Molecular evidence that rough endoplasmic reticulum is the site of calreticulin translation in Petunia pollen tubes growing in vitro.

PubMed

Suwińska, Anna; Lenartowski, Robert; Smoliński, Dariusz Jan; Lenartowska, Marta

2015-07-01

In germinating pollen grains and growing pollen tubes, CRT is translated on ER membrane-bound ribosomes in the regions where its activity is required for stabilization of tip-focused Ca (2+) gradient. Pollen tube growth requires coordination of signaling, exocytosis, and actin cytoskeletal organization. Many of these processes are thought to be controlled by finely tuned regulation of cytoplasmic Ca(2+) in discrete regions of the tube cytoplasm. Most notably, a mechanism must function to maintain a steep gradient of Ca(2+) that exists at the tip of growing pollen tube. Several pieces of evidence point to calreticulin (CRT) as a key Ca(2+)-binding/-buffering protein involved in pollen germination and pollen tube growth. We previously hypothesized that in germinating pollen and growing tubes, CRT is translated on the ribosomes associated with endoplasmic reticulum (ER) in the regions where its activity might be required. In this report, we have addressed this idea by identifying the sites where CRT mRNA, CRT protein, 18S rRNA, and rough ER are localized in Petunia pollen tubes. We observed all four components in the germinal aperture of pollen grains and in subapical regions of elongating tubes. These results seem to support our idea that CRT is translated on ER membrane-bound ribosomes during pollen germination and pollen tube growth. In elongated pollen tubes, we found CRT mainly localized in the subapical zone, where ER and Golgi stacks are abundant. In eukaryotic cells, these organelles serve as mobile intracellular stores of easily releasable Ca(2+), which can be buffered by proteins such as CRT. Therefore, we postulate that subapical-localized CRT is involved in pollen tube growth by maintaining the stable tip-focused Ca(2+) gradient and thus modulating local Ca(2+) concentration within the tube cytoplasm.

Practical lessons for bringing policy-makers on board in sexual and reproductive health research.

PubMed

Guieu, Aurore; Zhang, Wei-Hong; Lafort, Yves; Decat, Peter; De Meyer, Sara; Wang, Shuchen; Kerstens, Birgit; Duysburgh, Els

2016-11-11

The need to translate research into policy, i.e. making research findings a driving force in agenda-setting and policy change, is increasingly acknowledged. However, little is known about translation mechanisms in the field of sexual and reproductive health (SRH) outside North American or European contexts. This paper seeks to give an overview of the existing knowledge on this topic as well as to document practical challenges and remedies from the perspectives of researchers involved in four SRH research consortium projects in Latin America, sub-Saharan Africa, China and India. A literature review and relevant project documents were used to develop an interview guide through which researchers could reflect on their experiences in engaging with policy-makers, and particularly on the obstacles met and the strategies deployed by the four project consortia to circumvent them. Our findings confirm current recommendations on an early and steady involvement of policy-makers, however they also suggest that local barriers between researchers and policy-making spheres and individuals can represent major hindrances to the realization of translation objectives. Although many of the challenges might be common to different contexts, creating locally-adapted responses is deemed key to overcome them. Researchers' experiences also indicate that - although inevitable - recognizing and addressing these challenges is a difficult, time- and energy-consuming process for all partners involved. Despite a lack of existing knowledge on translation efforts in SRH research outside North American or European contexts, and more particularly in low and middle-income countries, it is clear that existing pressure on health and policy systems in these settings further complicates them. This article brings together literature findings and researchers' own experiences in translating research results into policy and highlights the major challenges research conducted on sexual and reproductive health outside North American or European contexts can meet. Future SRH projects should be particularly attentive to these potential obstacles in order to tailor appropriate and consistent strategies within their existing resources.

The translational regulator Cup controls NMJ presynaptic terminal morphology.

PubMed

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

2015-07-01

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

The translational regulator Cup controls NMJ presynaptic terminal morphology

PubMed Central

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

2015-01-01

During oogenesis and early embryonic development in Drosophila, translation of proteins from maternally deposited mRNAs is tightly controlled. We and others have previously shown that translational regulatory proteins that function during oogenesis also have essential roles in the nervous system. Here we examine the role of Cup in neuromuscular system development. Maternal Cup controls translation of localized mRNAs encoding the Oskar and Nanos proteins and binds to the general translation initiation factor eIF4E. In this paper, we show that zygotic Cup protein is localized to presynaptic terminals at larval neuromuscular junctions (NMJs). cup mutant NMJs have strong phenotypes characterized by the presence of small clustered boutons called satellite boutons. They also exhibit an increase in the frequency of spontaneous glutamate release events (mEPSPs). Reduction of eIF4E expression synergizes with partial loss of Cup expression to produce satellite bouton phenotypes. The presence of satellite boutons is often associated with increases in retrograde bone morphogenetic protein (BMP) signaling, and we show that synaptic BMP signaling is elevated in cup mutants. cup genetically interacts with four genes (EndoA, WASp, Dap160, and Synj) encoding proteins involved in endocytosis that are also neuronal modulators of the BMP pathway. Endophilin protein, encoded by the EndoA gene, is downregulated in a cup mutant. Our results are consistent with a model in which Cup and eIF4E work together to ensure efficient localization and translation of endocytosis proteins in motor neurons and control the strength of the retrograde BMP signal. PMID:26102195

Global and Local Translation Designs of Quantum Image Based on FRQI

NASA Astrophysics Data System (ADS)

Zhou, Ri-Gui; Tan, Canyun; Ian, Hou

2017-04-01

In this paper, two kinds of quantum image translation are designed based on FRQI, including global translation and local translation. Firstly, global translation is realized by employing adder modulo N, where all pixels in the image will be moved, and the circuit of right translation is designed. Meanwhile, left translation can also be implemented by using right translation. Complexity analysis shows that the circuits of global translation in this paper have lower complexity and cost less qubits. Secondly, local translation, consisted of single-column translation, multiple-columns translation and translation in the restricted area, is designed by adopting Gray code. In local translation, any parts of pixels in the image can be translated while other pixels remain unchanged. In order to lower complexity when the number of columns needing to be translated are more than one, multiple-columns translation is proposed, which has the approximate complexity with single-column translation. To perform multiple-columns translation, three conditions must be satisfied. In addition, all translations in this paper are cyclic.

A comparison of human and machine translation of health promotion materials for public health practice: time, costs, and quality.

PubMed

Turner, Anne M; Bergman, Margo; Brownstein, Megumu; Cole, Kate; Kirchhoff, Katrin

2014-01-01

Most local public health departments serve limited English proficiency groups but lack sufficient resources to translate the health promotion materials that they produce into different languages. Machine translation (MT) with human postediting could fill this gap and work toward decreasing health disparities among non-English speakers. (1) To identify the time and costs associated with human translation (HT) of public health documents, (2) determine the time necessary for human postediting of MT, and (3) compare the quality of postedited MT and HT. A quality comparison of 25 MT and HT documents was performed with public health translators. The public health professionals involved were queried about the workflow, costs, and time for HT of 11 English public health documents over a 20-month period. Three recently translated documents of similar size and topic were then machine translated, the time for human postediting was recorded, and a blind quality analysis was performed. Seattle/King County, Washington. Public health professionals. (1) Estimated times for various HT tasks; (2) observed postediting times for MT documents; (3) actual costs for HT; and (4) comparison of quality ratings for HT and MT. Human translation via local health department methods took 17 hours to 6 days. While HT postediting words per minute ranged from 1.58 to 5.88, MT plus human postediting words per minute ranged from 10 to 30. The cost of HT ranged from $130 to $1220; MT required no additional costs. A quality comparison by bilingual public health professionals showed that MT and HT were equivalently preferred. MT with human postediting can reduce the time and costs of translating public health materials while maintaining quality similar to HT. In conjunction with postediting, MT could greatly improve the availability of multilingual public health materials.

“Because we all trust and care about each other”: Exploring Tensions Translating a Theater-based HIV Prevention Intervention into a New Context

PubMed Central

Mouw, Mary Sherwyn; Taboada, Arianna; Steinert, Scarlett; Willis, Stephanie; Lightfoot, Alexandra F.

2016-01-01

Background A theater-based HIV prevention intervention developed in urban California was piloted with a new partnership in North Carolina. Objectives To describe the experience of translating a complex program with an enhanced partnership approach; barriers and facilitators of implementation in the new setting; and challenges and benefits of interdisciplinary, collaborative interventions. Methods We gathered perspectives of local stakeholders involved in program implementation through process evaluation interviews and focus groups with undergraduates, a college instructor, school district administrators, and high school teachers. Results Implementing the intervention in a new setting proved feasible and successful; however, mistaken assumptions and unrecognized similarities about teaching priorities, philosophies, and values produced latent tensions amongst stakeholder groups, and were a limiting factor in partnership functioning. Conclusions Implementing a cross-disciplinary intervention in a new setting is best achieved through a local community-engaged process, with active involvement of relevant stakeholders. We suggest strategies to strengthen community partnerships cooperating in implementation of complex, context-tailored interventions. PMID:27346770

Translational research needs us to go back to basics and collaborate: interview with Lars Sundstrom.

PubMed

Sundstrom, Lars

2016-09-01

Lars Sundstrom is Director of Enterprise and Translation at the West of England Academic Health Sciences Network [1] (UK), a Professor of Practice in Translational Medicine and Co-Director of the Elizabeth Blackwell Institute for Health Research at Bristol University [2] (UK), and an honorary Professor of Medicine at Cardiff University (UK). He has extensive experience in translational medicine and clinical neurosciences, holding positions at several eminent universities. He has also held executive and board-level positions at several SMEs, developing new therapeutics for neurological conditions and tools for drug discovery. He has also been an advisor to several UK and local government task forces and to the European Commission and the European Federation of Pharmaceutical Industry Associations. He was a founding member of the European Brain Council in Brussels, and set up the Severnside Alliance for Translational Research, developing a regional network partnership to link clinical and basic scientists. He was also involved in the creation of Health Research Wales.

The Benefits of Community and Juvenile Justice Involvement in Organizational Research

PubMed Central

Leukefeld, Carl G.; Cawood, Margaret; Wiley, Tisha; Robertson, Angela A.; Fisher, Jacqueline Horan; Arrigona, Nancy; Donohue, Patricia; Staples-Horne, Michelle; Harris, Philip W.; Dembo, Richard; Roysden, Judy; Marks, Katherine R.

2017-01-01

The Juvenile Justice (JJ) system has a number of local behavioral health service community linkages for substance abuse, mental health, and HIV services. However, there have only been a few systemic studies that examine and seek to improve these community behavioral health linkages for justice-involved youth. Implementation research is a way of identifying, testing, and understanding effective strategies for translating evidence-based treatment and prevention approaches into service delivery. This article explores benefits and challenges of participatory research within the context of the National Institute on Drug Abuse (NIDA)’s Juvenile Justice Translational Research on Interventions for Adolescents in the Legal System (JJ-TRIALS) implementation behavioral health study. The JJ-TRIALS study has involved JJ partners (representatives from state-level JJ agencies) throughout the study development, design, and implementation. Proponents of participatory research argue that such participation strengthens relations between the community and academia; ensures the relevancy of research questions; increases the capacity of data collection; and enhances program recruitment, sustainability, and extension. The extent of the impact that JJ partners have had on the JJ-TRIALS study will be discussed, as well as the benefits local JJ agencies can derive from both short- and long-term participation. Issues associated with the site selection, participation, and implementation of evidence-based practices also will be discussed. PMID:28828202

The Benefits of Community and Juvenile Justice Involvement in Organizational Research.

PubMed

Leukefeld, Carl G; Cawood, Margaret; Wiley, Tisha; Robertson, Angela A; Fisher, Jacqueline Horan; Arrigona, Nancy; Donohue, Patricia; Staples-Horne, Michelle; Harris, Philip W; Dembo, Richard; Roysden, Judy; Marks, Katherine R

2017-01-01

The Juvenile Justice (JJ) system has a number of local behavioral health service community linkages for substance abuse, mental health, and HIV services. However, there have only been a few systemic studies that examine and seek to improve these community behavioral health linkages for justice-involved youth. Implementation research is a way of identifying, testing, and understanding effective strategies for translating evidence-based treatment and prevention approaches into service delivery. This article explores benefits and challenges of participatory research within the context of the National Institute on Drug Abuse (NIDA)'s Juvenile Justice Translational Research on Interventions for Adolescents in the Legal System (JJ-TRIALS) implementation behavioral health study. The JJ-TRIALS study has involved JJ partners (representatives from state-level JJ agencies) throughout the study development, design, and implementation. Proponents of participatory research argue that such participation strengthens relations between the community and academia; ensures the relevancy of research questions; increases the capacity of data collection; and enhances program recruitment, sustainability, and extension. The extent of the impact that JJ partners have had on the JJ-TRIALS study will be discussed, as well as the benefits local JJ agencies can derive from both short- and long-term participation. Issues associated with the site selection, participation, and implementation of evidence-based practices also will be discussed.

Remote Control of Gene Function by Local Translation

PubMed Central

Jung, Hosung; Gkogkas, Christos G.; Sonenberg, Nahum; Holt, Christine E.

2014-01-01

The subcellular position of a protein is a key determinant of its function. Mounting evidence indicates that RNA localization, where specific mRNAs are transported subcellularly and subsequently translated in response to localized signals, is an evolutionarily conserved mechanism to control protein localization. On-site synthesis confers novel signaling properties to a protein and helps to maintain local proteome homeostasis. Local translation plays particularly important roles in distal neuronal compartments, and dysregulated RNA localization and translation cause defects in neuronal wiring and survival. Here, we discuss key findings in this area and possible implications of this adaptable and swift mechanism for spatial control of gene function. PMID:24679524

Dendritic Glutamate Receptor mRNAs Show Contingent Local Hotspot-Dependent Translational Dynamics

PubMed Central

Kim, Tae Kyung; Sul, Jai-Yoon; Helmfors, Henrik; Langel, Ulo; Kim, Junhyong; Eberwine, James

2014-01-01

SUMMARY Protein synthesis in neuronal dendrites underlies long-term memory formation in the brain. Local translation of reporter mRNAs has demonstrated translation in dendrites at focal points called translational hotspots. Various reports have shown that hundreds to thousands of mRNAs are localized to dendrites, yet the dynamics of translation of multiple dendritic mRNAs has remained elusive. Here, we show that the protein translational activities of two dendritically localized mRNAs are spatiotemporally complex but constrained by the translational hotspots in which they are colocalized. Cotransfection of glutamate receptor 2 (GluR2) and GluR4 mRNAs (engineered to encode different fluorescent proteins) into rat hippocampal neurons demonstrates a heterogeneous distribution of translational hotspots for the two mRNAs along dendrites. Stimulation with s-3,5-dihydroxy-phenylglycine modifies the translational dynamics of both of these RNAs in a complex saturable manner. These results suggest that the translational hotspot is a primary structural regulator of the simultaneous yet differential translation of multiple mRNAs in the neuronal dendrite. PMID:24075992

Recurrence case of rare scalp dermatofibrosarcoma protuberans: Two case reports of a wide radical excision, craniectomy bone involvement followed by cranioplasty and reconstruction

PubMed Central

Faried, Ahmad; Hadisaputra, Wargian; Arifin, Muhammad Z.

2017-01-01

Background: Dermatofibrosarcoma protuberans (DFSP) is a rare low-grade sarcoma of the fibroblast originating from the dermal layer of the skin, characterized by a locally aggressive growth and high rate of local recurrence. Case Description: Two patients underwent a wide radical excision of recurrent scalp DFSP which was reconstructed with translational skin flap and split-thickness skin graft. We described above cases several years ago with a local excision of the tumor; recently, they developed local recurrence of DFSP with calvarial involvement. We then performed a wide radical excision, with craniectomy of the cranial defect followed by cranioplasty using titanium mesh, continuing with reconstruction. Conclusion: A successful treatment and management depends on achieving local control and preventing cosmetic and functional deficit; all efforts should be made for complete excision. Postoperative follow-up recommended for highly suspicious cases and annual checkups should be performed up to 5 years after definitive therapy. PMID:28607816

RNA Transport and Local Control of Translation

PubMed Central

Kindler, Stefan; Wang, Huidong; Richter, Dietmar; Tiedge, Henri

2007-01-01

In eukaryotes, the entwined pathways of RNA transport and local translational regulation are key determinants in the spatio-temporal articulation of gene expression. One of the main advantages of this mechanism over transcriptional control in the nucleus lies in the fact that it endows local sites with independent decision-making authority, a consideration that is of particular relevance in cells with complex cellular architecture such as neurons. Localized RNAs typically contain codes, expressed within cis-acting elements, that specify subcellular targeting. Such codes are recognized by trans-acting factors, adaptors that mediate translocation along cytoskeletal elements by molecular motors. Most transported mRNAs are assumed translationally dormant while en route. In some cell types, especially in neurons, it is considered crucial that translation remains repressed after arrival at the destination site (e.g., a postsynaptic microdomain) until an appropriate activation signal is received. Several candidate mechanisms have been suggested to participate in the local implementation of translational repression and activation, and such mechanisms may target translation at the level of initiation and/or elongation. Recent data indicate that untranslated RNAs may play important roles in the local control of translation. PMID:16212494

DOE Office of Scientific and Technical Information (OSTI.GOV)

Quaresma, Alexandre J.C.; Bressan, G.C.; Institute of Biology, University of Campinas - UNICAMP, 13083-970, Campinas, SP

Eukaryotic gene expression is regulated on different levels ranging from pre-mRNA processing to translation. One of the most characterized families of RNA-binding proteins is the group of hnRNPs: heterogenous nuclear ribonucleoproteins. Members of this protein family play important roles in gene expression control and mRNAs metabolism. In the cytoplasm, several hnRNPs proteins are involved in RNA-related processes and they can be frequently found in two specialized structures, known as GW-bodies (GWbs), previously known as processing bodies: PBs, and stress granules, which may be formed in response to specific stimuli. GWbs have been early reported to be involved in the mRNAmore » decay process, acting as a site of mRNA degradation. In a similar way, stress granules (SGs) have been described as cytoplasmic aggregates, which contain accumulated mRNAs in cells under stress conditions and present reduced or inhibited translation. Here, we characterized the hnRNP Q localization after different stress conditions. hnRNP Q is a predominantly nuclear protein that exhibits a modular organization and several RNA-related functions. Our data suggest that the nuclear localization of hnRNP Q might be modified after different treatments, such as: PMA, thapsigargin, arsenite and heat shock. Under different stress conditions, hnRNP Q can fully co-localize with the endoplasmatic reticulum specific chaperone, BiP. However, under stress, this protein only co-localizes partially with the proteins: GW182 - GWbs marker protein and TIA-1 stress granule component.« less

A Comparison of Human and Machine Translation of Health Promotion Materials for Public Health Practice: Time, Costs, and Quality

PubMed Central

Turner, Anne M.; Bergman, Margo; Brownstein, Megumu; Cole, Kate; Kirchhoff, Katrin

2017-01-01

Context Most local public health departments serve limited English proficiency groups but lack sufficient resources to translate the health promotion materials that they produce into different languages. Machine translation (MT) with human postediting could fill this gap and work toward decreasing health disparities among non–English speakers. Objectives (1) To identify the time and costs associated with human translation (HT) of public health documents, (2) determine the time necessary for human postediting of MT, and (3) compare the quality of postedited MT and HT. Design A quality comparison of 25 MT and HT documents was performed with public health translators. The public health professionals involved were queried about the workflow, costs, and time for HT of 11 English public health documents over a 20-month period. Three recently translated documents of similar size and topic were then machine translated, the time for human postediting was recorded, and a blind quality analysis was performed. Setting Seattle/King County, Washington. Participants Public health professionals. Main Outcome Measures (1) Estimated times for various HT tasks; (2) observed postediting times for MT documents; (3) actual costs for HT; and (4) comparison of quality ratings for HT and MT. Results Human translation via local health department methods took 17 hours to 6 days. While HT postediting words per minute ranged from 1.58 to 5.88, MT plus human postediting words per minute ranged from 10 to 30. The cost of HT ranged from $130 to $1220; MT required no additional costs. A quality comparison by bilingual public health professionals showed that MT and HT were equivalently preferred. Conclusions MT with human postediting can reduce the time and costs of translating public health materials while maintaining quality similar to HT. In conjunction with postediting, MT could greatly improve the availability of multilingual public health materials. PMID:24084391

Cotranslational Coat Protein-Mediated Inhibition of Potyviral RNA Translation

PubMed Central

Besong-Ndika, Jane; Ivanov, Konstantin I.; Hafrèn, Anders; Michon, Thierry

2015-01-01

ABSTRACT Potato virus A (PVA) is a single-stranded positive-sense RNA virus and a member of the family Potyviridae. The PVA coat protein (CP) has an intrinsic capacity to self-assemble into filamentous virus-like particles, but the mechanism responsible for the initiation of viral RNA encapsidation in vivo remains unclear. Apart from virion assembly, PVA CP is also involved in the inhibition of viral RNA translation. In this study, we show that CP inhibits PVA RNA translation in a dose-dependent manner, through a mechanism involving the CP-encoding region. Analysis of this region, however, failed to identify any RNA secondary structure(s) preferentially recognized by CP, suggesting that the inhibition depends on CP-CP rather than CP-RNA interactions. In agreement with this possibility, insertion of an in-frame stop codon upstream of the CP sequence led to a marked decrease in the inhibition of viral RNA translation. Based on these results, we propose a model in which the cotranslational interactions between excess CP accumulating in trans and CP translated from viral RNA in cis are required to initiate the translational repression. This model suggests a mechanism for how viral RNA can be sequestered from translation and specifically selected for encapsidation at the late stages of viral infection. IMPORTANCE The main functions of the CP during potyvirus infection are to protect viral RNA from degradation and to transport it locally, systemically, and from host to host. Although virion assembly is a key step in the potyviral infectious cycle, little is known about how it is initiated and how viral RNA is selected for encapsidation. The results presented here suggest that CP-CP rather than CP-RNA interactions are predominantly involved in the sequestration of viral RNA away from translation. We propose that the cotranslational nature of these interactions may represent a mechanism for the selection of viral RNA for encapsidation. A better understanding of the mechanism of virion assembly may lead to development of crops resistant to potyviruses at the level of viral RNA encapsidation, thereby reducing the detrimental effects of potyvirus infections on food production. PMID:25631087

Proteomic Analysis of Flax Seeds from the Chernobyl Area Suggests Involvement of Stress, Signaling, and Transcription/Translation in Response to Ionizing Radiation

USDA-ARS?s Scientific Manuscript database

The accident at the Chernobyl Nuclear Power Plant (CNPP) on April 26, 1986 is the most serious nuclear disaster in human history. However, while the area proximal to the CNPP remains substantially contaminated with long-lived radioisotopes including 90Sr and 137Cs, the local ecosystem has been able...

ABA, porphyrins and plant TSPO-related protein.

PubMed

Guillaumot, Damien; Guillon, Stéphanie; Morsomme, Pierre; Batoko, Henri

2009-11-01

We have shown that, unexpectedly, AtTSPO (Arabidopsis thaliana TSPO-related protein) is an endoplasmic reticulum and Golgi-localized membrane protein in plant cells.(1) This localization contrasts with that of mammalian 18-kDa translocator protein (at least for the mostly studied isoform, 18-kDa TSPO), a mitochondrial outer membrane protein (reviewed in ref. 2). Whereas the potential functions of 18-kDa TSPO are well documented, involved mainly in mitochondrial physiology,(2) and its interest as drugs target is been explored,(3) the roles of TSPO-related proteins in plant growth and development are yet to be specified. AtTSPO is expressed in dry seeds and can be induced in vegetative tissues by osmotic and salt stress or abscisic acid (ABA) treatment. Moreover, it was shown that the ABA-dependent induction is transient, and that boosting tetrapyrroles biosynthesis through 5-aminolevulinic acid (ALA) feeding enhanced downregulation of AtTSPO, suggesting an inherent post-translational regulation mechanism also involving ABA and likely porphyrins. We present additional evidence that ABA can help stabilize constitutively expressed AtTSPO and that ALA feeding to knockout mutant seeds, induces substantial germination delay. Here we discuss the possible link between ABA and tetrapyrroles in AtTSPO expression and post-translational regulation.

How the Sequence of a Gene Specifies Structural Symmetry in Proteins

PubMed Central

Shen, Xiaojuan; Huang, Tongcheng; Wang, Guanyu; Li, Guanglin

2015-01-01

Internal symmetry is commonly observed in the majority of fundamental protein folds. Meanwhile, sufficient evidence suggests that nascent polypeptide chains of proteins have the potential to start the co-translational folding process and this process allows mRNA to contain additional information on protein structure. In this paper, we study the relationship between gene sequences and protein structures from the viewpoint of symmetry to explore how gene sequences code for structural symmetry in proteins. We found that, for a set of two-fold symmetric proteins from left-handed beta-helix fold, intragenic symmetry always exists in their corresponding gene sequences. Meanwhile, codon usage bias and local mRNA structure might be involved in modulating translation speed for the formation of structural symmetry: a major decrease of local codon usage bias in the middle of the codon sequence can be identified as a common feature; and major or consecutive decreases in local mRNA folding energy near the boundaries of the symmetric substructures can also be observed. The results suggest that gene duplication and fusion may be an evolutionarily conserved process for this protein fold. In addition, the usage of rare codons and the formation of higher order of secondary structure near the boundaries of symmetric substructures might have coevolved as conserved mechanisms to slow down translation elongation and to facilitate effective folding of symmetric substructures. These findings provide valuable insights into our understanding of the mechanisms of translation and its evolution, as well as the design of proteins via symmetric modules. PMID:26641668

BDNF regulates the translation of a select group of mRNAs by a mammalian target of rapamycin-phosphatidylinositol 3-kinase-dependent pathway during neuronal development.

PubMed

Schratt, Gerhard M; Nigh, Elizabeth A; Chen, Wen G; Hu, Linda; Greenberg, Michael E

2004-08-18

Local regulation of mRNA translation plays an important role in axon guidance, synaptic development, and neuronal plasticity. Little is known, however, regarding the mechanisms that control translation in neurons, and only a few mRNAs have been identified that are locally translated within axon and dendrites. Using Affymetrix gene arrays to identify mRNAs that are newly associated with polysomes after exposure to BDNF, we identified subsets of mRNAs for which translation is enhanced in neurons at different developmental stages. In mature neurons, many of these mRNAs encode proteins that are known to function at synapses, including CamKIIalpha, NMDA receptor subunits, and the postsynaptic density (PSD) scaffolding protein Homer2. BDNF regulates the translation of Homer2 locally in the synaptodendritic compartment by activating translational initiation via a mammalian target of rapamycin-phosphatidylinositol 3-kinase-dependent pathway. These findings suggest that BDNF likely regulates synaptic function by inducing the local synthesis of numerous synaptic proteins. The local translation of the cytoskeleton-associated protein Homer2 in particular might have important implications for growth cone dynamics and dendritic spine development.

Upstream open reading frames regulate the expression of the nuclear Wnt13 isoforms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang Tao; Rector, Kyle; Barnett, Corey D.

2008-02-22

Wnt proteins control cell survival and cell fate during development. Although Wnt expression is tightly regulated in a spatio-temporal manner, the mechanisms involved both at the transcriptional and translational levels are poorly defined. We have identified a downstream translation initiation codon, AUG(+74), in Wnt13B and Wnt13C mRNAs responsible for the expression of Wnt13 nuclear forms. In this report, we demonstrate that the expression of the nuclear Wnt13C form is translationally regulated in response to stress and apoptosis. Though the 5'-leaders of both Wnt13C and Wnt13B mRNAs have an inhibitory effect on translation, they did not display an internal ribosome entrymore » site activity as demonstrated by dicistronic reporter assays. However, mutations or deletions of the upstream AUG(-99) and AUG(+1) initiation codons abrogate these translation inhibitory effects, demonstrating that Wnt13C expression is controlled by upstream open reading frames. Since long 5'-untranslated region with short upstream open reading frames characterize other Wnt transcripts, our present data on the translational control of Wnt13 expression open the way to further studies on the translation control of Wnt expression as a modulator of their subcellular localization and activity.« less

Integrin binding and mechanical tension induce movement of mRNA and ribosomes to focal adhesions

NASA Technical Reports Server (NTRS)

Chicurel, M. E.; Singer, R. H.; Meyer, C. J.; Ingber, D. E.

1998-01-01

The extracellular matrix (ECM) activates signalling pathways that control cell behaviour by binding to cell-surface integrin receptors and inducing the formation of focal adhesion complexes (FACs). In addition to clustered integrins, FACs contain proteins that mechanically couple the integrins to the cytoskeleton and to immobilized signal-transducing molecules. Cell adhesion to the ECM also induces a rapid increase in the translation of preexisting messenger RNAs. Gene expression can be controlled locally by targeting mRNAs to specialized cytoskeletal domains. Here we investigate whether cell binding to the ECM promotes formation of a cytoskeletal microcompartment specialized for translational control at the site of integrin binding. High-resolution in situ hybridization revealed that mRNA and ribosomes rapidly and specifically localized to FACs that form when cells bind to ECM-coated microbeads. Relocation of these protein synthesis components to the FAC depended on the ability of integrins to mechanically couple the ECM to the contractile cytoskeleton and on associated tension-moulding of the actin lattice. Our results suggest a new type of gene regulation by integrins and by mechanical stress which may involve translation of mRNAs into proteins near the sites of signal reception.

Local Health Department Capacity for Community Engagement and Its Implications for Disaster Resilience

PubMed Central

Sell, Tara Kirk; Morhard, Ryan

2013-01-01

Over the past decade, community engagement has become a central tenet of US federal doctrine on public health emergency preparedness. Little is known, however, about how the vision of a ready, aware, and involved populace has translated into local practice, or which conditions thus far have advanced community involvement in what is typically considered the province of government authorities and emergency professionals. In 2011-12, to help close that knowledge gap, investigators carried out semistructured qualitative interviews with practitioners (N=25) from 7 local health departments about which conditions have advanced or inhibited community engagement in public health emergency preparedness. Among the organizational factors identified as enabling local health departments' involvement of community residents and groups in emergency preparedness were a supportive agency leadership and culture, sufficient staffing and programmatic funding, interested and willing partners, and external triggers such as federal grants and disaster experiences that spotlighted the importance of community relationships to effective response. Facing budget and staff cuts, local health departments feel increasingly constrained in efforts to build trusted and lasting preparedness ties with community partners. At the same time, some progress in preparedness partnerships may be possible in the context of agency leadership, culture, and climate that affirms the value of collaboration with the community. PMID:23718765

Translating an early childhood obesity prevention program for local community implementation: a case study of the Melbourne InFANT Program.

PubMed

Laws, R; Hesketh, K D; Ball, K; Cooper, C; Vrljic, K; Campbell, K J

2016-08-08

While there is a growing interest in the field of research translation, there are few published examples of public health interventions that have been effectively scaled up and implemented in the community. This paper provides a case study of the community-wide implementation of the Melbourne Infant, Feeding, Activity and Nutrition Trial (InFANT), an obesity prevention program for parents with infants aged 3-18 months. The study explored key factors influencing the translation of the Program into routine practice and the respective role of policy makers, researchers and implementers. Case studies were conducted of five of the eight prevention areas in Victoria, Australia who implemented the Program. Cases were selected on the basis of having implemented the Program for 6 months or more. Data were collected from January to June 2015 and included 18 individual interviews, one focus group and observation of two meetings. A total of 28 individuals, including research staff (n = 4), policy makers (n = 2) and implementers (n = 22), contributed to the data collected. Thematic analysis was conducted using cross case comparisons and key themes were verified through member checking. Key facilitators of implementation included availability of a pre-packaged evidence based program addressing a community need, along with support and training provided by research staff to local implementers. Partnerships between researchers and policy makers facilitated initial program adoption, while local partnerships supported community implementation. Community partnerships were facilitated by local coordinators through alignment of program goals with existing policies and services. Workforce capacity for program delivery and administration was a challenge, largely overcome by embedding the Program into existing roles. Adapting the Program to fit local circumstance was critical for feasible and sustainable delivery, however balancing this with program fidelity was a critical issue. The lack of ongoing funding to support translation activities was a barrier for researchers continued involvement in community implementation. Policy makers, researchers and practitioners have important and complementary roles to play in supporting the translation of effective research interventions into practice. New avenues need to be explored to strengthen partnerships between researchers and end users to support the integration of effective public health research interventions into practice.

The Uganda version of the Pediatric Evaluation of Disability Inventory (PEDI). Part I: Cross-cultural adaptation.

PubMed

Kakooza-Mwesige, A; Tumwine, J K; Forssberg, H; Eliasson, A-C

2018-03-12

The Pediatric Evaluation of Disability Inventory (PEDI) was developed and standardized to measure functional performance in American children. So far, no published study has examined the use of the PEDI in sub-Saharan Africa. This study describes the adaptation, translation, and validation process undertaken to develop a culturally relevant PEDI for Uganda (PEDI-UG). The cross-cultural adaptation and translation of the PEDI was performed in a series of steps. A project manager and a technical advisory group were involved in all steps of adaptation, translation, cognitive debriefing, and revision. Translation and back-translation between English and Luganda were performed by professional translators. Cognitive debriefing of two subsequent adapted revisions was performed by a field-testing team on a total of 75 caregivers of children aged 6 months to 7.5 years. The PEDI-UG was established in both English (the official language) and Luganda (a local language) and comprises 185 items. Revisions entailed deleting irrelevant items, modifying wording, inserting new items, and incorporating local examples while retaining the meaning of the original PEDI. Item statements were rephrased as questions. Seven new items were inserted and 19 items deleted. To accommodate major differences in living conditions between rural and urban areas, 10 alternative items were provided. The PEDI-UG is to be used to measure functional limitations in both clinical practice and research, in order to assess and evaluate rehabilitative procedures in children with developmental delay and disability in Uganda. In this study, we take the first step by translating and adapting the original PEDI version to the culture and life conditions in both rural and urban Uganda. In subsequent studies, the tool's psychometric properties will be examined, and the tool will be tested in children with developmental delay and disability. © 2018 The Authors. Child: Care, Health and Development Published by John Wiley & Sons Ltd.

Familiar Taste Induces Higher Dendritic Levels of Activity-Regulated Cytoskeleton-Associated Protein in the Insular Cortex than a Novel One

ERIC Educational Resources Information Center

Morin, Jean-Pascal; Quiroz, Cesar; Mendoza-Viveros, Lucia; Ramirez-Amaya, Victor; Bermudez-Rattoni, Federico

2011-01-01

The immediate early gene (IEG) "Arc" is known to play an important role in synaptic plasticity; its protein is locally translated in the dendrites where it has been involved in several types of plasticity mechanisms. Because of its tight coupling with neuronal activity, "Arc" has been widely used as a tool to tag behaviorally activated networks.…

Towards an Informed Mexican and Mexican-American Citizenry: Bridging the Gap to Increase Human Capacity and Information Dissemination

NASA Astrophysics Data System (ADS)

Ramirez, M. D.; Ramirez, D. M.

2008-12-01

The research translation and community outreach goal of The University of Arizona's (UA) Superfund Basic Research Program and U.S.-Mexico Binational Center for Environmental Sciences and Toxicology is to increase human capacity and information dissemination to diverse stakeholders, including federal, state, and local government agencies as well as northern Mexican and border community stakeholders. Due to Arizona's demographic characteristics and the UA's proximity to the U.S. - Mexico border, activities target primarily Mexican and Mexican-American populations. With this in mind, a model has been established that pulls from human capital, community-based participatory research and public participation theories. The theories applied to our target population have resulted in the creation of a successful model that is used in both research translation and community outreach work. The model contains four components: community needs (participation), science translation (information), engagement (outreach), and training (education). Examples of how this model operates for various stakeholders involved in environmental science and health issues will be discussed. A case in point of how this model has been applied effectively is the partnership with promotoras (community health advocates) to do environmental science and health trainings to increase the knowledge base of specific populations disproportionately exposed to contaminants of concern. Additional case studies and methodologies used to develop innovative communicative tools (that takes into consideration cultural idiosyncrasies) for stakeholders at all levels in Arizona, the border, and Mexico will be highlighted, such as: 1) information sheets regarding local environmental issues for communities neighboring contaminated sites, 2) SciTransfer Bulletins targeting professional level stakeholders such as Project Managers, Community Involvement Coordinators and the general public, 3) coordinating technical and scientific workshops in the U.S and Mexico and 4) participating in local community events. Lessons learned and knowledge gained in the past three years will also be presented.

Joining the dots - protein-RNA interactions mediating local mRNA translation in neurons.

PubMed

Gallagher, Christopher; Ramos, Andres

2018-06-01

Establishing and maintaining the complex network of connections required for neuronal communication requires the transport and in situ translation of large groups of mRNAs to create local proteomes. In this Review, we discuss the regulation of local mRNA translation in neurons and the RNA-binding proteins that recognise RNA zipcode elements and connect the mRNAs to the cellular transport networks, as well as regulate their translation control. However, mRNA recognition by the regulatory proteins is mediated by the combinatorial action of multiple RNA-binding domains. This increases the specificity and affinity of the interaction, while allowing the protein to recognise a diverse set of targets and mediate a range of mechanisms for translational regulation. The structural and molecular understanding of the interactions can be used together with novel microscopy and transcriptome-wide data to build a mechanistic framework for the regulation of local mRNA translation. © 2018 Federation of European Biochemical Societies.

Vision, Identity, and Career in the Clinical and Translational Sciences: Building upon the Formative Years.

PubMed

Manson, Spero M; Martinez, Dominic F; Buchwald, Dedra S; Rubio, Doris M; Moss, Marc

2015-10-01

This paper is the second in a five-part series on the clinical and translational science educational pipeline. It focuses on the role that Clinical and Translational Science Award (CTSA) programs can play in supporting science, technology, engineering, and math (STEM) education in primary and secondary schools, as well as in facilitating these interests during transition to undergraduate training. Special emphasis should be placed on helping to form and sustain an identity as a scientist, and on instilling the persistence necessary to overcome numerous barriers to its actualization. CTSAs can contribute to cementing this sense of self by facilitating peer support, mentorship, and family involvement that will reinforce early educational decisions leading to clinical and translational science research careers. Meanwhile, the interests, skills, and motivation induced by participation in STEM programs must be sustained in transition to the next level in the educational pipeline, typically undergraduate study. Examples of CTSA collaborations with local schools, businesses, interest groups, and communities at large illustrate the emerging possibilities and promising directions with respect to each of these challenges. © 2015 Wiley Periodicals, Inc.

Vision, Identity, and Career in the Clinical and Translational Sciences: Building upon the Formative Years

PubMed Central

Martinez, Dominic F.; Buchwald, Dedra S.; Rubio, Doris M.; Moss, Marc

2015-01-01

Abstract This paper is the second in a five‐part series on the clinical and translational science educational pipeline. It focuses on the role that Clinical and Translational Science Award (CTSA) programs can play in supporting science, technology, engineering, and math (STEM) education in primary and secondary schools, as well as in facilitating these interests during transition to undergraduate training. Special emphasis should be placed on helping to form and sustain an identity as a scientist, and on instilling the persistence necessary to overcome numerous barriers to its actualization. CTSAs can contribute to cementing this sense of self by facilitating peer support, mentorship, and family involvement that will reinforce early educational decisions leading to clinical and translational science research careers. Meanwhile, the interests, skills, and motivation induced by participation in STEM programs must be sustained in transition to the next level in the educational pipeline, typically undergraduate study. Examples of CTSA collaborations with local schools, businesses, interest groups, and communities at large illustrate the emerging possibilities and promising directions with respect to each of these challenges. PMID:26271774

Fertility and polarized cell growth depends on eIF5A for translation of polyproline-rich formins in Saccharomyces cerevisiae.

PubMed

Li, Tianlu; Belda-Palazón, Borja; Ferrando, Alejandro; Alepuz, Paula

2014-08-01

eIF5A is an essential and evolutionary conserved translation elongation factor, which has recently been proposed to be required for the translation of proteins with consecutive prolines. The binding of eIF5A to ribosomes occurs upon its activation by hypusination, a modification that requires spermidine, an essential factor for mammalian fertility that also promotes yeast mating. We show that in response to pheromone, hypusinated eIF5A is required for shmoo formation, localization of polarisome components, induction of cell fusion proteins, and actin assembly in yeast. We also show that eIF5A is required for the translation of Bni1, a proline-rich formin involved in polarized growth during shmoo formation. Our data indicate that translation of the polyproline motifs in Bni1 is eIF5A dependent and this translation dependency is lost upon deletion of the polyprolines. Moreover, an exogenous increase in Bni1 protein levels partially restores the defect in shmoo formation seen in eIF5A mutants. Overall, our results identify eIF5A as a novel and essential regulator of yeast mating through formin translation. Since eIF5A and polyproline formins are conserved across species, our results also suggest that eIF5A-dependent translation of formins could regulate polarized growth in such processes as fertility and cancer in higher eukaryotes. Copyright © 2014 by the Genetics Society of America.

Linguistic and Cultural Challenges in Communication and Translation in US-Sponsored HIV Prevention Research in Emerging Economies

PubMed Central

2015-01-01

Linguistic and cultural differences can impede comprehension among potential research participants during the informed consent process, but how researchers and IRBs respond to these challenges in practice is unclear. We conducted in-depth interviews with 15 researchers, research ethics committee (REC) chairs and members from 8 different countries with emerging economies, involved in HIV-related research sponsored by HIV Prevention Trials Network (HPTN), regarding the ethical and regulatory challenges they face in this regard. In the interviews, problems with translating study materials often arose as major concerns. Four sets of challenges were identified concerning linguistic and cultural translations of informed consent documents and other study materials, related to the: (1) context, (2) process, (3) content and (4) translation of these documents. Host country contextual issues included low literacy rates, education (e.g., documents may need to be written below 5th grade reading level), and experiences with research, and different views of written documentation. Certain terms and concepts may not exist in other languages, or have additional connotations that back translations do not always reveal. Challenges arise because of not only the content of word-for-word, literal translation, but the linguistic form of the language, such as tone (e.g., appropriate forms of politeness vs. legalese, seen as harsh), syntax, manner of questions posed, and the concept of the consent); and the contexts of use affect meaning. Problems also emerged in bilateral communications – US IRBs may misunderstand local practices, or communicate insufficiently the reasons for their decisions to foreign RECs. In sum, these data highlight several challenges that have received little, if any, attention in past literature on translation of informed consent and study materials, and have crucial implications for improving practice, education, research and policy, suggesting several strategies, including needs for broader open-source multilingual lexicons, and more awareness of the complexities involved. PMID:26225759

Linguistic and Cultural Challenges in Communication and Translation in US-Sponsored HIV Prevention Research in Emerging Economies.

PubMed

Hanrahan, Donna; Sexton, Patrina; Hui, Katrina; Teitcher, Jennifer; Sugarman, Jeremy; London, Alex John; Barnes, Mark; Purpura, James; Klitzman, Robert

2015-01-01

Linguistic and cultural differences can impede comprehension among potential research participants during the informed consent process, but how researchers and IRBs respond to these challenges in practice is unclear. We conducted in-depth interviews with 15 researchers, research ethics committee (REC) chairs and members from 8 different countries with emerging economies, involved in HIV-related research sponsored by HIV Prevention Trials Network (HPTN), regarding the ethical and regulatory challenges they face in this regard. In the interviews, problems with translating study materials often arose as major concerns. Four sets of challenges were identified concerning linguistic and cultural translations of informed consent documents and other study materials, related to the: (1) context, (2) process, (3) content and (4) translation of these documents. Host country contextual issues included low literacy rates, education (e.g., documents may need to be written below 5th grade reading level), and experiences with research, and different views of written documentation. Certain terms and concepts may not exist in other languages, or have additional connotations that back translations do not always reveal. Challenges arise because of not only the content of word-for-word, literal translation, but the linguistic form of the language, such as tone (e.g., appropriate forms of politeness vs. legalese, seen as harsh), syntax, manner of questions posed, and the concept of the consent); and the contexts of use affect meaning. Problems also emerged in bilateral communications--US IRBs may misunderstand local practices, or communicate insufficiently the reasons for their decisions to foreign RECs. In sum, these data highlight several challenges that have received little, if any, attention in past literature on translation of informed consent and study materials, and have crucial implications for improving practice, education, research and policy, suggesting several strategies, including needs for broader open-source multilingual lexicons, and more awareness of the complexities involved.

Close to the bench as well as at the bedside: involving service users in all phases of translational research

PubMed Central

Callard, Felicity; Rose, Diana; Wykes, Til

2011-01-01

Abstract Aim  The paper aims to develop a model of translational research in which service user and other stakeholder involvement are central to each phase. Background  ‘Translational’ is the current medical buzzword: translational research has been termed ‘bench to bedside’ research and promises to fast‐track biomedical advances in the service of patient benefit. Models usually conceive of translational research as a ‘pipeline’ that is divided into phases: the early phase is characterized as the province of basic scientists and laboratory‐based clinical researchers; the later phases focus on the implementation, dissemination and diffusion of health applications. If service user involvement is mentioned, it is usually restricted to these later phases. Methods  The paper critically reviews existing literature on translational research and medicine. The authors develop a theoretical argument that addresses why a reconceptualization of translational research is required on scientific, ethical and pragmatic grounds. Results  The authors reconceptualize the model of translational research as an interlocking loop rather than as a pipeline, one in which service user and other stakeholder involvement feed into each of its elements. The authors demonstrate that for the ‘interlocking loop’ model of translational research to be materialized in practice will require changes in how health research is structured and organized. Conclusion  The authors demonstrate the scientific, ethical and pragmatic benefits of involving service users in every phase of translational research. The authors’ reconceptualized model of translational research contributes to theoretical and policy debates regarding both translational research and service user involvement. PMID:21615638

The role of patient narratives in healthcare innovation: supporting translation and meaning making.

