), is responsible for the nucleic a
Schaeffer, Moritz; Dragsted, Barbara; Hvelplund, Kristian Tangsgaard
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...... 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...... evidence of co-activation. Results show that the number of translation alternatives for a single word and differences between source and target text in terms of word order have an effect on very early and late eye movement measures. Results are interpreted in terms of semantic and structural cross...
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…
Lin, Yuan; Liu, Jun; Liu, Xun; Ou, Yongbin; Li, Meng; Zhang, Huiling; Song, Botao; Xie, Conghua
The activity of vacuolar invertase (VI) is vital to potato cold-induced sweetening (CIS). A post-translational regulation of VI activity has been proposed which involves invertase inhibitor (VIH), but the mechanism for the interaction between VI and VIH has not been fully understood. To identify the potential partners of VI and VIH, two cDNA libraries were respectively constructed from CIS-resistant wild potato species Solanum berthaultii and CIS-sensitive potato cultivar AC035-01 for the yeast two-hybrid analysis. The StvacINV1 (one of the potato VIs) and StInvInh2B (one of the potato VIHs), previously identified to be associated with potato CIS, were used as baits to screen the two libraries. Through positive selection and sequencing, 27 potential target proteins of StvacINV1 and eight of StInvInh2B were clarified. The Kunitz-type protein inhibitors were captured by StvacINV1 in both libraries and the interaction between them was confirmed by bimolecular fluorescence complementation assay in tobacco cells, reinforcing a fundamental interaction between VI and VIH. Notably, a sucrose non-fermenting-1-related protein kinase 1 was captured by both the baits, suggesting that a protein complex could be necessary for fine turning of the invertase activity. The target proteins clarified in present research provide a route to elucidate the mechanism by which the VI activity can be subtly modulated.
Jing Dong Liu; Pak-Kwong Chung; Chun-Qing Zhang; Gangyan Si
Purpose: The purpose of the study was to examine the psychometric properties of the Chinese-translated Behavioral Regulation in Exercise Questionnaire-2 (C-BREQ-2) among Chinese university students from the Mainland and Hong Kong of China. Methods: University students from the Mainland (n=191) and Hong Kong (n =194) of China participated in this study. Factorial validity, discriminant validity, nomological validity, internal reliability, and measurement invariance across sample of the C-BREQ-2 were examined. Results:Confirmatory factor analysis provided support for the factorial validity of the 18-item, 5-factor structure C-BREQ-2. Examination of the 95%confidence interval of the inter-factor correlations suggested that the C-BREQ-2 assesses related but distinct constructs, which provided support for its discriminant validity. The internal consistency reliability of the C-BREQ-2 was found acceptable. Examination of the pattern of inter-factor correlations between different regulations suggested that a simplex-like pattern was displayed, which provided evidence for the nomological validity of C-BREQ-2. The results from multi-group confirmatory factor analysis suggested that the factor loadings and variances/covariances of the C-BREQ-2 measurement model were invariant across the Chinese university students in the Mainland and Hong Kong of China. Conclusion:The current study provided further psychometric evidence for the C-BREQ-2, which makes the further application and research of self-determination theory (SDT) based motivation in relation to exercise and physical activity in the Mainland of China context possible.
Tobacco class I cytosolic small heat shock proteins are under transcriptional and translational regulations in expression and heterocomplex prevails under the high-temperature stress condition in vitro.
Park, Soo Min; Kim, Keun Pill; Joe, Myung Kuk; Lee, Mi Ok; Koo, Hyun Jo; Hong, Choo Bong
Seven genomic clones of tobacco (Nicotiana tabacum W38) cytosolic class I small heat shock proteins (sHSPs), probably representing all members in the class, were isolated and found to have 66 to 92% homology between their nucleotide sequences. Even though all seven sHSP genes showed heat shock-responsive accumulation of their transcripts and proteins, each member showed discrepancies in abundance and timing of expression upon high-temperature stress. This was mainly the result of transcriptional regulation during mild stress conditions and transcriptional and translational regulation during strong stress conditions. Open reading frames (ORFs) of these genomic clones were expressed in Escherichia coli and the sHSPs were purified from E. coli. The purified tobacco sHSPs rendered citrate synthase and luciferase soluble under high temperatures. At room temperature, non-denaturing pore exclusion polyacrylamide gel electrophoresis on three sHSPs demonstrated that the sHSPs spontaneously formed homo-oligomeric complexes of 200 ∼ 240 kDa. However, under elevated temperatures, hetero-oligomeric complexes between the sHSPs gradually prevailed. Atomic force microscopy showed that the hetero-oligomer of NtHSP18.2/NtHSP18.3 formed a stable oligomeric particle similar to that of the NtHSP18.2 homo-oligomer. These hetero-oligomers positively influenced the revival of thermally inactivated luciferase. Amino acid residues mainly in the N-terminus are suggested for the exchange of the component sHSPs and the formation of dominant hetero-oligomers under high temperatures.
Xing, Shufan; van Deenen, Nicole; Magliano, Pasqualina; Frahm, Lea; Forestier, Edith; Nawrath, Christiane; Schaller, Hubert; Gronover, Christian S; Prüfer, Dirk; Poirier, Yves
Cytosolic acetyl-CoA is involved in the synthesis of a variety of compounds, including waxes, sterols and rubber, and is generated by the ATP citrate lyase (ACL). Plants over-expressing ACL were generated in an effort to understand the contribution of ACL activity to the carbon flux of acetyl-CoA to metabolic pathways occurring in the cytosol. Transgenic Arabidopsis plants synthesizing the polyester polyhydroxybutyrate (PHB) from cytosolic acetyl-CoA have reduced growth and wax content, consistent with a reduction in the availability of cytosolic acetyl-CoA to endogenous pathways. Increasing the ACL activity via the over-expression of the ACLA and ACLB subunits reversed the phenotypes associated with PHB synthesis while maintaining polymer synthesis. PHB production by itself was associated with an increase in ACL activity that occurred in the absence of changes in steady-state mRNA or protein level, indicating a post-translational regulation of ACL activity in response to sink strength. Over-expression of ACL in Arabidopsis was associated with a 30% increase in wax on stems, while over-expression of a chimeric homomeric ACL in the laticifer of roots of dandelion led to a four- and two-fold increase in rubber and triterpene content, respectively. Synthesis of PHB and over-expression of ACL also changed the amount of the cutin monomer octadecadien-1,18-dioic acid, revealing an unsuspected link between cytosolic acetyl-CoA and cutin biosynthesis. Together, these results reveal the complexity of ACL regulation and its central role in influencing the carbon flux to metabolic pathways using cytosolic acetyl-CoA, including wax and polyisoprenoids.
Huergo, Luciano F; Souza, Emanuel M; Steffens, Maria B R; Yates, M Geoffrey; Pedrosa, Fábio O; Chubatsu, Leda S
Nitrogen fixation in Azospirillum brasilense is regulated at transcriptional and post-translational levels. Post-translational control occurs through the reversible ADP-ribosylation of dinitrogenase reductase (Fe Protein), mediated by the dinitrogenase reductase ADP-ribosyltransferase (DraT) and dinitrogenase reductase glycohydrolase (DraG). Although the DraT and DraG activities are regulated in vivo, the molecules responsible for such regulation remain unknown. We have constructed broad-host-range plasmids capable of over-expressing, upon IPTG induction, the regulatory enzymes DraT and DraG as six-histidine-N-terminal fused proteins (His). Both DraT-His and DraG-His are functional in vivo. We have analyzed the effects of DraT-His and DraG-His over-expression on the post-translational modification of Fe Protein. The DraT-His over-expression led to Fe Protein modification in the absence of ammonium addition, while cells over-expressing DraG-His showed only partial ADP-ribosylation of Fe Protein by adding ammonium. These results suggest that both DraT-His and DraG-His lose their regulation upon over-expression, possible by titrating out negative regulators.
Full Text Available The formation of carbon nanotubes (CNTs, spherical carbon nanocapsules (CNCs, and carbon spheres (CSs is accomplished by using the method of reactions under autogenic pressure at elevated temperatures (RAPET. A powder mixture of naphthalene and nickel acetate tetrahydrate is dissociated under its autogenic pressure. The resultant CNTs and CNCs exhibit good graphitic quality, and the diameters range from 50~200 nm. Smooth and monodisperse CSs with the diameter ranging from 5~10 μm can be obtained by pyrolysis of pure naphthalene. Our results show that the reaction temperature and catalyst proportion play a key role in the formation of carbon nanostructures with RAPET method.
Cowings, P. S.
Experiments were performed on 24 men and women (aged 20-27 yr) in three equal groups who were taught to control their own heart rates by autogenic training and biofeedback under dark and sound-isolated conditions. Group I was parasympathetic dominant, group II was sympathetic dominant, and group III consisted of parasympathetic-dominant subjects and controls who received only biofeedback of their own heart rates. The results corroborate three hypotheses: (1) subjects with para-sympathetic-dominant autonomic profiles perform in a way that is both qualitatively and quantitatively different from subjects with sympathetic-dominant autonomic profiles; (2) tests of interindividual variability yield data relevant to individual performance in visceral learning tasks; and (3) the combined use of autogenic training, biofeedback, and verbal feedback is suitable for conditioning large stable autonomic responses in humans.
Gebreyesus, Fiyore; Cowings, Patricia S.; Toscano, William B.
Airsickness is experienced by about 50% of military aviators some time in their career. Aviators who suffer from recurrent episodes of airsickness are typically referred to the Naval Aerospace Medical Institute (NAMI) at Pensacola where they undergo extensive evaluation and 8 weeks of training in the Self-Paced Airsickness Desensitization (SPAD) program. Researchers at NASA Ames have developed an alternative mitigation training program, Autogenic Feedback Training Exercise (AFTE) that has demonstrated an 80% success rate for improving motion sickness tolerance.
Ian D. R. Mackinnon
Full Text Available High quality, micron-sized interpenetrating grains of MgB2, with high density, are produced at low temperatures (~420 °C < T < ~500 °C under autogenous pressure by pre-mixing Mg powder and NaBH4 and heating in an Inconel 601 alloy reactor for 5–15 h. Optimum production of MgB2, with yields greater than 75%, occurs for autogenous pressure in the range 1.0 MPa to 2.0 MPa, with the reactor at ~500 °C. Autogenous pressure is induced by the decomposition of NaBH4 in the presence of Mg and/or other Mg-based compounds. The morphology, transition temperature and magnetic properties of MgB2 are dependent on the heating regime. Significant improvement in physical properties accrues when the reactor temperature is held at 250 °C for >20 min prior to a hold at 500 °C.
TANG Jie; WANG Xue-mei; HU Jing; LUO En; QI Meng-chun
To evaluate autogenous vein grafts and inside-out vein grafts as conduits for the defects repair in the rabbit facial nerves.Methods:The 10 mm segments of buccal division of facial nerve were transected for 48 rabbits in this study.Then the gaps were immediately repaired by autogenous vein grafts or inside-out vein grafts in different groups. All the animals underwent the whisker movement test and electrophysiologic test during the following 16 weeks at different time points postoperatively. Subsequently,the histological examination was performed to observe the facial nerve regeneration morphologically.Results:At 8 weeks after operation,the facial nerve regeneration has significant difference between the experimental group and the control group in electrophysiologic test and histological observation. However,at the end of this study,16 weeks after operation,there was no significant difference between inside-out vein grafts and standard vein grafts in enhancing peripheral nerve regeneration.Conclusion:This study suggest that both kinds of vein grafts play positive roles in facial nerve regeneration after being repaired immediately,but the autogenous inside-out vein grafts might accelerate and facilitate axonal regeneration as compared with control.
Iida, J.; Ueda, Y.; Ohgushi, H.; Takakura, Y. [Nara Medical Univ., Kashihara (Japan). Dept. of Orthopedic Surgery; Yoshikawa, T. [Nara Medical Univ., Kashihara (Japan). Dept. of Orthopedic Surgery; Nara Medical Univ., Kashihara (Japan). Dept. of Phathology; Uemura, T.; Tateishi, T. [National Inst. for Advanced Interdisciplinary Research (NAIR), Ibaraki (Japan). Tsukuba Research Center; Enomoto, Y.; Ichijima, K. [Nara Medical Univ., Kashihara (Japan). Dept. of Phathology
Five ml of bone marrow was collected from the humerus of a 6 month old female dog by needle aspiration. The marrow was cultured in T-75 flask and expand the marrow mesenchymal cells. After 1 week in primary culture, cells were released by trypsin treatment, concentrated and loaded onto porous hydroxyapatite (HA) blocks. The marrow/HA constructs were subcultured in the presence of dexamethasone and beta-glycerophosphate (osteogenic medium). After 2 weeks of subculture, the autogenous cultured bone/HA constructs were subcutaneously implanted into the back of the dog. Histological findings of the constructs at 3 weeks after implantation revealed thick layer of lamellar bone together with active osteoblasts lining in many pore areas of the HA. High alkaline phosphatase activity could be detected in the construct. These results indicate that autogenous cultured bone/HA constructs can produce extensive bone formation after implantation in a large animal(dog). Therefore, based upon the fact that human marrow-derived culture bone/HA construct possesses osteogenic potential when it is grafted into nude mice, it can be expected that autogenous human cultured bone/ceramic grafts may be useful to reconstruct bone in the clinical setting. (orig.)
Niedzielska, Iwona; Borgiel-Marek, Halina; Różanowski, Bartosz
Background Removing a tooth from the jaw results in the occurrence of oroantral communication in beneficial anatomic conditions or in the case of a iatrogenic effect. Popularized treatments of the oroantral communication have numerous faults. Large bone defect eliminates the chance to introduce an implant. Purpose of this work was assessment of the usefulness of autogenous bone graft and PRF in normal bone regeneration in the site of oroantral communication. Material and Methods Bone regeneration in the site of oroantral communication was assessed in 20 patients. Bone defects were supplemented autogenous bone graft from mental protuberance in 14 cases and from oblique line in 6 cases. The graft was covered with a PRF membrane. Results In the study group in all cases closure of the oroantral communication was observed. The average width of the alveolar was 13 mm and the average height was 12.5 mm. In 3 patients an average increase of alveolar height of 1.5 mm was observed. Conclusions This method may be the best option to prepare alveolar for new implant and prosthetic solutions. Key words:Oroantral communication, oroantral fistula, autogenous bone graft, bone regeneration, platelet rich fibrin. PMID:27475687
Lee, Han-Joo; Telch, Michael J
We examined differences in a visual search-based latent inhibition (LI) task in 48 non-treatment seeking individuals diagnosed with obsessive-compulsive disorder (OCD) and 26 non-OCD controls, using a visual search-based LI task as a function of participants' primary obsessional presentation based on the autogenous-reactive subtype model of obsessions (Lee & Kwon, 2003; Lee & Telch, 2007). We hypothesized that LI would be significantly attenuated among OCD participants whose primary obsessions were characterized by aversive impulses, images, or thoughts with sexual, aggressive, blasphemous, and repulsive themes (autogenous obsessions) due to their weakened attentional inhibitory mechanisms and elevated schizotypal personality features, as compared with those whose primary obsessions were characterized by somewhat realistic aversive mental intrusions about contamination, mistakes, accidents, or disarray (reactive obsession) and non-OCD controls. Results showed that those primarily displaying autogenous obsessions failed to display LI, whereas those primarily displaying reactive obsessions and non-OCD controls displayed significant LI effects. Our data suggest that the magnitude of LI varies as a function of primary obsessional presentations among individuals with OCD.
Netto, Henrique Duque; Miranda Chaves, Maria das Graças Alfonso; Aatrstrup, Beatriz; Guerra, Renata; Olate, Sergio
SUMMARY The aim of this study is to compare the bone formation in maxillary sinus lift with an autogenous bone graft in histological evaluation at 2 or 6 months. A comparative study was designed where 10 patients with missing teeth bilaterally in the posterior zone of the maxilla were selected. Patients received a particulate autogenous bone graft under the same surgical conditions, selecting a site to collect a biopsy and histological study at two months and another at six months postoperatively. Histomorphometry was performed and were used Kolmogorov-Smirnov test, student’s t-test and Spearman’s correlation coefficient, considering a value of p<0.05. Differences were observed in inflammatory infiltrate and vascularization characteristics; however, the group analyzed at two months presented 38.12% ± 6.64 % of mineralized tissue, whereas the group studied at 6 months presented an average of 38.45 ± 9.27 %. There were no statistical differences between the groups. It is concluded that the bone formation may be similar in intrasinus particulate autogenous bone grafts in evaluations at two or six months; under these conditions, early installation of implants is viable. PMID:27867255
Full Text Available Introduction : Dental implants have been widely applied in clinic for many years. However, the success rate is still challenging mainly because of bone deficiency. An ideal bone graft is traditionally thought to guide and induce new bone regeneration as well as been absorbed completely by human body. The Hypothesis: Autogenous bone mixed with titanium granules might be an ideal bone graft for dental implantation. Evaluation of the Hypothesis: First, we analyzed advantages of grafts of autogenous bone mixed with titanium granules, such as serving as a s scaffold for wound healing and tissue regeneration, creating sui microenvironment for implant-bone integration, shortening the new bone′s creeping distance, etc. Then we creatively hypothesized a novel alternative bone graft with premixed autogenous bone and non-absorbent titanium granules. Apart from repairing bone deficiency, our hypothesis could promote the integration between new bone and titanium implant from the perspective of microenvironment. We believe that the method is promising and worth extension in clinical application.
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.
Haggie, Peter M.; Phuan, Puay-Wah; Tan, Joseph-Anthony; Xu, Haijin; Avramescu, Radu G.; Perdomo, Doranda; Zlock, Lorna; Nielson, Dennis W.; Finkbeiner, Walter E.; Lukacs, Gergely L.; Verkman, Alan S.
W1282X is the fifth most common cystic fibrosis transmembrane regulator (CFTR) mutation that causes cystic fibrosis. Here, we investigated the utility of a small molecule corrector/potentiator strategy, as used for ΔF508-CFTR, to produce functional rescue of the truncated translation product of the W1282X mutation, CFTR1281, without the need for read-through. In transfected cell systems, certain potentiators and correctors, including VX-809 and VX-770, increased CFTR1281 activity. To identify novel correctors and potentiators with potentially greater efficacy on CFTR1281, functional screens were done of ∼30,000 synthetic small molecules and drugs/nutraceuticals in CFTR1281-transfected cells. Corrector scaffolds of 1-arylpyrazole-4-arylsulfonyl-piperazine and spiro-piperidine-quinazolinone classes were identified with up to ∼5-fold greater efficacy than VX-809, some of which were selective for CFTR1281, whereas others also corrected ΔF508-CFTR. Several novel potentiator scaffolds were identified with efficacy comparable with VX-770; remarkably, a phenylsulfonamide-pyrrolopyridine acted synergistically with VX-770 to increase CFTR1281 function ∼8-fold over that of VX-770 alone, normalizing CFTR1281 channel activity to that of wild type CFTR. Corrector and potentiator combinations were tested in primary cultures and conditionally reprogrammed cells generated from nasal brushings from one W1282X homozygous subject. Although robust chloride conductance was seen with correctors and potentiators in homozygous ΔF508 cells, increased chloride conductance was not found in W1282X cells despite the presence of adequate transcript levels. Notwithstanding the negative data in W1282X cells from one human subject, we speculate that corrector and potentiator combinations may have therapeutic efficacy in cystic fibrosis caused by the W1282X mutation, although additional studies are needed on human cells from W1282X subjects. PMID:27895116
Olwig, Mette Fog
This article contributes to the growing scholarship on local development practitioners by re-examining conceptualizations of practitioners as ‘brokers’ strategically translating between ‘travelling’ (development institution) rationalities and ‘placed’ (recipient area) rationalities in relation...... and practice spurred by new challenges deriving from climate change anxiety, the study shows how local practitioners often make local activities fit into travelling development rationalities as a matter of habit, rather than as a conscious strategy. They may therefore cease to ‘translate’ between different...... rationalities. This is shown to have important implications for theory, research and practice concerning disaster risk reduction and climate change adaptation in which such translation is often expected....
Full Text Available The term “Translational Genomics” reflects both title and mission of this new journal. “Translational” has traditionally been understood as “applied research” or “development”, different from or even opposed to “basic research”. Recent scientific and societal developments have triggered a re-assessment of the connotation that “translational” and “basic” are either/or activities: translational research nowadays aims at feeding the best science into applications and solutions for human society. We therefore argue here basic science to be challenged and leveraged for its relevance to human health and societal benefits. This more recent approach and attitude are catalyzed by four trends or developments: evidence-based solutions; large-scale, high dimensional data; consumer/patient empowerment; and systems-level understanding.
Liao, Ying; Gu, Feng; Mao, Xiang; Niu, Qiaona; Wang, Huaxia; Sun, Yingjie; Song, Cuiping; Qiu, Xusheng; Tan, Lei; Ding, Chan
Viral infections result in cellular stress responses, which can trigger protein translation shutoff via phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α). Newcastle disease virus (NDV) causes severe disease in poultry and selectively kills human tumour cells. In this report, we determined that infection of HeLa human cervical cancer cells and DF-1 chicken fibroblast cells with NDV maintained protein at early infection times, 0-12 h post-infection (p.i.), and gradually inhibited global protein translation at late infection times, 12-24 h p.i. Mechanistic studies showed that translation inhibition at late infection times was accompanied by phosphorylation of eIF2α, a checkpoint of translation initiation. Meanwhile, the eIF2α kinase, PKR, was upregulated and activated by phosphorylation and another eIF2α kinase, PERK, was phosphorylated and cleaved into two fragments. Pharmacological inhibition experiments revealed that only PKR activity was required for eIF2α phosphorylation, suggesting that recognition of viral dsRNA by PKR was responsible for translation shutoff. High levels of phospho-eIF2α led to preferential translation of the transcription factor ATF4 and an increase in GADD34 expression. Functionally, GADD34, in conjunction with PP1, dephosphorylated eIF2a and restored protein translation, benefiting virus protein synthesis. However, PP1 was degraded at late infection times, functionally counteracting the upregulation of GADD34. Taken together, our data support that NDV-induced translation shutoff at late infection times was attributed to sustaining phosphorylation of eIF2α, which is mediated by continual activation of PKR and degradation of PP1.