PubMed

Pedersen, Anne Reff

2016-01-01

The purpose of this paper is to investigate the process and impact of patient involvement in locally defined improvement projects in two hospital clinics. The paper particularly aims to examine how patient narratives, in the form of diaries and radio montage, help to create new insights into patient experience for healthcare professionals, and support professionals' enrolment and mobilisation in innovation projects. Two case studies were undertaken. These drew upon qualitative interviews with staff and participant observation during innovation workshops. Patient diaries and a recorded montage of patient voices were also collected. The findings illuminate translation processes in healthcare innovation and the emergence of meaning making process for staff through the active use of patient narratives. The paper highlights the critical role of meaning making as an enabler of patient-centred change processes in healthcare via: local clinic mangers defining problems and ideas; collecting and sharing patient narratives in innovation workshops; and healthcare professionals' interpretation of patient narratives supporting new insights into patient experience. This study demonstrates how healthcare professionals' meaning making can be supported by articulating, constructing, listening and interpreting patient narratives. The two cases demonstrate how patient narratives serve as reflective devices for healthcare professionals. This study presents a novel demonstration of the importance of patient narratives for translating healthcare innovation in a clinical practice setting.

Processing of the 5'-UTR and existence of protein factors that regulate translation of tobacco chloroplast psbN mRNA.

PubMed

Kuroda, Hiroshi; Sugiura, Masahiro

2014-12-01

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.

Processing Translational Motion Sequences.

DTIC Science & Technology

1982-10-01

the initial ROADSIGN image using a (del)**2g mask with a width of 5 pixels The distinctiveness values were computed using features which were 5x5 pixel...the initial step size of the local search quite large. 34 4. EX P R g NTg The following experiments were performed using the roadsign and industrial...the initial image of the sequence. The third experiment involves processing the roadsign image sequence using the features extracted at the positions

Interactome of two diverse RNA granules links mRNA localization to translational repression in neurons.

PubMed

Fritzsche, Renate; Karra, Daniela; Bennett, Keiryn L; Ang, Foong Yee; Heraud-Farlow, Jacki E; Tolino, Marco; Doyle, Michael; Bauer, Karl E; Thomas, Sabine; Planyavsky, Melanie; Arn, Eric; Bakosova, Anetta; Jungwirth, Kerstin; Hörmann, Alexandra; Palfi, Zsofia; Sandholzer, Julia; Schwarz, Martina; Macchi, Paolo; Colinge, Jacques; Superti-Furga, Giulio; Kiebler, Michael A

2013-12-26

Transport of RNAs to dendrites occurs in neuronal RNA granules, which allows local synthesis of specific proteins at active synapses on demand, thereby contributing to learning and memory. To gain insight into the machinery controlling dendritic mRNA localization and translation, we established a stringent protocol to biochemically purify RNA granules from rat brain. Here, we identified a specific set of interactors for two RNA-binding proteins that are known components of neuronal RNA granules, Barentsz and Staufen2. First, neuronal RNA granules are much more heterogeneous than previously anticipated, sharing only a third of the identified proteins. Second, dendritically localized mRNAs, e.g., Arc and CaMKIIα, associate selectively with distinct RNA granules. Third, our work identifies a series of factors with known roles in RNA localization, translational control, and RNA quality control that are likely to keep localized transcripts in a translationally repressed state, often in distinct types of RNPs. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Position of the Translator as an Agent in Website Localization: The Case of Turkey

ERIC Educational Resources Information Center

Alkan, Sinem Canim

2017-01-01

The rapid growth of e-commerce has contributed to the development of website localization activity as a major professional industry. Despite the high volume of website localization practices, there is little research on translators participating in website localization projects. The purpose of this qualitative study was to explore the position of…

22 CFR 92.78 - Translating documents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Service are not authorized to translate documents or to certify to the correctness of translations... of a translation; to take an acknowledgment of the preparation of a translation; and to authenticate the seal and signature of a local official affixed to a translation. Separate fees should be charged...

CGG Repeats in the 5’UTR of FMR1 RNA Regulate Translation of Other RNAs Localized in the Same RNA Granules

PubMed Central

Rovozzo, René; Korza, George; Baker, Mei W.; Li, Meng; Bhattacharyya, Anita; Barbarese, Elisa; Carson, John H.

2016-01-01

CGG repeats in the 5’UTR of Fragile X Mental Retardation 1 (FMR1) RNA mediate RNA localization and translation in granules. Large expansions of CGG repeats (> 200 repeats) in FMR1, referred to as full mutations, are associated with fragile X syndrome (FXS). Smaller expansions (55–200 repeats), referred to as premutations, are associated with fragile X tremor ataxia syndrome (FXTAS) and fragile X premature ovarian insufficiency (FXPOI). TMPyP4 is a porphyrin ring compound that destabilizes CGG repeat RNA secondary structure. Here we show that exogenous CGG repeat RNA by itself, lacking the FMRP ORF, microinjected into hippocampal neurons is localized in RNA granules and inhibits translation of ARC RNA, which is localized in the same granules. TMPyP4 rescues translation of ARC RNA in granules. We also show that in human premutation fibroblasts with endogenous CGG repeat expansions in the FMR1 gene, translation of ARC RNA is inhibited and calcium homeostasis is disrupted and both phenotypes are rescued by TMPyP4. Inhibition of granule translation by expanded CGG repeats and rescue of granule translation by TMPy4, represent potential pathogenic mechanism and therapeutic strategy, respectively, for FXTAS and FXPOI. PMID:28005950

Reading for Repetition and Reading for Translation: Do They Involve the Same Processes?

ERIC Educational Resources Information Center

Macizo, Pedro; Bajo, M. Teresa

2006-01-01

Theories of translation differ in the role assigned to the reformulation process. One view, the ''horizontal'' approach, considers that translation involves on-line searches for matches between linguistic entries in the two languages involved [Gerver, D. (1976). Empirical studies of simultaneous interpretation: A review and a model. In R. W.…

Translating Oral Health-Related Quality of Life Measures: Are There Alternative Methodologies?

ERIC Educational Resources Information Center

Brondani, Mario; He, Sarah

2013-01-01

Translating existing sociodental indicators to another language involves a rigorous methodology, which can be costly. Free-of-charge online translator tools are available, but have not been evaluated in the context of research involving quality of life measures. To explore the value of using online translator tools to develop oral health-related…

Selectivity to Translational Egomotion in Human Brain Motion Areas

PubMed Central

Pitzalis, Sabrina; Sdoia, Stefano; Bultrini, Alessandro; Committeri, Giorgia; Di Russo, Francesco; Fattori, Patrizia; Galletti, Claudio; Galati, Gaspare

2013-01-01

The optic flow generated when a person moves through the environment can be locally decomposed into several basic components, including radial, circular, translational and spiral motion. Since their analysis plays an important part in the visual perception and control of locomotion and posture it is likely that some brain regions in the primate dorsal visual pathway are specialized to distinguish among them. The aim of this study is to explore the sensitivity to different types of egomotion-compatible visual stimulations in the human motion-sensitive regions of the brain. Event-related fMRI experiments, 3D motion and wide-field stimulation, functional localizers and brain mapping methods were used to study the sensitivity of six distinct motion areas (V6, MT, MST+, V3A, CSv and an Intra-Parietal Sulcus motion [IPSmot] region) to different types of optic flow stimuli. Results show that only areas V6, MST+ and IPSmot are specialized in distinguishing among the various types of flow patterns, with a high response for the translational flow which was maximum in V6 and IPSmot and less marked in MST+. Given that during egomotion the translational optic flow conveys differential information about the near and far external objects, areas V6 and IPSmot likely process visual egomotion signals to extract information about the relative distance of objects with respect to the observer. Since area V6 is also involved in distinguishing object-motion from self-motion, it could provide information about location in space of moving and static objects during self-motion, particularly in a dynamically unstable environment. PMID:23577096

Universality classes of order parameters composed of many-body bound states

DOE PAGES

Tsvelik, A. M.

2016-11-28

This theoretical paper discusses microscopic models giving rise to special types of order in which conduction electrons are bound together with localized spins to create composite order parameters. It is shown that composite order is related to the formation of a spin liquid with gapped excitations carrying quantum numbers which are a fraction of those of electron. These spin liquids are special in the sense that their formation necessarily involves spin degrees of freedom of both the conduction and the localized electrons and can be characterized by nonlocal order parameters. A detailed description of such spin liquid states is presentedmore » with a special care given to a demonstration of their robustness against local perturbations preserving the Lie group symmetry and the translational invariance.« less

Broadening measures of success: results of a behavioral health translational research training program.

PubMed

Baldwin, Julie A; Williamson, Heather J; Eaves, Emery R; Levin, Bruce L; Burton, Donna L; Massey, Oliver T

2017-07-24

While some research training programs have considered the importance of mentoring in inspiring professionals to engage in translational research, most evaluations emphasize outcomes specific to academic productivity as primary measures of training program success. The impact of such training or mentoring programs on stakeholders and local community organizations engaged in translational research efforts has received little attention. The purpose of this evaluation is to explore outcomes other than traditional academic productivity in a translational research graduate certificate program designed to pair graduate students and behavioral health professionals in collaborative service-learning projects. Semi-structured qualitative interviews with scholars, community mentors, and academic mentors were conducted regarding a translational research program to identify programmatic impacts. Interviews were transcribed and coded by the research team to identify salient themes related to programmatic outcomes. Results are framed using the Translational Research Impact Scale which is organized into three overarching domains of potential impact: (1) research-related impacts, (2) translational impacts, and (3) societal impacts. This evaluation demonstrates the program's impact in all three domains of the TRIS evaluation framework. Graduate certificate participants (scholars) reported that gaining experience in applied behavioral health settings added useful skills and expertise to their present careers and increased their interest in pursuing translational research. Scholars also described benefits resulting from networks gained through participation in the program, including valuable ties between the university and community behavioral health organizations. This evaluation of the outcomes of a graduate certificate program providing training in translational research highlights the need for more community-oriented and practice-based measures of success. Encouraging practitioner involvement in translational research is vital to translate knowledge into practice and to enable practice-based needs to inform research and policy. A more flexible approach to measuring programmatic success in research training programs can help bridge the knowledge translation gap.

Arginyltransferase ATE1 is targeted to the neuronal growth cones and regulates neurite outgrowth during brain development.

PubMed

Wang, Junling; Pavlyk, Iuliia; Vedula, Pavan; Sterling, Stephanie; Leu, N Adrian; Dong, Dawei W; Kashina, Anna

2017-10-01

Arginylation is an emerging protein modification mediated by arginyltransferase ATE1, shown to regulate embryogenesis and actin cytoskeleton, however its functions in different physiological systems are not well understood. Here we analyzed the role of ATE1 in brain development and neuronal growth by producing a conditional mouse knockout with Ate1 deletion in the nervous system driven by Nestin promoter (Nes-Ate1 mice). These mice were weaker than wild type, resulting in low postnatal survival rates, and had abnormalities in the brain that suggested defects in neuronal migration. Cultured Ate1 knockout neurons showed a reduction in the neurite outgrowth and the levels of doublecortin and F-actin in the growth cones. In wild type, ATE1 prominently localized to the growth cones, in addition to the cell bodies. Examination of the Ate1 mRNA sequence reveals the existence of putative zipcode-binding sequences involved in mRNA targeting to the cell periphery and local translation at the growth cones. Fluorescence in situ hybridization showed that Ate1 mRNA localized to the tips of the growth cones, likely due to zipcode-mediated targeting, and this localization coincided with spots of localization of arginylated β-actin, which disappeared in the presence of protein synthesis inhibitors. We propose that zipcode-mediated co-targeting of Ate1 and β-actin mRNA leads to localized co-translational arginylation of β-actin that drives the growth cone migration and neurite outgrowth. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Multiple cis-acting signals, some weak by necessity, collectively direct robust transport of oskar mRNA to the oocyte.

PubMed

Ryu, Young Hee; Kenny, Andrew; Gim, Youme; Snee, Mark; Macdonald, Paul M

2017-09-15

Localization of mRNAs can involve multiple steps, each with its own cis -acting localization signals and transport factors. How is the transition between different steps orchestrated? We show that the initial step in localization of Drosophila oskar mRNA - transport from nurse cells to the oocyte - relies on multiple cis -acting signals. Some of these are binding sites for the translational control factor Bruno, suggesting that Bruno plays an additional role in mRNA transport. Although transport of oskar mRNA is essential and robust, the localization activity of individual transport signals is weak. Notably, increasing the strength of individual transport signals, or adding a strong transport signal, disrupts the later stages of oskar mRNA localization. We propose that the oskar transport signals are weak by necessity; their weakness facilitates transfer of the oskar mRNA from the oocyte transport machinery to the machinery for posterior localization. © 2017. Published by The Company of Biologists Ltd.

Local health department translation processes: potential of machine translation technologies to help meet needs.

PubMed

Turner, Anne M; Mandel, Hannah; Capurro, Daniel

2013-01-01

Limited English proficiency (LEP), defined as a limited ability to read, speak, write, or understand English, is associated with health disparities. Despite federal and state requirements to translate health information, the vast majority of health materials are solely available in English. This project investigates barriers to translation of health information and explores new technologies to improve access to multilingual public health materials. We surveyed all 77 local health departments (LHDs) in the Northwest about translation needs, practices, barriers and attitudes towards machine translation (MT). We received 67 responses from 45 LHDs. Translation of health materials is the principle strategy used by LHDs to reach LEP populations. Cost and access to qualified translators are principle barriers to producing multilingual materials. Thirteen LHDs have used online MT tools. Many respondents expressed concerns about the accuracy of MT. Overall, respondents were positive about its potential use, if low costs and quality could be assured.

Local Health Department Translation Processes: Potential of Machine Translation Technologies to Help Meet Needs

PubMed Central

Turner, Anne M.; Mandel, Hannah; Capurro, Daniel

2013-01-01

Limited English proficiency (LEP), defined as a limited ability to read, speak, write, or understand English, is associated with health disparities. Despite federal and state requirements to translate health information, the vast majority of health materials are solely available in English. This project investigates barriers to translation of health information and explores new technologies to improve access to multilingual public health materials. We surveyed all 77 local health departments (LHDs) in the Northwest about translation needs, practices, barriers and attitudes towards machine translation (MT). We received 67 responses from 45 LHDs. Translation of health materials is the principle strategy used by LHDs to reach LEP populations. Cost and access to qualified translators are principle barriers to producing multilingual materials. Thirteen LHDs have used online MT tools. Many respondents expressed concerns about the accuracy of MT. Overall, respondents were positive about its potential use, if low costs and quality could be assured. PMID:24551414

Protein functional features are reflected in the patterns of mRNA translation speed.

PubMed

López, Daniel; Pazos, Florencio

2015-07-09

The degeneracy of the genetic code makes it possible for the same amino acid string to be coded by different messenger RNA (mRNA) sequences. These "synonymous mRNAs" may differ largely in a number of aspects related to their overall translational efficiency, such as secondary structure content and availability of the encoded transfer RNAs (tRNAs). Consequently, they may render different yields of the translated polypeptides. These mRNA features related to translation efficiency are also playing a role locally, resulting in a non-uniform translation speed along the mRNA, which has been previously related to some protein structural features and also used to explain some dramatic effects of "silent" single-nucleotide-polymorphisms (SNPs). In this work we perform the first large scale analysis of the relationship between three experimental proxies of mRNA local translation efficiency and the local features of the corresponding encoded proteins. We found that a number of protein functional and structural features are reflected in the patterns of ribosome occupancy, secondary structure and tRNA availability along the mRNA. One or more of these proxies of translation speed have distinctive patterns around the mRNA regions coding for certain protein local features. In some cases the three patterns follow a similar trend. We also show specific examples where these patterns of translation speed point to the protein's important structural and functional features. This support the idea that the genome not only codes the protein functional features as sequences of amino acids, but also as subtle patterns of mRNA properties which, probably through local effects on the translation speed, have some consequence on the final polypeptide. These results open the possibility of predicting a protein's functional regions based on a single genomic sequence, and have implications for heterologous protein expression and fine-tuning protein function.

Adenylyl cyclase A mRNA localized at the back of cells is actively translated in live chemotaxing Dictyostelium.

PubMed

Wang, Weiye; Chen, Song; Das, Satarupa; Losert, Wolfgang; Parent, Carole A

2018-05-04

Dictyostelium discoideum cells transport adenylyl cyclase A (ACA)-containing vesicles to the back of polarized cells to relay exogenous cAMP signals during chemotaxis. Fluorescence in situ hybridization (FISH) experiments showed that ACA mRNA is also asymmetrically distributed at the back of polarized cells. By using the MS2 bacteriophage system, we now visualize the distribution of ACA mRNA in live chemotaxing cells. We found that the ACA mRNA localization is not dependent on the translation of the protein product and requires multiple cis-acting elements within the ACA-coding sequence. We show that ACA mRNA is associated with actively translating ribosomes and is transported along microtubules towards the back of cells. By monitoring the recovery of ACA-YFP after photobleaching, we observed that local translation of ACA-YFP occurs at the back of cells. These data represent a novel functional role for localized translation in the relay of chemotactic signals during chemotaxis. © 2018. Published by The Company of Biologists Ltd.

Nonadiabatic Berry phase in nanocrystalline magnets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skomski, R.; Sellmyer, D. J.

2016-12-20

In this study, it is investigated how a Berry phase is created in polycrystalline nanomagnets and how the phase translates into an emergent magnetic field and into a topological Hall-effect contribution. The analysis starts directly from the spin of the conduction electrons and does not involve any adiabatic Hamiltonian. Completely random spin alignment in the nanocrystallites does not lead to a nonzero emergent field, but a modulation of the local magnetization does. As an explicit example, we consider a wire with a modulated cone angle.

A Non-Canonical Initiation Site Is Required for Efficient Translation of the Dendritically Localized Shank1 mRNA

PubMed Central

Studtmann, Katrin; Ölschläger-Schütt, Janin; Buck, Friedrich; Richter, Dietmar; Sala, Carlo; Bockmann, Jürgen; Kindler, Stefan; Kreienkamp, Hans-Jürgen

2014-01-01

Local protein synthesis in dendrites enables neurons to selectively change the protein complement of individual postsynaptic sites. Though it is generally assumed that this mechanism requires tight translational control of dendritically transported mRNAs, it is unclear how translation of dendritic mRNAs is regulated. We have analyzed here translational control elements of the dendritically localized mRNA coding for the postsynaptic scaffold protein Shank1. In its 5′ region, the human Shank1 mRNA exhibits two alternative translation initiation sites (AUG+1 and AUG+214), three canonical upstream open reading frames (uORFs1-3) and a high GC content. In reporter assays, fragments of the 5′UTR with high GC content inhibit translation, suggesting a contribution of secondary structures. uORF3 is most relevant to translation control as it overlaps with the first in frame start codon (AUG+1), directing translation initiation to the second in frame start codon (AUG+214). Surprisingly, our analysis points to an additional uORF initiated at a non-canonical ACG start codon. Mutation of this start site leads to an almost complete loss of translation initiation at AUG+1, demonstrating that this unconventional uORF is required for Shank1 synthesis. Our data identify a novel mechanism whereby initiation at a non-canonical site allows for translation of the main Shank1 ORF despite a highly structured 5′UTR. PMID:24533096

Minority Voices in Literary Fiction: A Case Study of Translating Multilingual Practices

ERIC Educational Resources Information Center

Nurmi, Arja

2016-01-01

Translating multilingual texts is still a new field of inquiry. Transplanting a text where the function of embraced multilingual practices is strongly related to local ethnic identities can provide challenges for translators and readers alike. This study discusses the translation strategies adopted by second-year translation students on an…

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

ERIC Educational Resources Information Center

Abdulwahid, Muntaha A.; Hamzah, Zaitul Azma Binti Zainon; Hajimaming, Pabiyah; Alkhawaja, Hussein W.

2017-01-01

Legal translation of contract agreements is a challenge to translators as it involves combining the literary translation with the technical terminological precision. In translating legal contract agreements, a legal translator must utilize the lexical or syntactic precision and, more importantly, the pragmatic awareness of the context. This will…

Single-Molecule Imaging of PSD-95 mRNA Translation in Dendrites and Its Dysregulation in a Mouse Model of Fragile X Syndrome

PubMed Central

Ifrim, Marius F.; Williams, Kathryn R.

2015-01-01

Fragile X syndrome (FXS) is caused by the loss of the fragile X mental retardation protein (FMRP), an RNA binding protein that regulates translation of numerous target mRNAs, some of which are dendritically localized. Our previous biochemical studies using synaptoneurosomes demonstrate a role for FMRP and miR-125a in regulating the translation of PSD-95 mRNA. However, the local translation of PSD-95 mRNA within dendrites and spines, as well as the roles of FMRP or miR-125a, have not been directly studied. Herein, local synthesis of a Venus-PSD-95 fusion protein was directly visualized in dendrites and spines using single-molecule imaging of a diffusion-restricted Venus-PSD-95 reporter under control of the PSD-95 3′UTR. The basal translation rates of Venus-PSD-95 mRNA was increased in cultured hippocampal neurons from Fmr1 KO mice compared with WT neurons, which correlated with a transient elevation of endogenous PSD-95 within dendrites. Following mGluR stimulation with (S)-3,5-dihydroxyphenylglycine, the rate of Venus-PSD-95 mRNA translation increased rapidly in dendrites of WT hippocampal neurons, but not in those of Fmr1 KO neurons or when the binding site of miR125a, previously shown to bind PSD-95 3′UTR, was mutated. This study provides direct support for the hypothesis that local translation within dendrites and spines is dysregulated in FXS. Impairments in the regulated local synthesis of PSD-95, a critical regulator of synaptic structure and function, may affect the spatiotemporal control of PSD-95 levels and affect dendritic spine development and synaptic plasticity in FXS. PMID:25948262

Single-Molecule Imaging of PSD-95 mRNA Translation in Dendrites and Its Dysregulation in a Mouse Model of Fragile X Syndrome.

PubMed

Ifrim, Marius F; Williams, Kathryn R; Bassell, Gary J

2015-05-06

Fragile X syndrome (FXS) is caused by the loss of the fragile X mental retardation protein (FMRP), an RNA binding protein that regulates translation of numerous target mRNAs, some of which are dendritically localized. Our previous biochemical studies using synaptoneurosomes demonstrate a role for FMRP and miR-125a in regulating the translation of PSD-95 mRNA. However, the local translation of PSD-95 mRNA within dendrites and spines, as well as the roles of FMRP or miR-125a, have not been directly studied. Herein, local synthesis of a Venus-PSD-95 fusion protein was directly visualized in dendrites and spines using single-molecule imaging of a diffusion-restricted Venus-PSD-95 reporter under control of the PSD-95 3'UTR. The basal translation rates of Venus-PSD-95 mRNA was increased in cultured hippocampal neurons from Fmr1 KO mice compared with WT neurons, which correlated with a transient elevation of endogenous PSD-95 within dendrites. Following mGluR stimulation with (S)-3,5-dihydroxyphenylglycine, the rate of Venus-PSD-95 mRNA translation increased rapidly in dendrites of WT hippocampal neurons, but not in those of Fmr1 KO neurons or when the binding site of miR125a, previously shown to bind PSD-95 3'UTR, was mutated. This study provides direct support for the hypothesis that local translation within dendrites and spines is dysregulated in FXS. Impairments in the regulated local synthesis of PSD-95, a critical regulator of synaptic structure and function, may affect the spatiotemporal control of PSD-95 levels and affect dendritic spine development and synaptic plasticity in FXS. Copyright © 2015 the authors 0270-6474/15/357116-15$15.00/0.

Lin-28 binds IGF-2 mRNA and participates in skeletal myogenesis by increasing translation efficiency.

PubMed

Polesskaya, Anna; Cuvellier, Sylvain; Naguibneva, Irina; Duquet, Arnaud; Moss, Eric G; Harel-Bellan, Annick

2007-05-01

Lin-28 is a highly conserved, RNA-binding, microRNA-regulated protein that is involved in regulation of developmental timing in Caenorhabditis elegans. In mammals, Lin-28 is stage-specifically expressed in embryonic muscle, neurons, and epithelia, as well as in embryonic carcinoma cells, but is suppressed in most adult tissues, with the notable exception of skeletal and cardiac muscle. The specific function and mechanism of action of Lin-28 are not well understood. Here we used loss-of-function and gain-of-function assays in cultured myoblasts to show that expression of Lin-28 is essential for skeletal muscle differentiation in mice. In order to elucidate the specific function of Lin-28, we used a combination of biochemical and functional assays, which revealed that, in differentiating myoblasts, Lin-28 binds to the polysomes and increases the efficiency of protein synthesis. An important target of Lin-28 is IGF-2, a crucial growth and differentiation factor for muscle tissue. Interaction of Lin-28 with translation initiation complexes in skeletal myoblasts and in the embryonic carcinoma cell line P19 was confirmed by localization of Lin-28 to the stress granules, temporary structures that contain stalled mRNA-protein translation complexes. Our results unravel novel mechanisms of translational regulation in skeletal muscle and suggest that Lin-28 performs the role of "translational enhancer" in embryonic and adult cells and tissues.

Processing of the major autolysin of E. faecalis, AtlA, by the zinc-metalloprotease, GelE, impacts AtlA septal localization and cell separation.

PubMed

Stinemetz, Emily K; Gao, Peng; Pinkston, Kenneth L; Montealegre, Maria Camila; Murray, Barbara E; Harvey, Barrett R

2017-01-01

AtlA is the major peptidoglycan hydrolase of Enterococcus faecalis involved in cell division and cellular autolysis. The secreted zinc metalloprotease, gelatinase (GelE), has been identified as an important regulator of cellular function through post-translational modification of protein substrates. AtlA is a known target of GelE, and their interplay has been proposed to regulate AtlA function. To study the protease-mediated post-translational modification of AtlA, monoclonal antibodies were developed as research tools. Flow cytometry and Western blot analysis suggests that in the presence of GelE, surface-bound AtlA exists primarily as a N-terminally truncated form whereas in the absence of GelE, the N-terminal domain of AtlA is retained. We identified the primary GelE cleavage site occurring near the transition between the T/E rich Domain I and catalytic region, Domain II via N-terminal sequencing. Truncation of AtlA had no effect on the peptidoglycan hydrolysis activity of AtlA. However, we observed that N-terminal cleavage was required for efficient AtlA-mediated cell division while unprocessed AtlA was unable to resolve dividing cells into individual units. Furthermore, we observed that the processed AtlA has the propensity to localize to the cell septum on wild-type cells whereas unprocessed AtlA in the ΔgelE strain were dispersed over the cell surface. Combined, these results suggest that AtlA septum localization and subsequent cell separation can be modulated by a single GelE-mediated N-terminal cleavage event, providing new insights into the post-translation modification of AtlA and the mechanisms governing chaining and cell separation.

Processing of the major autolysin of E. faecalis, AtlA, by the zinc-metalloprotease, GelE, impacts AtlA septal localization and cell separation

PubMed Central

Pinkston, Kenneth L.; Montealegre, Maria Camila; Murray, Barbara E.

2017-01-01

AtlA is the major peptidoglycan hydrolase of Enterococcus faecalis involved in cell division and cellular autolysis. The secreted zinc metalloprotease, gelatinase (GelE), has been identified as an important regulator of cellular function through post-translational modification of protein substrates. AtlA is a known target of GelE, and their interplay has been proposed to regulate AtlA function. To study the protease-mediated post-translational modification of AtlA, monoclonal antibodies were developed as research tools. Flow cytometry and Western blot analysis suggests that in the presence of GelE, surface-bound AtlA exists primarily as a N-terminally truncated form whereas in the absence of GelE, the N-terminal domain of AtlA is retained. We identified the primary GelE cleavage site occurring near the transition between the T/E rich Domain I and catalytic region, Domain II via N-terminal sequencing. Truncation of AtlA had no effect on the peptidoglycan hydrolysis activity of AtlA. However, we observed that N-terminal cleavage was required for efficient AtlA-mediated cell division while unprocessed AtlA was unable to resolve dividing cells into individual units. Furthermore, we observed that the processed AtlA has the propensity to localize to the cell septum on wild-type cells whereas unprocessed AtlA in the ΔgelE strain were dispersed over the cell surface. Combined, these results suggest that AtlA septum localization and subsequent cell separation can be modulated by a single GelE-mediated N-terminal cleavage event, providing new insights into the post-translation modification of AtlA and the mechanisms governing chaining and cell separation. PMID:29049345

Fragile X Mental Retardation Protein and Dendritic Local Translation of the Alpha Subunit of the Calcium/Calmodulin-Dependent Kinase II Messenger RNA Are Required for the Structural Plasticity Underlying Olfactory Learning.

PubMed

Daroles, Laura; Gribaudo, Simona; Doulazmi, Mohamed; Scotto-Lomassese, Sophie; Dubacq, Caroline; Mandairon, Nathalie; Greer, Charles August; Didier, Anne; Trembleau, Alain; Caillé, Isabelle

2016-07-15

In the adult brain, structural plasticity allowing gain or loss of synapses remodels circuits to support learning. In fragile X syndrome, the absence of fragile X mental retardation protein (FMRP) leads to defects in plasticity and learning deficits. FMRP is a master regulator of local translation but its implication in learning-induced structural plasticity is unknown. Using an olfactory learning task requiring adult-born olfactory bulb neurons and cell-specific ablation of FMRP, we investigated whether learning shapes adult-born neuron morphology during their synaptic integration and its dependence on FMRP. We used alpha subunit of the calcium/calmodulin-dependent kinase II (αCaMKII) mutant mice with altered dendritic localization of αCaMKII messenger RNA, as well as a reporter of αCaMKII local translation to investigate the role of this FMRP messenger RNA target in learning-dependent structural plasticity. Learning induces profound changes in dendritic architecture and spine morphology of adult-born neurons that are prevented by ablation of FMRP in adult-born neurons and rescued by an metabotropic glutamate receptor 5 antagonist. Moreover, dendritically translated αCaMKII is necessary for learning and associated structural modifications and learning triggers an FMRP-dependent increase of αCaMKII dendritic translation in adult-born neurons. Our results strongly suggest that FMRP mediates structural plasticity of olfactory bulb adult-born neurons to support olfactory learning through αCaMKII local translation. This reveals a new role for FMRP-regulated dendritic local translation in learning-induced structural plasticity. This might be of clinical relevance for the understanding of critical periods disruption in autism spectrum disorder patients, among which fragile X syndrome is the primary monogenic cause. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

A knowledge translation project on community-centred approaches in public health.

PubMed

Stansfield, J; South, J

2018-03-01

This article examines the development and impact of a national knowledge translation project aimed at improving access to evidence and learning on community-centred approaches for health and wellbeing. Structural changes in the English health system meant that knowledge on community engagement was becoming lost and a fragmented evidence base was seen to impact negatively on policy and practice. A partnership started between Public Health England, NHS England and Leeds Beckett University in 2014 to address these issues. Following a literature review and stakeholder consultation, evidence was published in a national guide to community-centred approaches. This was followed by a programme of work to translate the evidence into national strategy and local practice.The article outlines the key features of the knowledge translation framework developed. Results include positive impacts on local practice and national policy, for example adoption within National Institute for Health and Care Evidence (NICE) guidance and Local Authority public health plans and utilization as a tool for local audit of practice and commissioning. The framework was successful in its non-linear approach to knowledge translation across a range of inter-connected activity, built on national leadership, knowledge brokerage, coalition building and a strong collaboration between research institute and government agency.

Viral and Cellular mRNA Translation in Coronavirus-Infected Cells

PubMed Central

Nakagawa, K.; Lokugamage, K.G.; Makino, S.

2017-01-01

Coronaviruses have large positive-strand RNA genomes that are 5′ capped and 3′ polyadenylated. The 5′-terminal two-thirds of the genome contain two open reading frames (ORFs), 1a and 1b, that together make up the viral replicase gene and encode two large polyproteins that are processed by viral proteases into 15–16 nonstructural proteins, most of them being involved in viral RNA synthesis. ORFs located in the 3′-terminal one-third of the genome encode structural and accessory proteins and are expressed from a set of 5′ leader-containing subgenomic mRNAs that are synthesized by a process called discontinuous transcription. Coronavirus protein synthesis not only involves cap-dependent translation mechanisms but also employs regulatory mechanisms, such as ribosomal frameshifting. Coronavirus replication is known to affect cellular translation, involving activation of stress-induced signaling pathways, and employing viral proteins that affect cellular mRNA translation and RNA stability. This chapter describes our current understanding of the mechanisms involved in coronavirus mRNA translation and changes in host mRNA translation observed in coronavirus-infected cells. PMID:27712623

Bacterial translation elongation factor EF-Tu interacts and colocalizes with actin-like MreB protein.

PubMed

Defeu Soufo, Hervé Joël; Reimold, Christian; Linne, Uwe; Knust, Tobias; Gescher, Johannes; Graumann, Peter L

2010-02-16

We show that translation initiation factor EF-Tu plays a second important role in cell shape maintenance in the bacterium Bacillus subtilis. EF-Tu localizes in a helical pattern underneath the cell membrane and colocalizes with MreB, an actin-like cytoskeletal element setting up rod cell shape. The localization of MreB and of EF-Tu is interdependent, but in contrast to the dynamic MreB filaments, EF-Tu structures are more static and may serve as tracks for MreB filaments. In agreement with this idea, EF-Tu and MreB interact in vivo and in vitro. Lowering of the EF-Tu levels had a minor effect on translation but a strong effect on cell shape and on the localization of MreB, and blocking of the function of EF-Tu in translation did not interfere with the localization of MreB, showing that, directly or indirectly, EF-Tu affects the cytoskeletal MreB structure and thus serves two important functions in a bacterium.

Exosome Theranostics: Biology and Translational Medicine

PubMed Central

He, Chuanjiang; Zheng, Shu; Luo, Yan; Wang, Ben

2018-01-01

Exosomes are common membrane-bound nanovesicles that contain diverse biomolecules, such as lipids, proteins, and nucleic acids. Exosomes are derived from cells through exocytosis, are ingested by target cells, and can transfer biological signals between local or distant cells. Exosome secretion is a constitutive phenomenon that is involved in both physiological and pathological processes and determines both the exosomal surface molecules and the contents. Hence, we can exploit exosomes as biomarkers, vaccines and drug carriers and modify them rationally for therapeutic interventions. However, it is still a challenge to identify, isolate and quantify exosomes accurately, efficiently and selectively. Further studies on exosomes will explore their potential in translational medicine and provide new avenues for the creation of effective clinical diagnostics and therapeutic strategies; the use of exosomes in these applications can be called exosome theranostics. This review describes the fundamental processes of exosome formation and uptake. In addition, the physiological and pathological roles of exosomes in biology are also illustrated with a focus on how exosomes can be exploited or engineered as powerful tools in translational medicine. PMID:29290805

Boot camp translation: a method for building a community of solution.

PubMed

Norman, Ned; Bennett, Chris; Cowart, Shirley; Felzien, Maret; Flores, Martha; Flores, Rafael; Haynes, Connie; Hernandez, Mike; Rodriquez, Mary Petra; Sanchez, Norah; Sanchez, Sergio; Winkelman, Kathy; Winkelman, Steve; Zittleman, Linda; Westfall, John M

2013-01-01

A crucial yet currently insufficient step in biomedical research is the translation of scientific, evidence-based guidelines and recommendations into constructs and language accessible to every-day patients. By building a community of solution that integrates primary care with public health and community-based organizations, evidence-based medical care can be translated into language and constructs accessible to community members and readily implemented to improve health. Using a community-based participatory research approach, the High Plains Research Network (HPRN) and its Community Advisory Council developed a process to translate evidence into messages and dissemination methods to improve health in rural Colorado. This process, called Boot Camp Translation, has brought together various community members, organizations, and primary care practices to build a community of solution to address local health problems. The HPRN has conducted 4 Boot Camp Translations on topics including colon cancer prevention, asthma diagnosis and management, hypertension, and the patient-centered medical home. Thus far, the HPRN has used Boot Camp Translations to engage more than 1000 rural community members and providers. Dissemination of boot camp messaging through the community of solution has led to increased colon cancer screening, improved care for asthma, and increased rates of controlled blood pressure. Boot Camp Translation successfully engages community members in a process to translate evidence-based medical care into locally relevant and culturally appropriate language and constructs. Boot Camp Translation is an appropriate method for engaging community members in patient-centered outcomes research and may be an appropriate first step in building a local or regional community of solution.

Synaptic Plasticity and Translation Initiation

ERIC Educational Resources Information Center

Klann, Eric; Antion, Marcia D.; Banko, Jessica L.; Hou, Lingfei

2004-01-01

It is widely accepted that protein synthesis, including local protein synthesis at synapses, is required for several forms of synaptic plasticity. Local protein synthesis enables synapses to control synaptic strength independent of the cell body via rapid protein production from pre-existing mRNA. Therefore, regulation of translation initiation is…

Cross-cultural equivalence in translations of the oral health impact profile.

PubMed

MacEntee, Michael I; Brondani, Mario

2016-04-01

The Oral Health Impact Profile (OHIP) has been translated for comparisons across cultural boundaries. This report on a systematic search of literature published between 1994 and 2014 aims to identify an acceptable method of translating psychometric instruments for cross-cultural equivalence, and how they were used to translate the OHIP. An electronic search used the keywords 'cultural adaptation', 'validation', 'Oral Health Impact Profile' and 'OHIP' in MEDLINE and EMBASE databases supplemented by reference links and grey literature. It included papers on methods of cross-cultural translation and translations of the OHIP for dentulous adults and adolescents, and excluded papers without translational details or limited to specific disorders. The search identified eight steps to cross-cultural equivalence, and 36 (plus three supplemental) translations of the OHIP. The steps involve assessment of (i) forward/backward translation by committee, (ii) constructs, (iii) item interpretations, (iv) interval scales, (v) convergent validity, (vi) discriminant validity, (vii) responsiveness to clinical change and (viii) pilot tests. Most (>60%) of the translations involved forward/backward translation by committee, item interpretations, interval scales, convergence, discrimination and pilot tests, but fewer assessed the underlying theory (47%) or responsiveness to clinical change (28%). An acceptable method for translating quality of life-related psychometric instruments for cross-cultural equivalence has eight procedural steps, and most of the 36 OHIP translations involved at least five of the steps. Only translations to Saudi Arabian Arabic, Chinese Mandarin, German and Japanese used all eight steps to claim cultural equivalence with the original OHIP. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Rabies virus matrix protein interplay with eIF3, new insights into rabies virus pathogenesis

PubMed Central

Komarova, Anastassia V.; Real, Eléonore; Borman, Andrew M.; Brocard, Michèle; England, Patrick; Tordo, Noël; Hershey, John W.B.; Jacob, Yves

2007-01-01

Viral proteins are frequently multifunctional to accommodate the high density of information encoded in viral genomes. Matrix (M) protein of negative-stranded RNA viruses such as Rhabdoviridae is one such example. Its primary function is virus assembly/budding but it is also involved in the switch from viral transcription to replication and the concomitant down regulation of host gene expression. In this study we undertook a search for potential rabies virus (RV) M protein's cellular partners. In a yeast two-hybrid screen the eIF3h subunit was identified as an M-interacting cellular factor, and the interaction was validated by co-immunoprecipitation and surface plasmon resonance assays. Upon expression in mammalian cell cultures, RV M protein was localized in early small ribosomal subunit fractions. Further, M protein added in trans inhibited in vitro translation on mRNA encompassing classical (Kozak-like) 5′-UTRs. Interestingly, translation of hepatitis C virus IRES-containing mRNA, which recruits eIF3 via a different noncanonical mechanism, was unaffected. Together, the data suggest that, as a complement to its functions in virus assembly/budding and regulation of viral transcription, RV M protein plays a role in inhibiting translation in virus-infected cells through a protein–protein interaction with the cellular translation machinery. PMID:17287294

Visualization of the Interaction between the Precursors of VPg, the Viral Protein Linked to the Genome of Turnip Mosaic Virus, and the Translation Eukaryotic Initiation Factor iso 4E In Planta▿

PubMed Central

Beauchemin, Chantal; Boutet, Nathalie; Laliberté, Jean-François

2007-01-01

The RNA genome of Turnip mosaic virus is covalently linked at its 5′ end to a viral protein known as VPg. This protein binds to the translation eukaryotic initiation factor iso 4E [eIF(iso)4E]. This interaction has been shown to be important for virus infection, although its exact biological function(s) has not been elucidated. In this study, we investigated the subcellular site of the VPg-eIF(iso)4E interaction using bimolecular fluorescence complementation (BiFC). As a first step, eIF(iso)4E, 6K-VPg-Pro, and VPg-Pro were expressed as full-length green fluorescent protein (GFP) fusions in Nicotiana benthamiana, and their subcellular localizations were visualized by confocal microscopy. eIF(iso)4E was predominantly associated with the endoplasmic reticulum (ER), and VPg-Pro was observed in the nucleus and possibly the nucleolus, while 6K-VPg-Pro-GFP induced the formation of cytoplasmic vesicles budding from the ER. In BiFC experiments, reconstituted green fluorescence was observed throughout the nucleus, with a preferential accumulation in subnuclear structures when the GFP split fragments were fused to VPg-Pro and eIF(iso)4E. On the other hand, the interaction of 6K-VPg-Pro with eIF(iso)4E was observed in cytoplasmic vesicles embedded in the ER. These data suggest that the association of VPg with the translation factor might be needed for two different functions, depending of the VPg precursor involved in the interaction. VPg-Pro interaction with eIF(iso)4E may be involved in perturbing normal cellular functions, while 6K-VPg-Pro interaction with the translation factor may be needed for viral RNA translation and/or replication. PMID:17079311

Translational cancer vaccine: from mouse to human to cat

NASA Astrophysics Data System (ADS)

Levenson, Richard

2015-03-01

Acanthomatous ameloblastoma is a locally invasive tumor arising in the gingiva that can progress rapidly, invade and destroy bone. If the lesion involves the upper jaw, surgical excision may not be possible and while local control is imperative, other therapies have not been fully evaluated. The primary author's personal cat, Gabriella, developed this tumor, with gingival masses around teeth in the upper jaw and evidence of widespread bony destruction of the hard palate. Because of his involvement with Immunophotonics Inc. as an advisor, the author was aware of an in situ autologous cancer vaccine (inCVAX) that is currently under development by the company. One session was performed in a veterinary clinic in Arkansas, and two follow-up sessions at the small animal hospital at the UC Davis veterinary school. No other therapy was provided. As of this writing, 3+ years after first treatment and 3 years, 4 months after presentation, Gabriella is well, with no evidence of disease.

How normative interpretations of climate risk assessment affect local decision-making: an exploratory study at the city scale in Cork, Ireland.

PubMed

McDermott, T K J; Surminski, S

2018-06-13

Urban areas already suffer substantial losses in both economic and human terms from climate-related disasters. These losses are anticipated to grow substantially, in part as a result of the impacts of climate change. In this paper, we investigate the process of translating climate risk data into action for the city level. We apply a commonly used decision-framework as our backdrop and explore where in this process climate risk assessment and normative political judgements intersect. We use the case of flood risk management in Cork city in Ireland to investigate what is needed for translating risk assessment into action at the local city level. Evidence presented is based on focus group discussions at two stakeholder workshops, and a series of individual meetings and phone-discussions with stakeholders involved in local decision-making related to flood risk management and adaptation to climate change, in Ireland. Respondents were chosen on the basis of their expertise or involvement in the decision-making processes locally and nationally. Representatives of groups affected by flood risk and flood risk management and climate adaptation efforts were also included. The Cork example highlights that, despite ever more accurate data and an increasing range of theoretical approaches available to local decision-makers, it is the normative interpretation of this information that determines what action is taken. The use of risk assessments for decision-making is a process that requires normative decisions, such as setting 'acceptable risk levels' and identifying 'adequate' protection levels, which will not succeed without broader buy-in and stakeholder participation. Identifying and embracing those normative views up-front could strengthen the urban adaptation process-this may, in fact, turn out to be the biggest advantage of climate risk assessment: it offers an opportunity to create a shared understanding of the problem and enables an informed evaluation and discussion of remedial action.This article is part of the theme issue 'Advances in risk assessment for climate change adaptation policy'. © 2018 The Author(s).

How normative interpretations of climate risk assessment affect local decision-making: an exploratory study at the city scale in Cork, Ireland

NASA Astrophysics Data System (ADS)

McDermott, T. K. J.; Surminski, S.

2018-06-01

Urban areas already suffer substantial losses in both economic and human terms from climate-related disasters. These losses are anticipated to grow substantially, in part as a result of the impacts of climate change. In this paper, we investigate the process of translating climate risk data into action for the city level. We apply a commonly used decision-framework as our backdrop and explore where in this process climate risk assessment and normative political judgements intersect. We use the case of flood risk management in Cork city in Ireland to investigate what is needed for translating risk assessment into action at the local city level. Evidence presented is based on focus group discussions at two stakeholder workshops, and a series of individual meetings and phone-discussions with stakeholders involved in local decision-making related to flood risk management and adaptation to climate change, in Ireland. Respondents were chosen on the basis of their expertise or involvement in the decision-making processes locally and nationally. Representatives of groups affected by flood risk and flood risk management and climate adaptation efforts were also included. The Cork example highlights that, despite ever more accurate data and an increasing range of theoretical approaches available to local decision-makers, it is the normative interpretation of this information that determines what action is taken. The use of risk assessments for decision-making is a process that requires normative decisions, such as setting `acceptable risk levels' and identifying `adequate' protection levels, which will not succeed without broader buy-in and stakeholder participation. Identifying and embracing those normative views up-front could strengthen the urban adaptation process-this may, in fact, turn out to be the biggest advantage of climate risk assessment: it offers an opportunity to create a shared understanding of the problem and enables an informed evaluation and discussion of remedial action. This article is part of the theme issue `Advances in risk assessment for climate change adaptation policy'.

Tobacco etch virus protein P1 traffics to the nucleolus and associates with the host 60S ribosomal subunits during infection.