Guerrero, Santiago; Libre, Camille; Batisse, Julien; Mercenne, Gaëlle; Richer, Delphine; Laumond, Géraldine; Decoville, Thomas; Moog, Christiane; Marquet, Roland; Paillart, Jean-Christophe
The essential HIV-1 viral infectivity factor (Vif) allows productive infection of non-permissive cells expressing cytidine deaminases APOBEC3G (A3G) and A3F by decreasing their cellular level, and preventing their incorporation into virions. Unlike the Vif-induced degradation of A3G, the functional role of the inhibition of A3G translation by Vif remained unclear. Here, we show that two stem-loop structures within the 5'-untranslated region of A3G mRNA are crucial for translation inhibition by Vif in cells, and most Vif alleles neutralize A3G translation efficiently. Interestingly, K26R mutation in Vif abolishes degradation of A3G by the proteasome but has no effect at the translational level, indicating these two pathways are independent. These two mechanisms, proteasomal degradation and translational inhibition, similarly contribute to decrease the cellular level of A3G by Vif and to prevent its incorporation into virions. Importantly, inhibition of A3G translation is sufficient to partially restore viral infectivity in the absence of proteosomal degradation. These findings demonstrate that HIV-1 has evolved redundant mechanisms to specifically inhibit the potent antiviral activity of A3G.
The act of translation between languages and cultures has been going on for centuries, but the act of theorizing about-translation is of recent origin. In the last forty years translation scholars have attempted to understand the process of translation and evaluate its merits giving rise to a whole range of conceptualizing which is now called translation studies. Translation studies , therefore, has grown within important scholastic enclosures of the west attempting to conduct political and i...
Hassan, Khalid S
The use of composite bone grafts in dehiscence defects around immediate dental implants are aimed at improving the outcome of the regenerative process. The present study was designed to evaluate the efficacy of combinations of autogenous bone graft with a synthetic copolymer polylactic and polyglycolic acid (Fisiograft) on bone healing of buccal dehiscence defects around immediate dental implants. Sixteen adult male patients who each received an immediate implant for a single tooth replacement at a maxillary anterior or premolar site were included in this study. Patients were divided into 2 groups. One group received immediate dental implants augmented with autogenous bone graft combined with Fisiograft. The other group received immediate dental implants augmented with autogenous bone graft alone. The results revealed that both treatment modalities led to significant improvements for the primary outcome regarding bone fill as well as a significant reduction of probing pocket depth and gain of attachment level. Moreover, there were slightly statistically significant differences between the groups. In conclusion, the combination of autogenous bone graft and Fisiograft showed a slight superiority to autogenous bone graft alone, suggesting that it could be an optimum bone substitute for treatment of dehiscence around immediate dental implant.
Schou, Søren; Holmstrup, Palle; Skovgaard, Lene Theil;
autogenous bone graft; guided bone regeneration; histology; membrane; non-human primates; oral implants; osseointegration; pathalogy; peri-implantitis; stereology; treatment......autogenous bone graft; guided bone regeneration; histology; membrane; non-human primates; oral implants; osseointegration; pathalogy; peri-implantitis; stereology; treatment...
Rickert, D.; Vissink, A.; Slot, Jan; Sauerbier, S.; Meijer, H. J. A.; Raghoebar, G. M.
The purpose of this study was to assess implant survival and 1-year clinical performance of implants placed in the posterior maxilla that had been subjected to maxillary sinus floor elevation surgery with bovine bone mineral (BioOss (R)) mixed with autogenous bone marrow concentrate or autogenous bo
Purnima Rajkarnikar Sthapit
Full Text Available Introduction: To evaluate the cosmetic results and recurrence of unilateral frontalis sling surgery using a silicone rod compared with autogenous fascia lata in cases of simple congenital ptosis. Methods: This is a retrospective comparative study of 59 patients who underwent a frontalis sling operation for congenital ptosis. Patients were divided into two groups according to the sling material used; an autogeneous fascia lata (fl group (n = 24 and a silicone rod group (sl (n = 35. Cosmetic results and recurrence rates were compared between these 2 groups. The cosmetic results of the frontalis sling operation were assessed as good, fair, or poor based on the difference between the Margin Reflex Distance of both eyelids and graded as good if the difference in two eyes was ≤1mm and poor if it was 2mm or more. Recurrence was defined as the conversion of the cosmetic result from good or fair to poor category. Results: At postoperative day seven and 30, MRD of both the groups were good but on three months follow-up MRD of silicon rod group dropped, however it was not statistically significant .Lid contour was good in both the groups, however, lid symmetry was poor in two cases of fascia lata at three months follow-up. Repeat surgery for poor outcome was done in 8.6% of cases in silicon rod and 8.3% of fascia lata group. Conclusions: The frontalis sling operation using either a silicone rod or autogenous fascia lata showed equally good cosmetic results and lower recurrence rate at three months follow up. Keywords: congenital ptosis; fascia lata; frontalis sling surgery; margin reflex distance; silicone rod.
Sherman, Blake P; Lindley, Emily M; Turner, A Simon; Seim, Howard B; Benedict, James; Burger, Evalina L; Patel, Vikas V
A prospective, randomized study was performed in an ovine model to compare the efficacy of an anorganic bovine-derived hydroxyapatite matrix combined with a synthetic 15 amino acid residue (ABM/P-15) in facilitating lumbar interbody fusion when compared with autogenous bone harvested from the iliac crest. P-15 is a biomimetic to the cell-binding site of Type-I collagen for bone-forming cells. When combined with ABM, it creates the necessary scaffold to initiate cell invasion, binding, and subsequent osteogenesis. In this study, six adult ewes underwent anterior-lateral interbody fusion at L3/L4 and L4/L5 using PEEK interbody rings filled with autogenous bone at one level and ABM/P-15 at the other level and no additional instrumentation. Clinical CT scans were obtained at 3 and 6 months; micro-CT scans and histomorphometry analyses were performed after euthanization at 6 months. Clinical CT scan analysis showed that all autograft and ABM/P-15 treated levels had radiographically fused outside of the rings at the 3-month study time point. Although the clinical CT scans of the autograft treatment group showed significantly better fusion within the PEEK rings than ABM/P-15 at 3 months, micro-CT scans, clinical CT scans, and histomorphometric analyses showed there were no statistical differences between the two treatment groups at 6 months. Thus, ABM/P-15 was as successful as autogenous bone graft in producing lumbar spinal fusion in an ovine model, and it should be further evaluated in clinical studies.
Full Text Available Background: Autogenous bone graft, although considered as a gold standard, has been relegated to background because of limited quantity and donor site morbidity. Revival of interest in its use has been reflected by its tremendous capacity for regeneration in less than ideal situation. Bone blocks have been used for implant site augmentation, with varied success. Aim: Aim of the study was to evaluate the efficacy of autogenous bone block in the regeneration of bone, for saving teeth with a hopeless prognosis. Settings and Design: A total of six patients and 12 sites with grade II and III mobile teeth were treated with autogenous bone blocks and fiber splinting. Subjects and Methods: Attachment loss, probing depths, and radiographic bone loss were recorded at baseline and at 12 months interval. Statistical Analysis Used: The Student paired t test was used for evaluation of the changes from baseline to 12 months. Results: At 12 months post-operatively, there was a highly significant amount of bone gain as compared to the baseline. The mean amount of bone loss reduced from 9.41 ± 1.16 to 5.41 ± 1.01. The clinical attachment loss reduced from 7.37 ± 1.24 mm to 3.79 ± 0.89 mm and probing depth reduced from 7 ± 1.67 mm to 5.5 ± 0.63 mm. The grafted bone was observed to have been incorporated with the host bone in most of the sites as evidenced by radiographs. Conclusions: For teeth with hopeless prognosis, this method can be considered to be a very viable alternative to extraction and replacement by costly implants.
Donos, Nikolaos; Kostopoulos, Lambros; Karring, Thorkild
The aim of the present study was to evaluate the effect of augmenting the maxillary alveolar ridge and the lateral aspect of the mandible with onlay autogeneic cortico-cancellous bone grafts that were covered with e-PTFE membranes. The experiment was carried out in 51 rats. In 15 rats, the edentulous maxillary jaw between the incisor and the first molar was augmented by means of an autogeneic ischiac bone graft that was fixed with a gold-coated microimplant. In one side, the graft was covered with an e-PTFE membrane, while the other side, which served as control, was treated without a membrane. In the other 36 rats, the lateral aspect of the mandible was augmented in both sides by means of an autogeneic ischiac bone graft that was fixed with a gold-coated or a titanium microimplant. In one side, the augmented area was covered with an e-PTFE membrane, while the contralateral side was treated without a membrane. Histological analysis at 60, 120 and 180 days after augmentation of the maxilla showed that, in the case of the test sites (where most of the membranes were either exposed or lost), the bone grafts presented extensive resorption and there was a lack of bone continuity between the graft and the recipient site. Similar findings were made at the non-membrane-treated control sides. In the case of augmentation of the mandible with membranes, the bone grafts were not resorbed, but were integrated into newly formed bone at the recipient site. In the control sides, the grafts presented varying degrees of resorption and integration into the recipient bone. It is concluded that, in comparison to bone grafting alone, onlay ischiac bone grafting combined with guided tissue regeneration eliminates the risk of bone graft resorption and ensures integration of the graft into newly formed bone at the recipient site, provided that closure of the operated area can be maintained during healing.
Matet, Alexandre; Amar, Nawel; Mohand-Said, Saddek; Sahel, José-Alain; Barale, Pierre-Olivier
Introduction The Argus II retinal prosthesis is composed of an epiretinal electrode array positioned over the macula and connected to an extrascleral electronics case via a silicone cable, running through a sclerotomy. During implantation, the manufacturer recommends to cover the sclerotomy site with a patch of processed human pericardium to prevent postoperative hypotony and conjunctival erosion by the underlying electronics case. Due to biomedical regulations prohibiting the use of this material in France, we developed an alternative technique combining a scleral flap protecting the sclerotomy and an autogenous graft of superior temporalis fascia overlying the electronics case. Methods The purpose of this study is to describe the 4-year outcomes of this modified procedure in three subjects who underwent Argus II Retinal Prosthesis System implantation. Clinical data consisting of intraocular pressure measurements and tolerance in terms of conjunctival erosion or inflammation were retrospectively assessed over a 4-year postoperative follow-up. Results None of the three patients implanted with the modified technique developed ocular hypotony over 4 years. A normal, transient conjunctival inflammation occurred during the first postoperative month but conjunctival erosion was not observed in any of the three patients over 4 years. Four years after implantation, the autogenous temporalis fascia graft remained well tolerated and the retinal prosthesis was functional in all three patients. Conclusion The combination of an autograft of superficial temporalis fascia and a scleral flap efficiently prevented leakage through the sclerotomy site, ocular hypotony, and conjunctival erosion by the extrascleral electronics case. This modified technique is suitable for the implantation of existing and forthcoming retinal prostheses. Superficial temporalis fascia may also be used as alternative to commercial tectonic tissues for scleral wound repair in clinical settings where they
Maria Letizia Di Martino
Full Text Available VirF, an AraC-like activator, is required to trigger a regulatory cascade that initiates the invasive program of Shigella spp., the etiological agents of bacillary dysentery in humans. VirF expression is activated upon entry into the host and depends on many environmental signals. Here, we show that the virF mRNA is translated into two proteins, the major form, VirF30 (30 kDa, and the shorter VirF21 (21 kDa, lacking the N-terminal segment. By site-specific mutagenesis and toeprint analysis, we identified the translation start sites of VirF30 and VirF21 and showed that the two different forms of VirF arise from differential translation. Interestingly, in vitro and in vivo translation experiments showed that VirF21 is also translated from a leaderless mRNA (llmRNA whose 5′ end is at position +309/+310, only 1 or 2 nucleotides upstream of the ATG84 start codon of VirF21. The llmRNA is transcribed from a gene-internal promoter, which we identified here. Functional analysis revealed that while VirF30 is responsible for activation of the virulence system, VirF21 negatively autoregulates virF expression itself. Since VirF21 modulates the intracellular VirF levels, this suggests that transcription of the llmRNA might occur when the onset of the virulence program is not required. We speculate that environmental cues, like stress conditions, may promote changes in virF mRNA transcription and preferential translation of llmRNA.
Crystal L. Ramanujam
Full Text Available In the surgical treatment of severe diabetic foot infections, substantial soft tissue loss often accompanies partial foot amputations. These sizeable soft tissue defects require extensive care with the goal of expedited closure to inhibit further infection and to provide resilient surfaces capable of withstanding long-term ambulation. Definitive wound closure management in the diabetic population is dependent on multiple factors and can have a major impact on the risk of future diabetic foot complications. In this article, the authors provide an overview of autogenous skin grafting, including anatomical considerations, clinical conditions, surgical approach, and adjunctive treatments, for diabetic partial foot amputations.
Østergaard, Thomas; Jensen, Ole Mejlhede
of the thermal comparator is based on thermal expansion of aluminium. A particular characteristic of the measuring system is the fixation of the thermal comparator sensor to the deforming specimen. The modular system ensures effective thermostatic control of the hydrating cement paste samples. The technique......This paper describes a simple and accurate experimental device specially developed to measure autogenous deformation in hardening cement-based materials. The measuring system consists of a so-called thermal comparator sensor and a modular thermostatically controlled system. The operating principle...
Full Text Available Background/Aim. The mechanism of impaired bone healing in diabetes mellitus includes different tissue and cellular level activities due to micro- and macrovascular changes. As a chronic metabolic disease with vascular complications, diabetes affects a process of bone regeneration as well. The therapeutic approach in bone regeneration is based on the use of osteoinductive autogenous grafts as well as osteoconductive synthetic material, like a β-tricalcium phosphate. The aim of the study was to determine the quality and quantity of new bone formation after the use of autogenous bone and β-tricalcium phosphate in the model of calvarial critical-sized defect in rabbits with induced diabetes mellitus type I. Methods. The study included eight 4-month-old Chincilla rabbits with alloxan-induced diabetes mellitus type I. In all animals, there were surgically created two calvarial bilateral defects (diameter 12 mm, which were grafted with autogenous bone and β-tricalcium phosphate (n = 4 or served as unfilled controls (n = 4. After 4 weeks of healing, animals were sacrificed and calvarial bone blocks were taken for histologic and histomorphometric analysis. Beside descriptive histologic evaluation, the percentage of new bone formation, connective tissue and residual graft were calculated. All parameters were statistically evaluated by Friedman Test and post hock Wilcoxon Singed Ranks Test with a significance of p < 0.05. Results. Histology revealed active new bone formation peripherally with centrally located connective tissue, newly formed woven bone and well incorporated residual grafts in all treated defects. Control samples showed no bone bridging of defects. There was a significantly more new bone in autogeonous graft (53% compared with β-tricalcium phosphate (30%, (p < 0.030 and control (7%, (p < 0.000 groups. A significant difference was also recorded between β-tricalcium phosphate and control groups (p < 0.008. Conclusion. In the present
Lamiell, James T
Presents a preface from James T. Lamiell, who translates Wilhelm Wundt's Psychology's Struggle for Existence (Die Psychologie im Kampf ums Dasein), in which Wundt advised against the impending divorce of psychology from philosophy, into English. Lamiell comments that more than a decade into the 21st century, it appears that very few psychologists have any interest at all in work at the interface of psychology and philosophy. He notes that one clear indication of this is that the Society for Theoretical and Philosophical Psychology, which is Division 24 of the American Psychological Association (APA), remains one of the smallest of the APA's nearly 60 divisions. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
Feminist translation theory emerged in the late 70s and early 80s of 20th Century. It is the combination of the feminist movement and the“cultural turn”of translation. It was introduced to China in the 1980s, and with the development of the transla⁃tion theory and translation practice, more and more Chinese translators want to study the feminist translation theory from the deep levels.
Peviani, Alessia; Lastdrager, Jeroen; Hanson, Johannes; Snel, Berend
Basic leucine zippers (bZIPs) form a large plant transcription factor family. C and S1 bZIP groups can heterodimerize, fulfilling crucial roles in seed development and stress response. S1 sequences also harbor a unique regulatory mechanism, termed Sucrose-Induced Repression of Translation (SIRT). Th
Full Text Available Bone substitutes used in oral surgery include allografts, xenografts, and synthetic materials that are frequently used to compensate bone loss or to reinforce repaired bone, but little is currently known about their physicochemical characteristics. The aim of this study was to evaluate a number of physical and chemical properties in a variety of granulated mineral-based biomaterials used in dentistry and to compare them with those of autogenous bone. Autogenous bone and eight commercial biomaterials of human, bovine, and synthetic origins were studied by high-resolution X-ray diffraction, atomic absorption spectrometry, and laser diffraction to determine their chemical composition, calcium release concentration, crystallinity, and granulation size. The highest calcium release concentration was 24. 94 mg/g for Puros and the lowest one was 2.83 mg/g for Ingenios β-TCP compared to 20.15 mg/g for natural bone. The range of particles sizes, in terms of median size D50, varied between 1.32 μm for BioOss and 902.41 μm for OsteoSponge, compared to 282.1 μm for natural bone. All samples displayed a similar hexagonal shape as bone, except Ingenios β-TCP, Macrobone, and OsteoSponge, which showed rhomboid and triclinic shapes, respectively. Commercial bone substitutes significantly differ in terms of calcium concentration, particle size, and crystallinity, which may affect their in vivo performance.
Kim, Hyoung Rae [Kangwon National University, Chuncheon (Korea, Republic of)
The purpose of this study was to evaluate the efficacy of percutaneous transluminal angioplasty (PTA) in facilitating maturation of autogenous arteriovenous fistulae. There were 12 immature autogenous arteriovenous fistulae. We performed 15 PTAs transvenously. Post-intervention anatomic and clinical successes were estimated, and the 6-month and 1-year primary and secondary patency rates were calculated using Kaplan-Meier analysis. All immature fistulae had underlying stenosis (n=20): arteriovenous anastomosis (n=1) and venous outflow (n=19): 1) within 5 cm from the anastomosis (n=10); 2) more than 5 cm but less than 10 cm from the anastomosis (n=5); 3) more than 10 cm from the anastomosis, including central veins (n=4). Six fistulae had two or more stenoses. Repeat intervention was necessary in two patients. The anatomical success rate was 94.3%, and the clinical success rate was 86.7%. The 6-month and 1-year primary patency rates were 72.7% and 54.5%, and the secondary patency rates were 100% and 81.8%, respectively. All immature hemodialysis fistulae have underlying stenosis, most of which are located near the arteriovenous anastomosis. Early interventional procedures are helpful in the salvage and maintenance of immature arteriovenous fistulae, with a high degree of success
CHEN Hui; QIU Yong; WANG Bin; YU Yang; ZHU Ze-zhang ZHU Li-hua
Background Surgery for severe kyphoscoliosis is frequently unsatisfying because of loss of correction, high rate of pseudarthrosis and neurological complications.Several authors reported that the anterior fusion with strut grafts might improve the surgical outcome.This article describes and assesses the surgical strategies and the application of autogenous tibial strut in the treatment of severe kyphoscoliosis.Results The mean preoperative and postoperative kyphosis was 82°and 52°respectively, and the mean scoliosis was 84°and 44°respectively.Complications included pseudarthrosis (2 cases, one with graft fracture and the other with hook displacement), posterior elements fractures (4), pleura penetrations (3, in the plastic surgery of the thoracic cage), dura tear (2), exudative pleuritis (2, in the anterior surgery), and tibia fracture of the harvesting site (1).The mean loss of correction in coronal and sagittal plane was 6° and 7° respectively.Except for 1 case, the patients with incomplete paraplegia showed improvements to varying extents.Conclusion Autogenous tibial strut can provide excellent support to the kyphoscoliotic spine: it reduces pseudarthrodic rate, loss of correction and complications of graft harvest, it also prevents the occurrence of neurological impairment.
HE LiJuan; PEI XueTao; NAN Xue; WANG YunFang; GUAN LiDong; BAI CiXian; SHI ShuangShuang; YUAN HongFeng; CHEN Lin; LIU DaQing
To explore the feasibility of repairing clinical cutaneous deficiency, autogenic bone marrow mesenchymal stem cells (BMSCs) were isolated and differentiated into epidermal cells and fibroblasts in vitro supplemented with different inducing factors and biomaterials to construct functional tissueengineered skin. The results showed that after 72 h induction, BMSCs displayed morphologic changes such as typical epidermal cell arrangement, from spindle shape to round or oval; tonofibrils, melanosomes and keratohyaline granules were observed under a transmission electronic microscope. The differentiated cells expressed epidermal stem cell surface marker CK19 (59.66%±4.2%) and epidermal cells differentiation marker CK10. In addition, the induced epidermal cells acquired the anti-radiation capacity featured by lowered apoptosis following exposure to UVB. On the other hand, the collagen microfibrils deposition was noticed under a transmission electronic microscope after differentiating into dermis fibroblasts; RT-PCR identified collagen type Ⅰ mRNA expression in differentiated cells;radioimmunoassay detected the secretion of interleukin-6 (IL-6) and interleukin-8 (IL-8) (up to 115.06pg/mL and 0.84 ng/mL, respectively). Further in vivo implanting BMSCs with scaffold material shortened skin wound repair significantly. In one word, autogenic BMSCs have the potential to differentiate into epidermal cells and fibroblasts in vitro, and show clinical feasibility acting as epidermis-like and dermis-like seed cells in skin engineering.
Kronig, S A J; van der Mooren, R J G; Strabbing, E M; Stam, L H M; Tan, J A S L; de Jongh, E; van der Wal, K G H; Paridaens, D; Koudstaal, M J
The purpose of this study was to investigate the ophthalmic clinical findings following surgical reconstruction with autogenous bone grafts of pure blowout fractures. A retrospective review of 211 patients who underwent surgical repair of an orbital fracture between October 1996 and December 2013 was performed. Following data analysis, 60 patients who were followed up over a period of 1 year were included. A solitary floor fracture was present in 38 patients and a floor and a medial wall fracture in 22 patients. Comparing preoperative findings between these two groups, preoperative diplopia and enophthalmos were almost twice as frequent in the group with additional medial wall fractures: diplopia 8% and 14% and enophthalmos 18% and 55%, respectively. One year following surgery there was no diplopia present in either group. In the solitary floor fracture group, 3% still had enophthalmos. It can be concluded that at 1 year following the repair of pure orbital floor fractures using autogenous bone, good functional and aesthetic results can be obtained. In the group with both floor and medial wall fractures, no enophthalmos was found when both walls were reconstructed. When the medial wall was left unoperated, 29% of patients still suffered from enophthalmos after 1 year.
To explore the feasibility of repairing clinical cutaneous deficiency, autogenic bone marrow mesen-chymal stem cells (BMSCs) were isolated and differentiated into epidermal cells and fibroblasts in vitro supplemented with different inducing factors and biomaterials to construct functional tissue- engineered skin. The results showed that after 72 h induction, BMSCs displayed morphologic changes such as typical epidermal cell arrangement, from spindle shape to round or oval; tonofibrils, melano-somes and keratohyaline granules were observed under a transmission electronic microscope. The differentiated cells expressed epidermal stem cell surface marker CK19 (59.66% ± 4.2%) and epidermal cells differentiation marker CK10. In addition, the induced epidermal cells acquired the anti-radiation capacity featured by lowered apoptosis following exposure to UVB. On the other hand, the collagen microfibrils deposition was noticed under a transmission electronic microscope after differentiating into dermis fibroblasts; RT-PCR identified collagen type I mRNA expression in differentiated cells; radioimmunoassay detected the secretion of interleukin-6 (IL-6) and interleukin-8 (IL-8) (up to 115.06 pg/mL and 0.84 ng/mL, respectively). Further in vivo implanting BMSCs with scaffold material short-ened skin wound repair significantly. In one word, autogenic BMSCs have the potential to differentiate into epidermal cells and fibroblasts in vitro, and show clinical feasibility acting as epidermis-like and dermis-like seed cells in skin engineering.
Full Text Available Abstract Post-translational modifiers of the SUMO (Small Ubiquitin-related Modifier family have emerged as key regulators of protein function and fate. While the past few years have seen an enormous increase in knowledge on SUMO enzymes, substrates, and consequences of modification, regulation of SUMO conjugation is far from being understood. This brief review will provide an overview on recent advances concerning (i the interplay between sumoylation and other post-translational modifications at the level of individual targets and (ii global regulation of SUMO conjugation and deconjugation.
This paper is on the deconstructive reconsideration of the definition of translation, the relation of source text and translation, as well as the relation of translator and author. It also points out the differences between tranditioanal concepts of translation and deconstructive reconsideration of translation.
Douglas Robinson's Becoming a Translator:An Introduction to the Theory and Practice of Translation has been well received around the world.Fusing translation theory with advice and information about the practicalities of translating,it is an essential resource for novice and practicing translators.
The concern about translator has run for thousands of years on which many translators and translation scholars have made comments.A rough examination of the translator within translation studies at home and abroad is expounded in a loosely chronological way as follows.
Douglas Robinson’s Becoming a Translator:An Introduction to the Theory and Practice of Translation has been well received around the world.Fusing translation theory with advice and information about the practicalities of translating,it is an essential resource for novice and practicing translators.
There are many researches about translation theories and methods in western translation history. Equivalence in transla⁃tion has always been the central issue for discussion. This paper gives a general review and comment on equivalence in translation in terms of three representative translation theorists and their views about equivalence in translation.
Sophia Millonigg; Ryuji Minasaki; Marco Nousch; Jakub Novak; Eckmann, Christian R.
To avoid organ dysfunction as a consequence of tissue diminution or tumorous growth, a tight balance between cell proliferation and differentiation is maintained in metazoans. However, cell-intrinsic gene expression mechanisms controlling adult tissue homeostasis remain poorly understood. By focusing on the adult Caenorhabditis elegans reproductive tissue, we show that translational activation of mRNAs is a fundamental mechanism to maintain tissue homeostasis. Our genetic experiments identifi...
Grabowska, AD; Wandel, MP; Łasica, AM; Nesteruk, M; Roszczenko, P; Wyszyńska, A; Godlewska, R; Jagusztyn-Krynicka, EK
Abstract Background Many bacterial extracytoplasmic proteins are stabilized by intramolecular disulfide bridges that are formed post-translationally between their cysteine residues. This protein modification plays an important role in bacterial pathogenesis, and is facilitated by the Dsb (disulfide bond) family of the redox proteins. These proteins function in two parallel pathways in the periplasmic space: an oxidation pathway and an isomerization pathway. The Dsb oxidative pathway in Campyl...
Mohammad Reza Hojat Shamami
Full Text Available This work is an overview of the main issues at the core of theorizing translation practice and the features of a good translator or how to be a good translator and of course what are the Skills to become a Freelance Translator and Translation process. In this world of science and technology there is knowledge explosion every day. This knowledge which is generally written in the English language needs to be transmitted in various languages so that people who do not know how to speak and write the original language can get the knowledge necessary for industrial development and technological innovation to keep up with the rest of the world. To transmit this knowledge effectively, there is a need for competent translators in various languages. Keywords: Translation, Translator, SL, Accommodation, Text
There are differences between legal English and general English. Legal English relates to the legal profession. Law needs to maintain the impression of seriousness, standardization, accuracy and objectiveness, and as a result, legal English also has these characteristics. Compared to general everyday English, the application of legal English vocabulary requires consider-ation of these characteristics. In the translation of legal content, attention is also needed to be paid to the characteristics of foren-sic linguistics. Standardized legal terms are used in the translation of legal regulations and other content to keep the characteris-tics of faithfulness, accuracy, smoothness and consistency. In this paper, legal English vocabulary is discussed based on its char-acteristics, as well as the method of translation of legal content. For practical translation of legal English, translation methods in-clude literal translation, free translation and addition and omission. These methods are briefly discussed in this paper.
WANG Kuang zheng
There are differences between legal English and general English. Legal English relates to the legal profession. Law needs to maintain the impression of seriousness, standardization, accuracy and objectiveness, and as a result, legal English also has these characteristics. Compared to general everyday English, the application of legal English vocabulary requires consideration of these characteristics. In the translation of legal content, attention is also needed to be paid to the characteristics of forensic linguistics. Standardized legal terms are used in the translation of legal regulations and other content to keep the characteristics of faithfulness, accuracy, smoothness and consistency. In this paper, legal English vocabulary is discussed based on its characteristics, as well as the method of translation of legal content. For practical translation of legal English, translation methods include literal translation, free translation and addition and omission. These methods are briefly discussed in this paper.
This dissertation is a comparative study of "translation theory" and "translation studies" in China and the West. Its focus is to investigate whether there is translation theory in the Chinese tradition. My study begins with an examination of the debate in China over whether there has already existed a system of translation…
Dragsted, Barbara; Mees, Inger M.; Gorm Hansen, Inge
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...... output and keystrokes were recorded. Oral and written translation data were examined in order to investigate if task times and translation quality differed in the three modalities. Although task times were found to be highest in written translation, the quality was not consistently better. In addition...
Mangelsdorf, D.J.; Pike, J.W.; Haussler, M.R.
In vitro translation of cellular poly(A)/sup +/ RNA coupled with immunoprecipitation was developed as a technique for characterizing 1,25-dihydroxyvitamin D/sub 3/ (1,25-(OH)/sub 2/D/sub 3/) receptors and assessing receptor mRNA activity. Cell-free translation of poly(A)/sup +/ RNA isolated from chicken intestine revealed two immunoprecipitable forms of avian receptor at 60 kDa and 58 kDa. 1,25-(OH)/sub 2/D/sub 3/ receptors were also synthesized in vitro employing poly(A)/sup +/ RNA obtained from several cultured mammalian cell lines. Selective immunoprecipitation revealed a single form of receptor at 54 kDa in mouse fibroblasts (3T6) and pig kidney cells (LLC-PK/sub 1/) and a 52-kDa species in human breast carcinoma (T47D). Each of these in vitro translated mammalian 1,25-(OH)/sub 2/D/sub 3/ receptors migrated identically with its cellular counterpart that was synthesized in vivo employing metabolic labeling of cell protein with (/sup 35/S)methionine. These results are consistent with the conclusions that 1,25-(OH)/sub 2/D/sub 3/ receptors are protein species ranging from 52 to 60 kDa and that, though their functional and immunological domains have been evolutionarily conserved, an inverse relationship apparently exists between phylogenetic status and receptor mass. The data also support the hypothesis that the presence of 1,25-(OH)/sub 2/D/sub 3/ leads to a significant increase in receptor mRNA activity in 3T6 cells, indicative of receptor autoregulation.
Tian, Qian; Jensen, Ole Mejlhede
The use of a special corrugated mould enables transformation of volume strain into horizontal, linear strain measurement in the fluid stage. This allows continuous measurement of the autogenous shrinkage of cement-based materials since casting, and also effectively eliminates unwanted influence...... on the measuring results from gravity, temperature variation and mould restraint. In this paper the principle of the corrugated tube measurement is described. A systematic study was carried out on the influence on the measuring results of the material properties, size effects and encapsulated air in the corrugated...... tube. The experimental results show that there is a minor influence on the measuring results of the stiffness and size of the plastic tube as well as of the encapsulated air. However, the influence decreases with the hardening process and becomes negligible a few hours after final set....
Lin, X; Liu, W; Ding, Ming;
Objective To investigate the changes of the fluorescent gold retrograde tracing autogenous nerve transplantation on spinal cord injured in rats. Methods The animals were divided into two groups, with modified Allen impact method to establish model of spinal cord injury. After 4 weeks......, the transplantation group using autologous sural nerve graft to repair spinal cord injury period and non-transplantation group was only exposed incision without treatment. In the 4, 6 and 8 weeks after operation, the retrograde tracing of FG Fluoro-Gold was performed to discover the recovery of the axial plasma.......01). Conclusion After spinal cord injury, autologous nerve graft was repaired and survived well and promote the recovery of spinal cord injury segment shaft pulp transportation function....
Full Text Available Tooth transplantation can be considered a valid and predictable treatment option for rehabilitating young patients with permanent teeth loss. This study presents several cases of successful autogenous tooth transplantation with a 6-9 months follow-up. Tooth auto-transplantation can be considered a reasonable option for replacing missing teeth when a donor tooth is available. The auto-transplantation of a right mandibular third molar with compromised function and esthetics to replace the residual roots resulting from coronal destruction due to extensive carious lesion of the second molar in the same quadrant as shown in the presented cases can result a viable treatment alternative especially in a young patient that cannot undergo dental implant therapy. Transplantation of mature third molar seems to be a promising method for replacing a lost permanent molar tooth and restoring esthetics and function. This clinical procedure showed excellent functional and esthetical long-term results in the analyzed cases.
Nimčenko, Tatjana; Omerca, Gražvydas; Bramanti, Ennio; Cervino, Gabriele; Laino, Luigi; Cicciù, Marco
Tooth transplantation can be considered a valid and predictable treatment option for rehabilitating young patients with permanent teeth loss. This study presents several cases of successful autogenous tooth transplantation with a 6-9 months follow-up. Tooth auto-transplantation can be considered a reasonable option for replacing missing teeth when a donor tooth is available. The auto-transplantation of a right mandibular third molar with compromised function and esthetics to replace the residual roots resulting from coronal destruction due to extensive carious lesion of the second molar in the same quadrant as shown in the presented cases can result a viable treatment alternative especially in a young patient that cannot undergo dental implant therapy. Transplantation of mature third molar seems to be a promising method for replacing a lost permanent molar tooth and restoring esthetics and function. This clinical procedure showed excellent functional and esthetical long-term results in the analyzed cases. PMID:25540668
Mashoof, A Allen; Siddiqui, Saqib A; Otero, Marilyn; Tucci, James J
Twenty-seven consecutive patients with adolescent idiopathic scoliosis underwent posterior spinal fusion with pediatric Texas Scottish Rite Hospital instrumentation. Coralline hydroxyapatite (Interpore, Irvine, Calif) was mixed with limited autograft from posterior iliac crest (an approximate 70/30 ratio of coralline hydroxyapatite to autograft). Patient evaluation was based on clinical and radiographic findings. On initial radiographic evaluation, a "snowstorm" appearance consistent with the exoskeleton of the coralline hydroxyapatite was observed. After two years, the fusion mass had a "marble-like" appearance with distinct decreased visibility of the disk spaces in the fusion mass. This latter stage of "marbilization correlated with solid fusion clinically. All patients achieved solid fusion at an average follow-up of 27 months. Coralline hydroxyapatite is safe, biocompatible, and effective in augmenting autogenous bone graft in the treatment of idiopathic adolescent scoliosis with posterior spinal fusion. In addition to decreased donor site morbidity, this may be invaluable in cases where there is insufficient autograft available.
O'Moore, A M; O'Moore, R R; Harrison, R F; Murphy, G; Carruthers, M E
It has long been recognised that there is a relationship between emotional stress and some forms of infertility. We have endeavoured to estimate "stress' levels before and after Autogenic Training in 15 couples with infertility of at least two years' duration. Potential stress markers were: plasma prolactin, total urinary free cortisol and catecholamines, and four psychological tests: Spielberger State-Trait anxiety scale, Taylor Manifest Anxiety Scale, the Cattell 16 personality factor questionnaire, and the Eysenck Personality Questionnaire. A control group of ten normal couples was included for comparison. The biochemical finding of higher mean prolactin levels in the female patients vs their controls was of particular interest. The significant reduction of the prolactin level, in parallel with decreased anxiety scores following treatment, supports the hypothesis that the elevated prolactin levels in these patients are indeed linked with emotional stress.
Pietro, Lura; Ye, Guang; van Breugel, Klaas
In this paper, measurements of non-evaporable water content, chemical shrinkage, autogenous deformation, internal relative humidity (RH), pore solution composition, and early-age elastic modulus are presented and discussed. All experiments were performed on Portland cement and blast-furnace slag...... (BFS) cement pastes. Self-desiccation shrinkage of the BFS cement paste was modeled based on the RH measurements, following the capillary-tension approach. The main findings of this study are: 1) self-desiccation shrinkage can be related to self-desiccation both for Portland and for BFS cement pastes......, taking into account the influence of the dissolved salts in the pore solution, 2) the BFS cement paste studied shows pronounced self-desiccation and self-desiccation shrinkage, mainly caused by its very fine pore structure....
Wang, Baomin; Zhang, Wenping; Wang, Lijiu
The article adopts test data of neural network for autogenous shrinkage to train and predict on the data which doesn't join training. The article's prediction is on the basis of common medium sand, 5-31.5mm limestone rubble, second class fly-ash, P.O42.5 silicate cement, considering factors include five ones such as ratio of water and cement, sand rate, content of cement, content of fly ash, etc.By adjusting various parameters of neural network structure, it obtains three optimized results of neural network simulation. The error between concrete autogtenous shrinkage value of neural network prediction and trial value is within 3%, which can meet requirement of the concrete engineering.
Cowings, Patricia S.; Sharp, Joseph C.; Toscano, William B.; Kamiya, Joe; Miller, Neal E.
The progress made to date on the reduction of data for Spacelab 3 Shuttle experiment, No. 3AFT23 is reported. Four astronauts participated as subjects in this experiment. Crewmen A and B served as treatment subjects (i.e., received preflight training for control of their own motion sickness symptoms) and Crewmen C and D served as control (i.e., did not receive training). A preliminary evaluation of Autogenic Feedback Training (AFT) was made from visual inspections of graphs that were generated from the preflight and inflight and inflight physiological data which included: (1) Baseline rotating chair tests for all crewmen; (2) Posttraining rotating chair tests of treatment groups subjects; (3) Preflight data from Joint Integrated Simulations for all crewmen; and (4) Flight data for all crewmen during mission days 0 through 4, and mission day 6 for treatment subjects only. A summary of the findings suggested by these data is outlined.
A K Lakshminarayanan; K Shanmugam; V Balasubramanian
The effect of autogeneous arc welding processes on tensile and impact properties of ferritic stainless steel conformed to AISI 409M grade is studied.Rolled plates of 4 mm thickness have been used as the base material for preparing single pass butt welded jointa.Tensile and impact properties,microhardness,microstructure,and fracture surface morphology of continuous current gas tungsten arc welding (CCGTAW),pulsed current gas tungsten arc welding (PCGTAW),and plasma arc welding (PAW) joints are evaluated and the results are compared.It is found that the PAW joints of ferritic stainless steel show superior tensile and impact properties when compared with CCGTAW and PCGTAW joints,and this is mainly due to lower heat input,finer fusion zone grain diameter,and higher fusion zone hardness.
Ding Zhitao; Chen Wen
IT is no surprise Jost Zetzsche,an English-to-German translator,raised the question of whether machine translation would ever replace the human variety in front of 700 interpreters and translators who gathered in San Francisco to discuss topical issues in the translation industry.
The intricacies of language still eludes even the most sophisticated technology IT is no surprise Jost Zetzsche,an English-to-German translator,raised the question of whether machine translation would ever replace the human variety in front of 700 interpreters and translators who gathered in San Francisco to discuss topical issues in the translation industry.
Technology is not yet advanced enough to capture the nuances of language It is no surprise Jost Zetzsche,an English-to-German translator,raised the question of whether machine translation would ever replace the human variety in front of 700 interpreters and translators who gathered in San Francisco to discuss topical issues in the translation industry.
Nida's translation theories, especially for his "Dynamic equivalence theory", are highly praised and adopted in Chinese translation circle. Howev-er, there are a lot of criticism and misunderstanding at the same time. This paper explores the issue on translation equivalence so as to benefit our translation studies on both theory and practice level.
Hiramatsu, Nobuhiko; Messah, Carissa; Han, Jaeseok; LaVail, Matthew M; Kaufman, Randal J; Lin, Jonathan H
Endoplasmic reticulum (ER) protein misfolding activates the unfolded protein response (UPR) to help cells cope with ER stress. If ER homeostasis is not restored, UPR promotes cell death. The mechanisms of UPR-mediated cell death are poorly understood. The PKR-like endoplasmic reticulum kinase (PERK) arm of the UPR is implicated in ER stress-induced cell death, in part through up-regulation of proapoptotic CCAAT/enhancer binding protein homologous protein (CHOP). Chop((-)/(-)) cells are partially resistant to ER stress-induced cell death, and CHOP overexpression alone does not induce cell death. These findings suggest that additional mechanisms regulate cell death downstream of PERK. Here we find dramatic suppression of antiapoptosis XIAP proteins in response to chronic ER stress. We find that PERK down-regulates XIAP synthesis through eIF2α and promotes XIAP degradation through ATF4. Of interest, PERK's down-regulation of XIAP occurs independently of CHOP activity. Loss of XIAP leads to increased cell death, whereas XIAP overexpression significantly enhances resistance to ER stress-induced cell death, even in the absence of CHOP. Our findings define a novel signaling circuit between PERK and XIAP that operates in parallel with PERK to CHOP induction to influence cell survival during ER stress. We propose a "two-hit" model of ER stress-induced cell death involving concomitant CHOP up-regulation and XIAP down-regulation both induced by PERK.
The small molecule '1-(4-biphenylylcarbonyl)-4-(5-bromo-2-methoxybenzyl) piperazine oxalate' and its derivatives regulate global protein synthesis by inactivating eukaryotic translation initiation factor 2-alpha.
Hong, Mi-Na; Nam, Ky-Youb; Kim, Kyung Kon; Kim, So-Young; Kim, InKi
By environmental stresses, cells can initiate a signaling pathway in which eukaryotic translation initiation factor 2-alpha (eIF2-α) is involved to regulate the response. Phosphorylation of eIF2-α results in the reduction of overall protein neogenesis, which allows cells to conserve resources and to reprogram energy usage for effective stress control. To investigate the role of eIF2-α in cell stress responses, we conducted a viability-based compound screen under endoplasmic reticulum (ER) stress condition, and identified 1-(4-biphenylylcarbonyl)-4-(5-bromo-2-methoxybenzyl) piperazine oxalate (AMC-01) and its derivatives as eIF2-α-inactivating chemical. Molecular characterization of this signaling pathway revealed that AMC-01 induced inactivation of eIF2-α by phosphorylating serine residue 51 in a dose- and time-dependent manner, while the negative control compounds did not affect eIF2-α phosphorylation. In contrast with ER stress induction by thapsigargin, phosphorylation of eIF2-α persisted for the duration of incubation with AMC-01. By pathway analysis, AMC-01 clearly induced the activation of protein kinase RNA-activated (PKR) kinase and nuclear factor-κB (NF-κB), whereas it did not modulate the activity of PERK or heme-regulated inhibitor (HRI). Finally, we could detect a lower protein translation rate in cells incubated with AMC-01, establishing AMC-01 as a potent chemical probe that can regulate eIF2-α activity. We suggest from these data that AMC-01 and its derivative compounds can be used as chemical probes in future studies of the role of eIF2-α in protein synthesis-related cell physiology.
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.
Stylistic research is subordinate to language use research. The fast maturing modern stylistics has greatly boosted trans-lation studies. Translation has a close relationship with stylistics. Many problems can be solved in translation practice by stylis-tic theories and analysis methods. Based on a brief introduction of stylistics and the relationship between stylistics and transla-tion, this paper will give a specific analysis of the stylistic requirement for translation.
Ajzen, Sergio Aron; Moscatiello, Rafael Andrade; Lima, Aida Maria Custodio de; Moscatiello, Vitoria Aparecida Muglia; Helio Kiitiro Yamashita [Universidade Federal de Sao Paulo (UNIFESP/EPM), SP (Brazil). Dept. de Diagnostico por Imagem; Mosacatiello, Rafael Muglia; Nishiguchi, Celso Itiro [Universidade Federal de Sao Paulo (UNIFESP/EPM), SP (Brazil). Disciplina de Tecnica Operatoria e Cirurgia Experimental; Alves, Maria Teresa de Seixas [Universidade Federal de Sao Paulo (UNIFESP/EPM), SP (Brazil). Disciplina de Anatomia Patologica
The objective was to quantify bone formation within autogenous bone grafts and autogenous bone grafts in combination with platelet-rich plasma obtained either from apheresis or centrifugation using computed tomography. This prospective, double-blind study was conducted in 34 male and female adult patients (mean age of 28 years and 8 months), with either unilateral or bilateral pneumatization of the maxillary sinuses, requiring bone graft for dental implant. All patients were submitted to computed tomography examinations prior and six months after sinus lift surgery. Fifty-three maxillary sinuses were operated and divided into three distinct groups: autogenous bone graft, autogenous bone graft in combination with platelet-rich plasma obtained by centrifugation, and autogenous bone graft in combination with platelet-rich plasma obtained by apheresis. The results showed that computed tomography demonstrated bone growth in height and width between the initial and the follow-up computed tomography scans in all three groups. However, no statistical difference was found either for bone height or width. It was concluded that clinical evidence demonstrates the effectiveness of autogenous bone grafts, particularly when used in combination with bone growth factors such as platelet-rich plasma, which allow prosthetic and functional restoration of maxillofacial structures through fixation of dental implants. (author)
Pfleger, Brian; Mendez-Perez, Daniel
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.