PubMed

Martínez, Fernando; Daròs, José-Antonio

2014-09-01

The genus Potyvirus comprises a large group of positive-strand RNA plant viruses whose genome encodes a large polyprotein processed by three viral proteinases. P1 protein, the most amino-terminal product of the polyprotein, is an accessory factor stimulating viral genome amplification whose role during infection is not well understood. We infected plants with Tobacco etch virus (TEV; genus Potyvirus) clones in which P1 was tagged with a fluorescent protein to track its expression and subcellular localization or with an affinity tag to identify host proteins involved in complexes in which P1 also takes part during infection. Our results showed that TEV P1 exclusively accumulates in infected cells at an early stage of infection and that the protein displays a dynamic subcellular localization, trafficking in and out of the nucleus and nucleolus during infection. Inside the nucleolus, P1 particularly targets the dense granular component. Consistently, we found functional nucleolar localization and nuclear export signals in TEV P1 sequence. Our results also indicated that TEV P1 physically interacts with the host 80S cytoplasmic ribosomes and specifically binds to the 60S ribosomal subunits during infection. In vitro translation assays of reporter proteins suggested that TEV P1 stimulates protein translation, particularly when driven from the TEV internal ribosome entry site. These in vitro assays also suggested that TEV helper-component proteinase (HC-Pro) inhibits protein translation. Based on these findings, we propose that TEV P1 stimulates translation of viral proteins in infected cells. In this work, we researched the role during infection of tobacco etch virus P1 protease. P1 is the most mysterious protein of potyviruses, a relevant group of RNA viruses infecting plants. Our experiments showed that the viral P1 protein exclusively accumulates in infected cells at an early stage of infection and moves in and out of the nucleus of infected cells, particularly targeting the nucleolus. Our experiments also showed that P1 protein binds host ribosomes during infection. Based on these findings and other in vitro experiments we propose that P1 protein stimulates translation of viral proteins during infection. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

The brain cytoplasmic RNA BC1 regulates dopamine D2 receptor-mediated transmission in the striatum.

PubMed

Centonze, Diego; Rossi, Silvia; Napoli, Ilaria; Mercaldo, Valentina; Lacoux, Caroline; Ferrari, Francesca; Ciotti, Maria Teresa; De Chiara, Valentina; Prosperetti, Chiara; Maccarrone, Mauro; Fezza, Filomena; Calabresi, Paolo; Bernardi, Giorgio; Bagni, Claudia

2007-08-15

Dopamine D(2) receptor (D(2)DR)-mediated transmission in the striatum is remarkably flexible, and changes in its efficacy have been heavily implicated in a variety of physiological and pathological conditions. Although receptor-associated proteins are clearly involved in specific forms of synaptic plasticity, the molecular mechanisms regulating the sensitivity of D(2) receptors in this brain area are essentially obscure. We have studied the physiological responses of the D(2)DR stimulations in mice lacking the brain cytoplasmic RNA BC1, a small noncoding dendritically localized RNA that is supposed to play a role in mRNA translation. We show that the efficiency of D(2)-mediated transmission regulating striatal GABA synapses is under the control of BC1 RNA, through a negative influence on D(2) receptor protein level affecting the functional pool of receptors. Ablation of the BC1 gene did not result in widespread dysregulation of synaptic transmission, because the sensitivity of cannabinoid CB(1) receptors was intact in the striatum of BC1 knock-out (KO) mice despite D(2) and CB(1) receptors mediated similar electrophysiological actions. Interestingly, the fragile X mental retardation protein FMRP, one of the multiple BC1 partners, is not involved in the BC1 effects on the D(2)-mediated transmission. Because D(2)DR mRNA is apparently equally translated in the BC1-KO and wild-type mice, whereas the protein level is higher in BC1-KO mice, we suggest that BC1 RNA controls D(2)DR indirectly, probably regulating translation of molecules involved in D(2)DR turnover and/or stability.

Lessons Learned: Cultural and linguistic enhancement of surveys through community-based participatory research

PubMed Central

Formea, Christine M.; Mohamed, Ahmed A.; Hassan, Abdullahi; Osman, Ahmed; Weis, Jennifer A.; Sia, Irene G.; Wieland, Mark L.

2014-01-01

Background Surveys are frequently implemented in community-based participatory research (CBPR), but adaptation and translation of surveys can be logistically and methodologically challenging when working with immigrant and refugee populations. Objective To describe a process of participatory survey adaptation and translation. Methods Within an established CBPR partnership, a survey about diabetes was adapted for health literacy and local relevance and then translated through a process of forward translation, group deliberation, and back translation. Lessons Learned The group deliberation process was the most time-intensive and important component of the process. The process enhanced community ownership of the larger project while maximizing local applicability of the product. Conclusions A participatory process of survey adaptation and translation resulted in significant revisions to approximate semantic, cultural, and conceptual equivalence with the original surveys. This approach is likely to enhance community acceptance of the survey instrument during the implementation phase. PMID:25435559

Environmental outreach and fish pathology studies at a U.S. Army Superfund site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kane, A.S.; Reimschuessel, R.; Whaley, J.E.

1995-12-31

Aberdeen Proving Ground (APG), located on the upper Chesapeake Bay, in Aberdeen, MD, has served the US Army for more than 75 years as a site for research, development, and testing of munitions and military chemicals. Due to the toxic nature of many of the compounds which were disposed of on site, APG is on the National Priorities List for environmental contamination. This is a source of concern for local citizens and fishermen. In order to better understand effects of potential chemical contamination on local vertebrate fauna, and to enhance public relations between the US Army and local residents, themore » US Army and the University of Maryland Aquatic Pathobiology Center initiated a cooperative study. This effort involves public outreach and participation through an angler survey. Persons catching fish of questionable health near APG were encouraged to submit their specimens for diagnostic evaluation by the study. Animals were examined by gross necropsy and histopathology. Examination results were recorded according to standard pathology protocols and then translated for outreach to citizens and fishermen. Development of non-technical response formats for survey results as well as outreach to fishing clubs and citizens` groups represents an important venue for risk communication of technical information to the public. Survey design and outreach materials will be presented to show angler questionnaires, translated gross necropsy/histopathology reports and correspondence to survey participants.« less

Reformulation of the symmetries of first-order general relativity

NASA Astrophysics Data System (ADS)

Montesinos, Merced; González, Diego; Celada, Mariano; Díaz, Bogar

2017-10-01

We report a new internal gauge symmetry of the n-dimensional Palatini action with cosmological term (n>3 ) that is the generalization of three-dimensional local translations. This symmetry is obtained through the direct application of the converse of Noether’s second theorem on the theory under consideration. We show that diffeomorphisms can be expressed as linear combinations of it and local Lorentz transformations with field-dependent parameters up to terms involving the variational derivatives of the action. As a result, the new internal symmetry together with local Lorentz transformations can be adopted as the fundamental gauge symmetries of general relativity. Although their gauge algebra is open in general, it allows us to recover, without resorting to the equations of motion, the very well-known Lie algebra satisfied by translations and Lorentz transformations in three dimensions. We also report the analog of the new gauge symmetry for the Holst action with cosmological term, finding that it explicitly depends on the Immirzi parameter. The same result concerning its relation to diffeomorphisms and the open character of the gauge algebra also hold in this case. Finally, we consider the non-minimal coupling of a scalar field to gravity in n dimensions and establish that the new gauge symmetry is affected by this matter field. Our results indicate that general relativity in dimension greater than three can be thought of as a gauge theory.

Medical education for social justice: Paulo Freire revisited.

PubMed

DasGupta, Sayantani; Fornari, Alice; Geer, Kamini; Hahn, Louisa; Kumar, Vanita; Lee, Hyun Joon; Rubin, Susan; Gold, Marji

2006-01-01

Although social justice is an integral component of medical professionalism, there is little discussion in medical education about how to teach it to future physicians. Using adult learning theory and the work of Brazilian educator Paulo Freire, medical educators can teach a socially-conscious professionalism through educational content and teaching strategies. Such teaching can model non-hierarchical relationships to learners, which can translate to their clinical interactions with patients. Freirian teaching can additionally foster professionalism in both teachers and learners by ensuring that they are involved citizens in their local, national and international communities.

Role of the plasma membrane H+-ATPase in the regulation of organic acid exudation under aluminum toxicity and phosphorus deficiency

PubMed Central

Yu, Wenqian; Kan, Qi; Zhang, Jiarong; Zeng, Bingjie; Chen, Qi

2016-01-01

Aluminum (Al) toxicity and phosphorus (P) deficiency are 2 major limiting factors for plant growth and crop production in acidic soils. Organic acids exuded from roots have been generally regarded as a major resistance mechanism to Al toxicity and P deficiency. The exudation of organic acids is mediated by membrane-localized OA transporters, such as ALMT (Al-activated malate transporter) and MATE (multidrug and toxic compound extrusion). Beside on up-regulation expression of organic acids transporter gene, transcriptional, translational and post-translational regulation of the plasma membrane H+-ATPase are also involved in organic acid release process under Al toxicity and P deficiency. This mini-review summarizes the current knowledge about this field of study on the role of the plasma membrane H+-ATPase in organic acid exudation under Al toxicity and P deficiency conditions. PMID:26713714

Role of the plasma membrane H(+)-ATPase in the regulation of organic acid exudation under aluminum toxicity and phosphorus deficiency.

PubMed

Yu, Wenqian; Kan, Qi; Zhang, Jiarong; Zeng, Bingjie; Chen, Qi

2016-01-01

Aluminum (Al) toxicity and phosphorus (P) deficiency are 2 major limiting factors for plant growth and crop production in acidic soils. Organic acids exuded from roots have been generally regarded as a major resistance mechanism to Al toxicity and P deficiency. The exudation of organic acids is mediated by membrane-localized OA transporters, such as ALMT (Al-activated malate transporter) and MATE (multidrug and toxic compound extrusion). Beside on up-regulation expression of organic acids transporter gene, transcriptional, translational and post-translational regulation of the plasma membrane H(+)-ATPase are also involved in organic acid release process under Al toxicity and P deficiency. This mini-review summarizes the current knowledge about this field of study on the role of the plasma membrane H(+)-ATPase in organic acid exudation under Al toxicity and P deficiency conditions.

Challenges and opportunities in clinical translation of biomedical optical spectroscopy and imaging

NASA Astrophysics Data System (ADS)

Wilson, Brian C.; Jermyn, Michael; Leblond, Frederic

2018-03-01

Medical devices face many hurdles before they enter routine clinical practice to address unmet clinical needs. This is also the case for biomedical optical spectroscopy and imaging systems that are used here to illustrate the opportunities and challenges involved. Following initial concept, stages in clinical translation include instrument development, preclinical testing, clinical prototyping, clinical trials, prototype-to-product conversion, regulatory approval, commercialization, and finally clinical adoption and dissemination, all in the face of potentially competing technologies. Optical technologies face additional challenges from their being extremely diverse, often targeting entirely different diseases and having orders-of-magnitude differences in resolution and tissue penetration. However, these technologies can potentially address a wide variety of unmet clinical needs since they provide rich intrinsic biochemical and structural information, have high sensitivity and specificity for disease detection and localization, and are practical, safe (minimally invasive, nonionizing), and relatively affordable.

The specific localization of advanced glycation end-products (AGEs) in rat pancreatic islets.

PubMed

Morioka, Yuta; Teshigawara, Kiyoshi; Tomono, Yasuko; Wang, Dengli; Izushi, Yasuhisa; Wake, Hidenori; Liu, Keyue; Takahashi, Hideo Kohka; Mori, Shuji; Nishibori, Masahiro

2017-08-01

Advanced glycation end-products (AGEs) are produced by non-enzymatic glycation between protein and reducing sugar such as glucose. Although glyceraldehyde-derived AGEs (Glycer-AGEs), one of the AGEs subspecies, have been reported to be involved in the pathogenesis of various age-relating diseases such as diabetes mellitus or arteriosclerosis, little is known about the pathological and physiological mechanism of AGEs in vivo. In present study, we produced 4 kinds of polyclonal antibodies against AGEs subspecies and investigated the localization of AGEs-modified proteins in rat peripheral tissues, making use of these antibodies. We found that Glycer-AGEs and methylglyoxal-derived AGEs (MGO-AGEs) were present in pancreatic islets of healthy rats, distinguished clearly into the pancreatic α and β cells, respectively. Although streptozotocin-induced diabetic rats suffered from remarkable impairment of pancreatic islets, the localization and deposit levels of the Glycer- and MGO-AGEs were not altered in the remaining α and β cells. Remarkably, the MGO-AGEs in pancreatic β cells were localized into the insulin-secretory granules. These results suggest that the cell-specific localization of AGEs-modified proteins are presence generally in healthy peripheral tissues, involved in physiological intracellular roles, such as a post-translational modulator contributing to the secretory and/or maturational functions of insulin. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

A review of financial instruments to pay for predator conservation and encourage human–carnivore coexistence

PubMed Central

Dickman, Amy J.; Macdonald, Ewan A.; Macdonald, David W.

2011-01-01

One of the greatest challenges in biodiversity conservation today is how to facilitate protection of species that are highly valued at a global scale but have little or even negative value at a local scale. Imperiled species such as large predators can impose significant economic costs at a local level, often in poverty-stricken rural areas where households are least able to tolerate such costs, and impede efforts of local people, especially traditional pastoralists, to escape from poverty. Furthermore, the costs and benefits involved in predator conservation often include diverse dimensions, which are hard to quantify and nearly impossible to reconcile with one another. The best chance of effective conservation relies upon translating the global value of carnivores into tangible local benefits large enough to drive conservation “on the ground.” Although human–carnivore coexistence involves significant noneconomic values, providing financial incentives to those affected negatively by carnivore presence is a common strategy for encouraging such coexistence, and this can also have important benefits in terms of reducing poverty. Here, we provide a critical overview of such financial instruments, which we term “payments to encourage coexistence”; assess the pitfalls and potentials of these methods, particularly compensation and insurance, revenue-sharing, and conservation payments; and discuss how existing strategies of payment to encourage coexistence could be combined to facilitate carnivore conservation and alleviate local poverty. PMID:21873181

A review of financial instruments to pay for predator conservation and encourage human-carnivore coexistence.

PubMed

Dickman, Amy J; Macdonald, Ewan A; Macdonald, David W

2011-08-23

One of the greatest challenges in biodiversity conservation today is how to facilitate protection of species that are highly valued at a global scale but have little or even negative value at a local scale. Imperiled species such as large predators can impose significant economic costs at a local level, often in poverty-stricken rural areas where households are least able to tolerate such costs, and impede efforts of local people, especially traditional pastoralists, to escape from poverty. Furthermore, the costs and benefits involved in predator conservation often include diverse dimensions, which are hard to quantify and nearly impossible to reconcile with one another. The best chance of effective conservation relies upon translating the global value of carnivores into tangible local benefits large enough to drive conservation "on the ground." Although human-carnivore coexistence involves significant noneconomic values, providing financial incentives to those affected negatively by carnivore presence is a common strategy for encouraging such coexistence, and this can also have important benefits in terms of reducing poverty. Here, we provide a critical overview of such financial instruments, which we term "payments to encourage coexistence"; assess the pitfalls and potentials of these methods, particularly compensation and insurance, revenue-sharing, and conservation payments; and discuss how existing strategies of payment to encourage coexistence could be combined to facilitate carnivore conservation and alleviate local poverty.

Staging "Swissness": Inter- and Intracultural Theatre Translation

ERIC Educational Resources Information Center

Wilkinson, Jane

2005-01-01

This paper examines the choice to translate plays from "Hochdeutsch" (the standard form of the German language) into local dialect in German-speaking Switzerland. It first looks at the creative process of translating for the amateur stage and then at the reasons behind the choice to translate. It argues that this choice reflects a desire…

Galactoseismology and the local density of dark matter

DOE PAGES

Banik, Nilanjan; Widrow, Lawrence M.; Dodelson, Scott

2016-10-08

Here, we model vertical breathing mode perturbations in the Milky Way's stellar disc and study their effects on estimates of the local dark matter density, surface density, and vertical force. Evidence for these perturbations, which involve compression and expansion of the Galactic disc perpendicular to its midplane, come from the SEGUE, RAVE, and LAMOST surveys. We show that their existence may lead to systematic errors ofmore » $$10\\%$$ or greater in the vertical force $$K_z(z)$$ at $$|z|=1.1\\,{\\rm kpc}$$. These errors translate to $$\\gtrsim 25\\%$$ errors in estimates of the local dark matter density. Using different mono-abundant subpopulations as tracers offers a way out: if the inferences from all tracers in the Gaia era agree, then the dark matter determination will be robust. Disagreement in the inferences from different tracers will signal the breakdown of the unperturbed model and perhaps provide the means for determining the nature of the perturbation.« less

Wavefront sensing with a thin diffuser

NASA Astrophysics Data System (ADS)

Berto, Pascal; Rigneault, Hervé; Guillon, Marc

2017-12-01

We propose and implement a broadband, compact, and low-cost wavefront sensing scheme by simply placing a thin diffuser in the close vicinity of a camera. The local wavefront gradient is determined from the local translation of the speckle pattern. The translation vector map is computed thanks to a fast diffeomorphic image registration algorithm and integrated to reconstruct the wavefront profile. The simple translation of speckle grains under local wavefront tip/tilt is ensured by the so-called "memory effect" of the diffuser. Quantitative wavefront measurements are experimentally demonstrated both for the few first Zernike polynomials and for phase-imaging applications requiring high resolution. We finally provided a theoretical description of the resolution limit that is supported experimentally.

Methodological challenges involved in compiling the Nahua pharmacopeia.

PubMed

De Vos, Paula

2017-06-01

Recent work in the history of science has questioned the Eurocentric nature of the field and sought to include a more global approach that would serve to displace center-periphery models in favor of approaches that take seriously local knowledge production. Historians of Iberian colonial science have taken up this approach, which involves reliance on indigenous knowledge traditions of the Americas. These traditions present a number of challenges to modern researchers, including availability and reliability of source material, issues of translation and identification, and lack of systematization. This essay explores the challenges that emerged in the author's attempt to compile a pre-contact Nahua pharmacopeia, the reasons for these challenges, and the ways they may - or may not - be overcome.

Timing of translation in cross-language qualitative research.

PubMed

Santos, Hudson P O; Black, Amanda M; Sandelowski, Margarete

2015-01-01

Although there is increased understanding of language barriers in cross-language studies, the point at which language transformation processes are applied in research is inconsistently reported, or treated as a minor issue. Differences in translation timeframes raise methodological issues related to the material to be translated, as well as for the process of data analysis and interpretation. In this article we address methodological issues related to the timing of translation from Portuguese to English in two international cross-language collaborative research studies involving researchers from Brazil, Canada, and the United States. One study entailed late-phase translation of a research report, whereas the other study involved early phase translation of interview data. The timing of translation in interaction with the object of translation should be considered, in addition to the language, cultural, subject matter, and methodological competencies of research team members. © The Author(s) 2014.

Tax-1 and Tax-2 similarities and differences: focus on post-translational modifications and NF-κB activation

PubMed Central

Shirinian, Margret; Kfoury, Youmna; Dassouki, Zeina; El-Hajj, Hiba; Bazarbachi, Ali

2013-01-01

Although human T cell leukemia virus type 1 and 2 (HTLV-1 and HTLV-2) share similar genetic organization, they have major differences in their pathogenesis and disease manifestation. HTLV-1 is capable of transforming T lymphocytes in infected patients resulting in adult T cell leukemia/lymphoma whereas HTLV-2 is not clearly associated with lymphoproliferative diseases. Numerous studies have provided accumulating evidence on the involvement of the viral transactivators Tax-1 versus Tax-2 in T cell transformation. Tax-1 is a potent transcriptional activator of both viral and cellular genes. Tax-1 post-translational modifications and specifically ubiquitylation and SUMOylation have been implicated in nuclear factor-kappaB (NF-κB) activation and may contribute to its transformation capacity. Although Tax-2 has similar protein structure compared to Tax-1, the two proteins display differences both in their protein–protein interaction and activation of signal transduction pathways. Recent studies on Tax-2 have suggested ubiquitylation and SUMOylation independent mechanisms of NF-κB activation. In this present review, structural and functional differences between Tax-1 and Tax-2 will be summarized. Specifically, we will address their subcellular localization, nuclear trafficking and their effect on cellular regulatory proteins. A special attention will be given to Tax-1/Tax-2 post-translational modification such as ubiquitylation, SUMOylation, phosphorylation, acetylation, NF-κB activation, and protein–protein interactions involved in oncogenecity both in vivo and in vitro. PMID:23966989

47 CFR 73.3580 - Local public notice of filing of broadcast applications.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., other than a low power TV station license not locally originating programming as defined by § 74.701(h... originating programming as defined by § 74.701(h), an FM translator station or a TV translator station license... each calendar month. Stations broadcasting primarily in a foreign language should broadcast the...

47 CFR 73.3580 - Local public notice of filing of broadcast applications.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., other than a low power TV station license not locally originating programming as defined by § 74.701(h... originating programming as defined by § 74.701(h), an FM translator station or a TV translator station license... each calendar month. Stations broadcasting primarily in a foreign language should broadcast the...

Micro-structure and motion of two-dimensional dense short spherocylinder liquids

NASA Astrophysics Data System (ADS)

Wang, Wen; Lin, Jyun-Ting; Su, Yen-Shuo; I, Lin

2018-03-01

We numerically investigate the micro-structure and motion of 2D liquids composed of dense short spherocylinders, by reducing the shape aspect ratio from 3. It is found that reducing shape aspect ratio from 3 causes a smooth transition from heterogeneous structures composed of crystalline ordered domains with good tetratic alignment order to those with good hexagonal bond-orientational order at an aspect ratio equaling 1.35. In the intermediate regime, both structural orders are strongly deteriorated, and the translational hopping rate reaches a maximum due to the poor particle interlocking of the disordered structure. Shortening rod length allows easier rotation, induces monotonic increase of rotational hopping rates, and resumes the separation of rotational and translational hopping time scales at the small aspect ratio end, after the crossover of their rates in the intermediate regime. At the large shape aspect ratio end, the poor local tetratic order has the same positive effects on facilitating local rotational and translational hopping. In contrast, at the small shape aspect ratio end, the poor local bond orientational order has the opposite effects on facilitating local rotational and translational hopping.

Translational bioinformatics: linking the molecular world to the clinical world.

PubMed

Altman, R B

2012-06-01

Translational bioinformatics represents the union of translational medicine and bioinformatics. Translational medicine moves basic biological discoveries from the research bench into the patient-care setting and uses clinical observations to inform basic biology. It focuses on patient care, including the creation of new diagnostics, prognostics, prevention strategies, and therapies based on biological discoveries. Bioinformatics involves algorithms to represent, store, and analyze basic biological data, including DNA sequence, RNA expression, and protein and small-molecule abundance within cells. Translational bioinformatics spans these two fields; it involves the development of algorithms to analyze basic molecular and cellular data with an explicit goal of affecting clinical care.

Daisaku Ikeda and the Culture of Translation

ERIC Educational Resources Information Center

Gebert, Andrew

2012-01-01

Although not functionally multilingual or a translator himself, Daisaku Ikeda has been deeply involved in translation processes, both as a reader and as someone who has produced texts for translation into various languages. This article examines two sources of influence shaping Ikeda's attitude toward translation culture: the flourishing culture…

Tilt aftereffect following adaptation to translational Glass patterns

PubMed Central

Pavan, Andrea; Hocketstaller, Johanna; Contillo, Adriano; Greenlee, Mark W.

2016-01-01

Glass patterns (GPs) consist of randomly distributed dot pairs (dipoles) whose orientations are determined by specific geometric transforms. We assessed whether adaptation to stationary oriented translational GPs suppresses the activity of orientation selective detectors producing a tilt aftereffect (TAE). The results showed that adaptation to GPs produces a TAE similar to that reported in previous studies, though reduced in amplitude. This suggests the involvement of orientation selective mechanisms. We also measured the interocular transfer (IOT) of the GP-induced TAE and found an almost complete IOT, indicating the involvement of orientation selective and binocularly driven units. In additional experiments, we assessed the role of attention in TAE from GPs. The results showed that distraction during adaptation similarly modulates the TAE after adapting to both GPs and gratings. Moreover, in the case of GPs, distraction is likely to interfere with the adaptation process rather than with the spatial summation of local dipoles. We conclude that TAE from GPs possibly relies on visual processing levels in which the global orientation of GPs has been encoded by neurons that are mostly binocularly driven, orientation selective and whose adaptation-related neural activity is strongly modulated by attention. PMID:27005949

Cup regulates oskar mRNA stability during oogenesis.

PubMed

Broyer, Risa M; Monfort, Elena; Wilhelm, James E

2017-01-01

The proper regulation of the localization, translation, and stability of maternally deposited transcripts is essential for embryonic development in many organisms. These different forms of regulation are mediated by the various protein subunits of the ribonucleoprotein (RNP) complexes that assemble on maternal mRNAs. However, while many of the subunits that regulate the localization and translation of maternal transcripts have been identified, relatively little is known about how maternal mRNAs are stockpiled and stored in a stable form to support early development. One of the best characterized regulators of maternal transcripts is Cup - a broadly conserved component of the maternal RNP complex that in Drosophila acts as a translational repressor of the localized message oskar. In this study, we have found that loss of cup disrupts the localization of both the oskar mRNA and its associated proteins to the posterior pole of the developing oocyte. This defect is not due to a failure to specify the oocyte or to disruption of RNP transport. Rather, the localization defects are due to a drop in oskar mRNA levels in cup mutant egg chambers. Thus, in addition to its role in regulating oskar mRNA translation, Cup also plays a critical role in controlling the stability of the oskar transcript. This suggests that Cup is ideally positioned to coordinate the translational control function of the maternal RNP complex with its role in storing maternal transcripts in a stable form. Published by Elsevier Inc.

Role of eIF2α Kinases in Translational Control and Adaptation to Cellular Stress.

PubMed

Wek, Ronald C

2018-02-12

A central mechanism regulating translation initiation in response to environmental stress involves phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α). Phosphorylation of eIF2α causes inhibition of global translation, which conserves energy and facilitates reprogramming of gene expression and signaling pathways that help to restore protein homeostasis. Coincident with repression of protein synthesis, many gene transcripts involved in the stress response are not affected or are even preferentially translated in response to increased eIF2α phosphorylation by mechanisms involving upstream open reading frames (uORFs). This review highlights the mechanisms regulating eIF2α kinases, the role that uORFs play in translational control, and the impact that alteration of eIF2α phosphorylation by gene mutations or small molecule inhibitors can have on health and disease. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Lost in translation: a case-study of the travel of lean thinking in a hospital.

PubMed

Andersen, Hege; Røvik, Kjell Arne

2015-09-21

Lean thinking as a quality improvement approach is introduced in hospitals worldwide, although evidence for its impact is scarce. Lean initiatives are social, complex and context-dependent. This calls for a shift from cause-effect to conditional attributions to understand how lean works. In this study, we bring attention to the transformative power of local translation, which creates different versions of lean in different contexts, and thereby affect the evidence for lean as well as the success of lean initiatives within and among hospitals. We explored the travel of lean within a hospital in Norway by identifying local actors' perceptions of lean through their images of enablers for successful interventions. These attributions describe the characteristics of lean in use, i.e. the prevailing version of lean. Local actors' perceptions of enablers for lean interventions were collected through focus group interviews with three groups of stakeholders: managers, internal consultants and staff. A questionnaire was used to reveal the enablers relative importance. The enablers known from the literature were retrieved at the case hospital. The only exception was that external expert change agents were not believed to promote lean. In addition, the stakeholders added a number of new and supplementary enablers. Two-thirds of the most important enablers for success were novel, local ones. Among these were a problem, not method focus, a bottom-up approach, the need of internal consultants, credibility, realism and patience. The local actors told different stories about local enablers and had different images of lean depending on their hierarchical level. By comparing and analyzing the findings from the literature review, the focus groups and the survey, we deduced that the travel of lean within the hospital was affected by three principles of translation: the practical, the pragmatic, and the sceptical. Further, three logics of translation were in play: translation as a funnel, a conscious sell-in, and a wash-out. This resulted in various local versions of lean. We conclude that lean, introduced by the management, communicated by the internal consultants, and used by the staff, is transformed more than once within the hospital. Translation is part of the explanation for the lack of evidence for lean, and translation can be decisive for outcomes.

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

PubMed

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

2017-04-01

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

How Can Language Schools Enhance the Professional Relevance of the Translator?

ERIC Educational Resources Information Center

Lippmann, Erhard

1976-01-01

Some of the problems involving language education and the employability of translators are discussed here. (1) The selling of translation, when compared with the more marketable skills in areas such as accounting, physics, etc., is an issue in the translator's employability. It is more difficult for a translator to measure quantitative…

``Who polluted the Potomac?'' The translation and implementation of a US environmental story in Brazilian and Turkish classrooms

NASA Astrophysics Data System (ADS)

Oliveira, Alandeom W.; Colak, Huseyin; Akerson, Valarie L.

2009-03-01

In this study we examine how elementary teachers in Brazil and Turkey approached the translation and subsequent classroom implementation of an instructional activity that promotes environmental awareness through a combination of student role playing and teacher oral delivery of an environmental story about river pollution. A discourse analysis showed that translation into Portuguese was literal, an approach that fostered a classroom implementation that emphasized detached transmission of knowledge (the teacher frequently interrupted her delivery to provide textual, contextual and recontextualizing information to students). In contrast, translation into Turkish was free, that is, with many modifications that led to a decontextualized and detached text. Implementation of this text was focused on the creation of student involvement, being dominated by oral strategies such as religious analogies (heaven and hell), and parallel repetitions of statements of shared guilt. Based on these findings, it was concluded that neither translation promoted an equivalent form of environmental instruction (i.e., involved transmission of environmental knowledge). Furthermore, an argument is made that effective translation requires that original and translated curricula foster analogous levels of involvement (or detachment) as well as equivalent forms of classroom relationships and social roles (pragmatic equivalence).

Fast decoder for local quantum codes using Groebner basis

NASA Astrophysics Data System (ADS)

Haah, Jeongwan

2013-03-01

Based on arXiv:1204.1063. A local translation-invariant quantum code has a description in terms of Laurent polynomials. As an application of this observation, we present a fast decoding algorithm for translation-invariant local quantum codes in any spatial dimensions using the straightforward division algorithm for multivariate polynomials. The running time is O (n log n) on average, or O (n2 log n) on worst cases, where n is the number of physical qubits. The algorithm improves a subroutine of the renormalization-group decoder by Bravyi and Haah (arXiv:1112.3252) in the translation-invariant case. This work is supported in part by the Insitute for Quantum Information and Matter, an NSF Physics Frontier Center, and the Korea Foundation for Advanced Studies.

Emergency Medicine Resources within the Clinical Translational Science Institutes: A Cross-Sectional Study

PubMed Central

Meurer, William J.; Quinn, James; Lindsell, Christopher; Schneider, Sandra; Newgard, Craig D.

2016-01-01

Background The Clinical and Translational Science Award (CTSA) program aims to strengthen and support translational research by accelerating the process of translating laboratory discoveries into treatments for patients, training a new generation of clinical and translational researchers, and engaging communities in clinical research efforts. Yet, little is known about how emergency care researchers have interacted with and utilized the resources of academic institutions with CTSAs. Objective The purpose of this survey was to describe how emergency care researchers use local CTSA resources, to ascertain what proportion of CTSA consortium members have active emergency care research programs, and to solicit participation in a national CTSA-associated emergency care translational research network. Methods Survey of all emergency departments affiliated with a CTSA. Results Of the 65 CTSA consortium members, three had no emergency care research program and we obtained responses from 46 of the remaining 62 (74% response rate). The interactions with and resources used by emergency care researchers varied widely. Methodology and biostatistics support was most frequently accessed (77%), followed closely by education and training programs (60%). Several emergency care research programs (76%) had submitted for funding through CTSAs, with 71% receiving awards. Most CTSA consortium members had an active emergency care research infrastructure: 21 (46%) had 24/7 availability to recruit and screen for research, 21 (46%) had less than 24/7 research recruitment. A number of emergency care research programs participated in NIH research networks with the Neurological Emergencies Treatment Trials network most highly represented with 23 (59%) sites. Most emergency care research programs (96%) were interested in participating in a CTSA-based emergency care translational research network. Conclusions Despite little initial involvement in development of the CTSA program, there has been moderate interaction between CTSAs and emergency care. There is considerable interest in participating in a CTSA consortium based emergency care translational research network. PMID:26826059

Emergency Medicine Resources Within the Clinical Translational Science Institutes: A Cross-sectional Study.

PubMed

Meurer, William J; Quinn, James; Lindsell, Christopher; Schneider, Sandra; Newgard, Craig D

2016-06-01

The Clinical and Translational Science Award (CTSA) program aims to strengthen and support translational research by accelerating the process of translating laboratory discoveries into treatments for patients, training a new generation of clinical and translational researchers, and engaging communities in clinical research efforts. Yet, little is known about how emergency care researchers have interacted with and utilized the resources of academic institutions with CTSAs. The purpose of this survey was to describe how emergency care researchers use local CTSA resources, to ascertain what proportion of CTSA consortium members have active emergency care research (ECR) programs, and to solicit participation in a national CTSA-associated emergency care translational research network. This study was a survey of all emergency departments affiliated with a CTSA. Of the 65 CTSA consortium members, three had no ECR program and we obtained responses from 46 of the remaining 62 (74% response rate). The interactions with and resources used by emergency care researchers varied widely. Methodology and biostatistics support was most frequently accessed (77%), followed closely by education and training programs (60%). Several ECR programs (76%) had submitted for funding through CTSAs, with 71% receiving awards. Most CTSA consortium members had an active ECR infrastructure: 21 (46%) had 24/7 availability to recruit and screen for research, and 21 (46%) had less than 24/7 research recruitment. A number of emergency care research programs participated in National Institutes of Health research networks with the Neurological Emergencies Treatment Trials network most highly represented with 23 (59%) sites. Most ECR programs (96%) were interested in participating in a CTSA-based emergency care translational research network. Despite little initial involvement in development of the CTSA program, there has been moderate interaction between CTSAs and emergency care. There is considerable interest in participating in a CTSA consortium-based emergency care translational research network. © 2016 by the Society for Academic Emergency Medicine.

Glutamate Stimulates Local Protein Synthesis in the Axons of Rat Cortical Neurons by Activating α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors and Metabotropic Glutamate Receptors.

PubMed

Hsu, Wei-Lun; Chung, Hui-Wen; Wu, Chih-Yueh; Wu, Huei-Ing; Lee, Yu-Tao; Chen, En-Chan; Fang, Weilun; Chang, Yen-Chung

2015-08-21

Glutamate is the principal excitatory neurotransmitter in the mammalian CNS. By analyzing the metabolic incorporation of azidohomoalanine, a methionine analogue, in newly synthesized proteins, we find that glutamate treatments up-regulate protein translation not only in intact rat cortical neurons in culture but also in the axons emitting from cortical neurons before making synapses with target cells. The process by which glutamate stimulates local translation in axons begins with the binding of glutamate to the ionotropic AMPA receptors and metabotropic glutamate receptor 1 and members of group 2 metabotropic glutamate receptors on the plasma membrane. Subsequently, the activated mammalian target of rapamycin (mTOR) signaling pathway and the rise in Ca(2+), resulting from Ca(2+) influxes through calcium-permeable AMPA receptors, voltage-gated Ca(2+) channels, and transient receptor potential canonical channels, in axons stimulate the local translation machinery. For comparison, the enhancement effects of brain-derived neurotrophic factor (BDNF) on the local protein synthesis in cortical axons were also studied. The results indicate that Ca(2+) influxes via transient receptor potential canonical channels and activated the mTOR pathway in axons also mediate BDNF stimulation to local protein synthesis. However, glutamate- and BDNF-induced enhancements of translation in axons exhibit different kinetics. Moreover, Ca(2+) and mTOR signaling appear to play roles carrying different weights, respectively, in transducing glutamate- and BDNF-induced enhancements of axonal translation. Thus, our results indicate that exposure to transient increases of glutamate and more lasting increases of BDNF would stimulate local protein synthesis in migrating axons en route to their targets in the developing brain. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Glutamate Stimulates Local Protein Synthesis in the Axons of Rat Cortical Neurons by Activating α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors and Metabotropic Glutamate Receptors*

PubMed Central

Hsu, Wei-Lun; Chung, Hui-Wen; Wu, Chih-Yueh; Wu, Huei-Ing; Lee, Yu-Tao; Chen, En-Chan; Fang, Weilun; Chang, Yen-Chung

2015-01-01

Glutamate is the principal excitatory neurotransmitter in the mammalian CNS. By analyzing the metabolic incorporation of azidohomoalanine, a methionine analogue, in newly synthesized proteins, we find that glutamate treatments up-regulate protein translation not only in intact rat cortical neurons in culture but also in the axons emitting from cortical neurons before making synapses with target cells. The process by which glutamate stimulates local translation in axons begins with the binding of glutamate to the ionotropic AMPA receptors and metabotropic glutamate receptor 1 and members of group 2 metabotropic glutamate receptors on the plasma membrane. Subsequently, the activated mammalian target of rapamycin (mTOR) signaling pathway and the rise in Ca2+, resulting from Ca2+ influxes through calcium-permeable AMPA receptors, voltage-gated Ca2+ channels, and transient receptor potential canonical channels, in axons stimulate the local translation machinery. For comparison, the enhancement effects of brain-derived neurotrophic factor (BDNF) on the local protein synthesis in cortical axons were also studied. The results indicate that Ca2+ influxes via transient receptor potential canonical channels and activated the mTOR pathway in axons also mediate BDNF stimulation to local protein synthesis. However, glutamate- and BDNF-induced enhancements of translation in axons exhibit different kinetics. Moreover, Ca2+ and mTOR signaling appear to play roles carrying different weights, respectively, in transducing glutamate- and BDNF-induced enhancements of axonal translation. Thus, our results indicate that exposure to transient increases of glutamate and more lasting increases of BDNF would stimulate local protein synthesis in migrating axons en route to their targets in the developing brain. PMID:26134564

Translational Implications of Tamil "Hamlets."

ERIC Educational Resources Information Center

Kanakaraj, S.

1994-01-01

Discusses the use of translation when teaching English as a Second Language in a Tamil context. Singles out the fencing episode in Shakespeare's "Hamlet" to illustrate the difficulties of translating cultural aspects. Concludes that successful translations of Shakespeare into Indian languages should involve collaboration between…

Multiple-stage ambiguity in motion perception reveals global computation of local motion directions.

PubMed

Rider, Andrew T; Nishida, Shin'ya; Johnston, Alan

2016-12-01

The motion of a 1D image feature, such as a line, seen through a small aperture, or the small receptive field of a neural motion sensor, is underconstrained, and it is not possible to derive the true motion direction from a single local measurement. This is referred to as the aperture problem. How the visual system solves the aperture problem is a fundamental question in visual motion research. In the estimation of motion vectors through integration of ambiguous local motion measurements at different positions, conventional theories assume that the object motion is a rigid translation, with motion signals sharing a common motion vector within the spatial region over which the aperture problem is solved. However, this strategy fails for global rotation. Here we show that the human visual system can estimate global rotation directly through spatial pooling of locally ambiguous measurements, without an intervening step that computes local motion vectors. We designed a novel ambiguous global flow stimulus, which is globally as well as locally ambiguous. The global ambiguity implies that the stimulus is simultaneously consistent with both a global rigid translation and an infinite number of global rigid rotations. By the standard view, the motion should always be seen as a global translation, but it appears to shift from translation to rotation as observers shift fixation. This finding indicates that the visual system can estimate local vectors using a global rotation constraint, and suggests that local motion ambiguity may not be resolved until consistencies with multiple global motion patterns are assessed.

47 CFR 74.1250 - Transmitters and associated equipment.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Translator Stations and FM Broadcast Booster Stations § 74.1250 Transmitters and associated equipment. (a) FM translator and booster transmitting apparatus, and exciters employed to provide a locally generated and modulated input signal to translator and booster equipment, used by stations authorized under the provisions...

47 CFR 74.1250 - Transmitters and associated equipment.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Translator Stations and FM Broadcast Booster Stations § 74.1250 Transmitters and associated equipment. (a) FM translator and booster transmitting apparatus, and exciters employed to provide a locally generated and modulated input signal to translator and booster equipment, used by stations authorized under the provisions...

47 CFR 74.1250 - Transmitters and associated equipment.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Translator Stations and FM Broadcast Booster Stations § 74.1250 Transmitters and associated equipment. (a) FM translator and booster transmitting apparatus, and exciters employed to provide a locally generated and modulated input signal to translator and booster equipment, used by stations authorized under the provisions...

47 CFR 74.1250 - Transmitters and associated equipment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Translator Stations and FM Broadcast Booster Stations § 74.1250 Transmitters and associated equipment. (a) FM translator and booster transmitting apparatus, and exciters employed to provide a locally generated and modulated input signal to translator and booster equipment, used by stations authorized under the provisions...

The Open Translation MOOC: Creating Online Communities to Transcend Linguistic Barriers

ERIC Educational Resources Information Center

Beaven, Tita; Comas-Quinn, Anna; Hauck, Mirjam; de los Arcos, Beatriz; Lewis, Timothy

2013-01-01

One of the main barriers to the reuse of Open Educational Resources (OER) is language (OLnet, 2009). OER may be available but in a language that users cannot access, so a preliminary step to reuse is their translation or localization. One of the obvious solutions to the vast effort required to translate OER is to crowd-source the translation, as…

Sumoylation of Rap1 mediates the recruitment of TFIID to promote transcription of ribosomal protein genes

PubMed Central

Chymkowitch, Pierre; Nguéa P, Aurélie; Aanes, Håvard; Koehler, Christian J.; Thiede, Bernd; Lorenz, Susanne; Meza-Zepeda, Leonardo A.; Klungland, Arne; Enserink, Jorrit M.

2015-01-01

Transcription factors are abundant Sumo targets, yet the global distribution of Sumo along the chromatin and its physiological relevance in transcription are poorly understood. Using Saccharomyces cerevisiae, we determined the genome-wide localization of Sumo along the chromatin. We discovered that Sumo-enriched genes are almost exclusively involved in translation, such as tRNA genes and ribosomal protein genes (RPGs). Genome-wide expression analysis showed that Sumo positively regulates their transcription. We also discovered that the Sumo consensus motif at RPG promoters is identical to the DNA binding motif of the transcription factor Rap1. We demonstrate that Rap1 is a molecular target of Sumo and that sumoylation of Rap1 is important for cell viability. Furthermore, Rap1 sumoylation promotes recruitment of the basal transcription machinery, and sumoylation of Rap1 cooperates with the target of rapamycin kinase complex 1 (TORC1) pathway to promote RPG transcription. Strikingly, our data reveal that sumoylation of Rap1 functions in a homeostatic feedback loop that sustains RPG transcription during translational stress. Taken together, Sumo regulates the cellular translational capacity by promoting transcription of tRNA genes and RPGs. PMID:25800674

Strolling Toward New Concepts.

PubMed

Ito, Koreaki

2016-09-08

For more than four decades now, I have been studying how genetic information is transformed into protein-based cellular functions. This has included investigations into the mechanisms supporting cellular localization of proteins, disulfide bond formation, quality control of membranes, and translation. I tried to extract new principles and concepts that are universal among living organisms from our observations of Escherichia coli. While I wanted to distill complex phenomena into basic principles, I also tried not to overlook any serendipitous observations. In the first part of this article, I describe personal experiences during my studies of the Sec pathway, which have centered on the SecY translocon. In the second part, I summarize my views of the recent revival of translation studies, which has given rise to the concept that nonuniform polypeptide chain elongation is relevant for the subsequent fates of newly synthesized proteins. Our studies of a class of regulatory nascent polypeptides advance this concept by showing that the dynamic behaviors of the extraribosomal part of the nascent chain affect the ongoing translation process. Vibrant and regulated molecular interactions involving the ribosome, mRNA, and nascent polypeptidyl-tRNA are based, at least partly, on their autonomously interacting properties.

Evidence-based decision-making 7: Knowledge translation.

PubMed

Manns, Braden J

2015-01-01

There is a significant gap between what is known and what is implemented by key stakeholders in practice (the evidence to practice gap). The primary purpose of knowledge translation is to address this gap, bridging evidence to clinical practice. The knowledge to action cycle is one framework for knowledge translation that integrates policy-makers throughout the research cycle. The knowledge to action cycle begins with the identification of a problem (usually a gap in care provision). After identification of the problem, knowledge creation is undertaken, depicted at the center of the cycle as a funnel. Knowledge inquiry is at the wide end of the funnel, and moving down the funnel, the primary data is synthesized into knowledge products in the form of educational materials, guidelines, decision aids, or clinical pathways. The remaining components of the knowledge to action cycle refer to the action of applying the knowledge that has been created. This includes adapting knowledge to local context, assessing barriers to knowledge use, selecting, tailoring implementing interventions, monitoring knowledge use, evaluating outcomes, and sustaining knowledge use. Each of these steps is connected by bidirectional arrows and ideally involves healthcare decision-makers and key stakeholders at each transition.

The nuclear protein Sam68 is cleaved by the FMDV 3C protease redistributing Sam68 to the cytoplasm during FMDV infection of host cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lawrence, Paul; Schafer, Elizabeth A.; Rieder, Elizabeth, E-mail: elizabeth.rieder@ars.usda.gov

2012-03-30

Picornavirus infection can lead to disruption of nuclear pore traffic, shut-off of cell translation machinery, and cleavage of proteins involved in cellular signal transduction and the innate response to infection. Here, we demonstrated that the FMDV 3C{sup pro} induced the cleavage of nuclear RNA-binding protein Sam68 C-terminus containing the nuclear localization sequence (NLS). Consequently, it stimulated the redistribution of Sam68 to the cytoplasm. The siRNA knockdown of Sam68 resulted in a 1000-fold reduction in viral titers, which prompted us to study the effect of Sam68 on FMDV post-entry events. Interestingly, Sam68 interacts with the internal ribosomal entry site within themore » 5 Prime non-translated region of the FMDV genome, and Sam68 knockdown decreased FMDV IRES-driven activity in vitro suggesting that it could modulate translation of the viral genome. The results uncover a novel role for Sam68 in the context of picornaviruses and the proteolysis of a new cellular target of the FMDV 3C{sup pro}.« less

Construct validation of emotional labor scale for a sample of Pakistani corporate employees.