Pfleger, Brian; Mendez-Perez, Daniel
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.
Minia, Igor; Merce, Clementine; Terrao, Monica
African trypanosome procyclic forms multiply in the midgut of tsetse flies, and are routinely cultured at 27°C. Heat shocks of 37°C and above result in general inhibition of translation, and severe heat shock (41°C) results in sequestration of mRNA in granules. The mRNAs that are bound by the zinc-finger protein ZC3H11, including those encoding refolding chaperones, escape heat-induced translation inhibition. At 27°C, ZC3H11 mRNA is predominantly present as an untranslated cytosolic messenger ribonucleoprotein particle, but after heat shocks of 37°C—41°C, the ZC3H11 mRNA moves into the polysomal fraction. To investigate the scope and specificities of heat-shock translational regulation and granule formation, we analysed the distributions of mRNAs on polysomes at 27°C and after 1 hour at 39°C, and the mRNA content of 41°C heat shock granules. We found that mRNAs that bind to ZC3H11 remained in polysomes at 39°C and were protected from sequestration in granules at 41°C. As previously seen for starvation stress granules, the mRNAs that encode ribosomal proteins were excluded from heat-shock granules. 70 mRNAs moved towards the polysomal fraction after the 39°C heat shock, and 260 increased in relative abundance. Surprisingly, many of these mRNAs are also increased when trypanosomes migrate to the tsetse salivary glands. It therefore seems possible that in the wild, temperature changes due to diurnal variations and periodic intake of warm blood might influence the efficiency with which procyclic forms develop into mammalian-infective forms. PMID:27606618
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
Wæraas, Arild; Nielsen, Jeppe
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 mo......, 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.......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...
Particularly in the premaxillary area, the stability of hard and soft tissues plays a pivotal role in the success of the rehabilitation from both a functional and aesthetic aspect. The present case report describes the clinical management of a localized alveolar ridge atrophy in the area of the upper right canine associated with a thin gingival biotype with a lack of keratinized tissue. An autogenous bone block harvested from the chin associated with heterologous bone particles was used to replace the missing bone, allowing for a prosthetic driven implant placement. Soft tissues deficiency was corrected by means of a combined epithelialized and subepithelial connective tissue graft. The 3-year clinical and radiological follow-up demonstrated symmetric gingival levels of the upper canines, with physiological peri-implant probing depths and bone loss. Thus, the use of autogenous tissues combined with biomaterials might be considered a reliable technique in case of highly aesthetic demanding cases.
Full Text Available Particularly in the premaxillary area, the stability of hard and soft tissues plays a pivotal role in the success of the rehabilitation from both a functional and aesthetic aspect. The present case report describes the clinical management of a localized alveolar ridge atrophy in the area of the upper right canine associated with a thin gingival biotype with a lack of keratinized tissue. An autogenous bone block harvested from the chin associated with heterologous bone particles was used to replace the missing bone, allowing for a prosthetic driven implant placement. Soft tissues deficiency was corrected by means of a combined epithelialized and subepithelial connective tissue graft. The 3-year clinical and radiological follow-up demonstrated symmetric gingival levels of the upper canines, with physiological peri-implant probing depths and bone loss. Thus, the use of autogenous tissues combined with biomaterials might be considered a reliable technique in case of highly aesthetic demanding cases.
Khadka, A; Hu, J
Temporomandibular joint (TMJ) ankylosis is characterized by difficulty or inability to open the mouth due to fusion of the temporal and the mandible, resulting in facial symmetry/deformity, malocclusion and dental problems. The only treatment option for TMJ ankylosis is surgical with or without condylar reconstruction. Various autogenous grafts are available for condylar reconstruction after freeing the ankylotic mass such as costochondral, sternoclavicular, fibular, coronoid, and metatarsophalangeal. Costochondral graft is preferred by surgeons, but distraction osteogenesis is slowly gaining popularity and may ultimately become the standard procedure, providing a cost-effective approach with low morbidity and excellent functional outcomes. Tissue engineering is another budding field which has shown promising results in animal studies but has not been applied to humans. To date, there is no ideal autogenous graft for condylar reconstruction that satisfies the complex anatomy and the myriad of functions of a missing condyle.
Mees, Inger M.; Dragsted, Barbara; Gorm Hansen, Inge
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...... implications for the curriculum, (3) be pedagogically motivating, and (4) prepare students for employing translation technology in their future practice as translators. In a two-phase study in which 14 MA students translated texts in three modalities (sight, written, and oral translation using an SR program......), 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...
Better regulation in the European Union cannot be achieved without serious attention to transposition of EU law into national legislation. As a matter of fact, EU member states breach EU law – perpetuately. Why do member states miss deadlines when transposing EU internal market directives? What fact
Full Text Available Alexandre Matet,1,2 Nawel Amar,1,2 Saddek Mohand-Said,1–4 José-Alain Sahel,1–7 Pierre-Olivier Barale1,2 1INSERM and DHOS, CHNO des Quinze-Vingts, 2Sorbonne Universités, UPMC Univ Paris 6, Institut de la Vision, 3INSERM, 4CNRS, Paris, France; 5Institute of Ophthalmology, University College London, London, UK; 6Fondation Ophtalmologique Adolphe de Rothschild, 7Académie des Sciences, Institut de France, Paris, France Introduction: The Argus II retinal prosthesis is composed of an epiretinal electrode array positioned over the macula and connected to an extrascleral electronics case via a silicone cable, running through a sclerotomy. During implantation, the manufacturer recommends to cover the sclerotomy site with a patch of processed human pericardium to prevent postoperative hypotony and conjunctival erosion by the underlying electronics case. Due to biomedical regulations prohibiting the use of this material in France, we developed an alternative technique combining a scleral flap protecting the sclerotomy and an autogenous graft of superior temporalis fascia overlying the electronics case. Methods: The purpose of this study is to describe the 4-year outcomes of this modified procedure in three subjects who underwent Argus II Retinal Prosthesis System implantation. Clinical data consisting of intraocular pressure measurements and tolerance in terms of conjunctival erosion or inflammation were retrospectively assessed over a 4-year postoperative follow-up. Results: None of the three patients implanted with the modified technique developed ocular hypotony over 4 years. A normal, transient conjunctival inflammation occurred during the first postoperative month but conjunctival erosion was not observed in any of the three patients over 4 years. Four years after implantation, the autogenous temporalis fascia graft remained well tolerated and the retinal prosthesis was functional in all three patients. Conclusion: The combination of an
Objective To explore the effect of local autogenous fat grafting for glabellar wrinkles. Methods From September 2010 to April 2012, autogenous fat was grafted in sub-dermis of glabellar wrinkles in 8 cases. The transferee! fat strengthened the local skin tension, and made the wrinkle expand and smooth. Results Three months after autogenous fat grafting, glabellar wrinkles were disappeared in all cases with local smooth skin Left. The wrinkle was reappeared in half a year only in one case. Conclusion Local autogenous fat grafting could provide suspension and filling for the specific kind of glabellar wrinkles, and this method is simple, safe and effective,%目的 探索自体脂肪移植治疗川字纹的临床疗效.方法 201O年9月至2012年4月,对8例川字纹患者的累及皮肤区域内进行真皮下自体脂肪注射,提升局部皮肤张力.结果 8例川字纹患者均随访1年,自体脂肪移植3个月后川字纹皱折消失,局部皮肤平坦;6个月后只有1例患者川字纹复发.结论 对于特定类型的川字纹,局部自体脂肪移植可使得发生皱折的皮肤得到充填和支撑,本方法操作简便、安全,疗效良好.
Full Text Available Drought and heat tolerance are complex quantitative traits. Moreover, the adaptive significance of some stress-related traits is more related to plant survival than to agronomic performance. A web of regulatory mechanisms fine-tunes the expression of stress-related traits and integrates both environmental and developmental signals. Both post-transcriptional and post-translational modifications contribute substantially to this network with a pivotal regulatory function of the transcriptional changes related to cellular and plant stress response. Alternative splicing and RNA-mediated silencing control the amount of specific transcripts, while ubiquitin and SUMO modify activity, sub-cellular localization and half-life of proteins. Interactions across these modification mechanisms ensure temporally and spatially appropriate patterns of downstream-gene expression. For key molecular components of these regulatory mechanisms, natural genetic diversity exists among genotypes with different behavior in terms of stress tolerance, with effects upon the expression of adaptive morphological and/or physiological target traits.
Advertisement language is a special practical writing with abundant imagination, great creativity and instigation. During translation the diversity in social culture, language and ethnic psychology, etc. will be directly reflected into its effect, presenting both the trouble in business of translators and also significant influences on the business brand. Starting from the features of adver⁃tisement language itself, this paper integrates translation situations and measures from several schools over the latest 20 years, gives typical examples in advertising translation and analyzes from varies perspectives and points out some problems in today ’s ad⁃vertisement translation,aiming to provide some constructive opinions for translation of advertisements.
The paper investigates the feasibility and some of the possible consequences of applying quality management to translation. It first gives an introduction to two different schools of translation and to (total) quality management. It then examines whether quality management may, in theory......, be applied to translation and goes on to present a case study which involves a firm in the translation industry and which illustrates quality management in practice. The paper shows that applying quality management to translation is feasible and that doing so may translate into sustained growth....
<正>1.Introduction A good translation of the name should convey the information of the film and attract the audience’s desire for going to the cinema.Translation of film names should have business,information,culture,aesthetic features,while a short eye-catching name aims to leave the audience an unforgettable impression.This thesis discusses the translation of English film names from the aspects of the importance of English film name translation,principles for translating English film names and methods of English film name translation.
Tábata de Mello TERA
Full Text Available The aim of this study was to evaluate the resorption process during the repair of autogenous bone grafts with or without coverage by an expanded polytetrafluoroethylene (e-PTFE membrane in female rats with estrogen deficiency using the immunohistochemical technique. Eighty female rats were randomly divided into two groups (OVX and SHAM. The 40 female rats in the OVX group were subjected to ovariectomy, and the 40 female rats in the SHAM group were subjected to simulated ovariectomy. The two groups were further divided in subgroup E, which was subjected to surgery for placement of autogenous bone graft (ABG, and subgroup ME, in which the ABG was covered with an e-PTFE membrane. The animals were killed at 0, 7, 21, 45 and 60 days. The specimens were analyzed using immunohistochemistry for the bone resorption markers RANK, RANK-L and Osteoprotegerin (OPG. A higher remodeling rate was observed at 7 and 21 days after the autogenous bone grafts, when the markers were more intensely expressed. At the final time point, the specimens presented similar characteristics to those observed at the initial time point. The expression of immunohistochemical markers was not altered by the estrogen deficiency. The presence of the e-PTFE membrane delayed the bone resorption process, influencing the immunohistochemical expression of markers.
Functional characterization of the Arabidopsis eukaryotic translation initiation factor 5A-2 that plays a crucial role in plant growth and development by regulating cell division, cell growth, and cell death.
Feng, Haizhong; Chen, Qingguo; Feng, Jian; Zhang, Jian; Yang, Xiaohui; Zuo, Jianru
The eukaryotic translation initiation factor 5A (eIF-5A) is a highly conserved protein found in all eukaryotic organisms. Although originally identified as a translation initiation factor, recent studies in mammalian and yeast (Saccharomyces cerevisiae) cells suggest that eIF-5A is mainly involved in RNA metabolism and trafficking, thereby regulating cell proliferation, cell growth, and programmed cell death. In higher plants, the physiological function of eIF-5A remains largely unknown. Here, we report the identification and characterization of an Arabidopsis (Arabidopsis thaliana) mutant fumonisin B(1)-resistant12 (fbr12). The fbr12 mutant shows an antiapoptotic phenotype and has reduced dark-induced leaf senescence. Moreover, fbr12 displays severe defects in plant growth and development. The fbr12 mutant plant is extreme dwarf with substantially reduced size and number of all adult organs. During reproductive development, fbr12 causes abnormal development of floral organs and defective sporogenesis, leading to the abortion of both female and male germline cells. Microscopic studies revealed that these developmental defects are associated with abnormal cell division and cell growth. Genetic and molecular analyses indicated that FBR12 encodes a putative eIF-5A-2 protein. When expressed in a yeast mutant strain carrying a mutation in the eIF-5A gene, FBR12 cDNA is able to rescue the lethal phenotype of the yeast mutant, indicating that FBR12 is a functional eIF-5A. We propose that FBR12/eIF-5A-2 is fundamental for plant growth and development by regulating cell division, cell growth, and cell death.
A capability for translating between representation languages is critical for effective knowledge base reuse. A translation technology for knowledge representation languages based on the use of an interlingua for communicating knowledge is described. The interlingua-based translation process consists of three major steps: translation from the source language into a subset of the interlingua, translation between subsets of the interlingua, and translation from a subset of the interlingua into the target language. The first translation step into the interlingua can typically be specified in the form of a grammar that describes how each top-level form in the source language translates into the interlingua. In cases where the source language does not have a declarative semantics, such a grammar is also a specification of a declarative semantics for the language. A methodology for building translators that is currently under development is described. A 'translator shell' based on this methodology is also under development. The shell has been used to build translators for multiple representation languages and those translators have successfully translated nontrivial knowledge bases.
Full Text Available Collagen, type III, alpha-1 (COL3A1 is essential for normal collagen I fibrillogenesis in many organs. There are differences in phenotypes of mutations in the COL3A1 gene in humans and mutations in mice. In order to investigate whether the regulation and gene network of COL3A1 is the same in healthy populations of mice and humans, we compared the quantitative trait loci (QTL that regulate the expression level of COL3A1 and the gene network of COL3A1 pathways between humans and mice using whole genome expression profiles. Our results showed that, for the regulation of expression of Col3a1 in mice, an eQTL on chromosome (Chr 12 regulates the expression of Col3a1. However, expression of genes in the syntenic region on human Chr 7 has no association with the expression level of COL3A1. For the gene network comparison, we identified 44 top genes whose expression levels are strongly associated with that of Col3a1 in mice. We next identified 41 genes strongly associated with the expression level of COL3A1 in humans. There are a few but significant differences in the COL3A1 gene network between humans and mice. Several genes showed opposite association with expression of COL3A1. These genes are known to play important roles in development and function of the extracellular matrix of the lung. Difference in the molecular pathway of key genes in the COL3A1 gene network in humans and mice suggest caution should be used in extrapolating results from models of human lung diseases in mice to clinical lung diseases in humans. These differences may influence the efficacy of drugs in humans whose development employed mouse models.
Portelli, Michael; Siedlinski, Mateusz; Stewart, Ceri E.; Postma, Dirkje S; Nieuwenhuis, Maartje A.; Vonk, Judith M; Nurnberg, Peter; Altmuller, Janine; Moffatt, M. F.; Wardlaw, Andrew J.; Parker, Stuart G; Connolly, Martin J.; Koppelman, Gerard H; Sayers, Ian
The soluble cleaved urokinase plasminogen activator receptor (scuPAR) is a circulating protein detected in multiple diseases, including various cancers, cardiovascular disease, and kidney disease, where elevated levels of scuPAR have been associated with worsening prognosis and increased disease aggressiveness. We aimed to identify novel genetic and biomolecular mechanisms regulating scuPAR levels. Elevated serum scuPAR levels were identified in asthma (n=514) and chronic obstructive pulmonar...
Guo, Huabei; Nagy, Tamas; Pierce, Michael
Deletion of GnT-V (MGAT5), which synthesizes N-glycans with β(1,6)-branched glycans, reduced the compartment of cancer stem cells (CSC) in the her-2 mouse model of breast cancer, leading to delay of tumor onset. Because GnT-V levels are also commonly up-regulated in colon cancer, we investigated their regulation of colon CSC and adenoma development. Anchorage-independent cell growth and tumor formation induced by injection of colon tumor cells into NOD/SCID mice were positively associated with GnT-V levels, indicating regulation of proliferation and tumorigenicity. Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p cells, we found that FZD-7 receptors expressed N-linked β(1,6) branching, indicating that FZD-7 can be modified by GnT-V. The aberrant Wnt signaling observed after modulating GnT-V levels is likely to result from altered N-linked β(1,6) branching on FZD-7, thereby affecting Wnt signaling, the compartment of CSC, and tumor progression.
Kim, Ji Chang [Daejeon St Mary' s Hospital, Daejeon (Korea, Republic of); Cho, June Sik [Chungnam National University College of Medicine, Daejeon (Korea, Republic of)
Percutaneous trasnluminal angioplasty (PTA) of a malfunctioning arteriovenous fistula (AVF) in hemodialysis patients requires the use of contrast angiography and fluoroscopy guidance. We attempted to perform this procedure under duplex ultrasound guidance to reduce the amount of contrast agent administered and to reduce the radiation dose during the interventional procedures. From September 2006 to February 2007, 45 patients received interventional treatment due to malfunctioning hemodialysis access in our hospital. Among the patients, we selected 10 patients diagnosed with stenosis of an autogenous arteriovenous fistula based on a physical examination. There were six males and four females aged 51-78 years (mean age, 59 years). Seven of these patients had a Brescia-Cinimo type fistula and three patients had a basilic vein transposition. All procedures were performed in the angiography suite. All procedures that required angioplasty were performed under duplex ultrasound guidance and then contrast angiography was performed to confirm the final patency of the vessels. Conventional angioplasty was also performed under fluoroscopy guidance for any lesions that required an additional angioplasty. The volume flow before and after the PTA and procedure time were recorded. Clinical success was defined as the performance of one or more successful hemodialysis sessions after treatment. Eight of ten patients did not require an additional angioplasty by conventional angiography after the duplex- guided angioplasty. One case showed recoiling of stenosis after the duplex-guided PTA and another case was missed at duplex scanning due to the extremely short nature of the recoiling of stenosis. The mean volume flow before and after PTA was 167 ml/min (range, 80-259 ml/min) and 394.2 ml/min (range, 120-586 ml/min), respectively. No complications associated with the duplex-guide procedure occurred. In nine cases, PTA enabled hemodialysis to be conducted more than one time. In one
Granas, Anne Gerd; Nørgaard, Lotte Stig; Sporrong, Sofia Kälvemark
completely different meaning. Some dissimilarities reflect different cultural beliefs about medicines. CONCLUSION: When translating questionnaires, bilingual researchers should scrutinize translations across similar languages to address content validity across different countries and languages. PRACTICE...
Lykke Jakobsen, Arnt
Exaugural presentation. A retrospect of my personal itinerary from literature, across translation studies to translation process research and a look ahead. In the retrospect, I range over diverse topics, all of which have sprung from my concern with the phenomenon of translation. I reflect on how......, as humans, we generate meaning, interpret meaning, and reformulate or translate meaning. I also reflect on the way computing has influenced research into these phenomena as seen e.g. in my creation of the Translog program and in projects I have been involved in, such as OFT (Translation of Professional...... for global communication purposes, and for improving research into translation, the phenomenon of translation and the world of translation in which we all live....
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...... 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...
This is an article in a series illustrating the way scholars in communication have pursued translating their research into practice. The translational nature of communication accommodation theory and examples of its application are the focus of this contribution.
Full Text Available This paper examines the work of Samuel Beckett in the light of his early work as a translator of the works of other writers. In his translations for Negro: An Anthology (1934, the Anthology of Mexican Poetry (1958, or commissioned translations for journals such as “This Quarter”, early pre-figurings of Beckett’s own thematic and linguistic concerns abound. Rarely viewed as more than acts of raising money for himself, Beckett’s acts of translation, examined chronologically, demonstrate a writer discovering his craft, and developing his unique voice, unencumbered by the expectations of originality. This essay posits that Beckett’s works, with their distinctive voice and characterisation, owe much to the global perspective he gained through translating across cultural, continental divides, as well as experimenting with form, which became a staple of Beckett’s own work. Without formal training or theoretical grounding in translation, Beckett utilises the act of translation as a means of finding himself, revisiting it as a means of shaping his own unique literary voice.
Full Text Available Dedukti is a logical framework based on the lambda-Pi-calculus modulo rewriting, which extends the lambda-Pi-calculus with rewrite rules. In this paper, we show how to translate the proofs of a family of HOL proof assistants to Dedukti. The translation preserves binding, typing, and reduction. We implemented this translation in an automated tool and used it to successfully translate the OpenTheory standard library.
It is widely-acknowtedged that business correspondence works as a bridge between the writer and the reader.Taking its characteristics into consideration,this essay illustrates how to do business correspondence translation.Only by abiding by all those fcatures can the translator achieve the aim of translation.
This paper focuses on the art in translation.First,the translation and art are defined and some historic views are illustrated.Then the author lays emphasis on how to convey the artistic information and provides some methods on how to achieve artistic effect in translation.
In this paper, the author first analyzed the nature of metaphor and difficulties in metaphor translation, displayed the fac-tors that will influence the translation between English and Chinese metaphors, and then explored the metaphor translation strate-gies by taking some English and Chinese idioms as examples.
The 18th World Congress of the International Federation of Translators(FIT) is bound to increase China’s international exposure.Shortly before the congress,Guo Xiaoyong,Executive Vice President of the Translators Association of China(TAC),spoke to Beijing Review about his expectations for the event and his evaluation of translation and interpretation services in China.
Translating process is coordination of the source language and target language. As the source language and translation language readers are in different cultural background, so their understanding of the environment is different. When the translator express their understanding in the receptor language, he must figure out the best relevance between source language and target language, which can achieve pragmatic equivalence.
Manuel Marques Ferreira
Full Text Available Aim: The aim of this study was to assess the enamel matrix derivative (EMD as biomaterial used in autogenous tooth transplantation. Material and Methods: The study consisted of 3 beagle dogs, 5 months old, in which six incisors and six premolars were transplanted to mechanically prepared recipient alveolar sockets. One group of teeth was transplanted to a recipient bed, with EMD in the root surface. The second groups of teeth were transplanted using saline solution in the root surface. Every week, clinical examinations were done. Nine weeks later, the animals were killed and the specimens decalcified and prepared for histological and imunohistochemical analysis. Periodontal healing was evaluated by undertaking histomorphometric investigation and analyzed using the Mann- Whitney test (P = 0.05. Results: In both groups, all the transplanted teeth survived. Between the experimental groups, there was statistically significant difference in the complete healing (P = 0.004. There was statistically significant difference between the treatment group in the occurrence of inflammatory root resorption (P = 0.015 and the occurrence of replacement root resorption (P = 0.041. Conclusions: Emdogain gel used on the surface of transplanted teeth improves the occurrence of complete healing and reduces root resorption.
Shawyer, Andrew, E-mail: email@example.com [The Royal London Hospital, Radiology Department (United Kingdom); Fotiadis, Nicos I., E-mail: firstname.lastname@example.org [Royal Marsden Hospital, Radiology Department, The Royal Marsden NHS Foundation Trust (United Kingdom); Namagondlu, Girish, E-mail: email@example.com [The Royal London Hospital, Renal Medicine Department (United Kingdom); Iyer, Arun, E-mail: firstname.lastname@example.org [The Royal London Hospital, Radiology Department (United Kingdom); Blunden, Mark, E-mail: email@example.com; Raftery, Martin, E-mail: firstname.lastname@example.org; Yaqoob, Magdi, E-mail: email@example.com [The Royal London Hospital, Renal Medicine Department (United Kingdom)
Cephalic arch stenosis (CAS) is an important and common cause of dysfunction in autogenous haemodialysis fistulas that requires multiple reinterventions and aggressive surveillance. We evaluated the safety and efficacy of the Viabahn stent-graft for the management of CAS. Between April 2005 and October 2011, 11 consecutive patients [four men and seven women (mean age 56.7 years)] with CAS and dysfunctional fistulas were treated with insertion of 11 Viabahn stent-grafts. Six stent-grafts were inserted due to residual stenosis after angioplasty and five for fistuloplasty-induced rupture. No patient was lost to follow-up. The technical and clinical success rate was 100 %. Primary access patency rates were 81.8 % [95 % confidence interval (CI) 0.482-0.977] at 6 months and 72.7 % (95 % CI 0.390-0.939) at 12 months. Secondary access patency rates were 90.9 % at 6 months (95 % CI 0.587-0.997). There were no procedure-related complications. Mean follow-up was 543.8 days (range 156-2,282). The use of the Viabahn stent-graft in the management of CAS is technically feasible and, in this small series, showed patency rates that compare favorably with historical data of angioplasty and bare stents.
Jeong, Sun Min; Kim, Jeong Ho; Byun, Sung Su; Kang, Jin MMo; Choi, Sang Tae; Kim, Jong Woo; Kim, Hyung Sik; Choi, Hye Young [Gachon University Gil Medical Center, Incheon (Korea, Republic of); Park, Jae Hyung [Dept. of Radiology, Seonam University College of Medicine, Myongji Hospital, Goyang (Korea, Republic of)
The purpose of this study was to evaluate the effectiveness of percutaneous transluminal angioplasty (PTA) on stenosis of autogenous radiocephalic arteriovenous fistula (RCF) for hemodialysis and to determine the factors influencing patency. This retrospective study included 136 patients referred for PTA of RCF stenosis between March 2005 and July 2014. The technical success rate, complications, and patency rate were evaluated. The following factors were analyzed as they might influence patency: age, gender, site and duration of arteriovenous fistula, underlying disease, body mass index, hypercholesterolemia, smoking, peripheral artery or coronary artery occlusive disease, stenosis length/grade, cutting balloon, and balloon size. The initial technical success rate was 91.9% (125/136). Complications included vessel rupture (n = 2) and vessel dissection (n = 2). The patency rates at 6, 12, 24, and 48 months after PTA were 81.9, 67.1, 52.7, and 42.3%, respectively. The patency rate was higher in cases with longer (> 3 cm) stenosis (p = 0.04). Use of cutting balloon and larger size of balloon catheter made the patency longer, but this difference was not statistically significant (p = 0.637, 0.258). PTA is a safe and effective way to manage stenosis in RCF. The length of stenosis was the only factor which affected the patency rate in this study.
Full Text Available Abstract Background Bone grafts are widely used in oral and maxillofacial reconstruction. The influence of electromagnetic fields and magnets on the endogenous stimulation of target tissues has been investigated. This work aimed to assess the quality of bone healing in surgical cavities filled with autogenous bone grafts, under the influence of a permanent magnetic field produced by in vivo buried devices. Methods Metal devices consisting of commercially pure martensitic stainless steel washers and titanium screws were employed. Thirty male Wistar rats were divided into 3 experimental and 3 control groups. A surgical bone cavity was produced on the right femur, and a bone graft was collected and placed in each hole. Two metallic washers, magnetized in the experimental group but not in the control group, were attached on the borders of the cavity. Results The animals were sacrificed on postoperative days 15, 45 and 60. The histological analysis of control and experimental samples showed adequate integration of the bone grafts, with intense bone neoformation. On days 45 and 60, a continued influence of the magnetic field on the surgical cavity and on the bone graft was observed in samples from the experimental group. Conclusion The results showed intense bone neoformation in the experimental group as compared to control animals. The intense extra-cortical bone neoformation observed suggests that the osteoconductor condition of the graft may be more susceptible to stimulation, when submitted to a magnetic field.
Lindeboom, Ralph E F; Ferrer, Ivet; Weijma, Jan; van Lier, Jules B
Autogenerative High Pressure Digestion (AHPD) is a novel concept that integrates gas upgrading with anaerobic digestion by selective dissolution of CO2 at elevated biogas pressure. However, accumulation of CO2 and fatty acids after anaerobic digestion of glucose resulted in pH 3-5, which is incompatible with the commonly applied high-rate methanogenic processes. Therefore, we studied the use of wollastonite, olivine and anorthosite, with measured composition of CaSi1.05O3.4, Mg2Fe0.2Ni0.01Si1.2O5.3 and Na0.7Ca1K0.1Mg0.1Fe0.15Al3.1Si4O24, respectively, to scavenge CO2 during batch AHPD of glucose. Depending on the glucose to mineral ratio the pH increased to 6.0-7.5. Experiments with wollastonite showed that Ca(2+)-leaching was caused by volatile fatty acid (VFA) production during glucose digestion. At 1, 3 and 9 bar, the CH4 content reached 74%, 86% and 88%, respectively, indicating CO2 scavenging. Fixation of produced CO2 by CaCO3 precipitation in the sludge was confirmed by Fourier Transferred-InfraRed, Combined Field emission Scanning Electron Microscopy-Energy-dispersive X-ray spectroscopy and Thermogravimetric Analysis-Mass Spectroscopy.
Martschuk, V. [Inst. of the Cement Industry, Dusseldorf (Germany)
A study on the hydration of portland cement was presented. The paper presented special features of the chemical shrinkage of cement paste at high and low water-cement ratios. It also described the effect of silica fume on the deformation behaviour of cement paste, as well as on the behaviour of hardened binder paste at water-binder ratios of 0.40 and 0.25. High performance concrete has a high density and a tendency to chemically shrink because of its low water-cement ratio. The study showed that the autogenous shrinkage increases if silica fume is added. Theoretical calculations were performed and showed that the typical addition of silica fume results in an increase in total porosity, and therefore, to the deterioration of the packing density of the binder mixture. The specific surface area of the dry powder is also increased. It was concluded that replacing cement by optimized fine cements improves the theoretical packing density in binders. The hardened cement paste studies showed that this makes a cement that is denser with less tendency to shrink. 7 refs., 3 tabs., 8 figs.
Cowings, P. S.; Toscano, W. B.; Miller, N. E.; Pickering, T. G.; Shapiro, D.; Stevenson, J.; Maloney, S.; Knapp, J.
Postflight orthostatic intolerance has been identified as a serious biomedical problem associated with long-duration exposure to microgravity in space. High priority has been given to the development of countermeasures for this disorder that are both effective and practical. A considerable body of clinical research has demonstrated that people can be taught to increase their own blood pressure voluntarily, and that this is an effective treatment for chronic orthostatic intolerance in paralyzed patients. The current pilot study was designed to examine the feasibility of adding training in control of blood pressure to an existing preflight training program designed to facilitate astronaut adaptation to microgravity. Using an operant conditioning procedure, autogenic-feedback training (AFT), three men and two women participated in four to nine training (15-30-minute) sessions. At the end of training, the average increase in systolic and diastolic pressure, as well as mean arterial pressures, that the subjects made ranged between 20 and 50 mm Hg under both supine and 45 deg head-up tilt conditions. These findings indicate that AFT may be a useful alternative treatment or supplement to existing approaches for preventing postflight orthostatic intolerance. Furthermore, the use of operant conditioning methods for training cardiovascular responses may contribute to the general understanding of the mechanisms of orthostatic intolerance.
Cowings, Patricia S.; Toscano, William B.; Miller, Neil E.; Pickering, Thomas G.; Shapiro, David
Postflight orthostatic intolerance was identified as a serious biomedical problem associated with long duration exposure to microgravity in space. High priority was given to the development of countermeasures for this disorder which are both effective and practical. A considerable body of clinical research demonstrated that people can be taught to increase their own blood pressure voluntarily and that this is an effective treatment for chronic orthostatic intolerance in paralyzed patients. The present pilot study was designed to examine the feasibility of adding training in control of blood pressure to an existing preflight training program designed to facilitate astronaut adaptation to microgravity. Using an operant conditioning procedure, Autogenic-Feedback Training (AFT), three men and two women participated in four to nine (15-30 training sessions). At the end of training, the average increase in systolic and diastolic pressure, as well as mean arterial pressures that the subjects made, ranged between 20 and 5O mmHg under both supine and 45 deg head-up tilt conditions. These findings suggest that AFT may be a useful alternative treatment or supplement to existing approaches for preventing postflight orthostatic intolerance. Further, the use of operant conditioning methods for training cardiovascular responses may contribute to the general understanding of the mechanisms of orthostatic intolerance.
Li, Pei-Shan; -Liang Lee, I.; Yu, Wei-Lin; Sun, Jui-Sheng; Jane, Wann-Neng; Shen, Hsin-Hsin
Tissue scaffolds provide a framework for living tissue regeneration. However, traditional tissue scaffolds are exogenous, composed of metals, ceramics, polymers, and animal tissues, and have a defined biocompatibility and application. This study presents a new method for obtaining a tissue scaffold from blood albumin, the major protein in mammalian blood. Human, bovine, and porcine albumin was polymerised into albumin polymers by microbial transglutaminase and was then cast by freeze-drying-based moulding to form albumin tissue scaffolds. Scanning electron microscopy and material testing analyses revealed that the albumin tissue scaffold possesses an extremely porous structure, moderate mechanical strength, and resilience. Using a culture of human mesenchymal stem cells (MSCs) as a model, we showed that MSCs can be seeded and grown in the albumin tissue scaffold. Furthermore, the albumin tissue scaffold can support the long-term osteogenic differentiation of MSCs. These results show that the albumin tissue scaffold exhibits favourable material properties and good compatibility with cells. We propose that this novel tissue scaffold can satisfy essential needs in tissue engineering as a general-purpose substrate. The use of this scaffold could lead to the development of new methods of artificial fabrication of autogenic tissue substitutes.
Dr. Yuslina Mohamed
Full Text Available This research tries to contrive Jahiz's stands and ideas in translation which he has discussed in his two books named "Al-Bayan Wal-Tabyeen" and "Al-Haiwan". As it was known this issue of translation was emergence since long period of time, and there was no need toward translation, however, after Arabian and Persian assembled with Greek philosophers had increasingly the need and concerned on Religion Sciences and others, for instances: Mathematics, Medicine, Logic, Engineering, Business and others which were existed during that time. The translation movement had gone by several stages in the different periods and being developed during Abassid period for example, the works of "Hanen Ibn Ishaq" and his own school which the translators had faced difficulties and problems in their translation. To summarize, this research has found a number of results that the "Jahiz" was precedence than others who had stated the conditions of translation before 12th century ago. Besides, these conditions appropriate till nowadays, he had also pointed these conditions cannot be applied in translation of literature texts and holy texts because its might be obliterated the savoir faire. "Jahiz" had looked through this issue seriously, he tried to help translators in this area and he had stated in his famous books the conditions of translation and he had given his ideas toward translation benefited from his previous experience in translation the ancient philosopher's books from Persian to Arabic. Though, the readers could benefit his ideas in translation generally and for the translator specifically, also his books became as a heritage references and cannot be neglected at all in translation work.
Hedegaard, Steffen; Simonsen, Jakob Grue
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....
Sreejith, R K; Suresh, C G; Bhosale, Siddharth H; Bhavnani, Varsha; Kumar, Avinash; Gaikwad, Sushama M; Pal, Jayanta K
In mammalian cells, the heme-regulated inhibitor (HRI) plays a critical role in the regulation of protein synthesis at the initiation step through phosphorylation of α-subunit of the eukaryotic initiation factor 2 (eIF2). In this study we have cloned and performed biophysical characterization of the kinase catalytic domain (KD) of rabbit HRI. The KD described here comprises kinase 1, the kinase insertion domain (KI) and kinase 2. We report here the existence of an active and stable monomer of HRI (KD). The HRI (KD) containing three tryptophan residues was examined for its conformational transitions occurring under various denaturing conditions using steady-state and time-resolved tryptophan fluorescence, circular dichroism (CD) and hydrophobic dye binding. The parameter A and phase diagram analysis revealed multi-state unfolding and existence of three stable intermediates during guanidine hydrochloride (Gdn-HCl) induced unfolding of HRI (KD). The protein treated with 6 M Gdn-HCl showed collisional and static mechanism of acrylamide quenching and the constants (K(sv) = 3.08 M(-1) and K(s)= 5.62 M(-1)) were resolved using time resolved fluorescence titration. Based on pH, guanidine hydrochloride and temperature mediated transitions, HRI (KD) appears to exemplify a rigid molten globule-like intermediate with compact secondary structure, altered tertiary structure and exposed hydrophobic patches at pH 3.0. The results indicate the inherent structural stability of HRI (KD), a member of the class of stress response proteins.
The article deals with the French translation of the short story Amy by the Slovenian writer Mira Mihelič, made by Elza Jereb for the anthology Nouvelles slovènes (Paris, 1969). The original text, a classical narrative involving some modernist strategies, presents a syntactical feature rather unusual in Slovenian (although typical of the author Mira Mihelič): a very frequent use of participles and participial structures. Elza Jereb’s translation is accurate and precise, preserving not only th...
Lee, Han-Joo; Yost, Brittanie P; Telch, Michael J
It has been suggested that obsessive-compulsive disorder is characterized by impaired inhibitory control. Response inhibition is a cognitive process required for one to cancel or suppress dominant but inappropriate responses. The present study examined response inhibition among non-treatment seeking individuals diagnosed with OCD and individuals with low levels of OCD symptoms using a computerized visual go/no-go task. Specifically, we sought to examine a prediction from the autogenous-reactive subtype model of obsessions (Lee, H.-J., & Kwon, S.-M. (2003). Two different types of obsession: autogenous obsessions and reactive obsessions. Behaviour Research and Therapy, 41, 11-29; Lee, H.-J., & Telch, M. J. (2008). Autogenous obsessions and reactive obsessions. In J. Abramowitz, S. Taylor, & D. McKay (Eds.), Obsessive-compulsive disorder: subtypes and spectrum conditions. New York: Elsevier., asserting that OCD individuals presenting with the autogenous subtype of obsessions will display greater difficulty in inhibitory control relative to individuals presenting with obsessions of the reactive subtype. Results showed that individuals with OCD of the autogenous subtype displayed more deficient inhibitory control on the visual go/no-go task as indexed by a longer response delay between the original stimuli set and the reversed stimuli set compared to individuals with OCD of the reactive subtype or individuals with low levels of OCD symptoms.
Generally,the movie title translation strategy would be divided into two:domesticating translation strategy and foreignizing translation strategy.The movie title translation in Hong Kong is chosen to be the material for the analysis of the domesticating translation strategy and foreignizing translation strategy,compared with that of Mainland China.
LI Xin; ZHANG Zhe
Peter Newmark has written many preeminent works on translation theory. He classifies the translation texts into differ⁃ent types,and puts forward his great translation methods-communiative translation and semantic translation. This paper is aimed to explain the creative work by Peter Nwmark in the translation theory.
Full Text Available Although prolonged genetic pressure has been conjectured to be necessary for the eventual development of tumor immune evasion mechanisms, recent work is demonstrating that early genetic mutations are capable of moonlighting as both intrinsic and extrinsic modulators of the tumor immune microenvironment. The indoleamine 2,3-dioxygenase-1 (IDO immunoregulatory enzyme is emerging as a key player in tumor-mediated immune tolerance. While loss of the tumor suppressor, BIN-1, and the over-expression of cyclooxygenase-2 (COX-2 have been implicated in intrinsic regulation of IDO, recent findings have demonstrated the loss of TβRIII and the upregulation of Wnt5a by developing cancers to play a role in the extrinsic control of IDO activity by local dendritic cell populations residing within tumor and tumor-draining lymph node tissues. Together, these genetic changes are capable of modulating paracrine signaling pathways in the early stages of carcinogenesis to establish a site of immune privilege by promoting the differentiation and activation of local regulatory T cells. Additional investigation of these immune evasion pathways promises to provide opportunities for the development of novel strategies to synergistically enhance the efficacy of the evolving class of T cell-targeted ‘checkpoint’ inhibitors.
Mignone, B. K.
Effective solutions to the climate change problem will require unprecedented cooperation across space, continuity across time and coordination between disciplines. One well-known methodology for synthesizing the lessons of physical science, energy engineering and economics is integrated assessment. Typically, integrated assessment models use scientific and technological relationships as physical constraints in a larger macroeconomic optimization that is designed to either balance the costs and benefits of climate change mitigation or find the least-cost path to an exogenously prescribed endpoint (e.g. atmospheric CO2 stabilization). The usefulness of these models depends to a large extent on the quality of the assumptions and the relevance of the outcome metrics chosen by the user. In this study, I show how a scientifically-based emissions reduction scenario can be combined with engineering-based assumptions about the energy system (e.g. estimates of the marginal cost premium of carbon-free technology) to yield insights about the price path of CO2 under a future regulatory regime. I then show how this outcome metric (carbon price) relates to key decisions about the design of a future cap-and-trade system and the way in which future carbon markets may be regulated.
Translation strategy and translation standards are undoubtedly the core problems translators are confronted with in translation. There have arisen many kinds of translation strategies in translation history, among which the text type theory is considered an important breakthrough and a significant complement of traditional translation standards. This essay attempts to demonstrate the value of text typology (informative, expressive, and operative) to translation strategy, emphasizing the importance of text types and their communicative functions.
Karlsen, Tommy A; Jakobsen, Rune B; Mikkelsen, Tarjei S; Brinchmann, Jan E
Lesions of articular cartilage do not heal spontaneously. One treatment strategy would be to make cartilage in the laboratory by directed chondrogenic differentiation of mesenchymal stem cells (MSCs). To promote our understanding of the molecular control of chondrogenesis, we have compared the changes in microRNAs (miRNAs) during in vitro chondrogenesis of MSCs with those observed in uncultured and dedifferentiated articular chondrocytes (ACs). Several miRNAs showed a reciprocal relationship during the differentiation of MSCs and dedifferentiation of ACs. miR-140-5p and miR-140-3p changed the most during in vitro chondrogenesis, they were the miRNAs most highly expressed in tissue-engineered chondrocytes, and they were also among the miRNAs most highly expressed in uncultured ACs. There was a 57% overlap for the 100 most highly expressed miRNAs in differentiated MSCs and uncultured ACs, but for other miRNAs, the expression pattern was quite different. We transiently and stably inhibited and overexpressed miR-140-5p and miR-140-3p in differentiating MSCs and dedifferentiating ACs, respectively, to describe global effects and identify and validate new targets. Surprisingly, SOX9 and aggrecan proteins were found to be downregulated in anti-miR-140 transduced differentiating MSCs despite unchanged mRNA levels. This suggests that miR-140 stimulates in vitro chondrogenesis by the upregulation of these molecules at the protein level. RALA, a small GTPase, was identified as a miR-140 target and knockdown experiments showed that RALA regulated SOX9 at the protein level. These observations shed new light on the effect of miR-140 for chondrogenesis in vitro and in vivo.
Full Text Available Mouse apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like editing complex 3 (mA3, an intracellular antiviral factor, has 2 allelic variations that are linked with different susceptibilities to beta- and gammaretrovirus infections among various mouse strains. In virus-resistant C57BL/6 (B6 mice, mA3 transcripts are more abundant than those in susceptible BALB/c mice both in the spleen and bone marrow. These strains of mice also express mA3 transcripts with different splicing patterns: B6 mice preferentially express exon 5-deficient (Δ5 mA3 mRNA, while BALB/c mice produce exon 5-containing full-length mA3 mRNA as the major transcript. Although the protein product of the Δ5 mRNA exerts stronger antiretroviral activities than the full-length protein, how exon 5 affects mA3 antiviral activity, as well as the genetic mechanisms regulating exon 5 inclusion into the mA3 transcripts, remains largely uncharacterized. Here we show that mA3 exon 5 is indeed a functional element that influences protein synthesis at a post-transcriptional level. We further employed in vitro splicing assays using genomic DNA clones to identify two critical polymorphisms affecting the inclusion of exon 5 into mA3 transcripts: the number of TCCT repeats upstream of exon 5 and the single nucleotide polymorphism within exon 5 located 12 bases upstream of the exon 5/intron 5 boundary. Distribution of the above polymorphisms among different Mus species indicates that the inclusion of exon 5 into mA3 mRNA is a relatively recent event in the evolution of mice. The widespread geographic distribution of this exon 5-including genetic variant suggests that in some Mus populations the cost of maintaining an effective but mutagenic enzyme may outweigh its antiviral function.
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....