PubMed

Akhter, Noreen

2017-02-01

To translate, adapt and validate emotional labour scale for Pakistani corporate employees. This study was conducted in locale of Rawalpindi and Islamabad from October 2014 to December 2015, and comprised customer service employees of commercial banks and telecommunication companies. It comprised of two independent parts. Part one had two steps. Step one involved translation and adaptation of the instrument. In the second step psychometric properties of the translated scale were established by administering it to customer services employees from commercial banks and the telecommunication sector. Data of the pilot study was analysed by using exploratory factor analysis to extract the initial factor of emotional labour. Part two comprised the main study. Commercial bank employees were included in the sample by using convenient sampling technique. SPSS 20 was used for data analysis. There were 145 participants in the first study and 495 in the second study . Exploratory factor analysis initially generated three-factor model of emotional labour which was further confirmed by confirmatory factor analysis suggesting that emotional labour had three distinct dimensions, i.e. surface acting, deep acting and genuine expressions of emotions. The emotional labour scale was found to be a valid and reliable measure.

47 CFR 64.3002 - Transition to 911 as the universal emergency telephone number.

Code of Federal Regulations, 2010 CFR

2010-10-01

...: (a) Where a PSAP has been designated, telecommunications carriers shall complete all translation and... been designated, telecommunications carriers shall complete all translation and routing necessary to... shall complete the translation and routing necessary to deliver 911 calls to an appropriate local...

47 CFR 74.780 - Broadcast regulations applicable to translators, low power, and booster stations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... TV translator, low power TV, and TV booster stations: Section 73.653—Operation of TV aural and visual... stations locally originating programming as defined by § 74.701(h)). Section 73.1201—Station identification (for low power TV stations locally originating programming as defined by § 74.701(h)). Section 73.1206...

Collaborative Translations: Designing Bilingual Instructional Tools

ERIC Educational Resources Information Center

Keyes, Christopher S.; Puzio, Kelly; Jiménez, Robert T.

2014-01-01

Recognizing the role of collaboration and multilingual literacy as 21st-century skills, the authors used design research methods to present, analyze, and refine a strategic reading approach for bilingual students. The collaborative translation strategy involves reading an academic text, translating key passages, and evaluating these translations.…

The Measurement of Translation Ability.

ERIC Educational Resources Information Center

Stansfield, Charles W.; And Others

1992-01-01

Variables that constitute translation ability are discussed, based on a two-year development and validation study of job-related tests of translation ability for the Federal Bureau of Investigation. The project involved the development of two parallel forms of the Spanish into English Verbatim Translation Exam (SEVTE). (five references) (LB)

Does remote sensing help translating local SGD investigation to large spatial scales?

NASA Astrophysics Data System (ADS)

Moosdorf, N.; Mallast, U.; Hennig, H.; Schubert, M.; Knoeller, K.; Neehaul, Y.

2016-02-01

Within the last 20 years, studies on submarine groundwater discharge (SGD) have revealed numerous processes, temporal behavior and quantitative estimations as well as best-practice and localization methods. This plethora on information is valuable regarding the understanding of magnitude and effects of SGD for the respective location. Yet, since given local conditions vary, the translation of local understanding, magnitudes and effects to a regional or global scale is not trivial. In contrast, modeling approaches (e.g. 228Ra budget) tackling SGD on a global scale do provide quantitative global estimates but have not been related to local investigations. This gap between the two approaches, local and global, and the combination and/or translation of either one to the other represents one of the mayor challenges the SGD community currently faces. But what if remote sensing can provide certain information that may be used as translation between the two, similar to transfer functions in many other disciplines allowing an extrapolation from in-situ investigated and quantified SGD (discrete information) to regional scales or beyond? Admittedly, the sketched future is ambitious and we will certainly not be able to present a solution to the raised question. Nonetheless, we will show a remote sensing based approach that is already able to identify potential SGD sites independent on location or hydrogeological conditions. Based on multi-temporal thermal information of the water surface as core of the approach, SGD influenced sites display a smaller thermal variation (thermal anomalies) than surrounding uninfluenced areas. Despite the apparent simplicity, the automatized approach has helped to localize several sites that could be validated with proven in-situ methods. At the same time it embodies the risk to identify false positives that can only be avoided if we can `calibrate' the so obtained thermal anomalies to in-situ data. We will present all pros and cons of our approach with the intention to contribute to the solution of translating SGD investigation to larger scales.

Online Localization of "Zooniverse" Citizen Science Projects--On the Use of Translation Platforms as Tools for Translator Education

ERIC Educational Resources Information Center

Michalak, Krzysztof

2015-01-01

This paper aims at describing the way in which online translation platforms can facilitate the process of training translators. "Zooniverse," a website hosting a variety of citizen science projects in which everyone can take part, was used as an example of such a concept. The first section of this paper is focused on the history, idea…

Moving messages in the developing brain—emerging roles for mRNA transport and local translation in neural stem cells

PubMed Central

Pilaz, Louis-Jan; Silver, Debra L.

2017-01-01

The mammalian cerebral cortex is a complex brain structure integral to our higher cognition. During embryonic cortical development, radial glial progenitors (RGCs) produce neurons and serve as physical structures for migrating neurons. Recent discoveries highlight new roles for RNA localization and local translation in RGCs, both at the cell body and at distal structures called basal endfeet. By implementing technologies from the field of RNA research to brain development, investigators can manipulate RNA-binding proteins as well as visualize single-molecule RNAs, live movement of mRNAs and their binding proteins, and translation. Going forward, these studies establish a framework for investigating how post-transcriptional RNA regulation helps shape RGC function and triggers neurodevelopmental diseases. PMID:28304078

Transforming Business Communication by Building on Forman's Translation Metaphor.

ERIC Educational Resources Information Center

Sherblom, John C.

1998-01-01

Responds to an article in this issue. Reconceptualizes translation as a bidirectional, dynamically negotiated process that occurs within and between communities of scholars and that transforms the language, the person of the translator, the communities involved, and the cultural expectations. Argues that conception of translation predicts a…

Links between media communication and local perceptions of climate change in an indigenous society

PubMed Central

Fernández-Llamazares, Álvaro; Méndez-López, María Elena; Díaz-Reviriego, Isabel; McBride, Marissa F.; Pyhälä, Aili; Rosell-Melé, Antoni; Reyes-García, Victoria

2015-01-01

Indigenous societies hold a great deal of ethnoclimatological knowledge that could potentially be of key importance for both climate change science and local adaptation; yet, we lack studies examining how such knowledge might be shaped by media communication. This study systematically investigates the interplay between local observations of climate change and the reception of media information amongst the Tsimane’, an indigenous society of Bolivian Amazonia where the scientific discourse of anthropogenic climate change has barely reached. Specifically, we conducted a Randomized Evaluation with a sample of 424 household heads in 12 villages to test to what degree local accounts of climate change are influenced by externally influenced awareness. We randomly assigned villages to a treatment and control group, conducted workshops on climate change with villages in the treatment group, and evaluated the effects of information dissemination on individual climate change perceptions. Results of this work suggest that providing climate change information through participatory workshops does not noticeably influence individual perceptions of climate change. Such findings stress the challenges involved in translating between local and scientific framings of climate change, and gives cause for concern about how to integrate indigenous peoples and local knowledge with global climate change policy debates. PMID:26166919

Links between media communication and local perceptions of climate change in an indigenous society.

PubMed

Fernández-Llamazares, Álvaro; Méndez-López, María Elena; Díaz-Reviriego, Isabel; McBride, Marissa F; Pyhälä, Aili; Rosell-Melé, Antoni; Reyes-García, Victoria

2015-07-01

Indigenous societies hold a great deal of ethnoclimatological knowledge that could potentially be of key importance for both climate change science and local adaptation; yet, we lack studies examining how such knowledge might be shaped by media communication. This study systematically investigates the interplay between local observations of climate change and the reception of media information amongst the Tsimane', an indigenous society of Bolivian Amazonia where the scientific discourse of anthropogenic climate change has barely reached. Specifically, we conducted a Randomized Evaluation with a sample of 424 household heads in 12 villages to test to what degree local accounts of climate change are influenced by externally influenced awareness. We randomly assigned villages to a treatment and control group, conducted workshops on climate change with villages in the treatment group, and evaluated the effects of information dissemination on individual climate change perceptions. Results of this work suggest that providing climate change information through participatory workshops does not noticeably influence individual perceptions of climate change. Such findings stress the challenges involved in translating between local and scientific framings of climate change, and gives cause for concern about how to integrate indigenous peoples and local knowledge with global climate change policy debates.

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

PubMed Central

2018-01-01

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

An exploratory study examining the influence of translation on the validity and reliability of qualitative data in nursing research.

PubMed

Twinn, S

1997-08-01

Although the complexity of undertaking qualitative research with non-English speaking informants has become increasingly recognized, few empirical studies exist which explore the influence of translation on the findings of the study. The aim of this exploratory study was therefore to examine the influence of translation on the reliability and validity of the findings of a qualitative research study. In-depth interviews were undertaken in Cantonese with a convenience sample of six women to explore their perceptions of factors influencing their uptake of Pap smears. Data analysis involved three stages. The first stage involved the translation and transcription of all the interviews into English independently by two translators as well as transcription into Chinese by a third researcher. The second stage involved content analysis of the three data sets to develop categories and themes and the third stage involved a comparison of the categories and themes generated from the Chinese and English data sets. Despite no significant differences in the major categories generated from the Chinese and English data, some minor differences were identified in the themes generated from the data. More significantly the results of the study demonstrated some important issues to consider when using translation in qualitative research, in particular the complexity of managing data when no equivalent word exists in the target language and the influence of the grammatical style on the analysis. In addition the findings raise questions about the significance of the conceptual framework of the research design and sampling to the validity of the study. The importance of using only one translator to maximize the reliability of the study was also demonstrated. In addition the author suggests the findings demonstrate particular problems in using translation in phenomenological research designs.

Tonic dopamine induces persistent changes in the transient potassium current through translational regulation

PubMed Central

Rodgers, EW; Krenz, W-D; Baro, DJ

2012-01-01

Neuromodulatory effects can vary with their mode of transmission. Phasic release produces local and transient increases in dopamine (DA) up to micromolar concentrations. Additionally, since DA is released from open synapses and reuptake mechanisms are not nearby, tonic nanomolar DA exists in the extracellular space. Do phasic and tonic transmissions similarly regulate voltage dependent ionic conductances in a given neuron? It was previously shown that DA could immediately alter the transient potassium current (IA) of identified neurons in the stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus. Here we show that DA can also persistently alter IA, and that DA’s immediate and persistent effects oppose one another. The lateral pyloric neuron (LP) exclusively expresses type 1 DA receptors (D1Rs). Micromolar DA produces immediate depolarizing shifts in the voltage dependence of LP IA, whereas tonic nanomolar DA produces a persistent increase in LP IA maximal conductance (Gmax) through a translation dependent mechanism involving target of rapamycin (TOR). The pyloric dilator neuron (PD) exclusively expresses type 2 DA receptors (D2Rs). Micromolar DA produces an immediate hyperpolarizing shift in PD IA voltage dependence of activation, whereas tonic DA persistently decreases PD IA Gmax through a translation dependent mechanism not involving TOR. The persistent effects on IA Gmax do not depend on LP or PD activity. These data suggest a role for tonic modulators in the regulation of voltage gated ion channel number; and furthermore, that dopaminergic systems may be organized to limit the amount of change they can impose on a circuit. PMID:21917788

3D local structure around copper site of rabbit prion-related protein: Quantitative determination by XANES spectroscopy combined with multiple-scattering calculations

NASA Astrophysics Data System (ADS)

Cui, P. X.; Lian, F. L.; Wang, Y.; Wen, Yi; Chu, W. S.; Zhao, H. F.; Zhang, S.; Li, J.; Lin, D. H.; Wu, Z. Y.

2014-02-01

Prion-related protein (PrP), a cell-surface copper-binding glycoprotein, is considered to be responsible for a number of transmissible spongiform encephalopathies (TSEs). The structural conversion of PrP from the normal cellular isoform (PrPC) to the post-translationally modified form (PrPSc) is thought to be relevant to Cu2+ binding to histidine residues. Rabbits are one of the few mammalian species that appear to be resistant to TSEs, because of the structural characteristics of the rabbit prion protein (RaPrPC) itself. Here we determined the three-dimensional local structure around the C-terminal high-affinity copper-binding sites using X-ray absorption near-edge structure combined with ab initio calculations in the framework of the multiple-scattering (MS) theory. Result shows that two amino acid resides, Gln97 and Met108, and two histidine residues, His95 and His110, are involved in binding this copper(II) ion. It might help us understand the roles of copper in prion conformation conversions, and the molecular mechanisms of prion-involved diseases.

Translating national level forest service goals to local level land management: carbon sequestration

Treesearch

Steven McNulty; Emrys Treasure; Lisa Jennings; David Meriwether; David Harris; Paul Arndt

2017-01-01

The USDA Forest Service has many national level policies related to multiple use management. However, translating national policy to stand level forest management can be difficult. As an example of how a national policy can be put into action, we examined three case studies in which a desired future condition is evaluated at the national, region, and local scale. We...

Time-Resolved Intrafraction Target Translations and Rotations During Stereotactic Liver Radiation Therapy: Implications for Marker-based Localization Accuracy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bertholet, Jenny, E-mail: jennbe@rm.dk; Worm, Esben S.; Fledelius, Walther

Purpose: Image guided liver stereotactic body radiation therapy (SBRT) often relies on implanted fiducial markers. The target localization accuracy decreases with increased marker-target distance. This may occur partly because of liver rotations. The aim of this study was to examine time-resolved translations and rotations of liver marker constellations and investigate if time-resolved intrafraction rotational corrections can improve localization accuracy in liver SBRT. Methods and Materials: Twenty-nine patients with 3 implanted markers received SBRT in 3 to 6 fractions. The time-resolved trajectory of each marker was estimated from the projections of 1 to 3 daily cone beam computed tomography scans andmore » used to calculate the translation and rotation of the marker constellation. In all cone beam computed tomography projections, the time-resolved position of each marker was predicted from the position of another surrogate marker by assuming that the marker underwent either (1) the same translation as the surrogate marker; or (2) the same translation as the surrogate marker corrected by the rotation of the marker constellation. The localization accuracy was quantified as the root-mean-square error (RMSE) between the estimated and the actual marker position. For comparison, the RMSE was also calculated when the marker's position was estimated as its mean position for all the projections. Results: The mean translational and rotational range (2nd-98th percentile) was 2.0 mm/3.9° (right-left), 9.2 mm/2.9° (superior-inferior), 4.0 mm/4.0° (anterior-posterior), and 10.5 mm (3-dimensional). Rotational corrections decreased the mean 3-dimensional RMSE from 0.86 mm to 0.54 mm (P<.001) and halved the RMSE increase per millimeter increase in marker distance. Conclusions: Intrafraction rotations during liver SBRT reduce the accuracy of marker-guided target localization. Rotational correction can improve the localization accuracy with a factor of approximately 2 for large marker-target distances.« less

Comparison between electromagnetic transponders and radiographic imaging for prostate localization: A pelvic phantom study with rotations and translations.

PubMed

Hamilton, Daniel G; McKenzie, Dean P; Perkins, Anne E

2017-09-01

The aim of this study was to evaluate the differences in target localization between Calypso ® , kV orthogonal imaging and cone-beam computed tomography (CBCT) for combined translations and rotations of an anthropomorphic pelvic phantom. The phantom was localized using all three systems in 50 different positions, with applied translational and rotational offsets randomly sampled from representative normal distributions of prostate motion. Lin's concordance correlation coefficient (ρc) and 95% confidence intervals were calculated to assess the agreement between the localization systems. Mean differences and difference vectors between the three systems were also calculated. Agreement between systems for lateral, vertical, and longitudinal translations was excellent, with ρc values of greater than 0.98 between all three systems in all axes. There was excellent agreement between the systems for rotations around the lateral axis (pitch) (ρc > 0.99), and around the vertical axis (yaw) (ρc > 0.97). However, somewhat poorer agreement for rotations around the longitudinal axis (roll) was observed, with the lowest correlation observed between Calypso and kV orthogonal imaging (ρc = 0.895). Mean differences between the phantom position reported by Calypso and the radiographic systems were less than 1 mm and 1° for all translations and rotations. The results for translations are consistent with the publications of previous authors. There is no comparable published data for rotations. While there is lower correlation between the three systems for roll than for the other angles, the mean differences in reported rotations are not clinically significant. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

A precompiler for the formula manipulation system TRIGMAN.

NASA Technical Reports Server (NTRS)

Jefferys, W. H.

1972-01-01

Discussion of a translator designed to simplify the programming of problems involving the TRIGMAN formula manipulation system. The translator allows for the introduction of a new data type, SERIES, into a FORTRAN program and translates a user's program into legal FORTRAN. The translator is adaptable to other formula manipulation systems presently used in celestial mechanics.

Fe-S cluster coordination of the chromokinesin KIF4A alters its sub-cellular localization during mitosis.

PubMed

Ben-Shimon, Lilach; Paul, Viktoria D; David-Kadoch, Galit; Volpe, Marina; Stümpfig, Martin; Bill, Eckhard; Mühlenhoff, Ulrich; Lill, Roland; Ben-Aroya, Shay

2018-05-30

Fe-S clusters act as co-factors of proteins with diverse functions, e.g. in DNA repair. Down-regulation of the cytosolic iron-sulfur protein assembly (CIA) machinery promotes genomic instability by the inactivation of multiple DNA repair pathways. Furthermore, CIA deficiencies are associated with so far unexplained mitotic defects. Here, we show that CIA2B and MMS19, constituents of the CIA targeting complex involved in facilitating Fe-S cluster insertion into cytosolic and nuclear target proteins, co-localize with components of the mitotic machinery. Down-regulation of CIA2B and MMS19 impairs the mitotic cycle. We identify the chromokinesin KIF4A as a mitotic component involved in these effects. KIF4A binds a Fe-S cluster in vitro through its conserved cysteine-rich domain. We demonstrate in vivo that this domain is required for the mitosis-related KIF4A localization and for the mitotic defects associated with KIF4A knockout. KIF4A is the first identified mitotic component carrying such a post-translational modification. These findings suggest that the lack of Fe-S clusters in KIF4A upon down-regulation of the CIA targeting complex contributes to the mitotic defects. © 2018. Published by The Company of Biologists Ltd.

Lost in translation: conflicting views of deforestation, land use and identity in western Madagascar.

PubMed

Scales, Ivan R

2012-01-01

This paper focuses on the interplay between environmental narratives, identity politics and the management of forest resources in Madagascar. While efforts to conserve the island's biological diversity have centred primarily on the designation of protected areas, policies have increasingly focused on local communities. The experiences of the last 20 years have shown that community-based approaches to conservation offer considerable challenges due to the complex politics of natural resource use, which involve multiple and diverse stakeholders, often with very different and sometimes conflicting values. In this paper, I focus on the environmental perceptions and values of two groups in the Central Menabe region of western Madagascar – conservation organisations and rural households – revealing a contrasting set of views regarding the region's forest. I show that the conservation discourse has changed over time, increasingly emphasising the biological diversity of the region's tropical dry-deciduous forest and prioritising non-consumptive uses of natural resources. Although policy has changed in response to changing values, I show that it has been underpinned by the notion that hatsake (‘slash-and-burn’ agriculture) is an irrational practice driven by necessity rather than choice. Policy has thus sought to provide livelihood alternatives, firstly through forestry, then through changes in cultivation and increasingly through tourism. This misunderstands the local view of the forest, which sees hatsake as a way to make the land productive, as long as it is carried out responsibly according to local fady (taboos). As well as facing problems of translating conservation goals into local values and misunderstanding the motives for forest clearance, policy has been based on a narrative that attaches particular land use practices to ethnic identities. I argue that this ignores the history and fluid reality of both identity and land use.

Language translation challenges with Arabic speakers participating in qualitative research studies.

PubMed

Al-Amer, Rasmieh; Ramjan, Lucie; Glew, Paul; Darwish, Maram; Salamonson, Yenna

2016-02-01

This paper discusses how a research team negotiated the challenges of language differences in a qualitative study that involved two languages. The lead researcher shared the participants' language and culture, and the interviews were conducted using the Arabic language as a source language, which was then translated and disseminated in the English language (target language). The challenges in relation to translation in cross-cultural research were highlighted from a perspective of establishing meaning as a vital issue in qualitative research. The paper draws on insights gained from a study undertaken among Arabic-speaking participants involving the use of in-depth semi-structured interviews. The study was undertaken using a purposive sample of 15 participants with Type 2 Diabetes Mellitus and co-existing depression and explored their perception of self-care management behaviours. Data analysis was performed in two phases. The first phase entailed translation and transcription of the data, and the second phase entailed thematic analysis of the data to develop categories and themes. In this paper there is discussion on the translation process and its inherent challenges. As translation is an interpretive process and not merely a direct message transfer from a source language to a target language, translators need to systematically and accurately capture the full meaning of the spoken language. This discussion paper highlights difficulties in the translation process, specifically in managing data in relation to metaphors, medical terminology and connotation of the text, and importantly, preserving the meaning between the original and translated data. Recommendations for future qualitative studies involving interviews with non-English speaking participants are outlined, which may assist researchers maintain the integrity of the data throughout the translation process. Copyright © 2015 Elsevier Ltd. All rights reserved.

Translation and articulation in biological motion perception.

PubMed

Masselink, Jana; Lappe, Markus

2015-08-01

Recent models of biological motion processing focus on the articulational aspect of human walking investigated by point-light figures walking in place. However, in real human walking, the change in the position of the limbs relative to each other (referred to as articulation) results in a change of body location in space over time (referred to as translation). In order to examine the role of this translational component on the perception of biological motion we designed three psychophysical experiments of facing (leftward/rightward) and articulation discrimination (forward/backward and leftward/rightward) of a point-light walker viewed from the side, varying translation direction (relative to articulation direction), the amount of local image motion, and trial duration. In a further set of a forward/backward and a leftward/rightward articulation task, we additionally tested the influence of translational speed, including catch trials without articulation. We found a perceptual bias in translation direction in all three discrimination tasks. In the case of facing discrimination the bias was limited to short stimulus presentation. Our results suggest an interaction of articulation analysis with the processing of translational motion leading to best articulation discrimination when translational direction and speed match articulation. Moreover, we conclude that the global motion of the center-of-mass of the dot pattern is more relevant to processing of translation than the local motion of the dots. Our findings highlight that translation is a relevant cue that should be integrated in models of human motion detection.

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

PubMed

Klein, Gunnar O; Chen, Rong

2009-01-01

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

Nucleotide sequence of the gag gene and gag-pol junction of feline leukemia virus.

PubMed Central

Laprevotte, I; Hampe, A; Sherr, C J; Galibert, F

1984-01-01

The nucleotide sequence of the gag gene of feline leukemia virus and its flanking sequences were determined and compared with the corresponding sequences of two strains of feline sarcoma virus and with that of the Moloney strain of murine leukemia virus. A high degree of nucleotide sequence homology between the feline leukemia virus and murine leukemia virus gag genes was observed, suggesting that retroviruses of domestic cats and laboratory mice have a common, proximal evolutionary progenitor. The predicted structure of the complete feline leukemia virus gag gene precursor suggests that the translation of nonglycosylated and glycosylated gag gene polypeptides is initiated at two different AUG codons. These initiator codons fall in the same reading frame and are separated by a 222-base-pair segment which encodes an amino terminal signal peptide. The nucleotide sequence predicts the order of amino acids in each of the individual gag-coded proteins (p15, p12, p30, p10), all of which derive from the gag gene precursor. Stable stem-and-loop secondary structures are proposed for two regions of viral RNA. The first falls within sequences at the 5' end of the viral genome, together with adjacent palindromic sequences which may play a role in dimer linkage of RNA subunits. The second includes coding sequences at the gag-pol junction and is proposed to be involved in translation of the pol gene product. Sequence analysis of the latter region shows that the gag and pol genes are translated in different reading frames. Classical consensus splice donor and acceptor sequences could not be localized to regions which would permit synthesis of the expected gag-pol precursor protein. Alternatively, we suggest that the pol gene product (RNA-dependent DNA polymerase) could be translated by a frameshift suppressing mechanism which could involve cleavage modification of stems and loops in a manner similar to that observed in tRNA processing. PMID:6328019

Translation of an instrument. The US-Nordic Family Dynamics Nursing Research Project.

PubMed

White, M; Elander, G

1992-01-01

Translation of a research instrument questionnaire from English to another language is analyzed in relation to principles involved, procedures followed, and problems confronted by nurse researchers from the US-Nordic Family Dynamics Nursing Research Project. Of paramount importance in translation are translation equivalency, congruent value orientation, and careful use of colloquialisms. It is important to recognize that copyright guidelines apply in the translation of an instrument. Approaches to solving instrument translation problems are discussed.

Clinical and translational research in global health and emergency care: a research agenda.

PubMed

Runyon, Michael S; Sawe, Hendry R; Levine, Adam C; Pousson, Amelia; House, Darlene R; Agrawal, Pooja; Osei-Ampofo, Maxwell; Weiner, Scott G; Douglass, Katherine

2013-12-01

As policy-makers increasingly recognize emergency care to be a global health priority, the need for high-quality clinical and translational research in this area continues to grow. As part of the proceedings of the 2013 Academic Emergency Medicine consensus conference, this article discusses the importance of: 1) including clinical and translational research in the initial emergency care development plan, 2) defining the burden of acute disease and the barriers to conducting research in resource-limited settings, 3) assessing the appropriateness and effectiveness of local and global acute care guidelines within the local context, 4) studying the local research infrastructure needs to understand the best methods to build a sustainable research infrastructure, and 5) studying the long-term effects of clinical research programs on health care systems. © 2013 by the Society for Academic Emergency Medicine.

Granules harboring translationally active mRNAs provide a platform for P-body formation following stress.

PubMed

Lui, Jennifer; Castelli, Lydia M; Pizzinga, Mariavittoria; Simpson, Clare E; Hoyle, Nathaniel P; Bailey, Kathryn L; Campbell, Susan G; Ashe, Mark P

2014-11-06

The localization of mRNA to defined cytoplasmic sites in eukaryotic cells not only allows localized protein production but also determines the fate of mRNAs. For instance, translationally repressed mRNAs localize to P-bodies and stress granules where their decay and storage, respectively, are directed. Here, we find that several mRNAs are localized to granules in unstressed, actively growing cells. These granules play a key role in the stress-dependent formation of P-bodies. Specific glycolytic mRNAs are colocalized in multiple granules per cell, which aggregate during P-body formation. Such aggregation is still observed under conditions or in mutants where P-bodies do not form. In unstressed cells, the mRNA granules appear associated with active translation; this might enable a coregulation of protein expression from the same pathways or complexes. Parallels can be drawn between this coregulation and the advantage of operons in prokaryotic systems. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Digital image registration method based upon binary boundary maps

NASA Technical Reports Server (NTRS)

Jayroe, R. R., Jr.; Andrus, J. F.; Campbell, C. W.

1974-01-01

A relatively fast method is presented for matching or registering the digital data of imagery from the same ground scene acquired at different times, or from different multispectral images, sensors, or both. It is assumed that the digital images can be registed by using translations and rotations only, that the images are of the same scale, and that little or no distortion exists between images. It is further assumed that by working with several local areas of the image, the rotational effects in the local areas can be neglected. Thus, by treating the misalignments of local areas as translations, it is possible to determine rotational and translational misalignments for a larger portion of the image containing the local areas. This procedure of determining the misalignment and then registering the data according to the misalignment can be repeated until the desired degree of registration is achieved. The method to be presented is based upon the use of binary boundary maps produced from the raw digital imagery rather than the raw digital data.

Sumoylation Modulates the Activity of Spalt-like Proteins during Wing Development in Drosophila*

PubMed Central

Sánchez, Jonatan; Talamillo, Ana; Lopitz-Otsoa, Fernando; Pérez, Coralia; Hjerpe, Roland; Sutherland, James D.; Herboso, Leire; Rodríguez, Manuel S.; Barrio, Rosa

2010-01-01

The Spalt-like family of zinc finger transcription factors is conserved throughout evolution and is involved in fundamental processes during development and during embryonic stem cell maintenance. Although human SALL1 is modified by SUMO-1 in vitro, it is not known whether this post-translational modification plays a role in regulating the activity of this family of transcription factors. Here, we show that the Drosophila Spalt transcription factors are modified by sumoylation. This modification influences their nuclear localization and capacity to induce vein formation through the regulation of target genes during wing development. Furthermore, spalt genes interact genetically with the sumoylation machinery to repress vein formation in intervein regions and to attain the wing final size. Our results suggest a new level of regulation of Sall activity in vivo during animal development through post-translational modification by sumoylation. The evolutionary conservation of this family of transcription factors suggests a functional role for sumoylation in vertebrate Sall members. PMID:20562097

A Novel Latin Hypercube Algorithm via Translational Propagation

PubMed Central

Pan, Guang; Ye, Pengcheng

2014-01-01

Metamodels have been widely used in engineering design to facilitate analysis and optimization of complex systems that involve computationally expensive simulation programs. The accuracy of metamodels is directly related to the experimental designs used. Optimal Latin hypercube designs are frequently used and have been shown to have good space-filling and projective properties. However, the high cost in constructing them limits their use. In this paper, a methodology for creating novel Latin hypercube designs via translational propagation and successive local enumeration algorithm (TPSLE) is developed without using formal optimization. TPSLE algorithm is based on the inspiration that a near optimal Latin Hypercube design can be constructed by a simple initial block with a few points generated by algorithm SLE as a building block. In fact, TPSLE algorithm offers a balanced trade-off between the efficiency and sampling performance. The proposed algorithm is compared to two existing algorithms and is found to be much more efficient in terms of the computation time and has acceptable space-filling and projective properties. PMID:25276844

Downregulation of Ras C-terminal processing by JNK inhibition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mouri, Wataru; Department of Neurosurgery, Yamagata University School of Medicine, Yamagata 990-9585; Biology Division, National Cancer Center Research Institute, Tokyo 104-0045

2008-06-27

After translation, Ras proteins undergo a series of modifications at their C-termini. This post-translational C-terminal processing is essential for Ras to become functional, but it remains unknown whether and how Ras C-terminal processing is regulated. Here we show that the C-terminal processing and subsequent plasma membrane localization of H-Ras as well as the activation of the downstream signaling pathways by H-Ras are prevented by JNK inhibition. Conversely, JNK activation by ultraviolet irradiation resulted in promotion of C-terminal processing of H-Ras. Furthermore, increased cell density promoted C-terminal processing of H-Ras most likely through an autocrine/paracrine mechanism, which was also blocked undermore » JNK-inhibited condition. Ras C-terminal processing was sensitive to JNK inhibition in the case of H- and N-Ras but not K-Ras, and in a variety of cell types. Thus, our results suggest for the first time that Ras C-terminal processing is a regulated mechanism in which JNK is involved.« less

The RNA binding and transport proteins staufen and fragile X mental retardation protein are expressed by rat primary afferent neurons and localize to peripheral and central axons.

PubMed

Price, T J; Flores, C M; Cervero, F; Hargreaves, K M

2006-09-15

Neuronal proteins have been traditionally viewed as being derived solely from the soma; however, accumulating evidence indicates that dendritic and axonal sites are capable of a more autonomous role in terms of new protein synthesis. Such extra-somal translation allows for more rapid, on-demand regulation of neuronal structure and function than would otherwise be possible. While mechanisms of dendritic RNA transport have been elucidated, it remains unclear how RNA is trafficked into the axon for this purpose. Primary afferent neurons of the dorsal root (DRG) and trigeminal (TG) ganglia have among the longest axons in the neuraxis and such axonal protein synthesis would be advantageous, given the greater time involved for protein trafficking to occur via axonal transport. Therefore, we hypothesized that these primary sensory neurons might express proteins involved in RNA transport. Rat DRG and TG neurons expressed staufen (stau) 1 and 2 (detected at the mRNA level) and stau2 and fragile x mental retardation protein (FMRP; detected at the protein level). Stau2 mRNA was also detected in human TG neurons. Stau2 and FMRP protein were localized to the sciatic nerve and dorsal roots by immunohistochemistry and to dorsal roots by Western blot. Stau2 and FMRP immunoreactivities colocalized with transient receptor potential channel type 1 immunoreactivity in sensory axons of the sciatic nerve and dorsal root, suggesting that these proteins are being transported into the peripheral and central terminals of nociceptive sensory axons. Based on these findings, we propose that stau2 and FMRP proteins are attractive candidates to subserve RNA transport in sensory neurons, linking somal transcriptional events to axonal translation.

THE RNA BINDING AND TRANSPORT PROTEINS STAUFEN AND FRAGILE X MENTAL RETARDATION PROTEIN ARE EXPRESSED BY RAT PRIMARY AFFERENT NEURONS AND LOCALIZE TO PERIPHERAL AND CENTRAL AXONS

PubMed Central

PRICE, T. J.; FLORES, C. M.; CERVERO, F.; HARGREAVES, K. M.

2007-01-01

Neuronal proteins have been traditionally viewed as being derived solely from the soma; however, accumulating evidence indicates that dendritic and axonal sites are capable of a more autonomous role in terms of new protein synthesis. Such extra-somal translation allows for more rapid, on-demand regulation of neuronal structure and function than would otherwise be possible. While mechanisms of dendritic RNA transport have been elucidated, it remains unclear how RNA is trafficked into the axon for this purpose. Primary afferent neurons of the dorsal root (DRG) and trigeminal (TG) ganglia have among the longest axons in the neuraxis and such axonal protein synthesis would be advantageous, given the greater time involved for protein trafficking to occur via axonal transport. Therefore, we hypothesized that these primary sensory neurons might express proteins involved in RNA transport. Rat DRG and TG neurons expressed staufen (stau) 1 and 2 (detected at the mRNA level) and stau2 and fragile × mental retardation protein (FMRP; detected at the protein level). Stau2 mRNA was also detected in human TG neurons. Stau2 and FMRP protein were localized to the sciatic nerve and dorsal roots by immunohistochemistry and to dorsal roots by Western blot. Stau2 and FMRP immunoreactivities colocalized with transient receptor potential channel type 1 immunoreactivity in sensory axons of the sciatic nerve and dorsal root, suggesting that these proteins are being transported into the peripheral and central terminals of nociceptive sensory axons. Based on these findings, we propose that stau2 and FMRP proteins are attractive candidates to subserve RNA transport in sensory neurons, linking somal transcriptional events to axonal translation. PMID:16809002

Challenges facing translational research organizations in China: a qualitative multiple case study

PubMed Central

2013-01-01

Background Translational medicine is attracting much attention worldwide and many translational research organizations (TROs) have been established. In China, translational medicine has developed rapidly, but faces many challenges. This study was aimed at exploring these challenges faced by emerging TROs in China. Method A qualitative, multiple case study approach was used to assess the challenges faced by TROs in China. Data were collected between May and August 2012. Results Eight cases were identified. Overall, four themes that characterized TROs in China emerged from analyses: 1. objectives, organizer, and funding resources, 2. participating partners and research teams, 3. management, and 4. achievements. All TROs had objectives related to translating basic discovery to clinic treatment and cultivating translational researchers. In terms of organizer and funding resources, 7 out of 8 TROs were launched only by universities and/or hospitals, and funded mostly through research grants. As for participating partners and multidisciplinary research teams, all but one of the TROs only involved biomedical research institutions who were interested in translational research, and characterized as clinical research centers; 7 out of 8 TROs involved only researchers from biomedicine and clinical disciplines and none involved disciplines related to education, ethnicity, and sociology, or engaged the community. Current management of the TROs were generally nested within the traditional research management paradigms, and failed to adapt to the tenets of translational research. Half of the TROs were at developmental stages defined as infrastructure construction and recruitment of translational researchers. Conclusions TROs in China face the challenge of attracting sustainable funding sources, widening multidisciplinary cooperation, cultivating multi-disciplinary translational researchers and adapting current research management to translational research. Greater emphasis should be placed on increasing multidisciplinary cooperation, and innovating in education programs to cultivate of translational researchers. Efforts should be made to reform research management in TROs, and establish sustainable funding resources. PMID:24119837

Differential translation efficiency of orthologous genes is involved in phenotypic divergence of yeast species.

PubMed

Man, Orna; Pilpel, Yitzhak

2007-03-01

A major challenge in comparative genomics is to understand how phenotypic differences between species are encoded in their genomes. Phenotypic divergence may result from differential transcription of orthologous genes, yet less is known about the involvement of differential translation regulation in species phenotypic divergence. In order to assess translation effects on divergence, we analyzed approximately 2,800 orthologous genes in nine yeast genomes. For each gene in each species, we predicted translation efficiency, using a measure of the adaptation of its codons to the organism's tRNA pool. Mining this data set, we found hundreds of genes and gene modules with correlated patterns of translational efficiency across the species. One signal encompassed entire modules that are either needed for oxidative respiration or fermentation and are efficiently translated in aerobic or anaerobic species, respectively. In addition, the efficiency of translation of the mRNA splicing machinery strongly correlates with the number of introns in the various genomes. Altogether, we found extensive selection on synonymous codon usage that modulates translation according to gene function and organism phenotype. We conclude that, like factors such as transcription regulation, translation efficiency affects and is affected by the process of species divergence.

Human T-lymphotropic virus proteins and post-translational modification pathways

PubMed Central

Bidoia, Carlo

2012-01-01

Cell life from the cell cycle to the signaling transduction and response to stimuli is finely tuned by protein post-translational modifications (PTMs). PTMs alter the conformation, the stability, the localization, and hence the pattern of interactions of the targeted protein. Cell pathways involve the activation of enzymes, like kinases, ligases and transferases, that, once activated, act on many proteins simultaneously, altering the state of the cell and triggering the processes they are involved in. Viruses enter a balanced system and hijack the cell, exploiting the potential of PTMs either to activate viral encoded proteins or to alter cellular pathways, with the ultimate consequence to perpetuate through their replication. Human T-lymphotropic virus type 1 (HTLV-1) is known to be highly oncogenic and associates with adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy/tropical spastic paraparesis and other inflammatory pathological conditions. HTLV-1 protein activity is controlled by PTMs and, in turn, viral activity is associated with the modulation of cellular pathways based on PTMs. More knowledge is acquired about the PTMs involved in the activation of its proteins, like Tax, Rex, p12, p13, p30, HTLV-I basic leucine zipper factor and Gag. However, more has to be understood at the biochemical level in order to counteract the associated fatal outcomes. This review will focus on known PTMs that directly modify HTLV-1 components and on enzymes whose activity is modulated by viral proteins. PMID:24175216

A neo-strategic planning approach to enhance local tobacco control programs.

PubMed

Douglas, Malinda R; Carter, Sara Sally R; Wilson, Andrew P; Chan, Andie

2015-01-01

Research in tobacco control demonstrating best practices is widely disseminated; however, application at the local level is often difficult. Translating research into practice requires a concerted effort to develop an understanding of the evidence and how it can be applied within diverse contexts. A strategic planning infrastructure was developed to support the translation of evidence-based interventions into community practice. This paper highlights the strategic process of turning "know-what" into "know-how" to facilitate the strategic planning and implementation of tobacco control best practices at the local level. The purpose, people, process, and product strategies of knowledge management and translation provided a framework for the strategic planning infrastructure. The knowledge translation concepts of audience, motivations, and mechanisms were synergized in the neo-strategic planning component design. The participants were 20 community coalitions funded to implement local tobacco control programs. From 2004 to 2011, the strategic planners facilitated a cyclical process to translate research into practice using a trio of integrated tools, skill-building workshops on strategic planning, and grantee-driven technical assistance and consultation. In the short term, the usefulness of the strategic planning components to the programs was measured. The intermediate outcome was the successful movement of the community programs from the planning stage to the implementation stage. The achievement of community-level changes in planned tobacco control efforts was the overall outcome measure for the success of the local coalitions. Seventeen of 20 communities that began the planning process implemented strategic plans. All 17 of the programs implemented evidence-based practices, resulting in numerous tobacco-free policies, increased cessation, and increased support from the media and community. Bridging the gap between research and practice can enhance the practicality, efficiency, and effectiveness of tobacco control programs at the local level, maximizing the potential positive health impact. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

The significance of translation regulation in the stress response

PubMed Central

2013-01-01

Background The stress response in bacteria involves the multistage control of gene expression but is not entirely understood. To identify the translational response of bacteria in stress conditions and assess its contribution to the regulation of gene expression, the translational states of all mRNAs were compared under optimal growth condition and during nutrient (isoleucine) starvation. Results A genome-scale study of the translational response to nutritional limitation was performed in the model bacterium Lactococcus lactis. Two measures were used to assess the translational status of each individual mRNA: the fraction engaged in translation (ribosome occupancy) and ribosome density (number of ribosomes per 100 nucleotides). Under isoleucine starvation, half of the mRNAs considered were translationally down-regulated mainly due to decreased ribosome density. This pattern concerned genes involved in growth-related functions such as translation, transcription, and the metabolism of fatty acids, phospholipids and bases, contributing to the slowdown of growth. Only 4% of the mRNAs were translationally up-regulated, mostly related to prophagic expression in response to stress. The remaining genes exhibited antagonistic regulations of the two markers of translation. Ribosome occupancy increased significantly for all the genes involved in the biosynthesis of isoleucine, although their ribosome density had decreased. The results revealed complex translational regulation of this pathway, essential to cope with isoleucine starvation. To elucidate the regulation of global gene expression more generally, translational regulation was compared to transcriptional regulation under isoleucine starvation and to other post-transcriptional regulations related to mRNA degradation and mRNA dilution by growth. Translational regulation appeared to accentuate the effects of transcriptional changes for down-regulated growth-related functions under isoleucine starvation although mRNA stabilization and lower dilution by growth counterbalanced this effect. Conclusions We show that the contribution of translational regulation to the control of gene expression is significant in the stress response. Post-transcriptional regulation is complex and not systematically co-directional with transcription regulation. Post-transcriptional regulation is important to the understanding of gene expression control. PMID:23985063

Nuclear-Encoded Mitochondrial mRNAs: A Powerful Force in Axonal Growth and Development.

PubMed

Gale, Jenna R; Aschrafi, Armaz; Gioio, Anthony E; Kaplan, Barry B

2018-04-01

Axons, their growth cones, and synaptic nerve terminals are neuronal subcompartments that have high energetic needs. As such, they are enriched in mitochondria, which supply the ATP necessary to meet these demands. To date, a heterogeneous population of nuclear-encoded mitochondrial mRNAs has been identified in distal axons and growth cones. Accumulating evidence suggests that the local translation of these mRNAs is required for mitochondrial maintenance and axonal viability. Here, we review evidence that suggests a critical role for axonal translation of nuclear-encoded mitochondrial mRNAs in axonal growth and development. Additionally, we explore the role that site-specific translation at the mitochondria itself may play in this process. Finally, we briefly review the clinical implications of dysregulation of local translation of mitochondrial-related mRNAs in neurodevelopmental disorders.

Tackling health literacy: adaptation of public hypertension educational materials for an Indo-Asian population in Canada

PubMed Central

2011-01-01

Background Indo-Asians in Canada are at increased risk for cardiovascular diseases. There is a need for cultural and language specific educational materials relating to this risk. During this project we developed and field tested the acceptability of a hypertension public education pamphlet tailored to fit the needs of an at risk local Indo-Asian population, in Calgary, Alberta, Canada. Methods A community health board representing Calgary's Indo-Asian communities identified the culturally specific educational needs and language preferences of the local population. An adaptation of an existing English language Canadian Public Hypertension Recommendations pamphlet was created considering the literacy and translation challenges. The adapted pamphlet was translated into four Indo-Asian languages. The adapted pamphlets were disseminated as part of the initial educational component of a community-based culturally and language-sensitive cardiovascular risk factor screening and management program. Field testing of the materials was undertaken when participants returned for program follow-up seven to 12 months later. Results Fifty-nine English-speaking participants evaluated and confirmed the concept validity of the English adapted version. 28 non-English speaking participants evaluated the Gujarati (N = 13) and Punjabi (N = 15) translated versions of the adapted pamphlets. All participants found the pamphlets acceptable and felt they had improved their understanding of hypertension. Conclusions Involving the target community to identify health issues as well as help to create culturally, language and literacy sensitive health education materials ensures resources are highly acceptable to that community. Minor changes to the materials will be needed prior to formal testing of hypertension knowledge and health decision-making on a larger scale within this at risk community. PMID:21223580

Translating Knowledge into Action: Supporting Adaptation in Australia's Coastal Zone through Information Provision and Decision Support

NASA Astrophysics Data System (ADS)

Palutikof, J. P.; Rissik, D.; Tonmoy, F. N.; Boulter, S.

2015-12-01

Adaptation to risks from climate change and sea-level rise is particularly important in Australia, where 70% of the population live in major coastal cities and 85% within 50km of the coast. Adaptation activity focuses at local government level and, in the absence of strong leadership from central government, the extent to which local councils have taken action to adapt is highly variable across the nation. Also, although a number of councils have proceeded as far as identifying their exposure to risk and considering adaptation options, this fails to translate into action. A principal reason for this is concern over the response from coastal residents to actions which may affect property values, and fear of litigation. A project is underway to support councils to understand their risks, evaluate adaptation options and proceed to action. This support will consist of a three-pronged framework: provision of information, a tool to support decision-making, and a community forum. Delivery involves research to understand the barriers to adaptation and how these may be overcome, optimal methods for delivery of information, and the information needs of organizations, action-takers and communities. The presentation will focus on the results of consultation undertaken to understand users' information needs around content and delivery, and how understanding of these needs has translated into design of the framework. A strongly preference was expressed to learn from peers, and a challenge for the framework is to understand how to inject adaptation knowledge which is up-to-date and accurate into peer-to-peer conversations. The community forum is one mechanism to achieve this. The basic structure and delivery mechanisms of the framework are shown in the attached.