Objective: To examine the effects of autogenic training and abdominal breathing on heart rate and finger temperature. Methods: Forty-five healthy female university students were randomly assigned to three groups:control、autogenic training and deep abdominal breathing groups, and their physiological effects were compared. Results:The result of this experiment showed that both autogenic training and abdominal breathing increased finger temperature significantly, however, the increase magnitude didn't show significant differences in two groups.During autogenic training, the heart rate of autogenic training group declined significantly,the heart rate of deep abdominal breathing group decreased significantly after deep abdominal breathing. The decrease magnitude between the three groups showed no significant differences. Conclusion: Both the present techniques can decrease heart rate and increase finger temperature.
Larsen, L.; Watts, D.; Khurana, A.; Anderson, J. L.; Xu, C.; Merritts, D. J.
The classic signal of self-organization in nature is pattern formation. However, the interactions and feedbacks that organize depositional landscapes do not always result in regular or fractal patterns. How might we detect their existence and effects in these "irregular" landscapes? Emergent landscapes such as newly forming deltaic marshes or some restoration sites provide opportunities to study the autogenic processes that organize landscapes and their physical signatures. Here we describe a quest to understand autogenic vs. allogenic controls on landscape evolution in Big Spring Run, PA, a landscape undergoing restoration from bare-soil conditions to a target wet meadow landscape. The contemporary motivation for asking questions about autogenic vs. allogenic controls is to evaluate how important initial conditions or environmental controls may be for the attainment of management objectives. However, these questions can also inform interpretation of the sedimentary record by enabling researchers to separate signals that may have arisen through self-organization processes from those resulting from environmental perturbations. Over three years at Big Spring Run, we mapped the dynamic evolution of floodplain vegetation communities and distributions of abiotic variables and topography. We used principal component analysis and transition probability analysis to detect associative interactions between vegetation and geomorphic variables and convergent cross-mapping on lidar data to detect causal interactions between biomass and topography. Exploratory statistics revealed that plant communities with distinct morphologies exerted control on landscape evolution through stress divergence (i.e., channel initiation) and promoting the accumulation of fine sediment in channels. Together, these communities participated in a negative feedback that maintains low energy and multiple channels. Because of the spatially explicit nature of this feedback, causal interactions could not
Acromite, Michael T.; Cowings, Patricia; Toscano, William; Davis, Carl; Porter, Henry O.
Airsickness is the most significant medical condition affecting naval aviation training. A 2001 study showed that airsickness was reported in 81% of naval aviation students and was associated with 82% of below average flight scores. The cost to a single training air-wing was over $150,000 annually for fuel and maintenance costs alone. Resistent cases are sent to the Naval Aerospace Medical Institute (NAMI) for evaluation and desensitization in the self-paced airsickness desensitization (SPAD) program. This approach is 75% successful, but can take up to 8 weeks at a significant travel cost. NASA Ames Research Center's Autogenic Feedback Training Exercises (AFTE) uses physiological and biofeedback training for motion sickness prevention. It has a remote capability that has been used from Moffett Field, CA to Atlanta, GA . AFTE is administered in twelve (30-minute) training sessions. The success rate for the NASA AFTE program has been over 85%. Methods: Implementation Phases: Phase I: Transfer NASA AFTE to NAMI; NASA will remotely train aviation students at NAMI. Phase II: NAMI-centered AFTE application with NASA oversight. Phase III: NAMI-centered AFTE to remotely train at various Navy sites. Phase IV: NAMI to offer Tri-service application and examine research opportunities. Results: 1. Use available telemedicine connectivity between NAMI and NASA. 2. Save over $2,000 per student trained. 3. Reduce aviation training attrition. 4. Provide standardization of multi-location motion sickness training. 5. Future tri-service initiatives. 6. Data to NASA and Navy for QA and research opportunities.
Full Text Available Mahmoud Ahmed Elsamkary,1 Maged Maher Salib Roshdy1,2 1Ophthalmology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 2Pediatric Ophthalmology Department, Al Watany Eye Hospital, Cairo, Egypt Purpose: To study the effect of autogenous fascia lata sling (AFLS versus Gore-Tex suspension (GTS regarding the functional and aesthetic outcomes in patients with bilateral congenital ptosis. Patients and methods: A prospective comparative randomized single-center study enrolled 110 patients with bilateral congenital ptosis. One group (n=55 underwent AFLS and the second group (n=55 underwent GTS. Exclusion criteria were good levator function, absent Bell’s phenomenon, and abnormal ocular motility. Follow-up period was 2 years. Functional outcome was measured from digital photos by analysis of upper eyelid margin position relative to the superior limbus and classified as very good (<3 mm, good (3–5 mm, poor (>5 mm, and recurrent. Aesthetic outcome was assessed in terms of lid contour, symmetry of eyelid height, and lid crease presence. Complications were also reported. Results: Failure rate (recurrence and complications was less in AFLS (P=0.035. Symmetrical lid height and good contour were more frequently attained by AFLS (P=0.007 and 0.047, respectively. However, the frequency of very good, good, poor, recurrence, lagopthalmos, ectropion, infection, and formed lid crease individually showed no statistically significant difference (P=0.252, 0.482, 1, 0.489, 0.438, 1, 0.618, and 0.506, respectively. Conclusion: AFLS is a better choice in surgery for patients with bilateral congenital ptosis because it has fewer complications and a lesser recurrence rate than GTS. Keywords: ptosis surgery, surgical outcomes, ptosis recurrence, lagophthalmos
Current classification of autologous/autogenous (A/A) vaccines is commonly based on the concept of strain/antigen specificity associated with targeted treatment of a restricted number of animals. However, fulfilling these two conditions is not sufficient for immune-veterinary immunebiologicals to be excluded from the provisions of Directive 2001/82/EC. Indeed, non-inactivated A/A vaccines are not automatically considered out of the scope of the community code relating to veterinary medicinal products, in particular to immune-biologicals. As a major consequence of the "regulatory" exclusion from the requirements of EU rules, A/A vaccines can be usually manufactured and distributed without having obtained a marketing authorization by the competent authority of a Member State. Furthermore, strain specificity enables veterinarians to consider the use of these vaccines in quite a large variety of epidemiological circumstances where no "conventional" vaccines are yet available or are considered efficacious. In addition, in contrast to "conventional" vaccines, which are considered exclusively as a preventive tool against infectious diseases, A/A vaccines can also be used to treat "continuing" infections. Although the limited scientific value of these products and the poor investigations of the effector mechanisms involved are widely recognized, their use is still claimed in conditions where disorders in the immune system are suspected. Today, a more appropriate definition of A/A vaccines is one that takes into account their historical tradition and practical use, such as stable- or herd-specific vaccines, custom ("..ized") vaccines, therapeutic vaccines, pharmavaccines, vaccines used for biological therapy, etc. Although acknowledging the "regulatory autonomy" of A/A vaccines versus "conventional" vaccines, here it will be presented as an overview of the necessary points to consider, to guarantee an acceptable standard in the development and control of this particular
Shao Jun; Jiang Min
In perspective of relevance theory, translation is regarded as communication. According to relevance theory, communication not only requires encoding, transfer and decoding processes, but also involves inference in addition. As communication, translation decision-making is also based on the human beings' inferential mental faculty. Concentrating on relevance theory, this paper tries to analyze and explain some translation phenomena in two English versions of Cai Gen Tan-My Crude Philosophy of Life.
Firstly, this paper presents the definition of transliteration and its important position in EST translation. Secondly, in terms of the previous practice and experience in EST translation, four main transliteration techniques are concluded and analyzed. But meanwhile, there are still some negative issues and phenomena. As a result, it is worthy to make good use of the existing transliteration techniques and create more proper ones to remove the obstructions and promote the development of EST translation.
Meier, D; Leo, N; Jungk, T.; Soergel, E.; Becker, P.; Bohaty, L.; Fiebig, M.
Translation domains differing in the phase but not in the orientation of the corresponding order parameter are resolved in two types of multiferroics. Hexagonal (h-) YMnO$_3$ is a split-order-parameter multiferroic in which commensurate ferroelectric translation domains are resolved by piezoresponse force microscopy whereas MnWO$_4$ is a joint-order-parameter multiferroic in which incommensurate magnetic translation domains are observed by optical second harmonic generation. The pronounced ma...
Atif, Yacine; Serhani, Mohamed Adel; Campbell, Piers; Mathew, Sujith Samuel
Administering multilingual Web sites and applications reliably, involves interconnected and multipart tasks, where trust in the involved parties and content translation sources is paramount. Published Web sites may reflect content from databases, content management systems and other repositories to manage related Web content. But a Web site mirrored wholly or selectively onto a target language version requires streamlined trusted processes. Traditionally, files are translated and transferred via FTP, e-mail, or other communication means. Similarly, translation instructions are communicated between involved parties through verbal instruction, e-mail, and instruction files lead to a variety of inconsistencies and lack of trust in the translation process. This paper proposes a Web service approach to streamline the translation processes and an integration of trust properties in the proposed translation Web services. Web Services have been instrumental in handling problems inherent to systems integration, allowing web-based systems to converse and communicate data automatically. The OASIS Translation Web Services Technical Committee has released a standard way for Web Services to serve the translation and localization business. This article proposes a framework to centralize translation services at a reputable source providing a workflow and a mechanism to quantify service trust. An implementation of the framework is also described in the context of a localization case study.
In recent years, many researchers study on the relation between culture and language, language and translation, or culture and translation. Indeed, the three subjects are inseparable. It's incomprehensive to look into just two of them for a linguist. It's more useful for us to study on the relation between them, because we can extend our eyesight and searching scope and propel our translation business. Moreover, studying on them provides a rich material for other fields, such as sociology, translation, cross-cultural communication as well as give other subjects a lead to deep further.
Feminist translation studies have underg one rapid development in China in recent years.However,most of its research rema ins on the inquiry of the influence on the theoretical layer.In this thesis,I tr y to probe carefully into the translation of "Men and Women,Women and the City" done by Zhu Hong in an attempt to find out wh at is the difference that exits in the translation between the Chinese female tr anslators and the western feminist translators.
Bentires-Alj, Mohamed; Rajan, Abinaya; van Harten, Wim;
Translational research leaves no-one indifferent and everyone expects a particular benefit. We as EU-LIFE (www.eu-life.eu), an alliance of 13 research institutes in European life sciences, would like to share our experience in an attempt to identify measures to promote translational research with...... without undermining basic exploratory research and academic freedom.......Translational research leaves no-one indifferent and everyone expects a particular benefit. We as EU-LIFE (www.eu-life.eu), an alliance of 13 research institutes in European life sciences, would like to share our experience in an attempt to identify measures to promote translational research...
WANG Jie; WANG Ping
Translations contribute to our knowledge and understanding in various fields of daily life, as they open us to a greater awareness of the world in which we live. The deeper we are delved into the meaning of the translation, the more questions are raised, among which, translatable/untranslatable argument strikes the most. In this article, factors including cultural vocabulary va⁃cancy and different image associations leading to temporary untranslatability are presented. Besides, the strategies to change this situation to relatively translatable are given as well.
Unt, A.; Lappalainen, E.; Salminen, A.
This paper is focused on the welding of low alloy steels S355 and AH36 in thicknesses 6, 8 and 10 mm in T-joint configuration using either autogeneous laser welding or laser-arc hybrid welding (HLAW) with high power fiber lasers. The aim was to obtain understanding of the factors influencing the size of the fillet and weld geometry through methodologically studying effects of laser power, welding speed, beam alignment relative to surface, air gap, focal point position and order of processes (in case of HLAW) and to get a B quality class welds in all thicknesses after parameter optimization.
Collins, T A; Brown, G K; Johnson, N; Massey, J A; Nunn, B D
Predictable success of autogenous graft and implant reconstructions is critically dependent on preoperative alignment and prosthetic considerations planned by the surgeon and the restorative dentist in a team approach. In such cases the surgeon has an opportunity to place accurate bone grafts that allow implants to be secured in both the correct position and correct axis for good prosthetic restoration. With careful thought, the restorative dentist and surgeon can plan the location, shape, and volume of an implant-graft reconstruction. Nine requirements for successful onlay grating with implants and five case reports illustrating the team approach are presented.
Faulkner, Douglas J.; Larson, Phillip H.; Jol, Harry M.; Running, Garry L.; Loope, Henry M.; Goble, Ronald J.
A paucity of research exists regarding the millennial-scale response of inland alluvial streams to abrupt base-level fall. Studies of modern systems indicate that, over short time scales, the response is a diffusion-like process of upstream-propagating incision. In contrast, evidence from the lower Chippewa River (LCR), located in the upper Midwest of the USA, suggests that autogenic controls operating over time scales of several millennia can overwhelm diffusion, resulting in incision that is prolonged and episodic. During the Last Glacial Maximum, the LCR drained the Chippewa Lobe of the Laurentide Ice Sheet to the glacial upper Mississippi River (UMR). As a meltwater stream, it aggraded and filled its valley with glacial outwash, as did its largest tributaries, which were also meltwater streams. Its nonglacial tributaries aggraded, too, filling their valleys with locally derived sediment. During deglaciation, the UMR incised at least twice, abruptly lowering the LCR's base level - ~ 15 m at 16 ka or earlier and an additional 40 m at ca. 13.4 ka. Each of these base-level falls initiated incision of the LCR, led by upstream migrating knickpoints. The propagation of incision has, however, been a lengthy process. The optically stimulated luminescence (OSL) ages of terrace alluvium indicate that, by 13.5 ka, incision had advanced up the LCR only 15 km, and by 9 ka, only 55 km. The process has also been episodic, resulting in the formation of fill-cut terraces (inferred from GPR surveys and exposures of terrace alluvium) that are younger and more numerous in the upstream direction. Autogenic increases in sediment load and autogenic bed armoring, the result of periodic tributary-stream rejuvenation and preferential winnowing of fines by the incising river, may have periodically caused knickpoint migration and incision to slow and possibly stop, allowing lateral erosion and floodplain formation to dominate. A decline in sediment flux from stabilizing incised tributary
Aleidi, Shereen M.; Howe, Vicky; Sharpe, Laura J.; Yang, Alryel; Rao, Geetha; Brown, Andrew J.; Gelissen, Ingrid C.
The ATP-binding cassette transporter ABCG1 has an essential role in cellular cholesterol homeostasis, and dysregulation has been associated with a number of high burden diseases. Previous studies reported that ABCG1 is ubiquitinated and degraded via the ubiquitin proteasome system. However, so far the molecular mechanism, including the identity of any of the rate-limiting ubiquitination enzymes, or E3 ligases, is unknown. Using liquid chromatography mass spectrometry, we identified two HECT domain E3 ligases associated with ABCG1, named HUWE1 (HECT, UBA, and WWE domain containing 1, E3 ubiquitin protein ligase) and NEDD4-1 (Neural precursor cell-expressed developmentally down regulated gene 4), of which the latter is the founding member of the NEDD4 family of ubiquitin ligases. Silencing both HUWE1 and NEDD4-1 in cells overexpressing human ABCG1 significantly increased levels of the ABCG1 monomeric and dimeric protein forms, however ABCA1 protein expression was unaffected. In addition, ligase silencing increased ABCG1-mediated cholesterol export to HDL in cells overexpressing the transporter as well as in THP-1 macrophages. Reciprocally, overexpression of both ligases resulted in a significant reduction in protein levels of both the ABCG1 monomeric and dimeric forms. Like ABCG1, ABCG4 protein levels and cholesterol export activity were significantly increased after silencing both HUWE1 and NEDD4-1 in cells overexpressing this closely related ABC half-transporter. In summary, we have identified for the first time two E3 ligases that are fundamental enzymes in the post-translational regulation of ABCG1 and ABCG4 protein levels and cellular cholesterol export activity. PMID:26296893
Full Text Available When the system or structure of language is used and influenced by other languages, it is called interference, and it may ruin the concept of structures. This research is about Arabic phrase construction that influenced Javanese phrase construction in classical books translation (TKK. This involvement appears when the concept of Arabic’s construction is translated literally into Javanese. The research was carried out by applying theories of interference and translation. It’s analysis approach with contrastive analysis which is allegedly enabled errors to be predicted from a comparison between Arabic’s and Javanese’s phrase construction. The data were found and collected from several classical books in Arabic language (KKbA translated by different writers. The results show that Javanese phrase construction (as the target language, particularly, with noun phrases, with adjectival phrases, with numeral phrases, and with prepositional phrases was influenced by Arabic’s murakkab or Arabic phrase construction (as the source language. Arabic has its own concept of phrase construction. The phrase construction cannot be translated into Javanese directly through word-for-word translation or literal translation. Thus, Javanese in TKK became inconvenient and ungrammatical. Arabic phrase construction is flipped around (with noun phrases and adjectival phrases and prepositions are used and translated improperly or in the wrong position (with prepositional phrases. This research has many implications for further use, such as: for the identification and description of the deviation of Javanese phrase construction which has been affected by direct translation from the Arabic language, and furthermore, to increase the knowledge of those who are learning by increasing the realization and awareness in writing and translating (especially from Arabic to Javanese about the fact that Arabic and Javanese have their own regulations or
Advertisement translation and trademark translation are becoming more and more prevailing and influential under the increasing development of internationalization of business. This paper attempts to analyze the influence of cultural differences on advertisement translation and trademark translation. It finds that advertisement translation and trademark translation are under the impressive influence of the differences between Chinese and Western cultures. This paper aims to stress the cultural differences in advertisement translation and trademark translation and reminds translators of the importance of noticing cultural differences and finding a proper point between foreign cultures and native cultures.
Prior, Anat; Kroll, Judith F.; Macwhinney, Brian
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…
Eddington, Chelsea M.; Tokowicz, Natasha
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…
Henrique de Oliveira Lee
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.
We analyze the role played by local translational symmetry in the context of gauge theories of fundamental interactions. Translational connections and fields are introduced, with special attention being paid to their universal coupling to other variables, as well as to their contributions to field equations and to conserved quantities.
Babaee, Siamak; Wan Yahya, Wan Roselezam; Babaee, Ruzbeh
Some scholars (Bassnett-McGuire, Catford, Brislin) suggest that a good piece of translation should be a strict reflection of the style of the original text while some others (Gui, Newmark, Wilss) consider the original text untranslatable unless it is reproduced. Opposing views by different critics suggest that translation is still a challenging…
Bossé, Michael J.; Adu-Gyamfi, Kwaku; Chandler, Kayla
Understanding how students translate between mathematical representations is of both practical and theoretical importance. This study examined students' processes in their generation of symbolic and graphic representations of given polynomial functions. The purpose was to investigate how students perform these translations. The result of the study…
Horner, Bruce; Tetreault, Laura
This article explores translation as a useful point of departure and framework for taking a translingual approach to writing engaging globalization. Globalization and the knowledge economy are putting renewed emphasis on translation as a key site of contest between a dominant language ideology of monolingualism aligned with fast capitalist…
Rogowski, Wolf; John, Jürgen; IJzerman, Maarten; Scheffler, Richard M.
Translational health economics (THE) can be defined as the use of theoretical concepts and empirical methods in health economics to bridge the gap between the decision to fund and use a new health technology in clinical practice (the backend of translational medicine) and the decision to invest into
Objectifying the cultural diversity of visual fieldmethods - and the analysis of balancing the cultural known and unknown through anthropological analysis (aided by the analytical concept translation (Edwin Ardener 1989))......Objectifying the cultural diversity of visual fieldmethods - and the analysis of balancing the cultural known and unknown through anthropological analysis (aided by the analytical concept translation (Edwin Ardener 1989))...
Mees, Inger M.; Dragsted, Barbara; Gorm Hansen, Inge;
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) ha...
Culture difference is necessary to be paid attention to during the process of translating.Culture difference is caused by different history,regions,customs,religions and the modes of thinking.Having the awareness of the culture difference will make translation more accurate and successful.
Applebaum, Mark; Leikin, Roza
The translation principle allows students to solve problems in different branches of mathematics and thus to develop connectedness in their mathematical knowledge. Successful application of the translation principle depends on the classroom mathematical norms for the development of discussions and the comparison of different solutions to one…
di Stefano, B. Follkart
It is proposed that literary translation is intrinsically an act of literary criticism. This theory is illustrated by discussion of specific problems in translating Sartre's "La Nausee" and Leonard Forest's "Le pays de la Sagouine," especially the use of verb tense. (MSE)
, on messenger stability was examined. Depending on the translation initiation frequency, the chance of an initial ribosome trailing the RNA polymerase get better for better initiation sites, thus protecting transcription from termination by Rho. A polarity assay in which the activity of the downstream lac......-termination to be a global phenomena in gene regulation. The influence of codon usage in the early coding region on messenger stability was examined, in order to establish how fast or slow the ribosome has to decode the sequence for it to protect the messenger from degradation. The experiments demonstrated that very fast...
Mikicin, Mirosław; Kowalczyk, Marek
The aim of the present study was to investigate the effect of regular audio-visual relaxation combined with Schultz's autogenic training on: (1) the results of behavioral tests that evaluate work performance during burdensome cognitive tasks (Kraepelin test), (2) changes in classical EEG alpha frequency band, neocortex (frontal, temporal, occipital, parietal), hemisphere (left, right) versus condition (only relaxation 7-12 Hz). Both experimental (EG) and age-and skill-matched control group (CG) consisted of eighteen athletes (ten males and eight females). After 7-month training EG demonstrated changes in the amplitude of mean electrical activity of the EEG alpha bend at rest and an improvement was significantly changing and an improvement in almost all components of Kraepelin test. The same examined variables in CG were unchanged following the period without the intervention. Summing up, combining audio-visual relaxation with autogenic training significantly improves athlete's ability to perform a prolonged mental effort. These changes are accompanied by greater amplitude of waves in alpha band in the state of relax. The results suggest usefulness of relaxation techniques during performance of mentally difficult sports tasks (sports based on speed and stamina, sports games, combat sports) and during relax of athletes.
Mendonça José Carlos Garcia de
Full Text Available PURPOSE: Morphological study comparing castor oil polyurethane and autogenous bone graft to repair bone defect in zygomatic bone of rabbits. METHODS: Twenty-four adult, male New Zealand rabbits were randomly distributed between two groups of twelve. Bone defects of 5mm in diameter were cut through the zygomatic bone and filled with polyurethane discs in the experimental group or autogenous bone harvested from the tibia in the control group. Animals were sacrificed after 30, 60 or 90 days, and the zygomatic bones were macro- and microscopically analyzed. Student's, Fisher's, chi-squared and McNemar's tests were used for statistical analysis. RESULTS: Both the castor oil polyurethane and the autograft adapted well to the defect, with no need for fixation. Fibrous connective tissue encapsulated the polyurethane, but no inflammation or giant cell reaction was observed. Acidophilic and basophilic areas were observed inside the micropores of the polyurethane, suggesting cell nuclei. After 90 days, bone repair with a lamellar pattern of organization was observed in the control group. CONCLUSION: The castor oil polyurethane was biocompatible and did not cause inflammation. It may be considered an alternative to fill bone defects.
Full Text Available Purpose: to experimentally subsituate effectiveness of non traditional complex methodic of recreation in female basketball players’ training process. Material: 22 basketball players of women student’s team participated in the research. Pedagogic testing was conducted by 12 tests in special physical and technical fitness. Psycho-physiological testing was conducted by program PSYCHO-DIAGNOSTIC. Groups were trained by identical programs during 9 weeks. Results: we authors observed increased physical and technical fitness of basketball players. Besides, quantity of mistakes in response to visual irritator reduced. It indirectly witnesses about strengthening of nervous processes. There was registered influence of mind on quality of organism’s recreation after physical loads. Conclusions: the authors recommend methodic of cupping massage, combined with autogenic training. Autogenic training implies repeated pronouncing by instructor (or independently by sportswomen of text, describing coming turn by turn natural images. Peculiarities of massage were influence of massage passes on muscles and ligaments. Cupping massage was used after warming up classic massage techniques.
Francisley Ávila Souza
Full Text Available Background: Dentoalveolar trauma, especially when involving front teeth, negatively affect the patient’s life; in particular, tooth avulsion is a complex injury that affects multiple tissues, and no treatment option offers stable long-term outcomes. The aim of this study was to report a case of reconstruction of atrophic anterior alveolar ridge after tooth loss, performed with autograft harvested from the chin, and subsequent prosthetic rehabilitation with the use of an osseointegrated implant. Case report: A 23-years-old Caucasian girl, presented an atrophic alveolar bone in the area of tooth 11, as a result of tooth resorption 10 years after a tooth reimplantation procedure. Reconstruction was performed with autogenous bone harvested from the chin. After 6-months healing period to allow autograft incorporation, a dental implant was inserted. After further 6- months, a screw-retained implant supported metal-ceramic prosthesis was fabricated. Results The prosthetic rehabilitation was successful, and after a follow-up period of 5 years, the achieved result was stable. Conclusion: It can be concluded that the autogenous bone graft harvested from the chin, is a safe and effective option for alveolar ridge defects reconstruction, allowing a subsequent placement of a dental implant supporting a prosthetic restoration.
Margonar, Rogério; dos Santos, Pâmela Letícia; Queiroz, Thallita Pereira; Marcantonio, Elcio
Currently, there are several techniques for the rehabilitation of atrophic maxillary ridges in literature. The grafting procedure using autogenous bone is considered ideal by many researchers, as it shows osteogenic capability and causes no antigenic reaction. However, this type of bone graft has some shortcomings, mainly the restricted availability of donor sites. In recent years, several alternatives have been investigated to supply the disadvantages of autogenous bone grafts. In such studies, allogeneic bone grafts, which are obtained from individuals with different genetic load, but from the same species, have been extensively used. They can be indicated in cases of arthroplasty, surgical knee reconstruction, large bone defects, and in oral and maxillofacial reconstruction. Besides showing great applicability and biocompatibility, this type of bone is available in unlimited quantities. On the other hand, allogeneic bone may have the disadvantage of transmitting infectious diseases. Atrophic maxillae can be treated with bone grafts followed by osseointegrated implants to obtain aesthetic and functional oral rehabilitation. This study aimed to show the viability of allogeneic bone grafting in an atrophic maxilla, followed by oral rehabilitation with dental implant and protocol-type prosthesis within a 3-year follow-up period by means of a clinical case report.
Helwig, M; Khorooshi, R M H; Tups, A; Barrett, P; Archer, Z A; Exner, C; Rozman, J; Braulke, L J; Mercer, J G; Klingenspor, M
A remarkable feature of the seasonal adaptation displayed by the Siberian hamster (Phodopus sungorus) is the ability to decrease food intake and body weight (by up to 40%) in response to shortening photoperiod. The regulating neuroendocrine systems involved in this adaptation and their neuroanatomical and molecular bases are poorly understood. We investigated the effect of photoperiod on the expression of prohormone convertases 1 (PC1/3) and 2 (PC2) and the endoproteolytic processing of the neuropeptide precursor pro-opiomelanocortin (POMC) within key energy balance regulating centres of the hypothalamus. We compared mRNA levels and protein distribution of PC1/3, PC2, POMC, adrenocorticotrophic hormone (ACTH), alpha-melanocyte-stimulating hormone (MSH), beta-endorphin and orexin-A in selected hypothalamic areas of long day (LD, 16:8 h light:dark), short day (SD, 8:16 h light:dark) and natural-day (ND, photoperiod depending on time of the year) acclimated Siberian hamsters. The gene expression of PC2 was significantly higher within the arcuate nucleus (ARC, P < 0.01) in SD and in ND (versus LD), and is reflected in the day length profile between October and April in the latter. PC1/3 gene expression in the ARC and lateral hypothalamus was higher in ND but not in SD compared to the respective LD controls. The immunoreactivity of PC1/3 cleaved neuropeptide ACTH in the ARC and PC1/3-colocalised orexin-A in the lateral hypothalamus were not affected by photoperiod changes. However, increased levels of PC2 mRNA and protein were associated with higher abundance of the mature neuropeptides alpha-MSH and beta-endorphin (P < 0.01) in SD. This study provides a possible explanation for previous paradoxical findings showing lower food intake in SD associated with decreased POMC mRNA levels. Our results suggest that a major part of neuroendocrine body weight control in seasonal adaptation may be effected by post-translational processing mediated by the prohormone convertases PC1
Solano-Flores, Guillermo; Backhoff, Eduardo; Contreras-Nino, Luis Angel
In this article, we present a theory of test translation whose intent is to provide the conceptual foundation for effective, systematic work in the process of test translation and test translation review. According to the theory, translation error is multidimensional; it is not simply the consequence of defective translation but an inevitable fact…
Hu; Lu; He; Yan-ni
With the deepening of economic globalization,business English plays an increasingly vital role.In order to better translate business English,the translator has to adopt some important translation techniques.Thus,emphasis is placed on business English translation skills,such as omission,supplement and word conversion,etc,which provides some practical advice to the translation of business English.
Hu Lu; He Yan-ni
With the deepening of economic globalization, business English plays an increasingly vital role. In order to better translate business English, the translator has to adopt some important translation techniques. Thus, emphasis is placed on business English translation skills, such as omission, supplement and word conversion, etc, which provides some practical advice to the translation of business English.
Many linguists, translators, and theorists have been arguing over the approaches on translation. While putting these into use a translator may experience many pleasure and problems as well. The purpose of this article is to discuss the tasks of translation and the way of choosing the proper translation approaches according to the author’s own experience of practice.
On the basis of Halliday' s theory, this paper makes it clear that clause as the translation unit is operational in Chinese to English translation and expounds the application of clause as the translation unit with some examples.
Full Text Available Abstract Background Psychological stress plays an important role in the onset and course of Meniere's disease. Surgical therapy and intratympanic gentamicin treatment are options for cases that are intractable to conventional medical therapy. Psychotherapy, however, including autogenic training (AT, which can be used for general relaxation, is not widely accepted. This paper describes the successful administration of AT in a subject suffering from intractable Meniere's disease. Case presentation A 51-year-old male patient has suffered from fluctuating right sensorineural hearing loss with vertigo since 1994. In May 2002, he was first admitted to our hospital due to a severe vertigo attack accompanied by right sensorineural hearing loss. Spontaneous nystagmus toward the right side was observed. Since April 2004, he has experienced vertigo spells with right-sided tinnitus a few times per month that are intractable to conventional medical therapy. After four months, tympanic tube insertion was preformed in the right tympanic membrane. Intratympanic injection of dexamethasone was ineffective. He refused Meniett therapy and intratympanic gentamicin injection. In addition to his vertigo spells, he suffered from insomnia, tinnitus, and anxiety. Tranquilizers such as benzodiazepines and antidepressants such as serotonin selective re-uptake inhibitors (SSRIs failed to stop the vertigo and only slightly improved his insomnia. In December 2006, the patient began psychological counseling with a psychotherapist. After brief psychological counseling along with cognitive behavior therapy (CBT, he began AT. He diligently and regularly continued his AT training in his home according to a written timetable. His insomnia, tinnitus, and vertigo spells disappeared within a few weeks after only four psychotherapy sessions. In order to master the six standard formulas of AT, he underwent two more sessions. Thereafter, he underwent follow-up for 9 months with no
Full Text Available This work is a translation of the chapter “Descriptions – the intellectual background” serving as a complement to the chapter 5 of the book titled Exploring Translations Studies (2010 by Anthony Pym. The chapter outlines the relationship between Russian Formalism and some of the strands of the Translation Studies which emerged during the 19th century. It brings to the fore works done in Prague (Prague Circle, Bratislava, Leipzig, Holland and Flanders focusing specially on the Tel-Aviv School of Itamar-Even and Gideon Toury, the main forerunners of the Descriptive Translation Studies (DTS. By analyzing this academic context, not only it describes the type of approaches those theorists suggested, but it also discusses the ups and downs of such paradigms problematizing concepts like “translation shifts”, “assumed translations” and “norms”. This translation aims at presenting and sharing Pym’s work as clearly and fluid as the original is, so that it serves as both a historical reference and an introductory text to Translation Studies.
Language is the expression of human communication through which knowledge, belief, and behavior can be experi-enced, explained, and shared. It influences the way the speakers perceive the world. But as it has been long taken for granted, translation deals only with language. Cultural perspective, however, has never been brought into discussion. This paper first analyses the definitions of translation and culture, and then discusses why we should take culture into consideration and in the end, two translating strategies:domestication and foreignization are introduced.
Language is the expression of human communication through which knowledge, belief, and behavior can be experi- enced, explained, and shared. It influences the way the speakers perceive the world. But as it has been long taken for granted, translation deals only with language. Cultural perspective, however, has never been brought into discussion. This paper first analyses the definitions of translation and culture, and then discusses why we should take culture into consideration and in the end, two translating strategies: domestication and foreignization are introduced.
Jensen, Thomas; Schou, S; Stavropoulos, A
The objective of the present systematic review was to test the hypothesis of no differences between the use of Bio-Oss or Bio-Oss mixed with autogenous bone as graft for maxillary sinus floor augmentation (MSFA) applying the lateral window technique, as evaluated in animals. A MEDLINE (PubMed...
Jensen, Thomas; Schou, Søren; Stavropoulos, Andreas;
Aims: The objective of the present systematic review was to test the hypothesis of no differences in the implant treatment outcome when Bio-Oss or Bio-Oss mixed with autogenous bone is used as graft for the maxillary sinus floor augmentation (MSFA) applying the lateral window technique. Material ...
Merkx, M.A.W.; Fennis, J.P.M.; Verhagen, C.M.; Stoelinga, P.J.W.
The results are presented of eight patients who had partial mandibulectomies for malignant tumours and were secondarily reconstructed with pre-shaped 2.3 mm titanium plates, autogenous particulate cortico-cancellous bone grafts and platelet rich plasma. Healing was uneventful in all cases and when p
Fennis, J.P.M.; Stoelinga, P.J.W.; Jansen, J.A.
Twenty-eight goats underwent a continuity resection of the mandibular angle. In all goats primary reconstruction was carried out using specially designed pre-shaped osteosynthesis plates and monocortical screws. The original cortical scaffold was used to bridge the defect, filled with an autogenous
Full Text Available This brief chapter problematizes the hegemonic position of the English language in Cultural Studies, which, in the author's view, can be understood as a moment that stands against a true internationalisation of the project. Following an argu-ment referring to the necessary 'translation' process (here seen as 're-articulation', 'transcoding' or 'transculturation' Stuart Hall has put forward almost two decades ago, the essay, firstly, turns to the notion of 'linguistic translations', and deals, secondly, with what has been coined 'cultural translation'. Discussing approaches developed by Walter Benjamin, Umberto Eco and Homi Bhabha, the complex relationship between the two terms is being investigated. Finally, in a modest attempt to throw some light on this hegemonic structure, central aspects of the output of three important journals (European Journal of Cultural Studies, International Journal of Cultural Studies, Cultural Studies, i. e. an analysis of the linguistic and institutional backgrounds of the authors of the ten most-read and most-cited essays, are presented. Based on these findings I argue that it is not simply the addition of the discursive field (language to the academic space (institution that defines the mecha-nism of exclusion and inclusion. Rather, it is the articulation of both moments, i.e. that of language and that of the institution, which - in various contexts (but in their own very definite ways - can help to develop that structure which at present is still hindering a further, more profound internationalisation of the project that is Cultural Studies.
Metaphor is one of the important and forceful figures of speech in English. In practice of translating English metaphors into Chinese, some approaches are available: literal translation, changing metaphor into sim/h, conversion, liberal translation and complement.
Bos, J.E.; Correia Grácio, B.J.
BACKGROUND: Linear acceleration generally gives rise to translation perception. Centripetal acceleration during centrifugation, however, has never been reported giving rise to a radial, inward translation perception. OBJECTIVE: To study whether centrifugation can induce a radial translation percepti
Full Text Available The article begins with the differences betweenscientific and fictional translations, and focus on the second.The fictional translation works with meanings, opens itselfto the plurissignification in the purpose to create a similarity of the dissimilarity; in this process, the translator does nottranslate a language, but what a creative individuality makeswith a language. At last there is an approach to the knowledgeand skills necessaries to a translator of literature: theknowledge of the theories of the literature and of thetranslation, the capacity to preserve the national color ofthe original text and at the same time to respect the arrivallanguage, and the sensibility to his national languagevariations present in the daily and in the literary spheres.
This paper analyzes the necessity of adopting interactive approach in college English teaching and proposes that teachers are supposed to mobilize students＇ intrinsic motivation when following proper translation teaching procedures.
Schaeffer, Moritz; Dragsted, Barbara; Hvelplund, Kristian Tangsgaard
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...... 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...... evidence of co-activation. Results show that the number of translation alternatives for a single word and differences between source and target text in terms of word order have an effect on very early and late eye movement measures. Results are interpreted in terms of semantic and structural cross...
society is described as networks binding bits and pieces together. Humans are also themselves networks of skin, bones, enzymes, cells etc. What homogenize the many heterogeneous entities in networks are processes of translations (Schiølin 2010). Translation is never neutral, and is not meant like from...... and translations the social medium of Twitter opens for. The second, but most prioritized, aim of the paper is to present, compare and discuss the two theories: How do they understand what becomes visible in their different optics, which observations become possible in the one or the other – and is it possible...... to compare the semantics of their concepts. The paper first provides an analysis and discussion of language as the mechanism of structural coupling between the levels of psychic and social systems. Then the article provides an analysis and discussion of translation as a transformation process between actors...
Tarp, Sven; Dam, Helle Vrønning
Translation, interpreting and lexicography represent three separate areas of human activity, each of them with its own theories, models and methods and, hence, with its own disciplinary underpinnings. At the same time, all three disciplines are characterized by a marked interdisciplinary dimension...... in the sense that their practice fields are typically ‘about something else’. Translators may, for example, be called upon to translate medical texts, and interpreters may be assigned to work on medical speeches. Similarly, practical lexicography may produce medical dictionaries. In this perspective, the three...... disciplines frequently come into touch with each other. This chapter discusses and explores some of the basic aspects of this interrelationship, focusing on the (potential) contribution of lexicography to translation and interpreting and on explaining the basic concepts and methods of the former discipline...
A translational systems biology approach in both animals and humans identifies a functionally related module of accumbal genes involved in the regulation of reward processing and binge drinking in males
Stacey, David; Lourdusamy, Anbarasu; Ruggeri, Barbara; Maroteaux, Matthieu; Jia, Tianye; Cattrell, Anna; Nymberg, Charlotte; Banaschewski, Tobias; Bhattacharyya, Sohinee; Band, Hamid; Barker, Gareth; Bokde, Arun; Buchel, Christian; Carvalho, Fabiana; Conrod, Patricia; Desrivieres, Sylvane; Easton, Alanna; Fauth-Buehler, Mira; Fernandez-Medarde, Alberto; Flor, Herta; Frouin, Vincent; Gallinat, Jurgen; Garavanh, Hugh; Heinz, Andreas; Ittermann, Bernd; Lathrop, Mark; Lawrence, Claire; Loth, Eva; Mann, Karl; Martinot, Jean-Luc; Nees, Frauke; Paus, Tomas; Pausova, Zdenka; Rietschel, Marcella; Rotter, Andrea; Santos, Eugenio; Smolka, Michael; Sommer, Wolfgang; Mameli, Manuel; Spanagel, Rainer; Girault, Jean-Antoine; Mueller, Christian; Schumann, Gunter
Background The mesolimbic dopamine system, composed primarily of dopaminergic neurons in the ventral tegmental area that project to striatal structures, is considered to be the key mediator of reinforcement-related mechanisms in the brain. Prompted by a genome-wide association meta-analysis implicating the Ras-specific guanine nucleotide-releasing factor 2 (RASGRF2) gene in the regulation of alcohol intake in men, we have recently shown that male Rasgrf2−/− mice exhibit reduced ethanol intake and preference accompanied by a perturbed mesolimbic dopamine system. We therefore propose that these mice represent a valid model to further elucidate the precise genes and mechanisms regulating mesolimbic dopamine functioning. Methods Transcriptomic data from the nucleus accumbens (NAcc) of male Rasgrf2−/− mice and wild-type controls were analyzed by weighted gene coexpression network analysis (WGCNA). We performed follow-up genetic association tests in humans using a sample of male adolescents from the IMAGEN study characterized for binge drinking (n = 905) and ventral striatal activation during an fMRI reward task (n = 608). Results The WGCNA analyses using accumbal transcriptomic data revealed 37 distinct “modules,” or functionally related groups of genes. Two of these modules were significantly associated with Rasgrf2 knockout status: M5 (p < 0.001) and M6 (p < 0.001). In follow-up translational analyses we found that human orthologues for the M5 module were significantly (p < 0.01) enriched with genetic association signals for binge drinking in male adolescents. Furthermore, the most significant locus, originating from the EH-domain containing 4 (EHD4) gene (p < 0.001), was also significantly associated with altered ventral striatal activity in male adolescents performing an fMRI reward task (pempirical < 0.001). Limitations It was not possible to determine the extent to which the M5 module was dysregulated in Rasgrf2−/− mice by perturbed mesolimbic
Lass, Wiebke; Reusswig, Fritz
Lost in Translation? Introducing Planetary Boundaries into Social Systems. Fritz Reusswig, Wiebke Lass Potsdam Institute for Climate Impact Research, Potsdam, Germany Identifying and quantifying planetary boundaries by interdisciplinary science efforts is a challenging task—and a risky one, as the 1972 Limits to Growth publication has shown. Even if we may be assured that scientific understanding of underlying processes of the Earth system has significantly improved since then, the challenge of translating these findings into the social systems of the planet remains crucial for any kind of action, and in many respects far more challenging. We would like to conceptualize what could also be termed a problem of coupling social and natural systems as a nested set of social translation processes, well aware of the limited applicability of the language-related translation metaphor. Societies must, first, perceive these boundaries, and they have to understand their relevance. This includes, among many other things, the organization of transdisciplinary scientific cooperation. They will then have to translate this understood perception into possible actions, i.e. strategies for different local bodies, actors, and institutional settings. This implies a lot of 'internal' translation processes, e.g. from the scientific subsystem to the mass media, the political and the economic subsystem. And it implies to develop subsystem-specific schemes of evaluation for these alternatives, e.g. convincing narratives, cost-benefit analyses, or ethical legitimacy considerations. And, finally, societies do have to translate chosen action alternatives into monitoring and evaluation schemes, e.g. for agricultural production or renewable energies. This process includes the continuation of observing and re-analyzing the planetary boundary concept itself, as a re-adjustment of these boundaries in the light of new scientific insights cannot be excluded. Taken all together, societies may well
ZHU; Yu; WANG; Jin
Abstract:Translation is an independent discipline(Jean Delisle,1988).With the deepening of translation studies,translation teaching aroused widespread concern among translation academia,and gradually separated from language teaching,being a subj ect with its own obj ectives and a special position.This paper,firstly introduces the obj ectives and content of translation teaching,then points out several common problems in translation teaching.Finally,associated with the basic principles of translation teaching,it analyzes the strategies of English translation teaching.
Askehave, Inger; Zethsen, Karen Korning
This article deals with an aspect of patient information that differs somewhat from the traditional scope of this journal; namely the linguistic and translational aspects of Patient Information Leaflets (PILs). During the past decade much work has been dedicated to making the English PILs...... as informative and lay-friendly as possible. However, much of the good work is ruined when the PIL is translated. Why is this so and what can be done about it?...
<正>A translation criteria universally accepted is faithfulness, which can be examined from different dimensions of content, form and style.Among these three dimensions,faithfulness in content and form is easier to be noted,while the faithfulness in style is harder to judge.This paper will mainly focus on the study of stylistic features for the purpose of language providing methods to achieve stylistic adaptation in translation.
The paper describes the background, subjects, assumptions, procedure, and preliminary results of a small-scale experimental study of L2 translation (Danish into English) and picture verbalization in L2 (English).......The paper describes the background, subjects, assumptions, procedure, and preliminary results of a small-scale experimental study of L2 translation (Danish into English) and picture verbalization in L2 (English)....
Probabilistic Translation Dictionaries (PTD) are translation resources that can be obtained automatically from parallel corpora. Although this process is simple, it requires the existence of a parallel corpora for the involved languages. Minoritized languages have a limited amount of available resources. For example, while they can have a few parallel corpora, the number of parallel language-pairs uses to be restricted. We defend that if a minoritized language A has a parallel corpus with a l...
Semantics is the study of the meanings of words and sentences. While word is the most basic unit in every language and the understanding of the word meaning is the most important problem in translation. Therefore, the analysis of semantics just provides a very direct approach to doing translation. In this paper, I’d like to focus on the three kinds of word meaning in transla- tion, the ambiguities caused by the word meaning and how to deal with such ambiguities.