Tackling health literacy: adaptation of public hypertension educational materials for an Indo-Asian population in Canada.

PubMed

Jones, Charlotte A; Mawani, Shefina; King, Kathryn M; Allu, Selina Omar; Smith, Megan; Mohan, Sailesh; Campbell, Norman R C

2011-01-11

Indo-Asians in Canada are at increased risk for cardiovascular diseases. There is a need for cultural and language specific educational materials relating to this risk. During this project we developed and field tested the acceptability of a hypertension public education pamphlet tailored to fit the needs of an at risk local Indo-Asian population, in Calgary, Alberta, Canada. A community health board representing Calgary's Indo-Asian communities identified the culturally specific educational needs and language preferences of the local population. An adaptation of an existing English language Canadian Public Hypertension Recommendations pamphlet was created considering the literacy and translation challenges. The adapted pamphlet was translated into four Indo-Asian languages. The adapted pamphlets were disseminated as part of the initial educational component of a community-based culturally and language-sensitive cardiovascular risk factor screening and management program. Field testing of the materials was undertaken when participants returned for program follow-up seven to 12 months later. Fifty-nine English-speaking participants evaluated and confirmed the concept validity of the English adapted version. 28 non-English speaking participants evaluated the Gujarati (N = 13) and Punjabi (N = 15) translated versions of the adapted pamphlets. All participants found the pamphlets acceptable and felt they had improved their understanding of hypertension. Involving the target community to identify health issues as well as help to create culturally, language and literacy sensitive health education materials ensures resources are highly acceptable to that community. Minor changes to the materials will be needed prior to formal testing of hypertension knowledge and health decision-making on a larger scale within this at risk community.

Kinases of eIF2a Switch Translation of mRNA Subset during Neuronal Plasticity

PubMed Central

Chesnokova, Ekaterina; Bal, Natalia

2017-01-01

Compared to other types of cells, neurons express the largest number of diverse mRNAs, including neuron-specific ones. This mRNA diversity is required for neuronal function, memory storage, maintenance and retrieval. Regulation of translation in neurons is very complicated and involves various proteins. Some proteins, implementing translational control in other cell types, are used by neurons for synaptic plasticity. In this review, we discuss the neuron-specific activity of four kinases: protein kinase R (PKR), PKR-like endoplasmic reticulum kinase (PERK), general control nonderepressible 2 kinase (GCN2), and heme-reguated eIF2α kinase (HRI), the substrate for which is α-subunit of eukaryotic initiation factor 2 (eIF2α). Phosphorylation of eIF2α is necessary for the cell during stress conditions, such as lack of amino acids, energy stress or viral infection. We propose that, during memory formation, neurons use some mechanisms similar to those involved in the cellular stress. The four eIF2α kinases regulate translation of certain mRNAs containing upstream open reading frames (uORFs). These mRNAs encode proteins involved in the processes of long-term potentiation (LTP) or long-term depression (LTD). The review examines some neuronal proteins for which translation regulation by eIF2 was suggested and checked experimentally. Of such proteins, we pay close attention to protein kinase Mζ, which is involved in memory storage and regulated at the translational level. PMID:29065505

Noncommutative Translations and *-PRODUCT Formalism

NASA Astrophysics Data System (ADS)

Daszkiewicz, Marcin; Lukierski, Jerzy; Woronowicz, Mariusz

2008-09-01

We consider the noncommutative space-times with Lie-algebraic noncommutativity (e.g. κ-deformed Minkowski space). In the framework with classical fields we extend the *-product in order to represent the noncommutative translations in terms of commutative ones. We show the translational invariance of noncommutative bilinear action with local product of noncommutative fields. The quadratic noncommutativity is also briefly discussed.

77 FR 73545 - Implementation of the Local Community Radio Act of 2010; Revision of Service and Eligibility...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-11

... our FM translator licensing procedures and modify licensing and service rules for the low power FM... clarifications the comprehensive plan for licensing FM translators and LPFM stations adopted in the Fourth Report...-delayed processing of over 6,000 FM translator applications and establish a timeline for the opening of an...

Health in global context; beyond the social determinants of health?

PubMed Central

Krumeich, Anja; Meershoek, Agnes

2014-01-01

The rise of the social determinants of health (SDH) discourse on the basis of statistical evidence that correlates ill health to SDH and pictures causal pathways in comprehensive theoretical frameworks led to widespread awareness that health and health disparities are the outcome of complex pathways of interconnecting SDH. In this paper we explore whether and how SDH frameworks can be translated to effectively inform particular national health policies. To this end we identified major challenges for this translation followed by reflections on ways to overcome them. Most important challenges affecting adequate translation of these frameworks into concrete policy and intervention are 1) overcoming the inclination to conceptualize SDH as mere barriers to health behavior to be modified by lifestyle interventions by addressing them as structural factors instead; 2) obtaining sufficient in-depth insight in and evidence for the exact nature of the relationship between SDs and health; 3) to adequately translate the general determinants and pathways into explanations for ill health and limited access to health care in local settings; 4) to develop and implement policies and other interventions that are adjusted to those local circumstances. We conclude that to transform generic SDH models into useful policy tools and to prevent them to transform in SDH themselves, in depth understanding of the unique interplay between local, national and global SDH in a local setting, gathered by ethnographic research, is needed to be able to address structural SD in the local setting and decrease health inequity.

US Accreditation in Mexico: Quality in Higher Education as Symbol, Performance and Translation

ERIC Educational Resources Information Center

Blanco-Ramirez, Gerardo

2015-01-01

Quality practices in higher education involve more than mere compliance with standards and technical mandates; given the complexity of the decisions involved in quality in higher education, this concept, quality, can be analyzed as symbol and performance. This paper utilizes translation as heuristic to analyze the implementation of US…

Soviet Patent Bulletin Processing: A Particular Application of Machine Translation.

ERIC Educational Resources Information Center

Bostad, Dale A.

1985-01-01

Describes some of the processes involved in the data structure manipulation and machine translation of a specific text form, namely, Soviet patent bulletins. The effort to modify this system in order to do specialized processing and translation is detailed. (Author/SED)

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

PubMed

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

2011-09-01

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

Making a move in exercise referral: co-development of a physical activity referral scheme.

PubMed

Buckley, B J R; Thijssen, D H J; Murphy, R C; Graves, L E F; Whyte, G; Gillison, F B; Crone, D; Wilson, P M; Watson, P M

2018-04-24

Translational research is required to ensure exercise referral schemes (ERSs) are evidence-based and reflect local needs. This article reports process data from the co-development phase of an ERS, providing an insight into (i) factors that must be considered when translating evidence to practice in an ERS setting, and (ii) challenges and facilitators of conducting participatory research involving multiple stakeholders. An ERS was iteratively co-developed by a multidisciplinary stakeholder group (commissioners, managers, practitioners, patients and academics) via five participatory meetings and an online survey. Audio data (e.g. group discussions) and visual data (e.g. whiteboard notes) were recorded and analysed using NVivo-10 electronic software. Factors to consider when translating evidence to practice in an ERS setting included (i) current ERS culture; (ii) skills, safety and accountability; and (iii) resources and capacity. The co-development process was facilitated by needs-analysis, open questions, multidisciplinary debate and reflective practice. Challenges included contrasting views, irregular attendance and (mis)perceptions of evaluation. The multidisciplinary co-development process highlighted cultural and pragmatic issues related to exercise referral provision, resulting in an evidence-based intervention framework designed to be implemented within existing infrastructures. Further work is required to establish the feasibility and effectiveness of the co-developed intervention in practice.

Sumoylation of Rap1 mediates the recruitment of TFIID to promote transcription of ribosomal protein genes.

PubMed

Chymkowitch, Pierre; Nguéa, Aurélie P; Aanes, Håvard; Koehler, Christian J; Thiede, Bernd; Lorenz, Susanne; Meza-Zepeda, Leonardo A; Klungland, Arne; Enserink, Jorrit M

2015-06-01

Transcription factors are abundant Sumo targets, yet the global distribution of Sumo along the chromatin and its physiological relevance in transcription are poorly understood. Using Saccharomyces cerevisiae, we determined the genome-wide localization of Sumo along the chromatin. We discovered that Sumo-enriched genes are almost exclusively involved in translation, such as tRNA genes and ribosomal protein genes (RPGs). Genome-wide expression analysis showed that Sumo positively regulates their transcription. We also discovered that the Sumo consensus motif at RPG promoters is identical to the DNA binding motif of the transcription factor Rap1. We demonstrate that Rap1 is a molecular target of Sumo and that sumoylation of Rap1 is important for cell viability. Furthermore, Rap1 sumoylation promotes recruitment of the basal transcription machinery, and sumoylation of Rap1 cooperates with the target of rapamycin kinase complex 1 (TORC1) pathway to promote RPG transcription. Strikingly, our data reveal that sumoylation of Rap1 functions in a homeostatic feedback loop that sustains RPG transcription during translational stress. Taken together, Sumo regulates the cellular translational capacity by promoting transcription of tRNA genes and RPGs. © 2015 Chymkowitch et al.; Published by Cold Spring Harbor Laboratory Press.

RNA G-quadruplexes: emerging mechanisms in disease

PubMed Central

Cammas, Anne

2017-01-01

Abstract RNA G-quadruplexes (G4s) are formed by G-rich RNA sequences in protein-coding (mRNA) and non-coding (ncRNA) transcripts that fold into a four-stranded conformation. Experimental studies and bioinformatic predictions support the view that these structures are involved in different cellular functions associated to both DNA processes (telomere elongation, recombination and transcription) and RNA post-transcriptional mechanisms (including pre-mRNA processing, mRNA turnover, targeting and translation). An increasing number of different diseases have been associated with the inappropriate regulation of RNA G4s exemplifying the potential importance of these structures on human health. Here, we review the different molecular mechanisms underlying the link between RNA G4s and human diseases by proposing several overlapping models of deregulation emerging from recent research, including (i) sequestration of RNA-binding proteins, (ii) aberrant expression or localization of RNA G4-binding proteins, (iii) repeat associated non-AUG (RAN) translation, (iv) mRNA translational blockade and (v) disabling of protein–RNA G4 complexes. This review also provides a comprehensive survey of the functional RNA G4 and their mechanisms of action. Finally, we highlight future directions for research aimed at improving our understanding on RNA G4-mediated regulatory mechanisms linked to diseases. PMID:28013268

The MTL1 Pentatricopeptide Repeat Protein Is Required for Both Translation and Splicing of the Mitochondrial NADH DEHYDROGENASE SUBUNIT7 mRNA in Arabidopsis.

PubMed

Haïli, Nawel; Planchard, Noelya; Arnal, Nadège; Quadrado, Martine; Vrielynck, Nathalie; Dahan, Jennifer; des Francs-Small, Catherine Colas; Mireau, Hakim

2016-01-01

Mitochondrial translation involves a complex interplay of ancient bacteria-like features and host-derived functionalities. Although the basic components of the mitochondrial translation apparatus have been recognized, very few protein factors aiding in recruiting ribosomes on mitochondria-encoded messenger RNA (mRNAs) have been identified in higher plants. In this study, we describe the identification of the Arabidopsis (Arabidopsis thaliana) MITOCHONDRIAL TRANSLATION FACTOR1 (MTL1) protein, a new member of the Pentatricopeptide Repeat family, and show that it is essential for the translation of the mitochondrial NADH dehydrogenase subunit7 (nad7) mRNA. We demonstrate that mtl1 mutant plants fail to accumulate the Nad7 protein, even though the nad7 mature mRNA is produced and bears the same 5' and 3' extremities as in wild-type plants. We next observed that polysome association of nad7 mature mRNA is specifically disrupted in mtl1 mutants, indicating that the absence of Nad7 results from a lack of translation of nad7 mRNA. These findings illustrate that mitochondrial translation requires the intervention of gene-specific nucleus-encoded PPR trans-factors and that their action does not necessarily involve the 5' processing of their target mRNA, as observed previously. Interestingly, a partial decrease in nad7 intron 2 splicing was also detected in mtl1 mutants, suggesting that MTL1 is also involved in group II intron splicing. However, this second function appears to be less essential for nad7 expression than its role in translation. MTL1 will be instrumental to understand the multifunctionality of PPR proteins and the mechanisms governing mRNA translation and intron splicing in plant mitochondria. © 2016 American Society of Plant Biologists. All Rights Reserved.

Stakeholder engagement analysis - a bioethics dilemma in patient-targeted intervention: patients with temporomandibular joint disorders.

PubMed

Barkhordarian, Andre; Demerjian, Gary; Jan, Allison; Sama, Nateli; Nguyen, Mia; Du, Angela; Chiappelli, Francesco

2015-01-20

Modern health care in the field of Medicine, Dentistry and Nursing is grounded in fundamental philosophy and epistemology of translational science. Recently in the U.S major national initiatives have been implemented in the hope of closing the gaps that sometimes exist between the two fundamental components of translational science, the translational research and translational effectiveness. Subsequent to these initiatives, many improvements have been made; however, important bioethical issues and limitations do still exist that need to be addressed. One such issue is the stakeholder engagement and its assessment and validation. Federal, state and local organizations such as PCORI and AHRQ concur that the key to a better understanding of the relationship between translational research and translational effectiveness is the assessment of the extent to which stakeholders are actively engaged in the translational process of healthcare. The stakeholder engagement analysis identifies who the stakeholders are, maps their contribution and involvement, evaluates their priorities and opinions, and accesses their current knowledge base. This analysis however requires conceptualization and validation from the bioethics standpoint. Here, we examine the bioethical dilemma of stakeholder engagement analysis in the context of the person-environment fit (PE-fit) theoretical model. This model is an approach to quantifying stakeholder engagement analysis for the design of patient-targeted interventions. In our previous studies of Alzheimer patients, we have developed, validated and used a simple instrument based on the PE-fit model that can be adapted and utilized in a much less studied pathology as a clinical model that has a wide range of symptoms and manifestations, the temporomandibular joint disorders (TMD). The temporomandibular joint (TMJ) is the jaw joint endowed with sensory and motor innervations that project from within the central nervous system and its dysfunction can be manifested systemically in forms of movement disorders, and related pathological symptomatologies.Currently, there is limited reliable evidence available to fully understand the complexity of the various domains of translational effectiveness, particularly in the context of stakeholder engagement and its assessment, validation as well as the bioethical implications as they pertain to evidence-based, effectivness-focused and patient-centered care.

Image fusion using sparse overcomplete feature dictionaries

DOEpatents

Brumby, Steven P.; Bettencourt, Luis; Kenyon, Garrett T.; Chartrand, Rick; Wohlberg, Brendt

2015-10-06

Approaches for deciding what individuals in a population of visual system "neurons" are looking for using sparse overcomplete feature dictionaries are provided. A sparse overcomplete feature dictionary may be learned for an image dataset and a local sparse representation of the image dataset may be built using the learned feature dictionary. A local maximum pooling operation may be applied on the local sparse representation to produce a translation-tolerant representation of the image dataset. An object may then be classified and/or clustered within the translation-tolerant representation of the image dataset using a supervised classification algorithm and/or an unsupervised clustering algorithm.

Knowledge translation strategies to improve the use of evidence in public health decision making in local government: intervention design and implementation plan

PubMed Central

2013-01-01

Background Knowledge translation strategies are an approach to increase the use of evidence within policy and practice decision-making contexts. In clinical and health service contexts, knowledge translation strategies have focused on individual behavior change, however the multi-system context of public health requires a multi-level, multi-strategy approach. This paper describes the design of and implementation plan for a knowledge translation intervention for public health decision making in local government. Methods Four preliminary research studies contributed findings to the design of the intervention: a systematic review of knowledge translation intervention effectiveness research, a scoping study of knowledge translation perspectives and relevant theory literature, a survey of the local government public health workforce, and a study of the use of evidence-informed decision-making for public health in local government. A logic model was then developed to represent the putative pathways between intervention inputs, processes, and outcomes operating between individual-, organizational-, and system-level strategies. This formed the basis of the intervention plan. Results The systematic and scoping reviews identified that effective and promising strategies to increase access to research evidence require an integrated intervention of skill development, access to a knowledge broker, resources and tools for evidence-informed decision making, and networking for information sharing. Interviews and survey analysis suggested that the intervention needs to operate at individual and organizational levels, comprising workforce development, access to evidence, and regular contact with a knowledge broker to increase access to intervention evidence; develop skills in appraisal and integration of evidence; strengthen networks; and explore organizational factors to build organizational cultures receptive to embedding evidence in practice. The logic model incorporated these inputs and strategies with a set of outcomes to measure the intervention’s effectiveness based on the theoretical frameworks, evaluation studies, and decision-maker experiences. Conclusion Documenting the design of and implementation plan for this knowledge translation intervention provides a transparent, theoretical, and practical approach to a complex intervention. It provides significant insights into how practitioners might engage with evidence in public health decision making. While this intervention model was designed for the local government context, it is likely to be applicable and generalizable across sectors and settings. Trial registration Australia New Zealand Clinical Trials Register ACTRN12609000953235. PMID:24107358

Carotenogenesis Is Regulated by 5′UTR-Mediated Translation of Phytoene Synthase Splice Variants1[OPEN

PubMed Central

Voß, Björn; Maass, Dirk; Beyer, Peter

2016-01-01

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

Crosstalk: public cafés as places for knowledge translation concerning health care research.

PubMed

Reimer-Kirkham, Sheryl; Jule, Allyson

2015-01-01

This article explores the use of public cafés as a model for knowledge translation and community engagement. We base our discussion on a public café series organized around the theme of access to health care and held in three neighborhoods in the Lower Mainland of British Columbia, Canada. The cafés were part of the Canadian Institutes of Health Research Café Scientifique program. Our purposes for this series of cafés were threefold: (a) to provide a site of communication to connect research with members of the public, (b) to build a network among participants based on common connections to the local community, and (c) to explore through discussion how gendered and raced perspectives concerning access to health care may influence the lived experiences of Canadians today. We intended to promote an intergroup conversation, based on the assumption that people of First Nations descent, newcomers to Canada (whether through immigration or resettlement), and settlers (such as Euro-Canadians) would all benefit from hearing each other's perspectives on access to health care, as well as presentations by invited academics about their research on access to health care. A form of "crosstalk" emerged in the cafés, mediated by gender and ethnicity, where social differences and geographical distances between various groups were not easily bridged, and yet where opportunity was created for inclusive dialogic spaces. We conclude that knowledge translation is not easily accomplished with the café format, at least not with the type of critical knowledge we were aiming to translate and the depth of engagement we were hoping for. Our experiences highlighted three strategies that facilitate knowledge translation: relationships and shared goals; involvement of policymakers and decision makers; and tending to social relations of power.

Lost in Translation

NASA Astrophysics Data System (ADS)

Lass, Wiebke; Reusswig, Fritz

2014-05-01

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 get lost in translation here—and we have not yet mentioned the societal management of other problems, such as wars and civil wars, or 'taming' the global financial markets. After having sketched this conceptual outline in some detail, we would like to focus on three planetary boundaries for illustrative purposes: GHG emissions, nitrogen fertilization, and biodiversity loss, and highlight some similarities as well as dissimilarities in the social translation processes involved. We would limit the range of examples to the EU, USA, and India. In a last step, we would like to illustrate a promising way of translating one specific planetary boundary—anthropogenic climate change—by a case study on how it is translated into urban energy and climate policies with the example of climate neutral Berlin 2050.

Synthesis of Lipidated Proteins.

PubMed

Mejuch, Tom; Waldmann, Herbert

2016-08-17

Protein lipidation is one of the major post-translational modifications (PTM) of proteins. The attachment of the lipid moiety frequently determines the localization and the function of the lipoproteins. Lipidated proteins participate in many essential biological processes in eukaryotic cells, including vesicular trafficking, signal transduction, and regulation of the immune response. Malfunction of these cellular processes usually leads to various diseases such as cancer. Understanding the mechanism of cellular signaling and identifying the protein-protein and protein-lipid interactions in which the lipoproteins are involved is a crucial task. To achieve these goals, fully functional lipidated proteins are required. However, access to lipoproteins by means of standard expression is often rather limited. Therefore, semisynthetic methods, involving the synthesis of lipidated peptides and their subsequent chemoselective ligation to yield full-length lipoproteins, were developed. In this Review we summarize the commonly used methods for lipoprotein synthesis and the development of the corresponding chemoselective ligation techniques. Several key studies involving full-length semisynthetic lipidated Ras, Rheb, and LC3 proteins are presented.

LOCAL TRANSLATION. Comment on "Principles of ER cotranslational translocation revealed by proximity-specific ribosome profiling".

PubMed

Reid, David W; Nicchitta, Christopher V

2015-06-12

Jan et al. (Research Articles, 7 November 2014, p. 716) propose that ribosomes translating secretome messenger RNAs (mRNAs) traffic from the cytosol to the endoplasmic reticulum (ER) upon emergence of the signal peptide and return to the cytosol after termination. An accounting of controls demonstrates that mRNAs initiate translation on ER-bound ribosomes and that ribosomes are retained on the ER through many cycles of translation. Copyright © 2015, American Association for the Advancement of Science.

Training Tools for Translators and Interpreters

ERIC Educational Resources Information Center

Al-Qinai, Jamal

2010-01-01

The present paper reviews the traditional methodologies of translator training and proposes an eclectic multi-componential approach that involves a set of interdisciplinary skills with the ultimate objective of meeting market demand. Courses on translation for specific purposes (TSP) and think-aloud protocols (TAP) along with self-monitoring and…

Translation and Advertising: Going Global. Debate.

ERIC Educational Resources Information Center

Seguinot, Candace; And Others

1994-01-01

Discusses the identity-forming power of translation in advertising copy. In the marketing of goods and services across cultural boundaries, an understanding of culture and semiotics that goes well beyond both language and design is involved. Translators must understand marketing, the legal jurisdictions of their market, how cultural differences…

The 5'-untranslated region of p23 mRNA from the Ehrlich ascites tumor is involved in translation control of the growth related protein p23.

PubMed

Böhm, H; Gross, B; Gaestel, M; Bommer, U A; Ryffel, G; Bielka, H

1991-01-01

The growth-related protein p23 of the Ehrlich ascites tumor (EAT) is preferentially expressed in the exponentially growing tumor; its synthesis is translationally controlled. p23 mRNA is efficiently translated in the wheat germ cell-free lysate. In contrast, p23 mRNA present in poly(A)+RNA isolated from EAT is not translated in cell-free systems of EAT and reticulocytes. Moreover, translation of a p23 transcript is inhibited in the presence of total poly(A)+RNA. This inhibition is abolished by the removal of the 5'-UTR of the p23 transcript. Solution hybridization/RNase protection experiments point to the presence of a nucleotide sequence complementary to the 5'-UTR of p23 mRNA which might be involved in p23 mRNA inhibition.

Dendritic mRNA targeting and translation.

PubMed

Kindler, Stefan; Kreienkamp, Hans-Jürgen

2012-01-01

Selective targeting of specific mRNAs into neuronal dendrites and their locally regulated translation at particular cell contact sites contribute to input-specific synaptic plasticity. Thus, individual synapses become decision-making units, which control gene expression in a spatially restricted and nucleus-independent manner. Dendritic targeting of mRNAs is achieved by active, microtubule-dependent transport. For this purpose, mRNAs are packaged into large ribonucleoprotein (RNP) particles containing an array of trans-acting RNA-binding proteins. These are attached to molecular motors, which move their RNP cargo into dendrites. A variety of proteins may be synthesized in dendrites, including signalling and scaffold proteins of the synapse and neurotransmitter receptors. In some cases, such as the alpha subunit of the calcium/calmodulin-dependent protein kinase II (αCaMKII) and the activity-regulated gene of 3.1 kb (Arg3.1, also referred to as activity-regulated cDNA, Arc), their local synthesis at synapses can modulate long-term changes in synaptic efficiency. Local dendritic translation is regulated by several signalling cascades including Akt/mTOR and Erk/MAP kinase pathways, which are triggered by synaptic activity. More recent findings show that miRNAs also play an important role in protein synthesis at synapses. Disruption of local translation control at synapses, as observed in the fragile X syndrome (FXS) and its mouse models and possibly also in autism spectrum disorders, interferes with cognitive abilities in mice and men.

Genome Editing in Neuroepithelial Stem Cells to Generate Human Neurons with High Adenosine-Releasing Capacity.

PubMed

Poppe, Daniel; Doerr, Jonas; Schneider, Marion; Wilkens, Ruven; Steinbeck, Julius A; Ladewig, Julia; Tam, Allison; Paschon, David E; Gregory, Philip D; Reik, Andreas; Müller, Christa E; Koch, Philipp; Brüstle, Oliver

2018-06-01

As a powerful regulator of cellular homeostasis and metabolism, adenosine is involved in diverse neurological processes including pain, cognition, and memory. Altered adenosine homeostasis has also been associated with several diseases such as depression, schizophrenia, or epilepsy. Based on its protective properties, adenosine has been considered as a potential therapeutic agent for various brain disorders. Since systemic application of adenosine is hampered by serious side effects such as vasodilatation and cardiac suppression, recent studies aim at improving local delivery by depots, pumps, or cell-based applications. Here, we report on the characterization of adenosine-releasing human embryonic stem cell-derived neuroepithelial stem cells (long-term self-renewing neuroepithelial stem [lt-NES] cells) generated by zinc finger nuclease (ZFN)-mediated knockout of the adenosine kinase (ADK) gene. ADK-deficient lt-NES cells and their differentiated neuronal and astroglial progeny exhibit substantially elevated release of adenosine compared to control cells. Importantly, extensive adenosine release could be triggered by excitation of differentiated neuronal cultures, suggesting a potential activity-dependent regulation of adenosine supply. Thus, ZFN-modified neural stem cells might serve as a useful vehicle for the activity-dependent local therapeutic delivery of adenosine into the central nervous system. Stem Cells Translational Medicine 2018;7:477-486. © 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Downscaling SSPs in Bangladesh - Integrating Science, Modelling and Stakeholders Through Qualitative and Quantitative Scenarios

NASA Astrophysics Data System (ADS)

Allan, A.; Barbour, E.; Salehin, M.; Hutton, C.; Lázár, A. N.; Nicholls, R. J.; Rahman, M. M.

2015-12-01

A downscaled scenario development process was adopted in the context of a project seeking to understand relationships between ecosystem services and human well-being in the Ganges-Brahmaputra delta. The aim was to link the concerns and priorities of relevant stakeholders with the integrated biophysical and poverty models used in the project. A 2-stage process was used to facilitate the connection between stakeholders concerns and available modelling capacity: the first to qualitatively describe what the future might look like in 2050; the second to translate these qualitative descriptions into the quantitative form required by the numerical models. An extended, modified SSP approach was adopted, with stakeholders downscaling issues identified through interviews as being priorities for the southwest of Bangladesh. Detailed qualitative futures were produced, before modellable elements were quantified in conjunction with an expert stakeholder cadre. Stakeholder input, using the methods adopted here, allows the top-down focus of the RCPs to be aligned with the bottom-up approach needed to make the SSPs appropriate at the more local scale, and also facilitates the translation of qualitative narrative scenarios into a quantitative form that lends itself to incorporation of biophysical and socio-economic indicators. The presentation will describe the downscaling process in detail, and conclude with findings regarding the importance of stakeholder involvement (and logistical considerations), balancing model capacity with expectations and recommendations on SSP refinement at local levels.

Downscaling SSPs in the GBM Delta - Integrating Science, Modelling and Stakeholders Through Qualitative and Quantitative Scenarios

NASA Astrophysics Data System (ADS)

Allan, Andrew; Barbour, Emily; Salehin, Mashfiqus; Munsur Rahman, Md.; Hutton, Craig; Lazar, Attila

2016-04-01

A downscaled scenario development process was adopted in the context of a project seeking to understand relationships between ecosystem services and human well-being in the Ganges-Brahmaputra delta. The aim was to link the concerns and priorities of relevant stakeholders with the integrated biophysical and poverty models used in the project. A 2-stage process was used to facilitate the connection between stakeholders concerns and available modelling capacity: the first to qualitatively describe what the future might look like in 2050; the second to translate these qualitative descriptions into the quantitative form required by the numerical models. An extended, modified SSP approach was adopted, with stakeholders downscaling issues identified through interviews as being priorities for the southwest of Bangladesh. Detailed qualitative futures were produced, before modellable elements were quantified in conjunction with an expert stakeholder cadre. Stakeholder input, using the methods adopted here, allows the top-down focus of the RCPs to be aligned with the bottom-up approach needed to make the SSPs appropriate at the more local scale, and also facilitates the translation of qualitative narrative scenarios into a quantitative form that lends itself to incorporation of biophysical and socio-economic indicators. The presentation will describe the downscaling process in detail, and conclude with findings regarding the importance of stakeholder involvement (and logistical considerations), balancing model capacity with expectations and recommendations on SSP refinement at local levels.

Non-rigid Motion Correction in 3D Using Autofocusing with Localized Linear Translations

PubMed Central

Cheng, Joseph Y.; Alley, Marcus T.; Cunningham, Charles H.; Vasanawala, Shreyas S.; Pauly, John M.; Lustig, Michael

2012-01-01

MR scans are sensitive to motion effects due to the scan duration. To properly suppress artifacts from non-rigid body motion, complex models with elements such as translation, rotation, shear, and scaling have been incorporated into the reconstruction pipeline. However, these techniques are computationally intensive and difficult to implement for online reconstruction. On a sufficiently small spatial scale, the different types of motion can be well-approximated as simple linear translations. This formulation allows for a practical autofocusing algorithm that locally minimizes a given motion metric – more specifically, the proposed localized gradient-entropy metric. To reduce the vast search space for an optimal solution, possible motion paths are limited to the motion measured from multi-channel navigator data. The novel navigation strategy is based on the so-called “Butterfly” navigators which are modifications to the spin-warp sequence that provide intrinsic translational motion information with negligible overhead. With a 32-channel abdominal coil, sufficient number of motion measurements were found to approximate possible linear motion paths for every image voxel. The correction scheme was applied to free-breathing abdominal patient studies. In these scans, a reduction in artifacts from complex, non-rigid motion was observed. PMID:22307933

Traduccion automatica mediante el ordenador (Automatic Translation Using a Computer).

ERIC Educational Resources Information Center

Bueno, Julian L.

This report on machine translation contains a brief history of the field; a description of the processes involved; a discussion of systems currently in use, including three software packages on the market (Teaching Assistant, Translate, and Globalink); reflections on implications for teaching; observations of results obtained when elements of…

Transcriptome profile analysis of floral sex determination in cucumber.

PubMed

Wu, Tao; Qin, Zhiwei; Zhou, Xiuyan; Feng, Zhuo; Du, Yalin

2010-07-15

Cucumber has been widely studied as a model for floral sex determination. In this investigation, we performed genome-wide transcriptional profiling of apical tissue of a gynoecious mutant (Csg-G) and the monoecious wild-type (Csg-M) of cucumber in an attempt to isolate genes involved in sex determination, using the Solexa technology. The profiling analysis revealed numerous changes in gene expression attributable to the mutation, which resulted in the down-regulation of 600 genes and the up-regulation of 143 genes. The Solexa data were confirmed by reverse transcription polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR (qRT-PCR). Gene ontology (GO) analysis revealed that the differentially expressed genes were mainly involved in biogenesis, transport and organization of cellular component, macromolecular and cellular biosynthesis, localization, establishment of localization, translation and other processes. Furthermore, the expression of some of these genes depended upon the tissue and the developmental stage of the flowers of gynoecious mutant. The results of this study suggest two important concepts, which govern sex determination in cucumber. First, the differential expression of genes involved in plant hormone signaling pathways, such as ACS, Asr1, CsIAA2, CS-AUX1 and TLP, indicate that phytohormones and their crosstalk might play a critical role in the sex determination. Second, the regulation of some transcription factors, including EREBP-9, may also be involved in this developmental process. Copyright (c) 2010 Elsevier GmbH. All rights reserved.

Re-localization of Cellular Protein SRp20 during Poliovirus Infection: Bridging a Viral IRES to the Host Cell Translation Apparatus

PubMed Central

Fitzgerald, Kerry D.; Semler, Bert L.

2011-01-01

Poliovirus IRES-mediated translation requires the functions of certain canonical as well as non-canonical factors for the recruitment of ribosomes to the viral RNA. The interaction of cellular proteins PCBP2 and SRp20 in extracts from poliovirus-infected cells has been previously described, and these two proteins were shown to function synergistically in viral translation. To further define the mechanism of ribosome recruitment for the initiation of poliovirus IRES-dependent translation, we focused on the role of the interaction between cellular proteins PCBP2 and SRp20. Work described here demonstrates that SRp20 dramatically re-localizes from the nucleus to the cytoplasm of poliovirus-infected neuroblastoma cells during the course of infection. Importantly, SRp20 partially co-localizes with PCBP2 in the cytoplasm of infected cells, corroborating our previous in vitro interaction data. In addition, the data presented implicate the presence of these two proteins in viral translation initiation complexes. We show that in extracts from poliovirus-infected cells, SRp20 is associated with PCBP2 bound to poliovirus RNA, indicating that this interaction occurs on the viral RNA. Finally, we generated a mutated version of SRp20 lacking the RNA recognition motif (SRp20ΔRRM) and found that this protein is localized similar to the full length SRp20, and also partially co-localizes with PCBP2 during poliovirus infection. Expression of this mutated version of SRp20 results in a ∼100 fold decrease in virus yield for poliovirus when compared to expression of wild type SRp20, possibly via a dominant negative effect. Taken together, these results are consistent with a model in which SRp20 interacts with PCBP2 bound to the viral RNA, and this interaction functions to recruit ribosomes to the viral RNA in a direct or indirect manner, with the participation of additional protein-protein or protein-RNA interactions. PMID:21779168

38 CFR 200.6 - Public involvement.

Code of Federal Regulations, 2010 CFR

2010-07-01

... efforts may include, but are not limited to, special programs of community outreach, including cross-cultural programs, translations of pertinent documents, and ensuring that translators are available at...

Lamins in the nuclear interior - life outside the lamina.

PubMed

Naetar, Nana; Ferraioli, Simona; Foisner, Roland

2017-07-01

Nuclear lamins are components of the peripheral lamina that define the mechanical properties of nuclei and tether heterochromatin to the periphery. A-type lamins localize also to the nuclear interior, but the regulation and specific functions of this nucleoplasmic lamin pool are poorly understood. In this Commentary, we summarize known pathways that are potentially involved in the localization and dynamic behavior of intranuclear lamins, including their post-translational modifications and interactions with nucleoplasmic proteins, such as lamina-associated polypeptide 2α (LAP2α; encoded by TMPO ). In addition, new data suggest that lamins in the nuclear interior have an important role in chromatin regulation and gene expression through dynamic binding to both hetero- and euchromatic genomic regions and promoter subdomains, thereby affecting epigenetic pathways and chromatin accessibility. Nucleoplasmic lamins also have a role in spatial chromatin organization and may be involved in mechanosignaling. In view of this newly emerging concept, we propose that the previously reported cellular phenotypes in lamin-linked diseases are, at least in part, rooted in an impaired regulation and/or function of the nucleoplasmic lamin A/C pool. © 2017. Published by The Company of Biologists Ltd.

Translational Research from an Informatics Perspective

NASA Technical Reports Server (NTRS)

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

2007-01-01

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

Nonintegrable Schrodinger discrete breathers.

PubMed

Gómez-Gardeñes, J; Floría, L M; Peyrard, M; Bishop, A R

2004-12-01

In an extensive numerical investigation of nonintegrable translational motion of discrete breathers in nonlinear Schrödinger lattices, we have used a regularized Newton algorithm to continue these solutions from the limit of the integrable Ablowitz-Ladik lattice. These solutions are shown to be a superposition of a localized moving core and an excited extended state (background) to which the localized moving pulse is spatially asymptotic. The background is a linear combination of small amplitude nonlinear resonant plane waves and it plays an essential role in the energy balance governing the translational motion of the localized core. Perturbative collective variable theory predictions are critically analyzed in the light of the numerical results.

Implementing stakeholder-informed research in the substance abuse treatment sector: strategies used by Connections, a Canadian knowledge translation and exchange project.

PubMed

Henderson, Joanna; Sword, Wendy; Niccols, Alison; Dobbins, Maureen

2014-05-29

Researcher-stakeholder collaboration has been identified as critical to bridging research and health system change. While collaboration models vary, meaningful stakeholder involvement over time ("integrated knowledge translation") is advocated to improve the relevance of research to knowledge users. This short report describes the integrated knowledge translation efforts of Connections, a knowledge translation and exchange project to improve services for women with substance abuse problems and their children, and implementation barriers and facilitators. Strategies of varying intensities were used to engage diverse stakeholders, including policy makers and people with lived experience, and executive directors, program managers, and service providers from Canadian addiction agencies serving women. Barriers to participation included individual (e.g., interest), organizational (e.g., funding), and system level (e.g., lack of centralized stakeholder database) barriers. Similarly, facilitators included individual (e.g., perceived relevance) and organizational (e.g., support) facilitators, as well as initiative characteristics (e.g., multiple involvement opportunities). Despite barriers, Connections' stakeholder-informed research efforts proved essential for developing clinically relevant and feasible processes, measures, and implementation strategies. Stakeholder-researcher collaboration is possible and robust integrated knowledge translation efforts can be productive. Future work should emphasize developing and evaluating a range of strategies to address stakeholders' knowledge translation needs and to facilitate sustained and meaningful involvement in research.

Regulatory factors governing adenosine-to-inosine (A-to-I) RNA editing.

PubMed

Hong, HuiQi; Lin, Jaymie Siqi; Chen, Leilei

2015-03-31

Adenosine-to-inosine (A-to-I) RNA editing, the most prevalent mode of transcript modification in higher eukaryotes, is catalysed by the adenosine deaminases acting on RNA (ADARs). A-to-I editing imposes an additional layer of gene regulation as it dictates various aspects of RNA metabolism, including RNA folding, processing, localization and degradation. Furthermore, editing events in exonic regions contribute to proteome diversity as translational machinery decodes inosine as guanosine. Although it has been demonstrated that dysregulated A-to-I editing contributes to various diseases, the precise regulatory mechanisms governing this critical cellular process have yet to be fully elucidated. However, integration of previous studies revealed that regulation of A-to-I editing is multifaceted, weaving an intricate network of auto- and transregulations, including the involvement of virus-originated factors like adenovirus-associated RNA. Taken together, it is apparent that tipping of any regulatory components will have profound effects on A-to-I editing, which in turn contributes to both normal and aberrant physiological conditions. A complete understanding of this intricate regulatory network may ultimately be translated into new therapeutic strategies against diseases driven by perturbed RNA editing events. Herein, we review the current state of knowledge on the regulatory mechanisms governing A-to-I editing and propose the role of other co-factors that may be involved in this complex regulatory process.

The ICNP-BaT--a multilingual web-based tool to support the collaborative translation of the International Classification for Nursing Practice (ICNP).

PubMed

Schrader, Ulrich; Tackenberg, Peter; Widmer, Rudolf; Portenier, Lucien; König, Peter

2007-01-01

To ease and speed up the translation of the ICNP version 1 into the German language a web service was developed to support the collaborative work of all Austrian, Swiss, and German translators and subsequently of the evaluators of the resultant translation. The web service does help to support a modified Delphi technique. Since the web service is multilingual by design it can facilitate the translation of the ICNP into other languages as well. The process chosen can be adopted by other projects involved in translating terminologies.

The Translated Dowling Polynomials and Numbers.

PubMed

Mangontarum, Mahid M; Macodi-Ringia, Amila P; Abdulcarim, Normalah S

2014-01-01

More properties for the translated Whitney numbers of the second kind such as horizontal generating function, explicit formula, and exponential generating function are proposed. Using the translated Whitney numbers of the second kind, we will define the translated Dowling polynomials and numbers. Basic properties such as exponential generating functions and explicit formula for the translated Dowling polynomials and numbers are obtained. Convexity, integral representation, and other interesting identities are also investigated and presented. We show that the properties obtained are generalizations of some of the known results involving the classical Bell polynomials and numbers. Lastly, we established the Hankel transform of the translated Dowling numbers.

Integration of research and practice to improve public health and healthcare delivery through a collaborative 'Health Integration Team' model - a qualitative investigation.

PubMed

Redwood, Sabi; Brangan, Emer; Leach, Verity; Horwood, Jeremy; Donovan, Jenny L

2016-06-22

Economic considerations and the requirement to ensure the quality, safety and integration of research with health and social care provision have given rise to local developments of collaborative organisational forms and strategies to span the translational gaps. One such model - the Health Integration Team (HIT) model in Bristol in the United Kingdom (UK) - brings together National Health Service (NHS) organisations, universities, local authorities, patients and the public to facilitate the systematic application of evidence to promote integration across healthcare pathways. This study aimed to (1) provide empirical evidence documenting the evolution of the model; (2) to identify the social and organisational processes and theory of change underlying healthcare knowledge and practice; and (3) elucidate the key aspects of the HIT model for future development and translation to other localities. Contemporaneous documents were analysed, using procedures associated with Framework Analysis to produce summarised data for descriptive accounts. In-depth interviews were undertaken with key informants and analysed thematically. Comparative methods were applied to further analyse the two data sets. One hundred forty documents were analysed and 10 interviews conducted with individuals in leadership positions in the universities, NHS commissioning and provider organisations involved in the design and implementation of the HIT model. Data coalesced around four overarching themes: 'Whole system' engagement, requiring the active recruitment of all those who have a stake in the area of practice being considered, and 'collaboration' to enable coproduction were identified as 'process' themes. System-level integration and innovation were identified as potential 'outcomes' with far-reaching impacts on population health and service delivery. The HIT model emerged as a particular response to the perceived need for integration of research and practice to improve public health and healthcare delivery at a time of considerable organisational turmoil and financial constraints. The concept gained momentum and will likely be of interest to those involved in setting up similar arrangements, and researchers in the social and implementation sciences with an interest in their evaluation.

The Circadian Clock Coordinates Ribosome Biogenesis

PubMed Central

Symul, Laura; Martin, Eva; Atger, Florian; Naef, Felix; Gachon, Frédéric

2013-01-01

Biological rhythms play a fundamental role in the physiology and behavior of most living organisms. Rhythmic circadian expression of clock-controlled genes is orchestrated by a molecular clock that relies on interconnected negative feedback loops of transcription regulators. Here we show that the circadian clock exerts its function also through the regulation of mRNA translation. Namely, the circadian clock influences the temporal translation of a subset of mRNAs involved in ribosome biogenesis by controlling the transcription of translation initiation factors as well as the clock-dependent rhythmic activation of signaling pathways involved in their regulation. Moreover, the circadian oscillator directly regulates the transcription of ribosomal protein mRNAs and ribosomal RNAs. Thus the circadian clock exerts a major role in coordinating transcription and translation steps underlying ribosome biogenesis. PMID:23300384

Deficiency of the Survival of Motor Neuron Protein Impairs mRNA Localization and Local Translation in the Growth Cone of Motor Neurons.

PubMed

Fallini, Claudia; Donlin-Asp, Paul G; Rouanet, Jeremy P; Bassell, Gary J; Rossoll, Wilfried

2016-03-30

Spinal muscular atrophy (SMA) is a neurodegenerative disease primarily affecting spinal motor neurons. It is caused by reduced levels of the survival of motor neuron (SMN) protein, which plays an essential role in the biogenesis of spliceosomal small nuclear ribonucleoproteins in all tissues. The etiology of the specific defects in the motor circuitry in SMA is still unclear, but SMN has also been implicated in mediating the axonal localization of mRNA-protein complexes, which may contribute to the axonal degeneration observed in SMA. Here, we report that SMN deficiency severely disrupts local protein synthesis within neuronal growth cones. We also identify the cytoskeleton-associated growth-associated protein 43 (GAP43) mRNA as a new target of SMN and show that motor neurons from SMA mouse models have reduced levels ofGAP43mRNA and protein in axons and growth cones. Importantly, overexpression of two mRNA-binding proteins, HuD and IMP1, restoresGAP43mRNA and protein levels in growth cones and rescues axon outgrowth defects in SMA neurons. These findings demonstrate that SMN plays an important role in the localization and local translation of mRNAs with important axonal functions and suggest that disruption of this function may contribute to the axonal defects observed in SMA. The motor neuron disease spinal muscular atrophy (SMA) is caused by reduced levels of the survival of motor neuron (SMN) protein, which plays a key role in assembling RNA/protein complexes that are essential for mRNA splicing. It remains unclear whether defects in this well characterized housekeeping function cause the specific degeneration of spinal motor neurons observed in SMA. Here, we describe an additional role of SMN in regulating the axonal localization and local translation of the mRNA encoding growth-associated protein 43 (GAP43). This study supports a model whereby SMN deficiency impedes transport and local translation of mRNAs important for neurite outgrowth and stabilization, thus contributing to axon degeneration, muscle denervation, and motor neuron cell death in SMA. Copyright © 2016 the authors 0270-6474/16/363811-10$15.00/0.

Development of macaronic Hindi-English ‘Hinglish’ text message content for a coronary heart disease secondary prevention programme

PubMed Central

Thakkar, Jay; Karthikeyan, Ganesan; Purohit, Gaurav; Thakkar, Swetha; Sharma, Jitender; Verma, Sunilkumar; Parakh, Neeraj; Seth, Sandeep; Mishra, Sundeep; Yadav, Rakesh; Singh, Sandeep; Joshi, Rohina; Thiagalingam, Aravinda; Chow, Clara K; Redfern, Julie

2016-01-01

Background Coronary heart disease (CHD) is a leading cause of morbidity and mortality in India. Text message based prevention programs have demonstrated reduction in cardiovascular risk factors among patients with CHD in selected populations. Customisation is important as behaviour change is influenced by culture and linguistic context. Objectives To customise a mobile phone text message program supporting behaviour and treatment adherence in CHD for delivery in North India. Methods We used an iterative process with mixed methods involving three phases: (1) Initial translation, (2) Review and incorporation of feedback including review by cardiologists in India to assess alignment with local guidelines and by consumers on perceived utility and clarity and (3) Pilot testing of message management software. Results Messages were translated in three ways: symmetrical translation, asymmetrical translation and substitution. Feedback from cardiologists and 25 patients was incorporated to develop the final bank. Patients reported Hinglish messages were easy to understand (93%) and useful (78%). The software located in Australia successfully delivered messages to participants based in Delhi-surrounds (India). Conclusions Our process for customisation of a text message program considered cultural, linguistic and the medical context of potential participants. This is important in optimising intervention fidelity across populations enabling examination of the generalisability of text message programs across populations. We also demonstrated the customised program was acceptable to patients in India and that a centralised cross-country delivery model was feasible. This process could be used as a guide for other groups seeking to customise their programs. Trial registration number TEXTMEDS Australia (Parent study)—ACTRN 12613000793718. PMID:27752288

Lost in Translation: The Power of Language

ERIC Educational Resources Information Center

Farquhar, Sandy; Fitzsimons, Peter

2011-01-01

The paper examines some philosophical aspects of translation as a metaphor for education--a metaphor that avoids the closure of final definitions, in favour of an ongoing and tentative process of interpretation and revision. Translation, it is argued, is a complex process involving language, within and among cultures, and in the exercise of power.…

Development of German-English Machine Translation System. Final Technical Report.

ERIC Educational Resources Information Center

Lehmann, Winfred P.; Stachowitz, Rolf A.

This report describes work on a pilot system for a fully automatic, high-quality translation of German scientific and technical text into English and gives the results of an experiment designed to show the system's capability to produce quality mechanical translation. The areas considered were: (1) grammar formalism, mainly involving the addition…

From bench to bedside and to health policies: ethics in translational research.

PubMed

Petrini, C

2011-01-01

Translation of biomedical research knowledge to effective clinical treatment is essential to the public good. The first level of translation ("from bench to bedside") corresponds to efficacy studies under controlled conditions with careful attention to internal validity (clinical research). The second level is the translation of results from clinical studies into everyday clinical practice and health decision making. The article summarises the ethical issues involved in the translation of biomedical research advances to clinical applications and to clinical practice. In particular, the article synthesizes theory from clinical ethics, operational design, and philosophy to examine the unique bioethical issues raised by the recent focus on translational research. In this framework safety of study participants and balancing of risk due to treatment with the potential benefits of the research are crucial: in clinical research there is a danger that the emphasis on advancements in scientific knowledge might prevail over the protection of the people who participate in research. These issues involve basic scientists, clinicians and bioethicists because of their application to comparative effectiveness research, clinical trials and evidence-based medicine, as well basic biomedical research.

Monte Carlo solution of Boltzmann equation for a simple model of highly nonequilibrium diatomic gases: Translational rotational energy relaxation

NASA Technical Reports Server (NTRS)

Yoshikawa, K. K.

1978-01-01

The semiclassical transition probability was incorporated in the simulation for energy exchange between rotational and translational energy. The results provide details on the fundamental mechanisms of gas kinetics where analytical methods were impractical. The validity of the local Maxwellian assumption and relaxation time, rotational-translational energy transition, and a velocity analysis of the inelastic collision were discussed in detail.

Autogenous cross-regulation of Quaking mRNA processing and translation balances Quaking functions in splicing and translation

PubMed Central

Liu, Naiyou; Fair, Jeffrey Haskell; Shiue, Lily; Katzman, Sol; Donohue, John Paul

2017-01-01

Quaking protein isoforms arise from a single Quaking gene and bind the same RNA motif to regulate splicing, translation, decay, and localization of a large set of RNAs. However, the mechanisms by which Quaking expression is controlled to ensure that appropriate amounts of each isoform are available for such disparate gene expression processes are unknown. Here we explore how levels of two isoforms, nuclear Quaking-5 (Qk5) and cytoplasmic Qk6, are regulated in mouse myoblasts. We found that Qk5 and Qk6 proteins have distinct functions in splicing and translation, respectively, enforced through differential subcellular localization. We show that Qk5 and Qk6 regulate distinct target mRNAs in the cell and act in distinct ways on their own and each other's transcripts to create a network of autoregulatory and cross-regulatory feedback controls. Morpholino-mediated inhibition of Qk translation confirms that Qk5 controls Qk RNA levels by promoting accumulation and alternative splicing of Qk RNA, whereas Qk6 promotes its own translation while repressing Qk5. This Qk isoform cross-regulatory network responds to additional cell type and developmental controls to generate a spectrum of Qk5/Qk6 ratios, where they likely contribute to the wide range of functions of Quaking in development and cancer. PMID:29021242

Technology for Large-Scale Translation of Clinical Practice Guidelines: A Pilot Study of the Performance of a Hybrid Human and Computer-Assisted Approach.

PubMed

Van de Velde, Stijn; Macken, Lieve; Vanneste, Koen; Goossens, Martine; Vanschoenbeek, Jan; Aertgeerts, Bert; Vanopstal, Klaar; Vander Stichele, Robert; Buysschaert, Joost

2015-10-09

The construction of EBMPracticeNet, a national electronic point-of-care information platform in Belgium, began in 2011 to optimize quality of care by promoting evidence-based decision making. The project involved, among other tasks, the translation of 940 EBM Guidelines of Duodecim Medical Publications from English into Dutch and French. Considering the scale of the translation process, it was decided to make use of computer-aided translation performed by certificated translators with limited expertise in medical translation. Our consortium used a hybrid approach, involving a human translator supported by a translation memory (using SDL Trados Studio), terminology recognition (using SDL MultiTerm terminology databases) from medical terminology databases, and support from online machine translation. This resulted in a validated translation memory, which is now in use for the translation of new and updated guidelines. The objective of this experiment was to evaluate the performance of the hybrid human and computer-assisted approach in comparison with translation unsupported by translation memory and terminology recognition. A comparison was also made with the translation efficiency of an expert medical translator. We conducted a pilot study in which two sets of 30 new and 30 updated guidelines were randomized to one of three groups. Comparable guidelines were translated (1) by certificated junior translators without medical specialization using the hybrid method, (2) by an experienced medical translator without this support, and (3) by the same junior translators without the support of the validated translation memory. A medical proofreader who was blinded for the translation procedure, evaluated the translated guidelines for acceptability and adequacy. Translation speed was measured by recording translation and post-editing time. The human translation edit rate was calculated as a metric to evaluate the quality of the translation. A further evaluation was made of translation acceptability and adequacy. The average number of words per guideline was 1195 and the mean total translation time was 100.2 minutes/1000 words. No meaningful differences were found in the translation speed for new guidelines. The translation of updated guidelines was 59 minutes/1000 words faster (95% CI 2-115; P=.044) in the computer-aided group. Revisions due to terminology accounted for one third of the overall revisions by the medical proofreader. Use of the hybrid human and computer-aided translation by a non-expert translator makes the translation of updates of clinical practice guidelines faster and cheaper because of the benefits of translation memory. For the translation of new guidelines, there was no apparent benefit in comparison with the efficiency of translation unsupported by translation memory (whether by an expert or non-expert translator).

Technology for Large-Scale Translation of Clinical Practice Guidelines: A Pilot Study of the Performance of a Hybrid Human and Computer-Assisted Approach

PubMed Central

2015-01-01

Background The construction of EBMPracticeNet, a national electronic point-of-care information platform in Belgium, began in 2011 to optimize quality of care by promoting evidence-based decision making. The project involved, among other tasks, the translation of 940 EBM Guidelines of Duodecim Medical Publications from English into Dutch and French. Considering the scale of the translation process, it was decided to make use of computer-aided translation performed by certificated translators with limited expertise in medical translation. Our consortium used a hybrid approach, involving a human translator supported by a translation memory (using SDL Trados Studio), terminology recognition (using SDL MultiTerm terminology databases) from medical terminology databases, and support from online machine translation. This resulted in a validated translation memory, which is now in use for the translation of new and updated guidelines. Objective The objective of this experiment was to evaluate the performance of the hybrid human and computer-assisted approach in comparison with translation unsupported by translation memory and terminology recognition. A comparison was also made with the translation efficiency of an expert medical translator. Methods We conducted a pilot study in which two sets of 30 new and 30 updated guidelines were randomized to one of three groups. Comparable guidelines were translated (1) by certificated junior translators without medical specialization using the hybrid method, (2) by an experienced medical translator without this support, and (3) by the same junior translators without the support of the validated translation memory. A medical proofreader who was blinded for the translation procedure, evaluated the translated guidelines for acceptability and adequacy. Translation speed was measured by recording translation and post-editing time. The human translation edit rate was calculated as a metric to evaluate the quality of the translation. A further evaluation was made of translation acceptability and adequacy. Results The average number of words per guideline was 1195 and the mean total translation time was 100.2 minutes/1000 words. No meaningful differences were found in the translation speed for new guidelines. The translation of updated guidelines was 59 minutes/1000 words faster (95% CI 2-115; P=.044) in the computer-aided group. Revisions due to terminology accounted for one third of the overall revisions by the medical proofreader. Conclusions Use of the hybrid human and computer-aided translation by a non-expert translator makes the translation of updates of clinical practice guidelines faster and cheaper because of the benefits of translation memory. For the translation of new guidelines, there was no apparent benefit in comparison with the efficiency of translation unsupported by translation memory (whether by an expert or non-expert translator). PMID:26453372

The researchers' role in knowledge translation: a realist evaluation of the development and implementation of diagnostic pathways for cancer in two United Kingdom localities.

PubMed

Banks, Jon; Wye, Lesley; Hall, Nicola; Rooney, James; Walter, Fiona M; Hamilton, Willie; Gjini, Ardiana; Rubin, Greg

2017-12-13

In examining an initiative to develop and implement new cancer diagnostic pathways in two English localities, this paper evaluates 'what works' and examines the role of researchers in facilitating knowledge translation amongst teams of local clinicians and policy-makers. Using realist evaluation with a mixed methods case study approach, we conducted documentary analysis of meeting minutes and pathway iterations to map pathway development. We interviewed 14 participants to identify the contexts, mechanisms and outcomes (CMOs) that led to successful pathway development and implementation. Interviews were analysed thematically and four CMO configurations were developed. One site produced three fully implemented pathways, while the other produced two that were partly implemented. In explaining the differences, we found that a respected, independent, well-connected leader modelling partnership working and who facilitates a local, stable group that agree about the legitimacy of the data and project (context) can empower local teams to become sufficiently autonomous (mechanism) to develop and implement research-based pathways (outcome). Although both teams designed relevant, research-based cancer pathways, in the site where the pathways were successfully implemented the research team merely assisted, while, in the other, the research team drove the initiative. Based on our study findings, local stakeholders can apply local and research knowledge to develop and implement research-based pathways. However, success will depend on how academics empower local teams to create autonomy. Crucially, after re-packaging and translating research for local circumstances, identifying fertile environments with the right elements for implementation and developing collaborative relationships with local leaders, academics must step back.

Subcellular Fractionation and Localization Studies Reveal a Direct Interaction of the Fragile X Mental Retardation Protein (FMRP) with Nucleolin

PubMed Central

Taha, Mohamed S.; Nouri, Kazem; Milroy, Lech G.; Moll, Jens M.; Herrmann, Christian; Brunsveld, Luc; Piekorz, Roland P.; Ahmadian, Mohammad R.

2014-01-01

Fragile X mental Retardation Protein (FMRP) is a well-known regulator of local translation of its mRNA targets in neurons. However, despite its ubiquitous expression, the role of FMRP remains ill-defined in other cell types. In this study we investigated the subcellular distribution of FMRP and its protein complexes in HeLa cells using confocal imaging as well as detergent-free fractionation and size exclusion protocols. We found FMRP localized exclusively to solid compartments, including cytosolic heavy and light membranes, mitochondria, nuclear membrane and nucleoli. Interestingly, FMRP was associated with nucleolin in both a high molecular weight ribosomal and translation-associated complex (≥6 MDa) in the cytosol, and a low molecular weight complex (∼200 kDa) in the nucleoli. Consistently, we identified two functional nucleolar localization signals (NoLSs) in FMRP that are responsible for a strong nucleolar colocalization of the C-terminus of FMRP with nucleolin, and a direct interaction of the N-terminus of FMRP with the arginine-glycine-glycine (RGG) domain of nucleolin. Taken together, we propose a novel mechanism by which a transient nucleolar localization of FMRP underlies a strong nucleocytoplasmic translocation, most likely in a complex with nucleolin and possibly ribosomes, in order to regulate translation of its target mRNAs. PMID:24658146

Translating knowledge into best practice care bundles: a pragmatic strategy for EBP implementation via moving postprocedural pain management nursing guidelines into clinical practice.

PubMed

Saunders, Hannele

2015-07-01

To describe quantitative and qualitative best evidence as sources for practical interventions usable in daily care delivery in order to integrate best evidence into clinical decision-making at local practice settings. To illustrate the development, implementation and evaluation of a pain management nursing care bundle based on a clinical practice guideline via a real-world clinical exemplar. Successful implementation of evidence-based practice requires consistent integration of best evidence into daily clinical decision-making. Best evidence comprises high-quality knowledge summarised in systematic reviews and translated into guidelines. However, consistent integration of guidelines into care delivery remains challenging, partly due to guidelines not being in a usable form for daily practice or relevant for the local context. A position paper with a clinical exemplar of a nurse-led, evidence-based quality improvement project to design, implement and evaluate a pain management care bundle translated from a national nursing guideline. A pragmatic approach to integrating guidelines into daily practice is presented. Best evidence from a national nursing guideline was translated into a pain management care bundle and integrated into daily practice in 15 medical-surgical (med-surg) units of nine hospitals of a large university hospital system in Finland. Translation of best evidence from guidelines into usable form as care bundles adapted to the local setting may increase implementation and uptake of guidelines and improve quality and consistency of care delivery. A pragmatic approach to translating a nursing guideline into a pain management care bundle to incorporate best evidence into daily practice may help achieve more consistent and equitable integration of guidelines into care delivery, and better quality of pain management and patient outcomes. © 2015 John Wiley & Sons Ltd.

Building capacity for knowledge translation in occupational therapy: learning through participatory action research.

PubMed

Bennett, Sally; Whitehead, Mary; Eames, Sally; Fleming, Jennifer; Low, Shanling; Caldwell, Elizabeth

2016-10-01

There has been widespread acknowledgement of the need to build capacity in knowledge translation however much of the existing work focuses on building capacity amongst researchers rather than with clinicians directly. This paper's aim is to describe a research project for developing a knowledge translation capacity building program for occupational therapy clinicians. Participatory action research methods were used to both develop and evaluate the knowledge translation capacity-building program. Participants were occupational therapists from a large metropolitan hospital in Australia. Researchers and clinicians worked together to use the action cycle of the Knowledge to Action Framework to increase use of knowledge translation itself within the department in general, within their clinical teams, and to facilitate knowledge translation becoming part of the department's culture. Barriers and enablers to using knowledge translation were identified through a survey based on the Theoretical Domains Framework and through focus groups. Multiple interventions were used to develop a knowledge translation capacity-building program. Fifty-two occupational therapists participated initially, but only 20 across the first 18 months of the project. Barriers and enablers were identified across all domains of the Theoretical Domains Framework. Interventions selected to address these barriers or facilitate enablers were categorised into ten different categories: educational outreach; teams working on clinical knowledge translation case studies; identifying time blocks for knowledge translation; mentoring; leadership strategies; communication strategies; documentation and resources to support knowledge translation; funding a knowledge translation champion one day per week; setting goals for knowledge translation; and knowledge translation reporting strategies. Use of these strategies was, and continues to be monitored. Participants continue to be actively involved in learning and shaping the knowledge translation program across the department and within their specific clinical areas. To build capacity for knowledge translation, it is important to involve clinicians. The action cycle of the Knowledge to Action framework is a useful guide to introduce the knowledge translation process to clinicians. It may be used to engage the department as a whole, and facilitate the learning and application of knowledge translation within specific clinical areas. Research evaluating this knowledge translation program is being conducted.

Dynamic landscape of the local translation at activated synapses.

PubMed

Khlebodarova, T M; Kogai, V V; Trifonova, E A; Likhoshvai, V A

2018-01-01

The mammalian target of rapamycin (mTOR) signaling pathway is the central regulator of cap-dependent translation at the synapse. Disturbances in mTOR pathway have been associated with several neurological diseases, such as autism and epilepsy. RNA-binding protein FMRP, a negative regulator of translation initiation, is one of the key components of the local translation system. Activation and inactivation of FMRP occurs via phosphorylation by S6 kinase and dephosphorylation by PP2A phosphatase, respectively. S6 kinase and PP2A phosphatase are activated in response to mGluR receptor stimulation through different signaling pathways and at different rates. The dynamic aspects of this system are poorly understood. We developed a mathematical model of FMRP-dependent regulation of postsynaptic density (PSD) protein synthesis in response to mGluR receptor stimulation and conducted in silico experiments to study the regulatory circuit functioning. The modeling results revealed the possibility of generating oscillatory (cyclic and quasi-cyclic), chaotic and even hyperchaotic dynamics of postsynaptic protein synthesis as well as the presence of multiple attractors in a wide range of parameters of the local translation system. The results suggest that autistic disorders associated with mTOR pathway hyperactivation may be due to impaired proteome stability associated with the formation of complex dynamic regimes of PSD protein synthesis in response to stimulation of mGluR receptors on the postsynaptic membrane of excitatory synapses on pyramidal hippocampal cells.

High MMP-9 activity levels in fragile X syndrome are lowered by minocycline.

PubMed

Dziembowska, Magdalena; Pretto, Dalyir I; Janusz, Aleksandra; Kaczmarek, Leszek; Leigh, Mary Jacena; Gabriel, Nielsen; Durbin-Johnson, Blythe; Hagerman, Randi J; Tassone, Flora

2013-08-01

Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by lack of the FMR1 protein, FMRP, a translational repressor. Its absence leads to up-regulation of locally translated proteins involved in synaptic transmission and plasticity, including the matrix metalloproteinase-9 (MMP-9). In the Fmr1 knock-out (KO), a mouse model of FXS, an abnormal elevated expression of MMP-9 in the brain was pharmacologically down-regulated after treatment with the tetracycline derivative minocycline. Moreover, the rescue of immature dendritic spine morphology and a significant improvement of abnormal behavior were associated with down-regulation of MMP-9. Here, we report on high plasma activity of MMP-9 in individuals with FXS. In addition, we investigate MMP-9 changes in patients with FXS who have gone through a minocycline controlled clinical trial and correlate MMP-9 activity to clinical observations. The results of this study suggest that, in humans, activity levels of MMP-9 are lowered by minocycline and that, in some cases, changes in MMP-9 activity are positively associated with improvement based on clinical measures. Copyright © 2013 Wiley Periodicals, Inc.

Exploring Local Public Health Workflow in the Context of Automated Translation Technologies

PubMed Central

Mandel, Hannah; Turner, Anne M.

2013-01-01

Despite the growing limited English proficiency (LEP) population in the US, and federal regulations requiring multilingual health information be available for LEP individuals, there is a lack of available high quality multilingual health promotion materials. The costs and personnel time associated with creating high quality translations serve as barriers to their creation, especially in resource limited public health settings. To explore the potential adoption of novel machine translation and document dissemination technologies for improving the creation and sharing of translated public health materials, we interviewed key health department personnel in Washington State. We analyzed translation workflow, elucidated key themes regarding public health translation work, and assessed attitudes towards electronic document exchange and machine translation. Public health personnel expressed the need for human quality assurance and oversight, but appreciated the potential of novel information technologies to assist in the production and dissemination of translated materials for public health practice. PMID:24551385

From Quantum Fields to Local Von Neumann Algebras

NASA Astrophysics Data System (ADS)

Borchers, H. J.; Yngvason, Jakob

The subject of the paper is an old problem of the general theory of quantized fields: When can the unbounded operators of a Wightman field theory be associated with local algebras of bounded operators in the sense of Haag? The paper reviews and extends previous work on this question, stressing its connections with a noncommutive generalization of the classical Hamburger moment problem. Necessary and sufficient conditions for the existence of a local net of von Neumann algebras corresponding to a given Wightman field are formulated in terms of strengthened versions of the usual positivity property of Wightman functionals. The possibility that the local net has to be defined in an enlarged Hilbert space cannot be ruled out in general. Under additional hypotheses, e.g., if the field operators obey certain energy bounds, such an extension of the Hilbert space is not necessary, however. In these cases a fairly simple condition for the existence of a local net can be given involving the concept of “central positivity” introduced by Powers. The analysis presented here applies to translationally covariant fields with an arbitrary number of components, whereas Lorentz covariance is not needed. The paper contains also a brief discussion of an approach to noncommutative moment problems due to Dubois-Violette, and concludes with some remarks on modular theory for algebras of unbounded operators.

Golgi bypass for local delivery of axonal proteins, fact or fiction?

PubMed

González, Carolina; Cornejo, Víctor Hugo; Couve, Andrés

2018-04-06

Although translation of cytosolic proteins is well described in axons, much less is known about the synthesis, processing and trafficking of transmembrane and secreted proteins. A canonical rough endoplasmic reticulum or a stacked Golgi apparatus has not been detected in axons, generating doubts about the functionality of a local route. However, axons contain mRNAs for membrane and secreted proteins, translation factors, ribosomal components, smooth endoplasmic reticulum and post-endoplasmic reticulum elements that may contribute to local biosynthesis and plasma membrane delivery. Here we consider the evidence supporting a local secretory system in axons. We discuss exocytic elements and examples of autonomous axonal trafficking that impact development and maintenance. We also examine whether unconventional post-endoplasmic reticulum pathways may replace the canonical Golgi apparatus. Copyright © 2018. Published by Elsevier Ltd.

Introduction of new technologies and decision making processes: a framework to adapt a Local Health Technology Decision Support Program for other local settings.

PubMed

Poulin, Paule; Austen, Lea; Scott, Catherine M; Poulin, Michelle; Gall, Nadine; Seidel, Judy; Lafrenière, René

2013-01-01

Introducing new health technologies, including medical devices, into a local setting in a safe, effective, and transparent manner is a complex process, involving many disciplines and players within an organization. Decision making should be systematic, consistent, and transparent. It should involve translating and integrating scientific evidence, such as health technology assessment (HTA) reports, with context-sensitive evidence to develop recommendations on whether and under what conditions a new technology will be introduced. However, the development of a program to support such decision making can require considerable time and resources. An alternative is to adapt a preexisting program to the new setting. We describe a framework for adapting the Local HTA Decision Support Program, originally developed by the Department of Surgery and Surgical Services (Calgary, AB, Canada), for use by other departments. The framework consists of six steps: 1) development of a program review and adaptation manual, 2) education and readiness assessment of interested departments, 3) evaluation of the program by individual departments, 4) joint evaluation via retreats, 5) synthesis of feedback and program revision, and 6) evaluation of the adaptation process. Nine departments revised the Local HTA Decision Support Program and expressed strong satisfaction with the adaptation process. Key elements for success were identified. Adaptation of a preexisting program may reduce duplication of effort, save resources, raise the health care providers' awareness of HTA, and foster constructive stakeholder engagement, which enhances the legitimacy of evidence-informed recommendations for introducing new health technologies. We encourage others to use this framework for program adaptation and to report their experiences.

Superlattices: problems and new opportunities, nanosolids

PubMed Central

2011-01-01

Superlattices were introduced 40 years ago as man-made solids to enrich the class of materials for electronic and optoelectronic applications. The field metamorphosed to quantum wells and quantum dots, with ever decreasing dimensions dictated by the technological advancements in nanometer regime. In recent years, the field has gone beyond semiconductors to metals and organic solids. Superlattice is simply a way of forming a uniform continuum for whatever purpose at hand. There are problems with doping, defect-induced random switching, and I/O involving quantum dots. However, new opportunities in component-based nanostructures may lead the field of endeavor to new heights. The all important translational symmetry of solids is relaxed and local symmetry is needed in nanosolids. PMID:21711653

78 FR 23854 - Implementation of the Local Community Radio Act of 2010; Revision of Service and Eligibility...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-23

... cross-ownership of an LPFM station and up to two FM translator stations. Second, the FCC modified its... respect to interference to the input signals of FM translator or FM booster stations. We have revised the...

Post-translational Maturation of Dystroglycan Is Necessary for Pikachurin Binding and Ribbon Synaptic Localization*

PubMed Central

Kanagawa, Motoi; Omori, Yoshihiro; Sato, Shigeru; Kobayashi, Kazuhiro; Miyagoe-Suzuki, Yuko; Takeda, Shin'ichi; Endo, Tamao; Furukawa, Takahisa; Toda, Tatsushi

2010-01-01

Pikachurin, the most recently identified ligand of dystroglycan, plays a crucial role in the formation of the photoreceptor ribbon synapse. It is known that glycosylation of dystroglycan is necessary for its ligand binding activity, and hypoglycosylation is associated with a group of muscular dystrophies that often involve eye abnormalities. Because little is known about the interaction between pikachurin and dystroglycan and its impact on molecular pathogenesis, here we characterize the interaction using deletion constructs and mouse models of muscular dystrophies with glycosylation defects (Largemyd and POMGnT1-deficient mice). Pikachurin-dystroglycan binding is calcium-dependent and relatively less sensitive to inhibition by heparin and high NaCl concentration, as compared with other dystroglycan ligand proteins. Using deletion constructs of the laminin globular domains in the pikachurin C terminus, we show that a certain steric structure formed by the second and the third laminin globular domains is necessary for the pikachurin-dystroglycan interaction. Binding assays using dystroglycan deletion constructs and tissue samples from Large-deficient (Largemyd) mice show that Large-dependent modification of dystroglycan is necessary for pikachurin binding. In addition, the ability of pikachurin to bind to dystroglycan prepared from POMGnT1-deficient mice is severely reduced, suggesting that modification of the GlcNAc-β1,2-branch on O-mannose is also necessary for the interaction. Immunofluorescence analysis reveals a disruption of pikachurin localization in the photoreceptor ribbon synapse of these model animals. Together, our data demonstrate that post-translational modification on O-mannose, which is mediated by Large and POMGnT1, is essential for pikachurin binding and proper localization, and suggest that their disruption underlies the molecular pathogenesis of eye abnormalities in a group of muscular dystrophies. PMID:20682766

Development of a replicable process for translating science into practical health education messages.

PubMed

Tyus, Nadra C; Freeman, Randall J; Gibbons, M Christopher

2006-09-01

There has been considerable discussion about translating science into practical messages, especially among urban minority and "hard-to-reach" populations. Unfortunately, many research findings rarely make it back in useful format to the general public. Few innovative techniques have been established that provide researchers with a systematic process for developing health awareness and prevention messages for priority populations. The purpose of this paper is to describe the early development and experience of a unique community-based participatory process used to develop health promotion messages for a predominantly low-income, black and African-American community in Baltimore, MD. Scientific research findings from peer-reviewed literature were identified by academic researchers. Researchers then taught the science to graphic design students and faculty. The graphic design students and faculty then worked with both community residents and researchers to transform this information into evidence-based public health education messages. The final products were culturally and educationally appropriate, health promotion messages reflecting urban imagery that were eagerly desired by the community. This early outcome is in contrast to many previously developed messages and materials created through processes with limited community involvement and by individuals with limited practical knowledge of local community culture or expertise in marketing or mass communication. This process may potentially be utilized as a community-based participatory approach to enhance the translation of scientific research into desirable and appropriate health education messages.

Making On-line Science Course Materials Easily Translatable and Accessible Worldwide: Challenges and Solutions

NASA Astrophysics Data System (ADS)

Adams, Wendy K.; Alhadlaq, Hisham; Malley, Christopher V.; Perkins, Katherine K.; Olson, Jonathan; Alshaya, Fahad; Alabdulkareem, Saleh; Wieman, Carl E.

2012-02-01

The PhET Interactive Simulations Project partnered with the Excellence Research Center of Science and Mathematics Education at King Saud University with the joint goal of making simulations useable worldwide. One of the main challenges of this partnership is to make PhET simulations and the website easily translatable into any language. The PhET project team overcame this challenge by creating the Translation Utility. This tool allows a person fluent in both English and another language to easily translate any of the PhET simulations and requires minimal computer expertise. In this paper we discuss the technical issues involved in this software solution, as well as the issues involved in obtaining accurate translations. We share our solutions to many of the unexpected problems we encountered that would apply generally to making on-line scientific course materials available in many different languages, including working with: languages written right-to-left, different character sets, and different conventions for expressing equations, variables, units and scientific notation.

The eIF4E-binding proteins are modifiers of cytoplasmic eIF4E relocalization during the heat shock response.

PubMed

Sukarieh, R; Sonenberg, N; Pelletier, J

2009-05-01

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

Validity and Reliability of Internalized Stigma of Mental Illness (Cantonese)

ERIC Educational Resources Information Center

Young, Daniel Kim-Wan; Ng, Petrus Y. N.; Pan, Jia-Yan; Cheng, Daphne

2017-01-01

Purpose: This study aims to translate and test the reliability and validity of the Internalized Stigma of Mental Illness-Cantonese (ISMI-C). Methods: The original English version of ISMI is translated into the ISMI-C by going through forward and backward translation procedure. A cross-sectional research design is adopted that involved 295…

Ensuring Cross-Cultural Equivalence in Translation of Research Consents and Clinical Documents

PubMed Central

Lee, Cheng-Chih; Li, Denise; Arai, Shoshana; Puntillo, Kathleen

2010-01-01

The aim of this article is to describe a formal process used to translate research study materials from English into traditional Chinese characters. This process may be useful for translating documents for use by both research participants and clinical patients. A modified Brislin model was used as the systematic translation process. Four bilingual translators were involved, and a Flaherty 3-point scale was used to evaluate the translated documents. The linguistic discrepancies that arise in the process of ensuring cross-cultural congruency or equivalency between the two languages are presented to promote the development of patient-accessible cross-cultural documents. PMID:18948451

Translation and Cross-Cultural Adaptation of the Lymphoedema Functioning, Disability and Health Questionnaire for Lower Limb Lymphoedema into Portuguese Language.

PubMed

Ferreira, Kamila Rodrigues; Carvalho, Raquel Boechat de Moura; de Andrade, Mauro Figueiredo Carvalho; Thuler, Luiz Claudio Santos; Bergmann, Anke

2016-02-01

The objective of the study is to describe the process of translation and cross-cultural adaptation of the Lymphoedema Functioning, Disability, and Health Questionnaire for Lower Limb Lymphoedema (Lymph-ICF-LL) into (Brazilian) Portuguese. The process was comprised of five steps - translation, back translation, revision by an expert panel, pretest, and final translation. The first translation was performed by two professionals of the healthcare area, and the back translation was performed by two translators. An expert panel assessed the questions for semantics and idiomatic, cultural, and conceptual equivalence. The pretest was conducted on 10 patients with lymphedema. Small differences were identified between the translated and back-translated versions, which were revised by the expert panel. The patients included in the pretest found 10 questions difficult to understand; these questions were reassessed by the same expert panel. The results of the translation and cross-cultural adaptation of the Lymph-ICF-LL resulted in a Brazilian Portuguese version, which still requires validation with various samples of the local population. Thieme Publicações Ltda Rio de Janeiro, Brazil.

Insights into molecular plasticity in protein complexes from Trm9-Trm112 tRNA modifying enzyme crystal structure

PubMed Central

Létoquart, Juliette; van Tran, Nhan; Caroline, Vonny; Aleksandrov, Alexey; Lazar, Noureddine; van Tilbeurgh, Herman; Liger, Dominique; Graille, Marc

2015-01-01

Most of the factors involved in translation (tRNA, rRNA and proteins) are subject to post-transcriptional and post-translational modifications, which participate in the fine-tuning and tight control of ribosome and protein synthesis processes. In eukaryotes, Trm112 acts as an obligate activating platform for at least four methyltransferases (MTase) involved in the modification of 18S rRNA (Bud23), tRNA (Trm9 and Trm11) and translation termination factor eRF1 (Mtq2). Trm112 is then at a nexus between ribosome synthesis and function. Here, we present a structure-function analysis of the Trm9-Trm112 complex, which is involved in the 5-methoxycarbonylmethyluridine (mcm5U) modification of the tRNA anticodon wobble position and hence promotes translational fidelity. We also compare the known crystal structures of various Trm112-MTase complexes, highlighting the structural plasticity allowing Trm112 to interact through a very similar mode with its MTase partners, although those share less than 20% sequence identity. PMID:26438534

'2A-Like' Signal Sequences Mediating Translational Recoding: A Novel Form of Dual Protein Targeting.

PubMed

Roulston, Claire; Luke, Garry A; de Felipe, Pablo; Ruan, Lin; Cope, Jonathan; Nicholson, John; Sukhodub, Andriy; Tilsner, Jens; Ryan, Martin D

2016-08-01

We report the initial characterization of an N-terminal oligopeptide '2A-like' sequence that is able to function both as a signal sequence and as a translational recoding element. Owing to this translational recoding activity, two forms of nascent polypeptide are synthesized: (i) when 2A-mediated translational recoding has not occurred: the nascent polypeptide is fused to the 2A-like N-terminal signal sequence and the fusion translation product is targeted to the exocytic pathway, and, (ii) a translation product where 2A-mediated translational recoding has occurred: the 2A-like signal sequence is synthesized as a separate translation product and, therefore, the nascent (downstream) polypeptide lacks the 2A-like signal sequence and is localized to the cytoplasm. This type of dual-functional signal sequence results, therefore, in the partitioning of the translation products between the two sub-cellular sites and represents a newly described form of dual protein targeting. © 2016 The Authors. Traffic published by John Wiley & Sons Ltd.

Seismogenic rotational slumps and translational glides in pelagic deep-water carbonates. Upper Tithonian-Berriasian of Southern Tethyan margin (W Sicily, Italy)

NASA Astrophysics Data System (ADS)

Basilone, Luca

2017-07-01

Soft-sediment deformation structures (SSDSs), which reflect sediment mobilization processes, are helpful to identify punctual events of paleoenvironmental stresses. In the upper Tithonian-Berriasian calpionellid pelagic limestone of the Lattimusa Fm. outcropping in the Barracù section (W Sicily), paleoenvironmental restoration reveals the occurrence of a deep-water flat basin, characterised by undeformed planar bedding, laterally passing to a gentle slope where the deformed horizons alternate with undeformed beds. Here, two types of gravity slides have been differentiated on the basis of different kinds of SSDSs, brittle deformation, involved lithofacies, geometry and morphology. Type 1 slump sheets, involving marl-limestone couplets, are characterised by chaotic stratification, truncated beds, recumbent folds, tension gashes, clastic dikes and small-scale listric normal faults and thrusts. They moved downslope as a rotational slump, displaying the typical wedge-shaped morphology, becoming thicker toe-wards. Type 2 slump sheets, involving bed packages of lime mudstone, are characterised by arcuate slump scars developing downwards as listric normal faults, associated with rotational beds and bulging. Displaying tabular geometries, they moved coherently along an overall bedding parallel detachment surface as a translational glide characterised by sediment creep. Regional geology indicates that the basin (Sicanian), bordered by a stepped carbonate platform, was affected by synsedimentary tectonics throughout the Mesozoic. The synsedimentary extensional tectonics that affect the Upper Triassic-Jurassic deposits with steeped normal faults, causing tilt-block and instability of the seafloor through fluidization processes, triggered the rotational slumps of the lower portion of the section. Seismic shocks, induced by outside sector tectonics, like those recorded in the adjacent Busambra stepped carbonate platform margin, triggered the rotational slumps that are not related to local-scale faults. To explain the translational glides of the upper portion of the section, the aforementioned outside sector earthquakes produced instability of the sea-floor through thixotropy of marls. In this case, the driving forces (i.e., gravitational) were favoured by the uplifting trend that is well recorded in the Southern Tethyan continental margin. We suggest that the various early deformations represent rotational slump and sediment creep that may be characteristic for slump structures in pelagic carbonates, depending on the involved lithologies (i.e., paleoenvironmental setting) and the intensity/distance of the trigger mechanism (i.e., earthquake epicentre).

Principles of mRNA transport in yeast.

PubMed

Heym, Roland Gerhard; Niessing, Dierk

2012-06-01

mRNA localization and localized translation is a common mechanism by which cellular asymmetry is achieved. In higher eukaryotes the mRNA transport machinery is required for such diverse processes as stem cell division and neuronal plasticity. Because mRNA localization in metazoans is highly complex, studies at the molecular level have proven to be cumbersome. However, active mRNA transport has also been reported in fungi including Saccharomyces cerevisiae, Ustilago maydis and Candida albicans, in which these events are less difficult to study. Amongst them, budding yeast S. cerevisiae has yielded mechanistic insights that exceed our understanding of other mRNA localization events to date. In contrast to most reviews, we refrain here from summarizing mRNA localization events from different organisms. Instead we give an in-depth account of ASH1 mRNA localization in budding yeast. This approach is particularly suited to providing a more holistic view of the interconnection between the individual steps of mRNA localization, from transcriptional events to cytoplasmic mRNA transport and localized translation. Because of our advanced mechanistic understanding of mRNA localization in yeast, the present review may also be informative for scientists working, for example, on mRNA localization in embryogenesis or in neurons.

The early career researcher's toolkit: translating tissue engineering, regenerative medicine and cell therapy products.

PubMed

Rafiq, Qasim A; Ortega, Ilida; Jenkins, Stuart I; Wilson, Samantha L; Patel, Asha K; Barnes, Amanda L; Adams, Christopher F; Delcassian, Derfogail; Smith, David

2015-11-01

Although the importance of translation for the development of tissue engineering, regenerative medicine and cell-based therapies is widely recognized, the process of translation is less well understood. This is particularly the case among some early career researchers who may not appreciate the intricacies of translational research or make decisions early in development which later hinders effective translation. Based on our own research and experiences as early career researchers involved in tissue engineering and regenerative medicine translation, we discuss common pitfalls associated with translational research, providing practical solutions and important considerations which will aid process and product development. Suggestions range from effective project management, consideration of key manufacturing, clinical and regulatory matters and means of exploiting research for successful commercialization.

Fast kinase domain-containing protein 3 is a mitochondrial protein essential for cellular respiration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simarro, Maria; Gimenez-Cassina, Alfredo; Kedersha, Nancy

2010-10-22

Research highlights: {yields} Five members of the FAST kinase domain-containing proteins are localized to mitochondria in mammalian cells. {yields} The FASTKD3 interactome includes proteins involved in various aspects of mitochondrial metabolism. {yields} Targeted knockdown of FASTKD3 significantly reduces basal and maximal mitochondrial oxygen consumption. -- Abstract: Fas-activated serine/threonine phosphoprotein (FAST) is the founding member of the FAST kinase domain-containing protein (FASTKD) family that includes FASTKD1-5. FAST is a sensor of mitochondrial stress that modulates protein translation to promote the survival of cells exposed to adverse conditions. Mutations in FASTKD2 have been linked to a mitochondrial encephalomyopathy that is associated withmore » reduced cytochrome c oxidase activity, an essential component of the mitochondrial electron transport chain. We have confirmed the mitochondrial localization of FASTKD2 and shown that all FASTKD family members are found in mitochondria. Although human and mouse FASTKD1-5 genes are expressed ubiquitously, some of them are most abundantly expressed in mitochondria-enriched tissues. We have found that RNA interference-mediated knockdown of FASTKD3 severely blunts basal and stress-induced mitochondrial oxygen consumption without disrupting the assembly of respiratory chain complexes. Tandem affinity purification reveals that FASTKD3 interacts with components of mitochondrial respiratory and translation machineries. Our results introduce FASTKD3 as an essential component of mitochondrial respiration that may modulate energy balance in cells exposed to adverse conditions by functionally coupling mitochondrial protein synthesis to respiration.« less

Maize acetylcholinesterase is a positive regulator of heat tolerance in plants.

PubMed

Yamamoto, Kosuke; Sakamoto, Hikaru; Momonoki, Yoshie S

2011-11-01

We previously reported that native tropical zone plants showed high acetylcholinesterase (AChE) activity during heat stress, and that AChE activity in endodermal cells of maize seedlings was increased by heat treatment. However, the physiological role of AChE in heat stressed plants is still unclear. Here we report (1) tissue-specific expression and subcellular localization of maize AChE, (2) elevation of AChE activity and possible post-translational modifications of this enzyme under heat stress, and (3) involvement of AChE in plant heat stress tolerance. Maize AChE was mainly expressed in coleoptile nodes and seeds. Maize AChE fused with green fluorescent protein (GFP) was localized in extracellular spaces of transgenic rice plants. Therefore, in maize coleoptile nodes and seeds AChE mainly functions in the cell wall matrix. After heat treatment, enhanced maize AChE activity was observed by in vitro activity measurement and by in situ cytochemical staining; transcript and protein levels, however, were not changed. Protein gel blot analysis revealed two AChE isoforms (upper and lower); the upper-form gradually disappeared after heat treatment. Thus, maize AChE activity might be enhanced through a post-translational modification response to heat stress. Finally, we found that overexpression of maize AChE in transgenic tobacco plants enhanced heat tolerance relative to that of non-transgenic plants, suggesting AChE plays a positive role in maize heat tolerance. Copyright © 2011 Elsevier GmbH. All rights reserved.

"Letter-Space": Typographic Translations of Urban Place

ERIC Educational Resources Information Center

Naismith, Jacqueline; O'Sullivan, Annette

2011-01-01

This article discusses a Bachelor of Design honours year typography project in the medium of letterpress. The "Letter-space" project positioned letterpress as a textual, spatial and structural visual language, through which the experiences and meanings of a local urban place were translated, mapped and given form through typographic design. We…

Slow dynamics in translation-invariant quantum lattice models

NASA Astrophysics Data System (ADS)

Michailidis, Alexios A.; Žnidarič, Marko; Medvedyeva, Mariya; Abanin, Dmitry A.; Prosen, Tomaž; Papić, Z.

2018-03-01

Many-body quantum systems typically display fast dynamics and ballistic spreading of information. Here we address the open problem of how slow the dynamics can be after a generic breaking of integrability by local interactions. We develop a method based on degenerate perturbation theory that reveals slow dynamical regimes and delocalization processes in general translation invariant models, along with accurate estimates of their delocalization time scales. Our results shed light on the fundamental questions of the robustness of quantum integrable systems and the possibility of many-body localization without disorder. As an example, we construct a large class of one-dimensional lattice models where, despite the absence of asymptotic localization, the transient dynamics is exceptionally slow, i.e., the dynamics is indistinguishable from that of many-body localized systems for the system sizes and time scales accessible in experiments and numerical simulations.

Dubbing Projects for the Language Learner: A Framework for Integrating Audiovisual Translation into Task-Based Instruction

ERIC Educational Resources Information Center

Danan, Martine

2010-01-01

This article describes a series of exploratory L1 to L2 dubbing projects for which students translated and used editing software to dub short American film and TV clips into their target language. Translating and dubbing into the target language involve students in multifaceted, high-level language production tasks that lead to enhanced vocabulary…

Translation of P = kT into a Pictorial External Representation by High School Seniors

ERIC Educational Resources Information Center

Matijaševic, Igor; Korolija, Jasminka N.; Mandic, Ljuba M.

2016-01-01

This paper describes the results achieved by high school seniors on an item which involves translation of the equation P = kT into a corresponding pictorial external representation. The majority of students (the classes of 2011, 2012 and 2013) did not give the correct answer to the multiple choice part of the translation item. They chose pictorial…

Using Edit Distance to Analyse Errors in a Natural Language to Logic Translation Corpus

ERIC Educational Resources Information Center

Barker-Plummer, Dave; Dale, Robert; Cox, Richard; Romanczuk, Alex

2012-01-01

We have assembled a large corpus of student submissions to an automatic grading system, where the subject matter involves the translation of natural language sentences into propositional logic. Of the 2.3 million translation instances in the corpus, 286,000 (approximately 12%) are categorized as being in error. We want to understand the nature of…

Systematic analyses of the ultraviolet radiation resistance-associated gene product (UVRAG) protein interactome by tandem affinity purification.

PubMed

Son, Ji-Hye; Hwang, Eurim C; Kim, Joungmok

2016-03-01

Ultraviolet radiation resistance-associated gene product (UVRAG) was originally identified as a protein involved in cellular responses to UV irradiation. Subsequent studies have demonstrated that UVRAG plays as an important role in autophagy, a lysosome-dependent catabolic program, as a part of a pro-autophagy PIK3C3/VPS34 lipid kinase complex. Several recent studies have shown that UVRAG is also involved in autophagy-independent cellular functions, such as DNA repair/stability and vesicular trafficking/fusion. Here, we examined the UVRAG protein interactome to obtain information about its functional network. To this end, we screened UVRAG-interacting proteins using a tandem affinity purification method coupled with MALDI-TOF/MS analysis. Our results demonstrate that UVRAG interacts with various proteins involved in a wide spectrum of cellular functions, including genome stability, protein translational elongation, protein localization (trafficking), vacuole organization, transmembrane transport as well as autophagy. Notably, the interactome list of high-confidence UVRAG-interacting proteins is enriched for proteins involved in the regulation of genome stability. Our systematic UVRAG interactome analysis should provide important clues for understanding a variety of UVRAG functions.

Autogenous cross-regulation of Quaking mRNA processing and translation balances Quaking functions in splicing and translation.

PubMed

Fagg, W Samuel; Liu, Naiyou; Fair, Jeffrey Haskell; Shiue, Lily; Katzman, Sol; Donohue, John Paul; Ares, Manuel

2017-09-15

Quaking protein isoforms arise from a single Quaking gene and bind the same RNA motif to regulate splicing, translation, decay, and localization of a large set of RNAs. However, the mechanisms by which Quaking expression is controlled to ensure that appropriate amounts of each isoform are available for such disparate gene expression processes are unknown. Here we explore how levels of two isoforms, nuclear Quaking-5 (Qk5) and cytoplasmic Qk6, are regulated in mouse myoblasts. We found that Qk5 and Qk6 proteins have distinct functions in splicing and translation, respectively, enforced through differential subcellular localization. We show that Qk5 and Qk6 regulate distinct target mRNAs in the cell and act in distinct ways on their own and each other's transcripts to create a network of autoregulatory and cross-regulatory feedback controls. Morpholino-mediated inhibition of Qk translation confirms that Qk5 controls Qk RNA levels by promoting accumulation and alternative splicing of Qk RNA, whereas Qk6 promotes its own translation while repressing Qk5. This Qk isoform cross-regulatory network responds to additional cell type and developmental controls to generate a spectrum of Qk5/Qk6 ratios, where they likely contribute to the wide range of functions of Quaking in development and cancer. © 2017 Fagg et al.; Published by Cold Spring Harbor Laboratory Press.