Different nations have different or even opposite perception of color, which results in non-equivalence of color words in mutual translation between Chinese and English. This paper is to discuss non-equivalence of color words between Chinese and English on the two aspects and emphasizes the importance of transmitting cultural message accurately in the mutual translation between Chinese and English. Studying the cultural connotations of the words is of great importance for successful communication.
Cristina García de Toro
Full Text Available The article briefly outlines the main schools and approaches that make up the current landscape of Translation Studies. The purpose of this paper is to offer an introduction to translation theory for those who are beginning their studies in this field or whose knowledge of Translation Studies is tangential. The article starts with a few preliminary matters, such as the question of what Translation Studies is and how the discipline has been mapped out. Then it moves on to examine the theoretical considerations that have been developed since the second half of the 20th century, with special attention being paid to the most recent decades. In this section, which is devoted to theoretical considerations, I will review some of the fundamental issues from a theories of equivalence and comparisons between languages; b functionalist theories; c discursive approaches; d polysystem theory, descriptive studies and norms; e cultural studies; f philosophical theories; g latest contributions to the field of Translation Studies; and h interdisciplinary and integrating approaches. Keywords: translation studies, contemporary theories, linguistic approaches, descriptive studies, cultural studies.
Full Text Available Post-translational modifications increase proteome functionality for managing all aspects of normal cell biology. They are based on the covalent attachment of functional groups, leading to phosphorylation, acetylation, glycosylation, acylation, ubiquitination, SUMOylation and oxidation of protein targets. Post-translational modifications occur at any step of protein life cycle, modulating in time and space protein folding, subcellular localization and activity. Aberrant post-translational modifications of one or more culprit proteins may lead to neurodegeneration, as shown in paradigmatic neurological disorders such as Alzheimer’s, Parkinson’s and prion diseases. In this review, we report the most important post-translational modifications found in neurodegenerative disorders, illustrating the pathophysiological mechanisms in which they are involved. This work highlights the lack of a global framework of post-translational modifications in terms of complexity and regulation. Therefore, in the next future many efforts are required to describe the interplay existing between post-translational modifications and their combinatorial patterns on protein targets.
Varzande, Mohsen; Jadidi, Esmaeil
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…
Varzande, Mohsen; Jadidi, Esmaeil
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…
Both language teaching experts and translation theorists have proposed detailed analyses of the advantages and disadvantages of using translation in language teaching. However, in order to make translation a useful teaching resource, they have provided new and challenging insights into the nature of translation itself. Some of the principles among these insights will be outlined and discussed in this paper.
Full Text Available The translation of proper nouns is not as easy as that of other parts of speech as this is more challenging for certain reasons. The present article presents a descriptive study of proper nouns in translation, scrutinizing the challenges and exploring the solutions. Building on some scholars’ approach and suggestions from other researchers, the article clarifies the nature and problems of proper nouns in translation; it seeks to answer three questions: 1 Should proper nouns be translated? 2 What are the problems on the way of translation of the proper nouns? 3 How can the translator overcome such problems? Moreover, strategies applied by the researchers to make their translation easier are also discussed. It follows that translating proper nouns is not simple and there is little flexibility about translating proper nouns. Keywords: proper nouns, translation, strategies
Full Text Available This paper moves between two streets: Liverpool Road in the Sydney suburb of Ashfield and Via Sarpi in the Italian city of Milan. What connects these streets is that both have become important sites for businesses in the Chinese diaspora. Moreover, both are streets on which locals have expressed desires for Chinese signs to be translated into the national lingua franca. The paper argues that the cultural politics inherent in this demand for translation cannot be fully understood in the context of national debates about diversity and integration. It is also necessary to consider the emergence of the official Chinese Putonghua as global language, which competes with English but also colonizes dialects and minority languages. In the case of these dual language signs, the space between languages can neither be reduced to a contact zone of minority and majority cultures nor celebrated as a ‘third space’ where the power relations implied by such differences are subverted. At stake is rather a space characterised by what Naoki Sakai calls the schema of co-figuration, which allows the representation of translation as the passage between two equivalents that resemble each other and thus makes possible their determination as conceptually different and comparable. Drawing on arguments about translation and citizenship, the paper critically interrogates the ethos of interchangeability implied by this regime of translation. A closing argument is made for a vision of the common that implies neither civilisational harmony nor the translation of all values into a general equivalent. Primary sources include government reports, internet texts and media stories. These are analyzed using techniques of discourse analysis and interpreted with the help of secondary literature concerning globalisation, language and migration. The disciplinary matrix cuts and mixes between cultural studies, translation studies, citizenship studies, globalization studies and
Xi Jinping:The Governance of China is of great significance in asserting to the world the fundamental policies and state-craft of CPC. Its English translation is analyzed on the basis of Toury’s translation norm theory, which guide and regulate all the processes in the translation activities. Based on preliminary norms, initial norms and initial norms, factors influencing the choice of source text, the attitude of translators as well as the specific translation strategies in the translation activity are explored with detailed cases.
Cowings, Patricia S.; Toscano, William B.
Finding an effective treatment for the motion sickness-like symptoms that occur in space has become a high priority for NASA. The background research is reviewed and the experimental design of a formal life sciences shuttle flight experiment designed to prevent space motion sickness in shuttle crew members is presented. This experiment utilizes a behavioral medicine approach to solving this problem. This method, Autogenic-Feedback Training (AFT), involves training subjects to voluntarily control several of their own physiological responses to environmental stressors. AFT has been used reliably to increase tolerance to motion sickness during ground-based tests in over 200 men and women under a variety of conditions that induce motion sickness, and preliminary evidence from space suggests that AFT may be an effective treatment for space motion sickness as well. Proposed changes to this experiment for future manifests are included.
Broggini, Nina; Bosshardt, Dieter D; Jensen, Simon S;
The individual healing profile of a given bone substitute with respect to osteogenic potential and substitution rate must be considered when selecting adjunctive grafting materials for bone regeneration procedures. In this study, standardized mandibular defects in minipigs were filled with nanocr......The individual healing profile of a given bone substitute with respect to osteogenic potential and substitution rate must be considered when selecting adjunctive grafting materials for bone regeneration procedures. In this study, standardized mandibular defects in minipigs were filled...... with nanocrystalline hydroxyapatite (HA-SiO), deproteinized bovine bone mineral (DBBM), biphasic calcium phosphate (BCP) with a 60/40% HA/β-TCP (BCP 60/40) ratio, or particulate autogenous bone (A) for histological and histomorphometric analysis. At 2 weeks, percent filler amongst the test groups (DBBM (35.65%), HA...
@@ O.Introduction Institutional translation,which covers texts in diversified fields such as laws and regulations,politics,policies and institutional docu-merits,is an important part of all translation activities.For interlingua translation of political,legal,institutional documents plays a cracial role in maintaining the routine conununications of international com-munities as well as in domestic politics,prospective translators should not only recognize its significance but also master some char-acteristics of institutional translaLions.
Full Text Available In the last decade, a plethora of studies utilizing pharmacological, biochemical, and genetic approaches have shown that precise translational control is required for long-lasting synaptic plasticity and the formation of long-term memory. Moreover, more recent studies indicate that alterations in translational control are a common pathophysiological feature of human neurological disorders, including developmental disorders, neuropsychiatric disorders, and neurodegenerative diseases. Finally, translational control mechanisms are susceptible to modification by psychoactive drugs. Taken together, these findings point to a central role for translational control in the regulation of synaptic function and behavior.
Kol'tsova, A M; Voronkina, I V; Gordeeva, O F; Zenin, V V; Lifantseva, N V; Musorina, A S; Smagina, L V; Iakovleva, T K; Polianskaia, G G
A new feeder-free culture system for human embryonic stem cells (hESC) was developed. It consist of extracellular matrix proteins synthesized by feeder cells--mesenchymal stem cell line SC5-MSC, which was derived from initial hESC line SC5. The major ECM proteins--fibronectin and laminin--that maintain hESC growth in feeder-free system were identified. An essential component of this system is a SC5-MSC-conditioned medium. Two hESC sublines were derived. The subline SC5-FF was cultured in autogenic and subline SC7-FF in allogenic system. Sublines SC5-FF and SC7-FF passed through more than 300 and 115 cell population doublings, retained normal diploid karyotype and an ability of in vitro differentiation into derivates of three germ layers. These sublines express markers of undifferentiated hESC: alkaline phosphatase, Oct-4, SSEA-4, TRA-1-81 and multidrug resistance transporter--ABCG2. The RT-PCR analysis revealed that undifferentiated cells SC5-FF subline, like cells of initial feeder-maintained hESC line SC5, expressed genes OCT4 and NANOG, and germ line specific genes such as DPPA3/STELLA and DAZL. An expression of OCT4, NANOG, DPPA3/STELLA ans DAZL was down-regulated during embryonic bodies differentiation, whereas expression of somatic lineages specific genes like GATA4 and AFP (extra embryonic and embryonic endoderm), PAX6 (neuroectoderm) and BRY (mesoderm) was up-regulated. The comparative analysis of some typical features (karyotype structure, the average population doubling time and the number of undifferentiated cells in populations) did not reveal essential differences between initial SC5 and SC7 lines and their sublines SC5-FF and SC7-FF. This shows that feeder-free culture systems, which are much more stable than any feeder systems, do not break main hESC features during long cultivation and can be recommended for fundamental, biomedicine and pharmacological investigations, using hESCs.
Full Text Available Translation of literature is generally understood as a copy of an original. As such, it finds itself compared negatively to the original; judged and found lacking either the style or meaning of the original text it was seeking to translate. However, this paper will explore the relationship between the text and its translation through the work of Jacques Derrida and his neologisms such as the supplement and différance in addition to the work of Walter Benjamin. Through understanding the translation as a supplement, this paper will explore whether the original text was complete in and of itself. Through this and Derrida’s understanding of the play of language, I argue that translation can be understood as the palingenesis of literature, as it is only through translation that literature is reborn and lives on. Moreover, this paper will conclude with an examination of Blanchot’s distinction between the Book and the book in order to argue that literature is in itself a form of translation. Thus, the relationship between translation and literature is one of a cycle of genesis and palingenesis, as translation finds itself at both the beginning and continual rebirth of literature. La traduzione letteraria viene generalmente intesa come la copia di un originale. In quanto tale essa viene considerata negativamente in rapporto a quest’ultimo, giudicata manchevole quanto a stile o contenuto rispetto al testo originale che cerca di tradurre. Questo articolo intende esaminare la relazione tra il testo e la sua traduzione attraverso l’opera di Jacques Derrida e i suoi neologismi, come supplemento e différance, e sulla scorta degli studi di Walter Benjamin. Considerando la traduzione come un supplemento, l’articolo indaga se l’originale sia completo in e di per se stesso. Attraverso questo concetto e la prospettiva di Derrida sul gioco del linguaggio, la tesi sostenuta è che la traduzione possa essere considerata come palingenesi della
Chaitanya Pradeep Joshi
Full Text Available Background: A randomized, prospective clinical, radiographical, and histological study was conducted to evaluate healing after alveolar ridge preservation technique using two different graft materials, namely, a novel autogenous graft material i. e., autogenous tooth graft (ATG and beta-tricalcium phosphate (β-TCP alloplast. Materials and Methods: Fifteen patients undergoing extraction of at least three teeth were selected. Atraumatic extractions were performed. Of the three extraction sockets, one was grafted with ATG, other with β-TCP, and the third was left ungrafted. Cone-beam computed tomography scans were taken immediately after grafting and 4 months postoperatively to check the changes in alveolar crest height and width at all the sites. Three patients in whom implant placement was done after complete healing; bone samples were harvested using a 3 mm diameter trephine during osteotomy preparation from both the ridge preserved sites and studied histologically. Results: There was a statistically significant difference when the changes in width and height of alveolar crest were compared within all the three groups (P < 0.05. Among three sites, ATG-grafted sites showed the most superior results with a minimal reduction in alveolar crest height and width. Histological analysis also showed the same trend with more new bone formation at ATG-grafted sites as compared to β-TCP-grafted sites. Conclusion: Postextraction, ridge preservation leads to more predictable maintenance of alveolar ridge height and width. ATG as compared to β-TCP provided superior results. Based on this, we conclude that ATG material can serve as a better alternative to conventional bone graft materials.
Bauer, Miklós; Pytel, József; Vóna, Ida; Gerlinger, Imre
The first author has been using an autogenous cortical bone columella to replace the stapes removed during stapedectomy since 1965. The audiograms of 21 of the 271 patients operated on with this method between 1965 and 1989 (i.e. 7.7% of the possible candidates) were available 20-35 (average 26.8) years postoperatively. The operation could be regarded as successful in 20 and unsuccessful in 1 patient in the long run. The audiological data are presented individually as averages of the values obtained at 0.5, 1, 2 and 3 kHz. The averaged data (n = 21): preoperative air conduction, 58.27; bone conduction, 24.46; and air-bone gap, 33.81 dB. Postoperative best air conduction, 19.07; bone conduction, 14.10; and air-bone gap, 4.97 dB. Postoperative recent air conduction, 45.77; bone conduction, 38.45; and air-bone gap, 7.32 dB. The best values were measured 1-8 (average 1.57) years postoperatively. In relation to the postoperative best value, the recent value of the air-bone gap had deteriorated by 2.35 dB, and that of the bone conduction by 24.35 dB. The small air-bone gap indicates that the deterioration of the hearing is mainly caused by the deterioration of the function of the inner ear and not by that of the conductive apparatus. The progression of the deterioration differs individually (0.3-1.6, average 0.93 dB/year) and accelerates with age. This finding seems to be a problem that does not depend on the operative technique. The data show that the autogenous bone columella ensures the same good and lasting results as the alloplastic solutions; moreover, there is no problem with the incus-prosthesis connection.
Shimizu, Yusuke; Nagasao, Tomohisa; Shido, Hirokazu; Fujii, Takako; Kato, Tatsuya; Aoki, Marie; Takada, Keiko; Kishi, Kazuo
Frontalis suspension using autogenous fascia lata is a common procedure for blepharoptosis with poor levator function. However, donor-site morbidity associated with fascia lata harvest cannot be ignored. In conventional procedures, the required length of the fascia lata is usually >5-12 cm with a lateral thigh skin incision of approximately 5 cm or more. The present study introduces a new frontalis suspension procedure in which the required size (length and width) of the fascia lata and length of lateral thigh incision is much smaller. The harvested fascia lata is tailored to an inverted Y shape and the separated caudal legs are fixed to the tarsus while the cephalic end is grafted inside the eyebrow through a suborbital septum tunnel. In the present study, 11 patients who underwent the new procedure with a minimum of 6 months of follow-up were evaluated. The average length and width of the harvested fascia lata in unilateral ptosis cases were 2.85 and 0.89 cm, respectively. The average length of the lateral thigh incision was 1.25 cm. The margin reflex distance improved in all cases at 6 months postoperatively. The cosmetic result was graded as good to excellent in most of the patients. Trichiasis, widened donor scar, and eyebrow notch were noted as complications. The present method is a good alternative for the treatment of blepharoptosis with poor levator function. It potentially reduces donor-site morbidity as compared with conventional frontalis muscle suspension procedures using autogenous fascia lata.
尤文俊; 萧明第; 袁忠祥
Background This study was designed to investigate changes in mRNA levels of transforming growth factor-β(TGF-β), collagen Ⅰ, and collagen Ⅲ in autogenous vein grafts. Methods Twenty-four New Zealand rabbits were randomly divided into 4 groups with 6 rabbits each. The external jugular veins of the New Zealand rabbits were harvested and grafted into the ipsilateral carotid artery. All rabbits were fed with a standard diet. After the operation, the rabbits were sacrificed at 1, 2, 3, or 4 weeks. TGF-β, collagen Ⅰ, and collagen Ⅲ mRNA levels in the venous grafts were measured by semiquantitative methods at every time point. The contralateral external jugular veins were also harvested and analyzed as controls. Glyceraldehyde-3-phosphate dehydrogenase was used as an internal standard to normalize all samples for potential variations in mRNA content. In order to observe the expression of TGF-β protein, immunohistochemical SABC methods were used. Results One week postoperation, the mRNA level of TGF-β was upregulated to 1.73±0.19 in the vein graft and 1.21±0.16 in the control vein (P＜0.01). High mRNA levels were maintained until week 4 postoperation. The mRNA levels of collagen Ⅰ and collagen Ⅲ were also significantly increased to 2.18±0.21 versus 1.12±0.24 and 1.08±0.13 versus 0.83±0.12, respectively (P＜0.05). Immunohistochemical staining revealed a higher density of TGF-β expression in the vein grafts.Conclusions An uninterrupted increase in mRNA levels of TGF-β, collagen Ⅰ, and collagen Ⅲ is observed in autogenous vein grafts. This increase may be the major cause of intimal hyperplasia, sclerosis, and even graft failure.
This paper is an analysis of advertisement translation under skopos theory.It is explained that the nature of advertisement translation under skopos theory is reconstructing the information of the source text to persuade target audience. Three translation strategies are put forward in translating advertisements.
This paper is an analysis of advertisement translation under skopos theory.It is explained that the nature of advertisement translation under skopos theory is reconstructing the information of the source text to persuade target audience.Three translation strategies are put forward in translating advertisements.
Examines electronic aids to translation both as ways to automate it and as an approach to solve problems resulting from shortage of qualified translators. Describes the limitations of robotic MT (Machine Translation) systems, viewing MAT (Machine-Aided Translation) as the only practical solution and the best vehicle for further automation. (MES)
Corpus-based translation studies belong to a new translation study paradigm which rose at the beginning of 1990s. The rise of corpus brings the update of research tools and research methods, and lead to the emerging of Corpus Translation Stud-ies. It is necessary to introduce the theory basis of Translational English Corpus and its application in the translation, especially in the science and technology translation. Besides, it makes an analysis and discussion about the potential of Corpus Translation Stud-ies.
Yan Fu was famous translator in Chinese history, and proposed three standards of translation. The theory made great contribution to Chinese translation history. However, with the development of society at present, Yah Fu's theory had been out of date. More and more translators and scholars pay more attention on linguistics to translate appropriately nowadays. It is the aim to analysis this problem in the article and introduces more detailed knowledge to make flourish translation, so that it becomes true that Chinese translation develop step by step.
Larsson, Ola; Sonenberg, Nahum; Nadon, Robert
Regulation of gene expression through translational control is a fundamental mechanism implicated in many biological processes ranging from memory formation to innate immunity and whose dysregulation contributes to human diseases. Genome wide analyses of translational control strive to identify differential translation independent of cytosolic mRNA levels. For this reason, most studies measure genes' translation levels as log ratios (translation levels divided by corresponding cytosolic mRNA levels obtained in parallel). Counterintuitively, arising from a mathematical necessity, these log ratios tend to be highly correlated with the cytosolic mRNA levels. Accordingly, they do not effectively correct for cytosolic mRNA level and generate substantial numbers of biological false positives and false negatives. We show that analysis of partial variance, which produces estimates of translational activity that are independent of cytosolic mRNA levels, is a superior alternative. When combined with a variance shrinkage method for estimating error variance, analysis of partial variance has the additional benefit of having greater statistical power and identifying fewer genes as translationally regulated resulting merely from unrealistically low variance estimates rather than from large changes in translational activity. In contrast to log ratios, this formal analytical approach estimates translation effects in a statistically rigorous manner, eliminates the need for inefficient and error-prone heuristics, and produces results that agree with biological function. The method is applicable to datasets obtained from both the commonly used polysome microarray method and the sequencing-based ribosome profiling method.
Chan, Hsien W; Liu, Tianbing; Verdile, Giuseppe; Bishop, Glenda; Haasl, Ryan J; Smith, Mark A; Perry, George; Martins, Ralph N; Atwood, Craig S
The basic mechanism(s) by which altered Cu homeostasis is toxic to hepatocytes and neurons, the two major cell types affected in copper storage diseases such as Wilson's disease (WD), remain unclear. Using human M17 neuroblastoma cells as a model to examine Cu toxicity, we found that there was a time- and concentration-dependent induction of neuronal death, such that at 24 h there was a approximately 50 % reduction in viability with 25 muM Cu-glycine(2). Cu-glycine(2) (25:50 muM) treatment for 24 h significantly altered the expression of 296 genes, including 8 genes involved with apoptosis (BCL2-associated athanogene 3, BCL2/adenovirus E1B 19kDa interacting protein caspase 5, regulator of Fas-induced apoptosis, V-jun sarcoma virus 17 oncogene homolog, claudin 5, prostaglandin E receptor 3 and protein tyrosine phosphatase, non-receptor type 6). Surprisingly, changes in the expression of more 'traditional' apoptotic genes (Bcl-2, Bax, Bak and Bad) did not vary more than 20 %. To test whether the induction of apoptosis in neuroblastoma cells was via post-translational mechanisms, we measured the protein expression of these apoptotic markers in M17 neuroblastoma cells treated with Cu-glycine(2) (0-100 muM) for 24-48 h. Compared with glycine treated cells, Cu-glycine(2) reduced Bcl-2 expression by 50 %, but increased Bax and Bak expression by 130% and 400 %, respectively. To assess whether Cu also induced apoptotic cell death in a mouse model of WD, we measured the expression of these apoptotic markers in the liver and brain of mice expressing an ATP7b gene mutation (tx(J) mice) at 10 months of age (near the end of their lives when overt liver pathology is displayed). Changes in the liver expression of these apoptotic markers in tx(J) mice compared to background mice mirrored those of Cu treated neuroblastoma cells. In contrast, few changes in apoptotic protein expression were detected in the brain between tx(J) and background mice, indicating the tx(J) mouse is a good
Full Text Available Umberto Eco’s novel The Name of the Rose as a postmodern literary work is extensively based on transtextuality. There are series of quotations from the Bible, Petrus Abelardus, St. Bernard, Petrarch, Conan Doyle, Agatha Christie, Jorge L. Borges, Nietzsche, and other classic authors interwoven into the novel’s narrative. The text is a result of multiple translations, a truly intercultural adventure: Adso, a 14th-century German monk from the Melk monastery provides a Northern Italian travel experience in Latin language, this memoir is translated by the publishing narrator into the Italian language of the 20th century. The characters of the story come from different areas of Europe, as there are monks from England, Spain, Norway, Germany, and other countries. This paper sheds light on the problems that occurred during the novel’s translation.