Italian translation and cultural adaptation of the communication assessment tool in an outpatient surgical clinic.

PubMed

Scala, Daniela; Menditto, Enrica; Armellino, Mariano Fortunato; Manguso, Francesco; Monetti, Valeria Marina; Orlando, Valentina; Antonino, Antonio; Makoul, Gregory; De Palma, Maurizio

2016-04-29

The aim of the study is to translate and cross-culturally adapt, for use in the Italian context, the Communication Assessment Tool (CAT) developed by Makoul and colleagues. The study was performed in the out-patient clinic of the Surgical Department of Cardarelli Hospital in Naples, Italy. It involved a systematic, standardized, multi-step process adhering to internationally accepted and recommended guidelines. Corrections and adjustments to the translation addressed both linguistic factors and cultural components. The CAT was translated into Italian by two independent Italian mother-tongue translators. The consensus version was then back-translated by an English mother-tongue translator. This translation process was followed by a consensus meeting between the authors of translation and investigators, and then by two comprehension tests on a total of 65 patients. Results of the translation and cross-cultural adaptation were satisfactory and indicate that the Italian translation of the CAT can be used with confidence in the Italian context.

Characteristics of a Recent and Prehistoric Landslides in the Pine River Valley, BC: a Mapping Effort

NASA Astrophysics Data System (ADS)

Heijenk, R.; Geertsema, M.; Miller, B.; de Jong, S. M.

2015-12-01

Spreads and other low gradient landslides are common in glacial lake sediments in north eastern British Columbia. Both pre and post glacial lake sediments, largely derived from shale bedrock are susceptible to low-gradient landslides. Bank erosion by rivers and streams and high pore pressures, have contributed to the landslides. We used LiDAR for mapping the extent of the glaciolacustrine sediments and map and characterise landslides in the Pine River valley, near Chetwynd, British Columbia. We included metrics such as travel angle, length, area, and elevation to distinguish rotational and translational landslides. We mapped 45 landslides in the Pine River valley distinguishing between rotational and translational landslides. The rotational landslides commonly have a smaller area and smaller travel length than translational landslides. Most rotational slides involved overlying alluvial fans, while most translational slides involved terraces.

Alternative role of HuD splicing variants in neuronal differentiation.

PubMed

Hayashi, Satoru; Yano, Masato; Igarashi, Mana; Okano, Hirotaka James; Okano, Hideyuki

2015-03-01

HuD is a neuronal RNA-binding protein that plays an important role in neuronal differentiation of the nervous system. HuD has been reported to have three RNA recognition motifs (RRMs) and three splice variants (SVs) that differ in their amino acid sequences between RRM2 and RRM3. This study investigates whether these SVs have specific roles in neuronal differentiation. In primary neural epithelial cells under differentiating conditions, HuD splice variant 1 (HuD-sv1), which is a general form, and HuD-sv2 were expressed at all tested times, whereas HuD-sv4 was transiently expressed at the beginning of differentiation, indicating that HuD-sv4 might play a role compared different from that of HuD-sv1. Indeed, HuD-sv4 did not promote neuronal differentiation in epithelial cells, whereas HuD-sv1 did promote neuronal differentiation. HuD-sv4 overexpression showed less neurite-inducing activity than HuD-sv1 in mouse neuroblastoma N1E-115 cells; however, HuD-sv4 showed stronger growth-arresting activity. HuD-sv1 was localized only in the cytoplasm, whereas HuD-sv4 was localized in both the cytoplasm and the nuclei. The Hu protein has been reported to be involved in translation and alternative splicing in the cytoplasm and nuclei, respectively. Consistent with this observation, HuD-sv1 showed translational activity on p21, which plays a role in growth arrest and neuronal differentiation, whereas HuD-sv4 did not. By contrast, HuD-sv4 showed stronger pre-mRNA splicing activity than did HuD-sv1 on Clasp2, which participates in cell division. Therefore, HuD SVs might play a role in controlling the timing of proliferation/differentiation switching by controlling the translation and alternative splicing of target genes. © 2014 Wiley Periodicals, Inc.

The eIF4E-binding proteins are modifiers of cytoplasmic eIF4E relocalization during the heat shock response

PubMed Central

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

2009-01-01

Stress granules (SGs) arise as a consequence of cellular stress, contain stalled translation preinitiation complexes, and are associated with cell survival during environmental insults. SGs are dynamic entities with proteins relocating into and out of them during stress. Among the repertoire of proteins present in SGs is eukaryotic initiation factor 4E (eIF4E), a translation factor required for cap-dependent translation and that regulates a rate-limiting step for protein synthesis. Herein, we demonstrate that localization of eIF4E to SGs is dependent on the presence of a family of repressor proteins, eIF4E-binding proteins (4E-BPs). Our results demonstrate that 4E-BPs regulate the SG localization of eIF4E. PMID:19244480

Parallelization of Rocket Engine System Software (Press)

NASA Technical Reports Server (NTRS)

Cezzar, Ruknet

1996-01-01

The main goal is to assess parallelization requirements for the Rocket Engine Numeric Simulator (RENS) project which, aside from gathering information on liquid-propelled rocket engines and setting forth requirements, involve a large FORTRAN based package at NASA Lewis Research Center and TDK software developed by SUBR/UWF. The ultimate aim is to develop, test, integrate, and suitably deploy a family of software packages on various aspects and facets of rocket engines using liquid-propellants. At present, all project efforts by the funding agency, NASA Lewis Research Center, and the HBCU participants are disseminated over the internet using world wide web home pages. Considering obviously expensive methods of actual field trails, the benefits of software simulators are potentially enormous. When realized, these benefits will be analogous to those provided by numerous CAD/CAM packages and flight-training simulators. According to the overall task assignments, Hampton University's role is to collect all available software, place them in a common format, assess and evaluate, define interfaces, and provide integration. Most importantly, the HU's mission is to see to it that the real-time performance is assured. This involves source code translations, porting, and distribution. The porting will be done in two phases: First, place all software on Cray XMP platform using FORTRAN. After testing and evaluation on the Cray X-MP, the code will be translated to C + + and ported to the parallel nCUBE platform. At present, we are evaluating another option of distributed processing over local area networks using Sun NFS, Ethernet, TCP/IP. Considering the heterogeneous nature of the present software (e.g., first started as an expert system using LISP machines) which now involve FORTRAN code, the effort is expected to be quite challenging.

Adopting, manipulating, transforming: tactics used by gender practitioners in South African NGOs to translate international gender policies into local practice.

PubMed

Mannell, Jenevieve

2014-11-01

This paper looks at what is lost and gained through the process of translating international policy from a global to a local space. It does this by sharing results from a multisite ethnographic study of gender practices in foreign-funded South African health organisations. This study identifies a number of tactics used by practitioners to deal with the funding constraints and unique knowledge systems that characterise local spaces, including: using policy to appeal to donors; merging gender with better resourced programmes; and redirecting funding allocations. These tactics point to how practitioners are adopting, manipulating and transforming international policies in order to suit their everyday working realities. Copyright © 2014 Elsevier Ltd. All rights reserved.

Application of statistical machine translation to public health information: a feasibility study.

PubMed

Kirchhoff, Katrin; Turner, Anne M; Axelrod, Amittai; Saavedra, Francisco

2011-01-01

Accurate, understandable public health information is important for ensuring the health of the nation. The large portion of the US population with Limited English Proficiency is best served by translations of public-health information into other languages. However, a large number of health departments and primary care clinics face significant barriers to fulfilling federal mandates to provide multilingual materials to Limited English Proficiency individuals. This article presents a pilot study on the feasibility of using freely available statistical machine translation technology to translate health promotion materials. The authors gathered health-promotion materials in English from local and national public-health websites. Spanish versions were created by translating the documents using a freely available machine-translation website. Translations were rated for adequacy and fluency, analyzed for errors, manually corrected by a human posteditor, and compared with exclusively manual translations. Machine translation plus postediting took 15-53 min per document, compared to the reported days or even weeks for the standard translation process. A blind comparison of machine-assisted and human translations of six documents revealed overall equivalency between machine-translated and manually translated materials. The analysis of translation errors indicated that the most important errors were word-sense errors. The results indicate that machine translation plus postediting may be an effective method of producing multilingual health materials with equivalent quality but lower cost compared to manual translations.

Application of statistical machine translation to public health information: a feasibility study

PubMed Central

Turner, Anne M; Axelrod, Amittai; Saavedra, Francisco

2011-01-01

Objective Accurate, understandable public health information is important for ensuring the health of the nation. The large portion of the US population with Limited English Proficiency is best served by translations of public-health information into other languages. However, a large number of health departments and primary care clinics face significant barriers to fulfilling federal mandates to provide multilingual materials to Limited English Proficiency individuals. This article presents a pilot study on the feasibility of using freely available statistical machine translation technology to translate health promotion materials. Design The authors gathered health-promotion materials in English from local and national public-health websites. Spanish versions were created by translating the documents using a freely available machine-translation website. Translations were rated for adequacy and fluency, analyzed for errors, manually corrected by a human posteditor, and compared with exclusively manual translations. Results Machine translation plus postediting took 15–53 min per document, compared to the reported days or even weeks for the standard translation process. A blind comparison of machine-assisted and human translations of six documents revealed overall equivalency between machine-translated and manually translated materials. The analysis of translation errors indicated that the most important errors were word-sense errors. Conclusion The results indicate that machine translation plus postediting may be an effective method of producing multilingual health materials with equivalent quality but lower cost compared to manual translations. PMID:21498805

Translating National Level Forest Service Goals to Local Level Land Management: Carbon Sequestration

NASA Astrophysics Data System (ADS)

McNulty, S.; Treasure, E.

2017-12-01

The USDA Forest Service has many national level policies related to multiple use management. However, translating national policy to stand level forest management can be difficult. As an example of how a national policy can be put into action, we examined three case studies in which a desired future condition is evaluated at the national, region and local scale. We chose to use carbon sequestration as the desired future condition because climate change has become a major area of concern during the last decade. Several studies have determined that the 193 million acres of US national forest land currently sequester 11% to 15% of the total carbon emitted as a nation. This paper provides a framework by which national scale strategies for maintaining or enhancing forest carbon sequestration is translated through regional considerations and local constraints in adaptive management practices. Although this framework used the carbon sequestration as a case study, this framework could be used with other national level priorities such as the National Environmental Protection Act (NEPA) or the Endangered Species Act (ESA).

Rat Humanin is encoded and translated in mitochondria and is localized to the mitochondrial compartment where it regulates ROS production.

PubMed

Paharkova, Vladislava; Alvarez, Griselda; Nakamura, Hiromi; Cohen, Pinchas; Lee, Kuk-Wha

2015-09-15

Evidence for the putative mitochondrial origin of the Humanin (HN) peptide has been lacking, although its cytoprotective activity has been demonstrated in a variety of organismal and cellular systems. We sought to establish proof-of-principle for a mitochondria-derived peptide (MDP) in a rat-derived cellular system as the rat HN sequence is predicted to lack nuclear insertions of mitochondrial origin (NUMT). We found that the rat HN (Rattin; rHN) homologue is derived from the mitochondrial genome as evidenced by decreased production in Rho-0 cells, and that peptide translation occurs in the mitochondria as it is unaffected by cycloheximide. Rat HN localizes to the mitochondria in cellular subfractionation and immunohistochemical studies. Addition of a HN analogue to isolated mitochondria from rat INS-1 beta cells reduced hydrogen peroxide production by 55%. In summary, a locally bioactive peptide is derived and translated from an open reading frame (ORF) within rat mitochondrial DNA encoding 16S rRNA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Translating an Evidence-Based Behavioral Intervention for Women Living with HIV into Clinical Practice: The SMART/EST Women's Program.

PubMed

Weiss, Stephen M; Tobin, Jonathan N; Lopez, Maria; Simons, Hannah; Cook, Ryan; Jones, Deborah L

2015-06-01

The process of translating scientific findings into clinical and public health settings has only recently received priority attention within the scientific community. Fueled by "Funding Opportunity Announcements" from the National Institutes of Health and Centers for Disease Control and Prevention, scientists have begun to explore the pathways to effectively "transfer" promising research accomplishments into effective and sustainable service programs within the health care delivery system. Using Glasgow's RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) model as a guide, this research team enrolled 428 socially disadvantaged, culturally diverse women living with HIV/AIDS to test the dissemination and implementation of an evidence-based behavioral intervention designed to improve and sustain the physical and emotional health of participants into the Community Health Center (CHC) setting when conducted by trained CHC staff. Findings demonstrate the ability of trained CHC staff group leaders to attain results equivalent or superior to those achieved when conducted by research staff on the three principal study outcomes: depression, medication adherence and HIV viral load. Four of five CHCs involved in the study also identified and successfully obtained funding to continue to run intervention groups, supporting the adoption and sustainability components of the translation model. This study confirmed (a) the "translatability" of the Stress Management And Relaxation Training/Emotional Supportive Therapy (SMART/EST) Women's Program, from academic to CHC settings in two geographic regions with high HIV prevalence among women, (b) the ability of local staff (using the "train the trainer" model) to successfully achieve program fidelity and clinical outcomes, and (c) the sustainability the program beyond the auspices of research support, through supportive CHC leadership securing continued program funding.

Metabotropic glutamate receptor-mediated use-dependent down-regulation of synaptic excitability involves the fragile X mental retardation protein.

PubMed

Repicky, Sarah; Broadie, Kendal

2009-02-01

Loss of the mRNA-binding protein FMRP results in the most common inherited form of both mental retardation and autism spectrum disorders: fragile X syndrome (FXS). The leading FXS hypothesis proposes that metabotropic glutamate receptor (mGluR) signaling at the synapse controls FMRP function in the regulation of local protein translation to modulate synaptic transmission strength. In this study, we use the Drosophila FXS disease model to test the relationship between Drosophila FMRP (dFMRP) and the sole Drosophila mGluR (dmGluRA) in regulation of synaptic function, using two-electrode voltage-clamp recording at the glutamatergic neuromuscular junction (NMJ). Null dmGluRA mutants show minimal changes in basal synapse properties but pronounced defects during sustained high-frequency stimulation (HFS). The double null dfmr1;dmGluRA mutant shows repression of enhanced augmentation and delayed onset of premature long-term facilitation (LTF) and strongly reduces grossly elevated post-tetanic potentiation (PTP) phenotypes present in dmGluRA-null animals. Null dfmr1 mutants show features of synaptic hyperexcitability, including multiple transmission events in response to a single stimulus and cyclic modulation of transmission amplitude during prolonged HFS. The double null dfmr1;dmGluRA mutant shows amelioration of these defects but does not fully restore wildtype properties in dfmr1-null animals. These data suggest that dmGluRA functions in a negative feedback loop in which excess glutamate released during high-frequency transmission binds the glutamate receptor to dampen synaptic excitability, and dFMRP functions to suppress the translation of proteins regulating this synaptic excitability. Removal of the translational regulator partially compensates for loss of the receptor and, similarly, loss of the receptor weakly compensates for loss of the translational regulator.

Translation initiation on mRNAs bound by nuclear cap-binding protein complex CBP80/20 requires interaction between CBP80/20-dependent translation initiation factor and eukaryotic translation initiation factor 3g.

PubMed

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

2012-05-25

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

Remodeling of the pioneer translation initiation complex involves translation and the karyopherin importin β

PubMed Central

Sato, Hanae; Maquat, Lynne E.

2009-01-01

Mammalian mRNAs lose and acquire proteins throughout their life span while undergoing processing, transport, translation, and decay. How translation affects messenger RNA (mRNA)–protein interactions is largely unknown. The pioneer round of translation uses newly synthesized mRNA that is bound by cap-binding protein 80 (CBP80)–CBP20 (also known as the cap-binding complex [CBC]) at the cap, poly(A)-binding protein N1 (PABPN1) and PABPC1 at the poly(A) tail, and, provided biogenesis involves pre-mRNA splicing, exon junction complexes (EJCs) at exon–exon junctions. Subsequent rounds of translation engage mRNA that is bound by eukaryotic translation initiation factor 4E (eIF4E) at the cap and PABPC1 at the poly(A) tail, but that lacks detectable EJCs and PABPN1. Using the level of intracellular iron to regulate the translation of specific mRNAs, we show that translation promotes not only removal of EJC constituents, including the eIF4AIII anchor, but also replacement of PABPN1 by PABPC1. Remarkably, translation does not affect replacement of CBC by eIF4E. Instead, replacement of CBC by eIF4E is promoted by importin β (IMPβ): Inhibiting the binding of IMPβ to the complex of CBC–IMPα at an mRNA cap using the IMPα IBB (IMPβ-binding) domain or a RAN variant increases the amount of CBC-bound mRNA and decreases the amount of eIF4E-bound mRNA. Our studies uncover a previously unappreciated role for IMPβ and a novel paradigm for how newly synthesized messenger ribonucleoproteins (mRNPs) are matured. PMID:19884259

Isolation and characterization of beta-glucan synthase: A potential biochemical regulator of gravistimulated differential cell wall loosening

NASA Technical Reports Server (NTRS)

Kuzmanoff, K. M.

1984-01-01

In plants, gravity stimulates differential growth in the upper and lower halves of horizontally oriented organs. Auxin regulation of cell wall loosening and elongation is the basis for most models of this phenomenon. Auxin treatment of pea stem tissue rapidly increases the activity of Golgi-localized Beta-1,4-glucan synthase, an enzyme involved in biosynthesis of wall xyloglucan which apparently constitutes the substrate for the wall loosening process. The primary objective is to determine if auxin induces de novo formation of Golgi glucan synthase and increases the level of this glucan synthase mRNA. This shall be accomplished by (a) preparation of a monoclonal antibody to the synthase, (b) isolation, and characterization of the glucan synthase, and (c) examination for cross reactivity between the antibody and translation products of auxin induced mRNAs in pea tissue. The antibody will also be used to localize the glucan synthase in upper and lower halves of pea stem tissue before, during and after the response to gravity.

Driven Phases of Quantum Matter

NASA Astrophysics Data System (ADS)

Khemani, Vedika; von Keyserlingk, Curt; Lazarides, Achilleas; Moessner, Roderich; Sondhi, Shivaji

Clean and interacting periodically driven quantum systems are believed to exhibit a single, trivial ``infinite-temperature'' Floquet-ergodic phase. By contrast, I will show that their disordered Floquet many-body localized counterparts can exhibit distinct ordered phases with spontaneously broken symmetries delineated by sharp transitions. Some of these are analogs of equilibrium states, while others are genuinely new to the Floquet setting. I will show that a subset of these novel phases are absolutely stableto all weak local deformations of the underlying Floquet drives, and spontaneously break Hamiltonian dependent emergent symmetries. Strikingly, they simultaneously also break the underlying time-translation symmetry of the Floquet drive and the order parameter exhibits oscillations at multiples of the fundamental period. This ``time-crystallinity'' goes hand in hand with spatial symmetry breaking and, altogether, these phases exhibit a novel form of simultaneous long-range order in space and time. I will describe how this spatiotemporal order can be detected in experiments involving quenches from a broad class of initial states.

Ultralow-power switching via defect engineering in germanium telluride phase-change memory devices.

PubMed

Nukala, Pavan; Lin, Chia-Chun; Composto, Russell; Agarwal, Ritesh

2016-01-25

Crystal-amorphous transformation achieved via the melt-quench pathway in phase-change memory involves fundamentally inefficient energy conversion events; and this translates to large switching current densities, responsible for chemical segregation and device degradation. Alternatively, introducing defects in the crystalline phase can engineer carrier localization effects enhancing carrier-lattice coupling; and this can efficiently extract work required to introduce bond distortions necessary for amorphization from input electrical energy. Here, by pre-inducing extended defects and thus carrier localization effects in crystalline GeTe via high-energy ion irradiation, we show tremendous improvement in amorphization current densities (0.13-0.6 MA cm(-2)) compared with the melt-quench strategy (∼50 MA cm(-2)). We show scaling behaviour and good reversibility on these devices, and explore several intermediate resistance states that are accessible during both amorphization and recrystallization pathways. Existence of multiple resistance states, along with ultralow-power switching and scaling capabilities, makes this approach promising in context of low-power memory and neuromorphic computation.

Ultralow-power switching via defect engineering in germanium telluride phase-change memory devices

PubMed Central

Nukala, Pavan; Lin, Chia-Chun; Composto, Russell; Agarwal, Ritesh

2016-01-01

Crystal–amorphous transformation achieved via the melt-quench pathway in phase-change memory involves fundamentally inefficient energy conversion events; and this translates to large switching current densities, responsible for chemical segregation and device degradation. Alternatively, introducing defects in the crystalline phase can engineer carrier localization effects enhancing carrier–lattice coupling; and this can efficiently extract work required to introduce bond distortions necessary for amorphization from input electrical energy. Here, by pre-inducing extended defects and thus carrier localization effects in crystalline GeTe via high-energy ion irradiation, we show tremendous improvement in amorphization current densities (0.13–0.6 MA cm−2) compared with the melt-quench strategy (∼50 MA cm−2). We show scaling behaviour and good reversibility on these devices, and explore several intermediate resistance states that are accessible during both amorphization and recrystallization pathways. Existence of multiple resistance states, along with ultralow-power switching and scaling capabilities, makes this approach promising in context of low-power memory and neuromorphic computation. PMID:26805748

The applicability of Lean and Six Sigma techniques to clinical and translational research.

PubMed

Schweikhart, Sharon A; Dembe, Allard E

2009-10-01

Lean and Six Sigma are business management strategies commonly used in production industries to improve process efficiency and quality. During the past decade, these process improvement techniques increasingly have been applied outside the manufacturing sector, for example, in health care and in software development. This article concerns the potential use of Lean and Six Sigma in improving the processes involved in clinical and translational research. Improving quality, avoiding delays and errors, and speeding up the time to implementation of biomedical discoveries are prime objectives of the National Institutes of Health (NIH) Roadmap for Medical Research and the NIH's Clinical and Translational Science Award program. This article presents a description of the main principles, practices, and methods used in Lean and Six Sigma. Available literature involving applications of Lean and Six Sigma to health care, laboratory science, and clinical and translational research is reviewed. Specific issues concerning the use of these techniques in different phases of translational research are identified. Examples of Lean and Six Sigma applications that are being planned at a current Clinical and Translational Science Award site are provided, which could potentially be replicated elsewhere. We describe how different process improvement approaches are best adapted for particular translational research phases. Lean and Six Sigma process improvement methods are well suited to help achieve NIH's goal of making clinical and translational research more efficient and cost-effective, enhancing the quality of the research, and facilitating the successful adoption of biomedical research findings into practice.

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

PubMed

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

2005-01-01

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

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

PubMed Central

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

2005-01-01

Translation initiation is a multistep process involving several canonical translation factors, which assemble at the 5′-end of the mRNA to promote the recruitment of the ribosome. Although the 3′ poly(A) tail of eukaryotic mRNAs and its major bound protein, the poly(A)-binding protein (PABP), have been studied extensively, their mechanism of action in translation is not well understood and is confounded by differences between in vivo and in vitro systems. Here, we provide direct evidence for the involvement of PABP in key steps of the translation initiation pathway. Using a new technique to deplete PABP from mammalian cell extracts, we show that extracts lacking PABP exhibit dramatically reduced rates of translation, reduced efficiency of 48S and 80S ribosome initiation complex formation, and impaired interaction of eIF4E with the mRNA cap structure. Supplementing PABP-depleted extracts with wild-type PABP completely rectified these deficiencies, whereas a mutant of PABP, M161A, which is incapable of interacting with eIF4G, failed to restore translation. In addition, a stronger inhibition (approximately twofold) of 80S as compared to 48S ribosome complex formation (∼65% vs. ∼35%, respectively) by PABP depletion suggests that PABP plays a direct role in 60S subunit joining. PABP can thus be considered a canonical translation initiation factor, integral to initiation complex formation at the 5′-end of mRNA. PMID:15630022

Novel Mechanisms in the Regulation of G Protein-coupled Receptor Trafficking to the Plasma Membrane*

PubMed Central

Tholanikunnel, Baby G.; Joseph, Kusumam; Kandasamy, Karthikeyan; Baldys, Aleksander; Raymond, John R.; Luttrell, Louis M.; McDermott, Paul J.; Fernandes, Daniel J.

2010-01-01

β2-Adrenergic receptors (β2-AR) are low abundance, integral membrane proteins that mediate the effects of catecholamines at the cell surface. Whereas the processes governing desensitization of activated β2-ARs and their subsequent removal from the cell surface have been characterized in considerable detail, little is known about the mechanisms controlling trafficking of neo-synthesized receptors to the cell surface. Since the discovery of the signal peptide, the targeting of the integral membrane proteins to plasma membrane has been thought to be determined by structural features of the amino acid sequence alone. Here we report that localization of translationally silenced β2-AR mRNA to the peripheral cytoplasmic regions is critical for receptor localization to the plasma membrane. β2-AR mRNA is recognized by the nucleocytoplasmic shuttling RNA-binding protein HuR, which silences translational initiation while chaperoning the mRNA-protein complex to the cell periphery. When HuR expression is down-regulated, β2-AR mRNA translation is initiated prematurely in perinuclear polyribosomes, leading to overproduction of receptors but defective trafficking to the plasma membrane. Our results underscore the importance of the spatiotemporal relationship between β2-AR mRNA localization, translation, and trafficking to the plasma membrane, and establish a novel mechanism whereby G protein-coupled receptor (GPCR) responsiveness is regulated by RNA-based signals. PMID:20739277

The receptor-like pseudokinase MRH1 interacts with the voltage-gated potassium channel AKT2.

PubMed

Sklodowski, Kamil; Riedelsberger, Janin; Raddatz, Natalia; Riadi, Gonzalo; Caballero, Julio; Chérel, Isabelle; Schulze, Waltraud; Graf, Alexander; Dreyer, Ingo

2017-03-16

The potassium channel AKT2 plays important roles in phloem loading and unloading. It can operate as inward-rectifying channel that allows H + -ATPase-energized K + uptake. Moreover, through reversible post-translational modifications it can also function as an open, K + -selective channel, which taps a 'potassium battery', providing additional energy for transmembrane transport processes. Knowledge about proteins involved in the regulation of the operational mode of AKT2 is very limited. Here, we employed a large-scale yeast two-hybrid screen in combination with fluorescence tagging and null-allele mutant phenotype analysis and identified the plasma membrane localized receptor-like kinase MRH1/MDIS2 (AT4G18640) as interaction partner of AKT2. The phenotype of the mrh1-1 knockout plant mirrors that of akt2 knockout plants in energy limiting conditions. Electrophysiological analyses showed that MRH1/MDIS2 failed to exert any functional regulation on AKT2. Using structural protein modeling approaches, we instead gathered evidence that the putative kinase domain of MRH1/MDIS2 lacks essential sites that are indispensable for a functional kinase suggesting that MRH1/MDIS2 is a pseudokinase. We propose that MRH1/MDIS2 and AKT2 are likely parts of a bigger protein complex. MRH1 might help to recruit other, so far unknown partners, which post-translationally regulate AKT2. Additionally, MRH1 might be involved in the recognition of chemical signals.

The receptor-like pseudokinase MRH1 interacts with the voltage-gated potassium channel AKT2

NASA Astrophysics Data System (ADS)

Sklodowski, Kamil; Riedelsberger, Janin; Raddatz, Natalia; Riadi, Gonzalo; Caballero, Julio; Chérel, Isabelle; Schulze, Waltraud; Graf, Alexander; Dreyer, Ingo

2017-03-01

The potassium channel AKT2 plays important roles in phloem loading and unloading. It can operate as inward-rectifying channel that allows H+-ATPase-energized K+ uptake. Moreover, through reversible post-translational modifications it can also function as an open, K+-selective channel, which taps a ‘potassium battery’, providing additional energy for transmembrane transport processes. Knowledge about proteins involved in the regulation of the operational mode of AKT2 is very limited. Here, we employed a large-scale yeast two-hybrid screen in combination with fluorescence tagging and null-allele mutant phenotype analysis and identified the plasma membrane localized receptor-like kinase MRH1/MDIS2 (AT4G18640) as interaction partner of AKT2. The phenotype of the mrh1-1 knockout plant mirrors that of akt2 knockout plants in energy limiting conditions. Electrophysiological analyses showed that MRH1/MDIS2 failed to exert any functional regulation on AKT2. Using structural protein modeling approaches, we instead gathered evidence that the putative kinase domain of MRH1/MDIS2 lacks essential sites that are indispensable for a functional kinase suggesting that MRH1/MDIS2 is a pseudokinase. We propose that MRH1/MDIS2 and AKT2 are likely parts of a bigger protein complex. MRH1 might help to recruit other, so far unknown partners, which post-translationally regulate AKT2. Additionally, MRH1 might be involved in the recognition of chemical signals.

Comprehensive Identification of mRNA-Binding Proteins of Leishmania donovani by Interactome Capture.

PubMed

Nandan, Devki; Thomas, Sneha A; Nguyen, Anne; Moon, Kyung-Mee; Foster, Leonard J; Reiner, Neil E

2017-01-01

Leishmania are unicellular eukaryotes responsible for leishmaniasis in humans. Like other trypanosomatids, leishmania regulate protein coding gene expression almost exclusively at the post-transcriptional level with the help of RNA binding proteins (RBPs). Due to the presence of polycystronic transcription units, leishmania do not regulate RNA polymerase II-dependent transcription initiation. Recent evidence suggests that the main control points in gene expression are mRNA degradation and translation. Protein-RNA interactions are involved in every aspect of RNA biology, such as mRNA splicing, polyadenylation, localization, degradation, and translation. A detailed picture of these interactions would likely prove to be highly informative in understanding leishmania biology and virulence. We developed a strategy involving covalent UV cross-linking of RBPs to mRNA in vivo, followed by interactome capture using oligo(dT) magnetic beads to define comprehensively the mRNA interactome of growing L. donovani amastigotes. The protein mass spectrometry analysis of captured proteins identified 79 mRNA interacting proteins which withstood very stringent washing conditions. Strikingly, we found that 49 of these mRNA interacting proteins had no orthologs or homologs in the human genome. Consequently, these may represent high quality candidates for selective drug targeting leading to novel therapeutics. These results show that this unbiased, systematic strategy has the promise to be applicable to study the mRNA interactome during various biological settings such as metabolic changes, stress (low pH environment, oxidative stress and nutrient deprivation) or drug treatment.

Risk, Scientific Uncertainty, and Policy Implications of Global Climate Change Models

NASA Astrophysics Data System (ADS)

Briggs, C.; Sahagian, D.

2006-12-01

The risks of global climate change to human populations and natural environments have received increasing attention in recent years. With high-profile events such as hurricane Katrina in the United States, rapid melting of the Greenland ice sheet, shifting precipitation patterns in Europe and elsewhere, more political attention has been given to the risks posed by anthropogenic changes in the earth's atmosphere. Yet despite increasing scientific evidence of such environmental risks, reactions from political sources have been far from consistent. While some states have adopted emissions regulations on greenhouse gases, other states or national governments have downplayed the existence of any significant risk. Explanations for why political actors or the public may appear unaware of scientific data relate to the nature of uncertainty in environmental risk models and decisions. Professional scientific methodologies must approach uncertainty in a far different manner than government agencies or members of the public, and these varying types of uncertainty create spaces for translation of scientific data into incompatible conclusions. Such conclusions depend not only upon the translation of scientific data, but also perception of the risks involved, differential local impacts of climate change, and available policy alternatives and resources. Scientists involved in climate research bear a particular responsibility for how their data are interpreted politically, but this requires awareness of the manners in which uncertainty is employed, the ethics of applying research to policy questions, and realization that risks will be perceived differently according to political cultures and geographic regions.

Investigation of the structure of /sup 4/He in a translationally invariant oscillator basis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bartaya, O.L.; Macharadze, T.S.

1977-12-01

The binding energy, mean square radius, and charge form factor of the /sup 4/He nucleus are calculated using a translationally invariant basis. The realistic local nucleon-nucleon potential of Gogni, Pires, and De Tourreil (Phys. Lett. B 32B, 591 (1970)) is used in the calculations. Taken into account in the basis are all translationally invariant oscillator states with spatial symmetry (f)=4) and number of excitation quanta N< or =8 and with symmetry (f)=22) and N< or =6.

Developing Evidence for Public Health Policy and Practice: The Implementation of a Knowledge Translation Approach in a Staged, Multi-Methods Study in England, 2007-09

ERIC Educational Resources Information Center

South, Jane; Cattan, Mima

2014-01-01

Effective knowledge translation processes are critical for the development of evidence-based public health policy and practice. This paper reports on the design and implementation of an innovative approach to knowledge translation within a mixed methods study on lay involvement in public health programme delivery. The study design drew on…

Protein synthesis in sperm: dialog between mitochondria and cytoplasm.

PubMed

Gur, Yael; Breitbart, Haim

2008-01-30

Ejaculated sperm are capable of using mRNAs transcripts for protein translation during the final maturation steps before fertilization. In a capacitation-dependent process, nuclear-encoded mRNAs are translated by mitochondrial-type ribosomes while the cytoplasmic translation machinery is not involved. Our findings suggest that new proteins are synthesized to replace degraded proteins while swimming and waiting in the female reproductive tract before fertilization, or produced due to the specific needs of the capacitating spermatozoa. In addition, a growing number of articles have reported evidence for the correlation of nuclear-encoded mRNA and protein synthesis in somatic mitochondria. It is known that all of the proteins necessary for the replication, transcription and translation of the genes encoded in mtDNA are now encoded in the nuclear genome. This genetic investment is far out of proportion to the number of proteins involved, as there have been multiple movements and duplications of genes. However, the evolutionary retention (or secondary uptake) of the mitochondrial machinery for translation of nuclear-encoded mRNAs may shed light on this paradox.

Translational co-regulation of a ligand and inhibitor by a conserved RNA element

PubMed Central

Zaucker, Andreas; Nagorska, Agnieszka; Kumari, Pooja; Hecker, Nikolai; Wang, Yin; Huang, Sizhou; Cooper, Ledean; Sivashanmugam, Lavanya; VijayKumar, Shruthi; Brosens, Jan; Gorodkin, Jan

2018-01-01

Abstract In many organisms, transcriptional and post-transcriptional regulation of components of pathways or processes has been reported. However, to date, there are few reports of translational co-regulation of multiple components of a developmental signaling pathway. Here, we show that an RNA element which we previously identified as a dorsal localization element (DLE) in the 3′UTR of zebrafish nodal-related1/squint (ndr1/sqt) ligand mRNA, is shared by the related ligand nodal-related2/cyclops (ndr2/cyc) and the nodal inhibitors, lefty1 (lft1) and lefty2 mRNAs. We investigated the activity of the DLEs through functional assays in live zebrafish embryos. The lft1 DLE localizes fluorescently labeled RNA similarly to the ndr1/sqt DLE. Similar to the ndr1/sqt 3′UTR, the lft1 and lft2 3′UTRs are bound by the RNA-binding protein (RBP) and translational repressor, Y-box binding protein 1 (Ybx1), whereas deletions in the DLE abolish binding to Ybx1. Analysis of zebrafish ybx1 mutants shows that Ybx1 represses lefty1 translation in embryos. CRISPR/Cas9-mediated inactivation of human YBX1 also results in human NODAL translational de-repression, suggesting broader conservation of the DLE RNA element/Ybx1 RBP module in regulation of Nodal signaling. Our findings demonstrate translational co-regulation of components of a signaling pathway by an RNA element conserved in both sequence and structure and an RBP, revealing a ‘translational regulon’. PMID:29059375

Knowledge Translation to Advance Evidence-Based Health Policy in Thailand

ERIC Educational Resources Information Center

Ti, Lianlian; Hayashi, Kanna; Ti, Lianping; Kaplan, Karyn; Suwannawong, Paisan; Kerr, Thomas

2017-01-01

Significant gaps between scientific evidence and policy have resulted in growing interest in the role that knowledge translation (KT) can play in informing evidence-based policy. The Mitsampan Community Research Project, in consultation with the local community of people who inject drugs, developed a comprehensive KT strategy that aimed to…

State Policy Directives and Middle-Tier Translation in a Swedish Example

ERIC Educational Resources Information Center

Nordholm, Daniel

2016-01-01

Purpose: The purpose of this paper is to analyse the Swedish National Agency for Education's launch of the nationwide Lgr11 curriculum reform and how local education authorities (LEAs) in one municipality translated and responded to the National Agency's directives. Design/methodology/approach: This paper presents empirical data from a qualitative…

Translations of Policy and Shifting Demands of Teacher Professionalism: From CPD to Professional Learning

ERIC Educational Resources Information Center

Watson, Cate; Michael, Maureen K.

2016-01-01

This article concerns policy implementation and examines the processes of translation through which policy may be enacted at local level. In particular, it focuses on education policy and constructions of teacher professionalism, drawing on a framework of critical logics--social, political and fantasmatic--which examine different dimensions of…

Effect of electronic stability control on automobile crash risk.

PubMed

Farmer, Charles

2004-12-01

Per vehicle crash involvement rates were compared for otherwise identical vehicle models with and without electronic stability control (ESC) systems. ESC was found to affect single-vehicle crashes to a greater extent than multiple-vehicle crashes, and crashes with fatal injuries to a greater extent than less severe crashes. Based on all police-reported crashes in 7 states over 2 years, ESC reduced single-vehicle crash involvement risk by approximately 41 percent (95 percent confidence limits 3348) and single-vehicle injury crash involvement risk by 41 percent (2752). This translates to an estimated 7 percent reduction in overall crash involvement risk (310) and a 9 percent reduction in overall injury crash involvement risk (314). Based on all fatal crashes in the United States over 3 years, ESC was found to have reduced single-vehicle fatal crash involvement risk by 56 percent (3968). This translates to an estimated 34 percent reduction in overall fatal crash involvement risk (2145).

Insights into molecular plasticity in protein complexes from Trm9-Trm112 tRNA modifying enzyme crystal structure.

PubMed

Létoquart, Juliette; van Tran, Nhan; Caroline, Vonny; Aleksandrov, Alexey; Lazar, Noureddine; van Tilbeurgh, Herman; Liger, Dominique; Graille, Marc

2015-12-15

Most of the factors involved in translation (tRNA, rRNA and proteins) are subject to post-transcriptional and post-translational modifications, which participate in the fine-tuning and tight control of ribosome and protein synthesis processes. In eukaryotes, Trm112 acts as an obligate activating platform for at least four methyltransferases (MTase) involved in the modification of 18S rRNA (Bud23), tRNA (Trm9 and Trm11) and translation termination factor eRF1 (Mtq2). Trm112 is then at a nexus between ribosome synthesis and function. Here, we present a structure-function analysis of the Trm9-Trm112 complex, which is involved in the 5-methoxycarbonylmethyluridine (mcm(5)U) modification of the tRNA anticodon wobble position and hence promotes translational fidelity. We also compare the known crystal structures of various Trm112-MTase complexes, highlighting the structural plasticity allowing Trm112 to interact through a very similar mode with its MTase partners, although those share less than 20% sequence identity. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Active crystals on a sphere

NASA Astrophysics Data System (ADS)

Praetorius, Simon; Voigt, Axel; Wittkowski, Raphael; Löwen, Hartmut

2018-05-01

Two-dimensional crystals on curved manifolds exhibit nontrivial defect structures. Here we consider "active crystals" on a sphere, which are composed of self-propelled colloidal particles. Our work is based on a phase-field-crystal-type model that involves a density and a polarization field on the sphere. Depending on the strength of the self-propulsion, three different types of crystals are found: a static crystal, a self-spinning "vortex-vortex" crystal containing two vortical poles of the local velocity, and a self-translating "source-sink" crystal with a source pole where crystallization occurs and a sink pole where the active crystal melts. These different crystalline states as well as their defects are studied theoretically here and can in principle be confirmed in experiments.

Structure and Function of Centromeric and Pericentromeric Heterochromatin in Arabidopsis thaliana.

PubMed

Simon, Lauriane; Voisin, Maxime; Tatout, Christophe; Probst, Aline V

2015-01-01

The centromere is a specific chromosomal region where the kinetochore assembles to ensure the faithful segregation of sister chromatids during mitosis and meiosis. Centromeres are defined by a local enrichment of the specific histone variant CenH3 mostly at repetitive satellite sequences. A larger pericentromeric region containing repetitive sequences and transposable elements surrounds the centromere that adopts a particular chromatin state characterized by specific histone variants and post-translational modifications and forms a transcriptionally repressive chromosomal environment. In the model organism Arabidopsis thaliana centromeric and pericentromeric domains form conspicuous heterochromatin clusters called chromocenters in interphase. Here we discuss, using Arabidopsis as example, recent insight into mechanisms involved in maintenance and establishment of centromeric and pericentromeric chromatin signatures as well as in chromocenter formation.

Tissue preservation with mass spectroscopic analysis: Implications for cancer diagnostics.

PubMed

Hall, O Morgan; Peer, Cody J; Figg, William D

2018-05-17

Surgical intervention is a common treatment modality for localized cancer. Post-operative analysis involves evaluation of surgical margins to assess whether all malignant tissue has been resected because positive surgical margins lead to a greater likelihood of recurrence. Secondary treatments are utilized to minimize the negative effects of positive surgical margins. Recently, in Science Translational Medicine, Zhang et al describe a new mass spectroscopic technique that could potentially decrease the likelihood of positive surgical margins. Their nondestructive in vivo tissue sampling leads to a highly accurate and rapid cancer diagnosis with great precision between healthy and malignant tissue. This new tool has the potential to improve surgical margins and accelerate cancer diagnostics by analyzing biomolecular signatures of various tissues and diseases.

Improved ALE mesh velocities for complex flows

DOE PAGES

Bakosi, Jozsef; Waltz, Jacob I.; Morgan, Nathaniel Ray

2017-05-31

A key choice in the development of arbitrary Lagrangian-Eulerian solution algorithms is how to move the computational mesh. The most common approaches are smoothing and relaxation techniques, or to compute a mesh velocity field that produces smooth mesh displacements. We present a method in which the mesh velocity is specified by the irrotational component of the fluid velocity as computed from a Helmholtz decomposition, and excess compression of mesh cells is treated through a noniterative, local spring-force model. This approach allows distinct and separate control over rotational and translational modes. In conclusion, the utility of the new mesh motion algorithmmore » is demonstrated on a number of 3D test problems, including problems that involve both shocks and significant amounts of vorticity.« less

Clocks in Feynman's computer and Kitaev's local Hamiltonian: Bias, gaps, idling, and pulse tuning

NASA Astrophysics Data System (ADS)

Caha, Libor; Landau, Zeph; Nagaj, Daniel

2018-06-01

We present a collection of results about the clock in Feynman's computer construction and Kitaev's local Hamiltonian problem. First, by analyzing the spectra of quantum walks on a line with varying end-point terms, we find a better lower bound on the gap of the Feynman Hamiltonian, which translates into a less strict promise gap requirement for the quantum-Merlin-Arthur-complete local Hamiltonian problem. We also translate this result into the language of adiabatic quantum computation. Second, introducing an idling clock construction with a large state space but fast Cesaro mixing, we provide a way for achieving an arbitrarily high success probability of computation with Feynman's computer with only a logarithmic increase in the number of clock qubits. Finally, we tune and thus improve the costs (locality and gap scaling) of implementing a (pulse) clock with a single excitation.

Poly(A)-binding proteins and mRNA localization: who rules the roost?

PubMed

Gray, Nicola K; Hrabálková, Lenka; Scanlon, Jessica P; Smith, Richard W P

2015-12-01

RNA-binding proteins are often multifunctional, interact with a variety of protein partners and display complex localizations within cells. Mammalian cytoplasmic poly(A)-binding proteins (PABPs) are multifunctional RNA-binding proteins that regulate multiple aspects of mRNA translation and stability. Although predominantly diffusely cytoplasmic at steady state, they shuttle through the nucleus and can be localized to a variety of cytoplasmic foci, including those associated with mRNA storage and localized translation. Intriguingly, PABP sub-cellular distribution can alter dramatically in response to cellular stress or viral infection, becoming predominantly nuclear and/or being enriched in induced cytoplasmic foci. However, relatively little is known about the mechanisms that govern this distribution/relocalization and in many cases PABP functions within specific sites remain unclear. Here we discuss the emerging evidence with respect to these questions in mammals. © 2015 Authors; published by Portland Press Limited.

Mechanisms of dendritic mRNA transport and its role in synaptic tagging

PubMed Central

Doyle, Michael; Kiebler, Michael A

2011-01-01

The localization of RNAs critically contributes to many important cellular processes in an organism, such as the establishment of polarity, asymmetric division and migration during development. Moreover, in the central nervous system, the local translation of mRNAs is thought to induce plastic changes that occur at synapses triggered by learning and memory. Here, we will critically review the physiological functions of well-established dendritically localized mRNAs and their associated factors, which together form ribonucleoprotein particles (RNPs). Second, we will discuss the life of a localized transcript from transcription in the nucleus to translation at the synapse and introduce the concept of the ‘RNA signature' that is characteristic for each transcript. Finally, we present the ‘sushi belt model' of how localized RNAs within neuronal RNPs may dynamically patrol multiple synapses rather than being anchored at a single synapse. This new model integrates our current understanding of synaptic function ranging from synaptic tagging and capture to functional and structural reorganization of the synapse upon learning and memory. PMID:21878995

Optical mapping of brain activation during the English to Chinese and Chinese to English sight translation

PubMed Central

He, Yan; Wang, Meng-Yun; Li, Defeng; Yuan, Zhen

2017-01-01

Translating from Chinese into another language or vice versa is becoming a widespread phenomenon. However, current neuroimaging studies are insufficient to reveal the neural mechanism underlying translation asymmetry during Chinese/English sight translation. In this study, functional near infrared spectroscopy (fNIRS) was used to extract the brain activation patterns associated with Chinese/English sight translation. Eleven unbalanced Chinese (L1)/English (L2) bilinguals participated in this study based on an intra-group experimental design, in which two translation and two reading aloud tasks were administered: forward translation (from L1 to L2), backward translation (from L2 to L1), L1 reading, and L2 reading. As predicted, our findings revealed that forward translation elicited more pronounced brain activation in Broca’s area, suggesting that neural correlates of translation vary according to the direction of translation. Additionally, significant brain activation in the left PFC was involved in backward translation, indicating the importance of this brain region during the translation process. The identical activation patterns could not be discovered in forward translation, indicating the cognitive processing of reading logographic languages (i.e. Chinese) might recruit incongruent brain regions. PMID:29296476

A global slowdown of tropical-cyclone translation speed.

PubMed

Kossin, James P

2018-06-01

As the Earth's atmosphere warms, the atmospheric circulation changes. These changes vary by region and time of year, but there is evidence that anthropogenic warming causes a general weakening of summertime tropical circulation 1-8 . Because tropical cyclones are carried along within their ambient environmental wind, there is a plausible a priori expectation that the translation speed of tropical cyclones has slowed with warming. In addition to circulation changes, anthropogenic warming causes increases in atmospheric water-vapour capacity, which are generally expected to increase precipitation rates 9 . Rain rates near the centres of tropical cyclones are also expected to increase with increasing global temperatures 10-12 . The amount of tropical-cyclone-related rainfall that any given local area will experience is proportional to the rain rates and inversely proportional to the translation speeds of tropical cyclones. Here I show that tropical-cyclone translation speed has decreased globally by 10 per cent over the period 1949-2016, which is very likely to have compounded, and possibly dominated, any increases in local rainfall totals that may have occurred as a result of increased tropical-cyclone rain rates. The magnitude of the slowdown varies substantially by region and by latitude, but is generally consistent with expected changes in atmospheric circulation forced by anthropogenic emissions. Of particular importance is the slowdown of 30 per cent and 20 per cent over land areas affected by western North Pacific and North Atlantic tropical cyclones, respectively, and the slowdown of 19 per cent over land areas in the Australian region. The unprecedented rainfall totals associated with the 'stall' of Hurricane Harvey 13-15 over Texas in 2017 provide a notable example of the relationship between regional rainfall amounts and tropical-cyclone translation speed. Any systematic past or future change in the translation speed of tropical cyclones, particularly over land, is therefore highly relevant when considering potential changes in local rainfall totals.

Factors in Dubbing Television Comedy.

ERIC Educational Resources Information Center

Zabalbeascoa, Patrick

1994-01-01

Advocates a greater awareness of the factors involved with dubbing television comedies. Considers the translation of jokes and provides an outline of the various kinds of jokes in television shows. Calls for more research on comedy dubbing and television translation in general. (HB)

Genome-wide assessment of differential translations with ribosome profiling data.

PubMed

Xiao, Zhengtao; Zou, Qin; Liu, Yu; Yang, Xuerui

2016-04-04

The closely regulated process of mRNA translation is crucial for precise control of protein abundance and quality. Ribosome profiling, a combination of ribosome foot-printing and RNA deep sequencing, has been used in a large variety of studies to quantify genome-wide mRNA translation. Here, we developed Xtail, an analysis pipeline tailored for ribosome profiling data that comprehensively and accurately identifies differentially translated genes in pairwise comparisons. Applied on simulated and real datasets, Xtail exhibits high sensitivity with minimal false-positive rates, outperforming existing methods in the accuracy of quantifying differential translations. With published ribosome profiling datasets, Xtail does not only reveal differentially translated genes that make biological sense, but also uncovers new events of differential translation in human cancer cells on mTOR signalling perturbation and in human primary macrophages on interferon gamma (IFN-γ) treatment. This demonstrates the value of Xtail in providing novel insights into the molecular mechanisms that involve translational dysregulations.

Signaling Pathways Involved in the Regulation of mRNA Translation

PubMed Central

2018-01-01

ABSTRACT Translation is a key step in the regulation of gene expression and one of the most energy-consuming processes in the cell. In response to various stimuli, multiple signaling pathways converge on the translational machinery to regulate its function. To date, the roles of phosphoinositide 3-kinase (PI3K)/AKT and the mitogen-activated protein kinase (MAPK) pathways in the regulation of translation are among the best understood. Both pathways engage the mechanistic target of rapamycin (mTOR) to regulate a variety of components of the translational machinery. While these pathways regulate protein synthesis in homeostasis, their dysregulation results in aberrant translation leading to human diseases, including diabetes, neurological disorders, and cancer. Here we review the roles of the PI3K/AKT and MAPK pathways in the regulation of mRNA translation. We also highlight additional signaling mechanisms that have recently emerged as regulators of the translational apparatus. PMID:29610153

Cultural adaptation and translation of measures: an integrated method.

PubMed

Sidani, Souraya; Guruge, Sepali; Miranda, Joyal; Ford-Gilboe, Marilyn; Varcoe, Colleen

2010-04-01

Differences in the conceptualization and operationalization of health-related concepts may exist across cultures. Such differences underscore the importance of examining conceptual equivalence when adapting and translating instruments. In this article, we describe an integrated method for exploring conceptual equivalence within the process of adapting and translating measures. The integrated method involves five phases including selection of instruments for cultural adaptation and translation; assessment of conceptual equivalence, leading to the generation of a set of items deemed to be culturally and linguistically appropriate to assess the concept of interest in the target community; forward translation; back translation (optional); and pre-testing of the set of items. Strengths and limitations of the proposed integrated method are discussed. (c) 2010 Wiley Periodicals, Inc.

The Selenocysteine-Specific Elongation Factor Contains Unique Sequences That Are Required for Both Nuclear Export and Selenocysteine Incorporation.

PubMed

Dubey, Aditi; Copeland, Paul R

2016-01-01

Selenocysteine (Sec) is a critical residue in at least 25 human proteins that are essential for antioxidant defense and redox signaling in cells. Sec is inserted into proteins cotranslationally by the recoding of an in-frame UGA termination codon to a Sec codon. In eukaryotes, this recoding event requires several specialized factors, including a dedicated, Sec-specific elongation factor called eEFSec, which binds Sec-tRNASec with high specificity and delivers it to the ribosome for selenoprotein production. Unlike most translation factors, including the canonical elongation factor eEF1A, eEFSec readily localizes to the nucleus of mammalian cells and shuttles between the cytoplasmic and nuclear compartments. The functional significance of eEFSec's nuclear localization has remained unclear. In this study, we have examined the subcellular localization of eEFSec in the context of altered Sec incorporation to demonstrate that reduced selenoprotein production does not correlate with changes in the nuclear localization of eEFSec. In addition, we identify several novel sequences of the protein that are essential for localization as well as Sec insertion activity, and show that eEFSec utilizes CRM1-mediated nuclear export pathway. Our findings argue for two distinct pools of eEFSec in the cell, where the cytoplasmic pool participates in Sec incorporation and the nuclear pool may be involved in an as yet unknown function.

Exploiting Measurement Uncertainty Estimation in Evaluation of GOES-R ABI Image Navigation Accuracy Using Image Registration Techniques

NASA Technical Reports Server (NTRS)

Haas, Evan; DeLuccia, Frank

2016-01-01

In evaluating GOES-R Advanced Baseline Imager (ABI) image navigation quality, upsampled sub-images of ABI images are translated against downsampled Landsat 8 images of localized, high contrast earth scenes to determine the translations in the East-West and North-South directions that provide maximum correlation. The native Landsat resolution is much finer than that of ABI, and Landsat navigation accuracy is much better than ABI required navigation accuracy and expected performance. Therefore, Landsat images are considered to provide ground truth for comparison with ABI images, and the translations of ABI sub-images that produce maximum correlation with Landsat localized images are interpreted as ABI navigation errors. The measured local navigation errors from registration of numerous sub-images with the Landsat images are averaged to provide a statistically reliable measurement of the overall navigation error of the ABI image. The dispersion of the local navigation errors is also of great interest, since ABI navigation requirements are specified as bounds on the 99.73rd percentile of the magnitudes of per pixel navigation errors. However, the measurement uncertainty inherent in the use of image registration techniques tends to broaden the dispersion in measured local navigation errors, masking the true navigation performance of the ABI system. We have devised a novel and simple method for estimating the magnitude of the measurement uncertainty in registration error for any pair of images of the same earth scene. We use these measurement uncertainty estimates to filter out the higher quality measurements of local navigation error for inclusion in statistics. In so doing, we substantially reduce the dispersion in measured local navigation errors, thereby better approximating the true navigation performance of the ABI system.

Screening the Molecular Framework Underlying Local Dendritic mRNA Translation

PubMed Central

Namjoshi, Sanjeev V.; Raab-Graham, Kimberly F.

2017-01-01

In the last decade, bioinformatic analyses of high-throughput proteomics and transcriptomics data have enabled researchers to gain insight into the molecular networks that may underlie lasting changes in synaptic efficacy. Development and utilization of these techniques have advanced the field of learning and memory significantly. It is now possible to move from the study of activity-dependent changes of a single protein to modeling entire network changes that require local protein synthesis. This data revolution has necessitated the development of alternative computational and statistical techniques to analyze and understand the patterns contained within. Thus, the focus of this review is to provide a synopsis of the journey and evolution toward big data techniques to address still unanswered questions regarding how synapses are modified to strengthen neuronal circuits. We first review the seminal studies that demonstrated the pivotal role played by local mRNA translation as the mechanism underlying the enhancement of enduring synaptic activity. In the interest of those who are new to the field, we provide a brief overview of molecular biology and biochemical techniques utilized for sample preparation to identify locally translated proteins using RNA sequencing and proteomics, as well as the computational approaches used to analyze these data. While many mRNAs have been identified, few have been shown to be locally synthesized. To this end, we review techniques currently being utilized to visualize new protein synthesis, a task that has proven to be the most difficult aspect of the field. Finally, we provide examples of future applications to test the physiological relevance of locally synthesized proteins identified by big data approaches. PMID:28286470

Translation and adaption of the interRAI suite to local requirements in Belgian hospitals

PubMed Central

2012-01-01

Background The interRAI Suite contains comprehensive geriatric assessment tools designed for various healthcare settings. Although each instrument is developed for a particular population, together they form an integrated health evaluation system. The interRAI Acute Care Minimum Data Set (interRAI AC) is tailored for hospitalized older persons. Our aim in this study was to translate and adapt the interRAI AC to the Belgian hospital context, where it can be used together with the interRAI Home Care (HC) and the interRAI Long Term Care Facility (LTCF). Methods A systematic, comprehensive, and rigorous 10-step approach was used to adapt the interRAI AC to local requirements. After linguistic translation by an official translator, five researchers assessed the translation for appropriate hospital jargon. Three researchers double-checked for translation accuracy and proposed additional items. A provisional version was converted into the three official languages of Belgium—Flemish, French, and German. Next, a multidisciplinary panel of nine experts judged item relevance to the Belgian care context and advised which country-specific items should be added. After these suggestions were incorporated into the interRAI AC, hospital staff from nine Flemish hospitals field-tested the tool in their practice. After evaluating field-test results, we compared the interRAI AC with Belgian versions of the interRAI HC and interRAI LTCF. Next, the Flemish, French, and German versions of the Belgian interRAI portfolio were harmonized. Finally, we submitted the Belgian interRAI AC to the interRAI organization for ratification. Results Eighteen administrative items of the interRAI AC were adapted to the Belgian healthcare context (e.g., usual residence, formal community services prior to admission). Fourteen items assessing the ‘informal caregiver’, and 17 items, including country-specific items, were added (e.g., advanced directive for euthanasia). Conclusions The interRAI AC was adapted to local requirements using a meticulous and recursive 10-step approach. As use of the interRAI Suite continues to grow worldwide and as it continues to expand to other care settings and populations, this procedure can guide future translations. This procedure might also be used by others facing similar challenges of complex translation and adaptation situations, where multidimensional instruments are used across multiple care settings in multiple languages. PMID:22958520

Virus maturation: dynamics and mechanism of a stabilizing structural transition that leads to infectivity.

PubMed

Steven, Alasdair C; Heymann, J Bernard; Cheng, Naiqian; Trus, Benes L; Conway, James F

2005-04-01

For many viruses, the final stage of assembly involves structural transitions that convert an innocuous precursor particle into an infectious agent. This process -- maturation -- is controlled by proteases that trigger large-scale conformational changes. In this context, protease inhibitor antiviral drugs act by blocking maturation. Recent work has succeeded in determining the folds of representative examples of the five major proteins -- major capsid protein, scaffolding protein, portal, protease and accessory protein -- that are typically involved in capsid assembly. These data provide a framework for detailed mechanistic investigations and elucidation of mutations that affect assembly in various ways. The nature of the conformational change has been elucidated: it entails rigid-body rotations and translations of the arrayed subunits that transfer the interactions between them to different molecular surfaces, accompanied by refolding and redeployment of local motifs. Moreover, it has been possible to visualize maturation at the submolecular level in movies based on time-resolved cryo-electron microscopy.

Identifying Unstable Regions of Proteins Involved in Misfolding Diseases

NASA Astrophysics Data System (ADS)

Guest, Will; Cashman, Neil; Plotkin, Steven

2009-05-01

Protein misfolding is a necessary step in the pathogenesis of many diseases, including Creutzfeldt-Jakob disease (CJD) and familial amyotrophic lateral sclerosis (fALS). Identifying unstable structural elements in their causative proteins elucidates the early events of misfolding and presents targets for inhibition of the disease process. An algorithm was developed to calculate the Gibbs free energy of unfolding for all sequence-contiguous regions of a protein using three methods to parameterize energy changes: a modified G=o model, changes in solvent-accessible surface area, and all-atoms molecular dynamics. The entropic effects of disulfide bonds and post-translational modifications are treated analytically. It incorporates a novel method for finding local dielectric constants inside a protein to accurately handle charge effects. We have predicted the unstable parts of prion protein and superoxide dismutase 1, the proteins involved in CJD and fALS respectively, and have used these regions as epitopes to prepare antibodies that are specific to the misfolded conformation and show promise as therapeutic agents.

UPF1 Governs Synaptic Plasticity through Association with a STAU2 RNA Granule.

PubMed

Graber, Tyson E; Freemantle, Erika; Anadolu, Mina N; Hébert-Seropian, Sarah; MacAdam, Robyn L; Shin, Unkyung; Hoang, Huy-Dung; Alain, Tommy; Lacaille, Jean-Claude; Sossin, Wayne S

2017-09-20

Neuronal mRNAs can be packaged in reversibly stalled polysome granules before their transport to distant synaptic locales. Stimulation of synaptic metabotropic glutamate receptors (mGluRs) reactivates translation of these particular mRNAs to produce plasticity-related protein; a phenomenon exhibited during mGluR-mediated LTD. This form of plasticity is deregulated in Fragile X Syndrome, a monogenic form of autism in humans, and understanding the stalling and reactivation mechanism could reveal new approaches to therapies. Here, we demonstrate that UPF1, known to stall peptide release during nonsense-mediated RNA decay, is critical for assembly of stalled polysomes in rat hippocampal neurons derived from embryos of either sex. Moreover, UPF1 and its interaction with the RNA binding protein STAU2 are necessary for proper transport and local translation from a prototypical RNA granule substrate and for mGluR-LTD in hippocampal neurons. These data highlight a new, neuronal role for UPF1, distinct from its RNA decay functions, in regulating transport and/or translation of mRNAs that are critical for synaptic plasticity. SIGNIFICANCE STATEMENT The elongation and/or termination steps of mRNA translation are emerging as important control points in mGluR-LTD, a form of synaptic plasticity that is compromised in a severe monogenic form of autism, Fragile X Syndrome. Deciphering the molecular mechanisms controlling this type of plasticity may thus open new therapeutic opportunities. Here, we describe a new role for the ATP-dependent helicase UPF1 and its interaction with the RNA localization protein STAU2 in mediating mGluR-LTD through the regulation of mRNA translation complexes stalled at the level of elongation and/or termination. Copyright © 2017 the authors 0270-6474/17/379116-16$15.00/0.

Actor or arena: contrasting translations of a law on interorganizational integration.

PubMed

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

2012-01-01

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

Developing a Conceptually Equivalent Type 2 Diabetes Risk Score for Indian Gujaratis in the UK

PubMed Central

Patel, Naina; Stone, Margaret; Barber, Shaun; Gray, Laura; Davies, Melanie; Khunti, Kamlesh

2016-01-01

Aims. To apply and assess the suitability of a model consisting of commonly used cross-cultural translation methods to achieve a conceptually equivalent Gujarati language version of the Leicester self-assessment type 2 diabetes risk score. Methods. Implementation of the model involved multiple stages, including pretesting of the translated risk score by conducting semistructured interviews with a purposive sample of volunteers. Interviews were conducted on an iterative basis to enable findings to inform translation revisions and to elicit volunteers' ability to self-complete and understand the risk score. Results. The pretest stage was an essential component involving recruitment of a diverse sample of 18 Gujarati volunteers, many of whom gave detailed suggestions for improving the instructions for the calculation of the risk score and BMI table. Volunteers found the standard and level of Gujarati accessible and helpful in understanding the concept of risk, although many of the volunteers struggled to calculate their BMI. Conclusions. This is the first time that a multicomponent translation model has been applied to the translation of a type 2 diabetes risk score into another language. This project provides an invaluable opportunity to share learning about the transferability of this model for translation of self-completed risk scores in other health conditions. PMID:27703985

Alternative 3' UTRs Modify the Localization, Regulatory Potential, Stability, and Plasticity of mRNAs in Neuronal Compartments.

PubMed

Tushev, Georgi; Glock, Caspar; Heumüller, Maximilian; Biever, Anne; Jovanovic, Marko; Schuman, Erin M

2018-05-02

Neurons localize mRNAs near synapses where their translation can be regulated by synaptic demand and activity. Differences in the 3' UTRs of mRNAs can change their localization, stability, and translational regulation. Using 3' end RNA sequencing of microdissected rat brain slices, we discovered a huge diversity in mRNA 3' UTRs, with many transcripts showing enrichment for a particular 3' UTR isoform in either somata or the neuropil. The 3' UTR isoforms of localized transcripts are significantly longer than the 3' UTRs of non-localized transcripts and often code for proteins associated with axons, dendrites, and synapses. Surprisingly, long 3' UTRs add not only new, but also duplicate regulatory elements. The neuropil-enriched 3' UTR isoforms have significantly longer half-lives than somata-enriched isoforms. Finally, the 3' UTR isoforms can be significantly altered by enhanced activity. Most of the 3' UTR plasticity is transcription dependent, but intriguing examples of changes that are consistent with altered stability, trafficking between compartments, or local "remodeling" remain. Copyright © 2018 Elsevier Inc. All rights reserved.

RNG105/caprin1, an RNA granule protein for dendritic mRNA localization, is essential for long-term memory formation.

PubMed

Nakayama, Kei; Ohashi, Rie; Shinoda, Yo; Yamazaki, Maya; Abe, Manabu; Fujikawa, Akihiro; Shigenobu, Shuji; Futatsugi, Akira; Noda, Masaharu; Mikoshiba, Katsuhiko; Furuichi, Teiichi; Sakimura, Kenji; Shiina, Nobuyuki

2017-11-21

Local regulation of synaptic efficacy is thought to be important for proper networking of neurons and memory formation. Dysregulation of global translation influences long-term memory in mice, but the relevance of the regulation specific for local translation by RNA granules remains elusive. Here, we demonstrate roles of RNG105/caprin1 in long-term memory formation. RNG105 deletion in mice impaired synaptic strength and structural plasticity in hippocampal neurons. Furthermore, RNG105-deficient mice displayed unprecedentedly severe defects in long-term memory formation in spatial and contextual learning tasks. Genome-wide profiling of mRNA distribution in the hippocampus revealed an underlying mechanism: RNG105 deficiency impaired the asymmetric somato-dendritic localization of mRNAs. Particularly, RNG105 deficiency reduced the dendritic localization of mRNAs encoding regulators of AMPAR surface expression, which was consistent with attenuated homeostatic AMPAR scaling in dendrites and reduced synaptic strength. Thus, RNG105 has an essential role, as a key regulator of dendritic mRNA localization, in long-term memory formation.

Spatial Decomposition of Translational Water–Water Correlation Entropy in Binding Pockets

PubMed Central

2015-01-01

A number of computational tools available today compute the thermodynamic properties of water at surfaces and in binding pockets by using inhomogeneous solvation theory (IST) to analyze explicit-solvent simulations. Such methods enable qualitative spatial mappings of both energy and entropy around a solute of interest and can also be applied quantitatively. However, the entropy estimates of existing methods have, to date, been almost entirely limited to the first-order terms in the IST’s entropy expansion. These first-order terms account for localization and orientation of water molecules in the field of the solute but not for the modification of water–water correlations by the solute. Here, we present an extension of the Grid Inhomogeneous Solvation Theory (GIST) approach which accounts for water–water translational correlations. The method involves rewriting the two-point density of water in terms of a conditional density and utilizes the efficient nearest-neighbor entropy estimation approach. Spatial maps of this second order term, for water in and around the synthetic host cucurbit[7]uril and in the binding pocket of the enzyme Factor Xa, reveal mainly negative contributions, indicating solute-induced water–water correlations relative to bulk water; particularly strong signals are obtained for sites at the entrances of cavities or pockets. This second-order term thus enters with the same, negative, sign as the first order translational and orientational terms. Numerical and convergence properties of the methodology are examined. PMID:26636620

A Brazilian Portuguese cross-cultural adaptation of the modified JOA scale for myelopathy.

PubMed

Pratali, Raphael R; Smith, Justin S; Motta, Rodrigo L N; Martins, Samuel M; Motta, Marcel M; Rocha, Ricardo D; Herrero, Carlos Fernando P S

2017-02-01

To develop a version of the modified Japanese Orthopaedic Association (mJOA) scale that had been translated into Portuguese and cross-culturally adapted for the Brazilian population. The well-established process of forward-backward translation was employed along with cross-cultural adaptation. Three bilingual translators (English and native Portuguese) performed the forward translation of the mJOA scale from English to Portuguese based on iterative discussions used to reach a consensus translation. The translated version of the mJOA scale was then back-translated into English by a native English-speaking translator unaware of the concepts involved with the mJOA scale. The original mJOA scale and the back-translated version were compared by a native North American neurosurgeon, and as they were considered equivalent, the final version of the mJOA scale that had been translated into Portuguese and cross-culturally adapted was defined. To facilitate global and cross-cultural comparisons of the severity of cervical myelopathy, this study presents a version of the mJOA scale that was translated into Portuguese and cross-culturally adapted for the Brazilian population.

Translational Vestibulo-Ocular Reflex and Motion Perception During Interaural Linear Acceleration: Comparison of Different Motion Paradigms

NASA Technical Reports Server (NTRS)

Beaton, K. H.; Holly, J. E.; Clement, G. R.; Wood, S. J.

2011-01-01

The neural mechanisms to resolve ambiguous tilt-translation motion have been hypothesized to be different for motion perception and eye movements. Previous studies have demonstrated differences in ocular and perceptual responses using a variety of motion paradigms, including Off-Vertical Axis Rotation (OVAR), Variable Radius Centrifugation (VRC), translation along a linear track, and tilt about an Earth-horizontal axis. While the linear acceleration across these motion paradigms is presumably equivalent, there are important differences in semicircular canal cues. The purpose of this study was to compare translation motion perception and horizontal slow phase velocity to quantify consistencies, or lack thereof, across four different motion paradigms. Twelve healthy subjects were exposed to sinusoidal interaural linear acceleration between 0.01 and 0.6 Hz at 1.7 m/s/s (equivalent to 10 tilt) using OVAR, VRC, roll tilt, and lateral translation. During each trial, subjects verbally reported the amount of perceived peak-to-peak lateral translation and indicated the direction of motion with a joystick. Binocular eye movements were recorded using video-oculography. In general, the gain of translation perception (ratio of reported linear displacement to equivalent linear stimulus displacement) increased with stimulus frequency, while the phase did not significantly vary. However, translation perception was more pronounced during both VRC and lateral translation involving actual translation, whereas perceptions were less consistent and more variable during OVAR and roll tilt which did not involve actual translation. For each motion paradigm, horizontal eye movements were negligible at low frequencies and showed phase lead relative to the linear stimulus. At higher frequencies, the gain of the eye movements increased and became more inphase with the acceleration stimulus. While these results are consistent with the hypothesis that the neural computational strategies for motion perception and eye movements differ, they also indicate that the specific motion platform employed can have a significant effect on both the amplitude and phase of each.

Development of an Agile Knowledge Engineering Framework in Support of Multi-Disciplinary Translational Research

PubMed Central

Borlawsky, Tara B.; Dhaval, Rakesh; Hastings, Shannon L.; Payne, Philip R. O.

2009-01-01

In October 2006, the National Institutes of Health launched a new national consortium, funded through Clinical and Translational Science Awards (CTSA), with the primary objective of improving the conduct and efficiency of the inherently multi-disciplinary field of translational research. To help meet this goal, the Ohio State University Center for Clinical and Translational Science has launched a knowledge management initiative that is focused on facilitating widespread semantic interoperability among administrative, basic science, clinical and research computing systems, both internally and among the translational research community at-large, through the integration of domain-specific standard terminologies and ontologies with local annotations. This manuscript describes an agile framework that builds upon prevailing knowledge engineering and semantic interoperability methods, and will be implemented as part this initiative. PMID:21347164

Development of an agile knowledge engineering framework in support of multi-disciplinary translational research.

PubMed

Borlawsky, Tara B; Dhaval, Rakesh; Hastings, Shannon L; Payne, Philip R O

2009-03-01

In October 2006, the National Institutes of Health launched a new national consortium, funded through Clinical and Translational Science Awards (CTSA), with the primary objective of improving the conduct and efficiency of the inherently multi-disciplinary field of translational research. To help meet this goal, the Ohio State University Center for Clinical and Translational Science has launched a knowledge management initiative that is focused on facilitating widespread semantic interoperability among administrative, basic science, clinical and research computing systems, both internally and among the translational research community at-large, through the integration of domain-specific standard terminologies and ontologies with local annotations. This manuscript describes an agile framework that builds upon prevailing knowledge engineering and semantic interoperability methods, and will be implemented as part this initiative.

Response to “Comment on ‘General rotating quantum vortex filaments in the low-temperature Svistunov model of the local induction approximation’” [Phys. Fluids 26, 119101 (2014)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Gorder, Robert A., E-mail: rav@knights.ucf.edu

2014-11-15

In R. A. Van Gorder, “General rotating quantum vortex filaments in the low-temperature Svistunov model of the local induction approximation,” Phys. Fluids 26, 065105 (2014) I discussed properties of generalized vortex filaments exhibiting purely rotational motion under the low-temperature Svistunov model of the local induction approximation. Such solutions are stationary in terms of translational motion. In the Comment [N. Hietala, “Comment on ‘General rotating quantum vortex filaments in the low-temperature Svistunov model of the local induction approximation’ [Phys. Fluids 26, 065105 (2014)],” Phys. Fluids 26, 119101 (2014)], the author criticizes my paper for not including translational motion (although it wasmore » clearly stated that the filament motion was assumed rotational). As it turns out, if one is interested in studying the geometric structure of solutions (which was the point of my paper), one obtains the needed qualitative results on the structure of such solutions by studying the purely rotational case. Nevertheless, in this Response I shall discuss the vortex filaments that have both rotational and translational motions. I then briefly discuss why one might want to study such generalized rotating filament solutions, in contrast to simple the standard helical or planar examples (which are really special cases). I also discuss how one can study the time evolution of filaments which exhibit more complicated dynamics than pure translation and rotation. Doing this, one can study non-stationary solutions which initially appear purely rotational and gradually display other dynamics as the filaments evolve.« less

Knowledge translation in rehabilitation engineering research and development: a knowledge ecosystem framework.

PubMed

Chau, Tom; Moghimi, Saba; Popovic, Milos R

2013-01-01

Rehabilitation engineering is concerned with technology innovations and technology-mediated treatments for the improvement of quality of care and quality of life of individuals with disability. Unlike many other fields of health research, the knowledge translation (KT) cycle of rehabilitation engineering research and development (R&D) is often considered incomplete until a technology product or technology-facilitated therapy is available to target clientele. As such, the KT journey of rehabilitation engineering R&D is extremely challenging, necessarily involving knowledge exchange among numerous players across multiple sectors. In this article, we draw on recent literature about the knowledge trichotomy in technology-based rehabilitation R&D and propose a knowledge ecosystem to frame the rehabilitation engineering KT process from need to product. Identifying the principal process of the ecosystem as one of knowledge flow, we elucidate the roles of repository and networked knowledge, identify key consumers and producers in a trinity of communities of practice, and draw on knowledge management literature to describe different knowledge flows. The article concludes with instantiations of this knowledge ecosystem for 2 local rehabilitation engineering research-development-commercialization endeavors. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Galectin-3: A novel substrate for c-Abl kinase.

PubMed

Balan, Vitaly; Nangia-Makker, Pratima; Jung, Young Suk; Wang, Yi; Raz, Avraham

2010-10-01

Galectin-3, a beta-galactoside-binding lectin, is found in cellular and extracellular location of the cell and has pleiotropic biological functions such as cell growth, cell adhesion and cell-cell interaction. It may exhibit anti- or pro-apoptotic activity depending on its localization and post-translational modifications. Two important post-translational modifications of galectin-3 have been reported: its cleavage and phosphorylation. Cleavage of galectin-3 was reported to be involved with angiogenic potential and apoptotic resistance. Phosphorylation of galectin-3 regulates its sugar-binding ability. In this report we have identified novel tyrosine phosphorylation sites in galectin-3 as well as the kinase responsible for its phosphorylation. Our results demonstrate that tyrosines at positions 79, 107 and 118 can be phosphorylated in vitro and in vivo by c-Abl kinase. Tyrosine 107 is the main target of c-Abl. Expression of galectin-3 Y107F mutant in galectin-3 null SK-Br-3 cells leads to morphological changes and increased motility compared to wild type galectin-3. Further investigation is needed to better understand the functional significance of the novel tyrosine phosphorylated sites of galectin-3. Copyright © 2010 Elsevier B.V. All rights reserved.

Extensive cross-regulation of post-transcriptional regulatory networks in Drosophila

DOE PAGES

Stoiber, Marcus H.; Olson, Sara; May, Gemma E.; ...

2015-08-20

In eukaryotic cells, RNAs exist as ribonucleoprotein particles (RNPs). Despite the importance of these complexes in many biological processes, including splicing, polyadenylation, stability, transportation, localization, and translation, their compositions are largely unknown. We affinity-purified 20 distinct RNA-binding proteins (RBPs) from cultured Drosophila melanogaster cells under native conditions and identified both the RNA and protein compositions of these RNP complexes. We identified “high occupancy target” (HOT) RNAs that interact with the majority of the RBPs we surveyed. HOT RNAs encode components of the nonsense-mediated decay and splicing machinery, as well as RNA-binding and translation initiation proteins. The RNP complexes contain proteinsmore » and mRNAs involved in RNA binding and post-transcriptional regulation. Genes with the capacity to produce hundreds of mRNA isoforms, ultracomplex genes, interact extensively with heterogeneous nuclear ribonuclear proteins (hnRNPs). Our data are consistent with a model in which subsets of RNPs include mRNA and protein products from the same gene, indicating the widespread existence of auto-regulatory RNPs. Lastly, from the simultaneous acquisition and integrative analysis of protein and RNA constituents of RNPs, we identify extensive cross-regulatory and hierarchical interactions in post-transcriptional control.« less

Extensive cross-regulation of post-transcriptional regulatory networks in Drosophila

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stoiber, Marcus H.; Olson, Sara; May, Gemma E.

In eukaryotic cells, RNAs exist as ribonucleoprotein particles (RNPs). Despite the importance of these complexes in many biological processes, including splicing, polyadenylation, stability, transportation, localization, and translation, their compositions are largely unknown. We affinity-purified 20 distinct RNA-binding proteins (RBPs) from cultured Drosophila melanogaster cells under native conditions and identified both the RNA and protein compositions of these RNP complexes. We identified “high occupancy target” (HOT) RNAs that interact with the majority of the RBPs we surveyed. HOT RNAs encode components of the nonsense-mediated decay and splicing machinery, as well as RNA-binding and translation initiation proteins. The RNP complexes contain proteinsmore » and mRNAs involved in RNA binding and post-transcriptional regulation. Genes with the capacity to produce hundreds of mRNA isoforms, ultracomplex genes, interact extensively with heterogeneous nuclear ribonuclear proteins (hnRNPs). Our data are consistent with a model in which subsets of RNPs include mRNA and protein products from the same gene, indicating the widespread existence of auto-regulatory RNPs. Lastly, from the simultaneous acquisition and integrative analysis of protein and RNA constituents of RNPs, we identify extensive cross-regulatory and hierarchical interactions in post-transcriptional control.« less

A role for post-transcriptional control of endoplasmic reticulum dynamics and function in C. elegans germline stem cell maintenance.

PubMed

Maheshwari, Richa; Pushpa, Kumari; Subramaniam, Kuppuswamy

2016-09-01

Membrane-bound receptors, which are crucial for mediating several key developmental signals, are synthesized on endoplasmic reticulum (ER). The functional integrity of ER must therefore be important for the regulation of at least some developmental programs. However, the developmental control of ER function is not well understood. Here, we identify the C. elegans protein FARL-11, an ortholog of the mammalian STRIPAK complex component STRIP1/2 (FAM40A/B), as an ER protein. In the C. elegans embryo, we find that FARL-11 is essential for the cell cycle-dependent morphological changes of ER and for embryonic viability. In the germline, FARL-11 is required for normal ER morphology and for membrane localization of the GLP-1/Notch receptor involved in germline stem cell (GSC) maintenance. Furthermore, we provide evidence that PUF-8, a key translational regulator in the germline, promotes the translation of farl-11 mRNA. These findings reveal that ER form and function in the C. elegans germline are post-transcriptionally regulated and essential for the niche-GSC signaling mediated by GLP-1. © 2016. Published by The Company of Biologists Ltd.

A Federated Network for Translational Cancer Research Using Clinical Data and Biospecimens

PubMed Central

Becich, Michael J.; Bollag, Roni J.; Chavan, Girish; Corrigan, Julia; Dhir, Rajiv; Feldman, Michael D.; Gaudioso, Carmelo; Legowski, Elizabeth; Maihle, Nita J.; Mitchell, Kevin; Murphy, Monica; Sakthivel, Mayur; Tseytlin, Eugene; Weaver, JoEllen

2015-01-01

Advances in cancer research and personalized medicine will require significant new bridging infrastructures, including more robust biorepositories that link human tissue to clinical phenotypes and outcomes. In order to meet that challenge, four cancer centers formed the TIES Cancer Research Network, a federated network that facilitates data and biospecimen sharing among member institutions. Member sites can access pathology data that is de-identified and processed with the TIES natural language processing system, which creates a repository of rich phenotype data linked to clinical biospecimens. TIES incorporates multiple security and privacy best practices that, combined with legal agreements, network policies and procedures, enable regulatory compliance. The TIES Cancer Research Network now provides integrated access to investigators at all member institutions, where multiple investigator-driven pilot projects are underway. Examples of federated search across the network illustrate the potential impact on translational research, particularly for studies involving rare cancers, rare phenotypes, and specific biologic behaviors. The network satisfies several key desiderata including local control of data and credentialing, inclusion of rich phenotype information, and applicability to diverse research objectives. The TIES Cancer Research Network presents a model for a national data and biospecimen network. PMID:26670560

Assessing Research Interest and Capacity in Community Health Centers

PubMed Central

Bhuiya, Nazmim; Pernice, Joan; Khan, Sami M.; Sequist, Thomas D.; Tendulkar, Shalini A.

2013-01-01

Abstract Objective Community health centers (CHCs) have great potential to participate in the development of evidence‐based primary care but face obstacles to engagement in clinical translational research. Methods To understand factors associated with CHC interest in building research infrastructure, Harvard Catalyst and the Massachusetts League of Community Health Centers conducted an online survey of medical directors in all 50 Massachusetts CHC networks. Results Thirty‐two (64%) medical directors completed the survey representing 126 clinical sites. Over 80% reported that their primary care providers (PCPs) were slightly to very interested in future clinical research and that they were interested in building research infrastructure at their CHC. Frequently cited barriers to participation in research included financial issues, lack of research skills, and lack of research infrastructure. In bivariate analyses, PCP interest in future clinical research and a belief that involvement in research contributed to PCP retention were significantly associated with interest in building research infrastructure. Conclusion CHCs critical role in caring for vulnerable populations ideally positions them to raise relevant research questions and translate evidence into practice. Our findings suggest a high interest in engagement in research among CHC leadership. CTSAs have a unique opportunity to support local CHCs in this endeavor. PMID:24127928

Translating Change into Improved Practice: Analysis of Teachers' Attempts to Generate a New Emerging Pedagogy in Scotland

ERIC Educational Resources Information Center

Thorburn, Malcolm; Carse, Nicola; Jess, Mike; Atencio, Matthew

2011-01-01

In Scotland, substantial changes in the management of education at national, local authority and school/community levels are afoot. Central to future improvements are how teachers translate curriculum guidelines, with an increased focus on health and wellbeing and holistic learning experiences, into constructivist inclined pedagogical practices.…

Emerging good practices for Translatability Assessment (TA) of Patient-Reported Outcome (PRO) measures.

PubMed

Acquadro, Catherine; Patrick, Donald L; Eremenco, Sonya; Martin, Mona L; Kuliś, Dagmara; Correia, Helena; Conway, Katrin

2017-01-01

This paper presents emerging Good Practices for Translatability Assessment (TA) of Patient-Reported Outcome (PRO) Measures. The ISOQOL Translation and Cultural Adaptation Special Interest Group (TCA-SIG) undertook the review of several TA approaches, with the collaboration of organizations who are involved in conducting TA, and members of the TCA-SIG. The effort led to agreement by the writing group on Good Practices for 1) the terminology to be used in referring to translatability process, 2) the best definition of TA, 3) the methodology that is recommended at each step of the process, 4) the persons involved in TA, 5) the timing of assessment, 6) the review criteria for TA, and 7) the recommendations to be made at the end of the TA process. With input from the TCA-SIG membership and in consultation with experts in the field, these emerging good practices can guide the future use of TA in the development of PROs.

Nucleolin promotes in vitro translation of feline calicivirus genomic RNA.

PubMed

Hernández, Beatriz Alvarado; Sandoval-Jaime, Carlos; Sosnovtsev, Stanislav V; Green, Kim Y; Gutiérrez-Escolano, Ana Lorena

2016-02-01

Feline calicivirus depends on host-cell proteins for its replication. We previously showed that knockdown of nucleolin (NCL), a phosphoprotein involved in ribosome biogenesis, resulted in the reduction of FCV protein synthesis and virus yield. Here, we found that NCL may not be involved in FCV binding and entry into cells, but it binds to both ends of the FCV genomic RNA, and stimulates its translation in vitro. AGRO100, an aptamer that specifically binds and inactivates NCL, caused a strong reduction in FCV protein synthesis. This effect could be reversed by the addition of full-length NCL but not by a ΔrNCL, lacking the N-terminal domain. Consistent with this, FCV infection of CrFK cells stably expressing ΔrNCL led to a reduction in virus protein translation. These results suggest that NCL is part of the FCV RNA translational complex, and that the N-terminal part of the protein is required for efficient FCV replication. Copyright © 2015 Elsevier Inc. All rights reserved.

Translation technology fills important niche.

PubMed

2007-06-01

Software systems that can interpret and translate foreign languages can augment existing services and be available immediately, when live interpreters or even phone services may not be. Knowledge of their capabilities and cost can help you narrow your decision. Systems will take you from registration process through triage to diagnosis. All systems will provide text and audio translation. The more sophisticated systems also offer video services and sign language for deaf patients. The cost can be more than $100,000, but local foundations may offer grants that will cover your expenses.

Translating Research Evidence Into Practice to Reduce Health Disparities: A Social Determinants Approach

PubMed Central

Koh, Howard K.; Massin-Short, Sarah B.; Emmons, Karen M.; Geller, Alan C.; Viswanath, K.

2010-01-01

Translating research evidence to reduce health disparities has emerged as a global priority. The 2008 World Health Organization Commission on Social Determinants of Health recently urged that gaps in health attributable to political, social, and economic factors should be closed in a generation. Achieving this goal requires a social determinants approach to create public health systems that translate efficacy documented by research into effectiveness in the community. We review the scope, definitions, and framing of health disparities and explore local, national, and global programs that address specific health disparities. Such efforts translate research evidence into real-world settings and harness collaborative social action for broad-scale, sustainable change. PMID:20147686

Dengue Virus Selectively Annexes Endoplasmic Reticulum-Associated Translation Machinery as a Strategy for Co-opting Host Cell Protein Synthesis.

PubMed

Reid, David W; Campos, Rafael K; Child, Jessica R; Zheng, Tianli; Chan, Kitti Wing Ki; Bradrick, Shelton S; Vasudevan, Subhash G; Garcia-Blanco, Mariano A; Nicchitta, Christopher V

2018-04-01

A primary question in dengue virus (DENV) biology is the molecular strategy for recruitment of host cell protein synthesis machinery. Here, we combined cell fractionation, ribosome profiling, and transcriptome sequencing (RNA-seq) to investigate the subcellular organization of viral genome translation and replication as well as host cell translation and its response to DENV infection. We report that throughout the viral life cycle, DENV plus- and minus-strand RNAs were highly partitioned to the endoplasmic reticulum (ER), identifying the ER as the primary site of DENV translation. DENV infection was accompanied by an ER compartment-specific remodeling of translation, where ER translation capacity was subverted from host transcripts to DENV plus-strand RNA, particularly at late stages of infection. Remarkably, translation levels and patterns in the cytosol compartment were only modestly affected throughout the experimental time course of infection. Comparisons of ribosome footprinting densities of the DENV plus-strand RNA and host mRNAs indicated that DENV plus-strand RNA was only sparsely loaded with ribosomes. Combined, these observations suggest a mechanism where ER-localized translation and translational control mechanisms, likely cis encoded, are used to repurpose the ER for DENV virion production. Consistent with this view, we found ER-linked cellular stress response pathways commonly associated with viral infection, namely, the interferon response and unfolded protein response, to be only modestly activated during DENV infection. These data support a model where DENV reprograms the ER protein synthesis and processing environment to promote viral survival and replication while minimizing the activation of antiviral and proteostatic stress response pathways. IMPORTANCE DENV, a prominent human health threat with no broadly effective or specific treatment, depends on host cell translation machinery for viral replication, immune evasion, and virion biogenesis. The molecular mechanism by which DENV commandeers the host cell protein synthesis machinery and the subcellular organization of DENV replication and viral protein synthesis is poorly understood. Here, we report that DENV has an almost exclusively ER-localized life cycle, with viral replication and translation largely restricted to the ER. Surprisingly, DENV infection largely affects only ER-associated translation, with relatively modest effects on host cell translation in the cytosol. DENV RNA translation is very inefficient, likely representing a strategy to minimize disruption of ER proteostasis. Overall these findings demonstrate that DENV has evolved an ER-compartmentalized life cycle; thus, targeting the molecular signatures and regulation of the DENV-ER interaction landscape may reveal strategies for therapeutic intervention. Copyright © 2018 American Society for Microbiology.

The Applicability of Lean and Six Sigma Techniques to Clinical and Translational Research

PubMed Central

Schweikhart, Sharon A.; Dembe, Allard E

2010-01-01

Background Lean and Six Sigma are business management strategies commonly used in production industries to improve process efficiency and quality. During the past decade, these process improvement techniques increasingly have been applied outside of the manufacturing sector, for example, in health care and in software development. This article concerns the potential use of Lean and Six Sigma to improve the processes involved in clinical and translational research. Improving quality, avoiding delays and errors, and speeding up the time to implementation of biomedical discoveries are prime objectives of the NIH Roadmap for Biomedical Research and the NIH Clinical and Translational Science Award (CTSA) program. Methods This article presents a description of the main principles, practices, and methodologies used in Lean and Six Sigma. Available literature involving applications of Lean and Six Sigma to health care, laboratory science, and clinical and translational research is reviewed. Specific issues concerning the use of these techniques in different phases of translational research are identified. Results Examples are provided of Lean and Six Sigma applications that are being planned at a current CTSA site, which could potentially be replicated elsewhere. We describe how different process improvement approaches are best adapted for particularly translational research phases. Conclusions Lean and Six Sigma process improvement methodologies are well suited to help achieve NIH’s goal of making clinical and translational research more efficient and cost-effective, enhancing the quality of the research, and facilitating the successful adoption of biomedical research findings into practice. PMID:19730130

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

PubMed

Sheverdin, Vadim; Jung, Jiwon; Lee, Kyunglim

2013-09-01

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

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

PubMed Central

Sheverdin, Vadim; Jung, Jiwon; Lee, Kyunglim

2013-01-01

Translationally controlled tumor protein (TCTP) is a housekeeping protein, highly conserved among various species. It plays a major role in cell differentiation, growth, proliferation, apoptosis and carcinogenesis. Studies reported so far on TCTP expression in different digestive organs have not led to any understanding of the role of TCTP in digestion, so we localized TCTP in organs of the mouse digestive system employing immunohistochemical techniques. Translationally controlled tumor protein was found expressed in all organs studied: tongue, salivary glands, esophagus, stomach, small and large intestines, liver and pancreas. The expression of TCTP was found to be predominant in epithelia and neurons of myenteric nerve ganglia; high in serous glands (parotid, submandibular, gastric, intestinal crypts, pancreatic acini) and in neurons of myenteric nerve ganglia, and moderate to low in epithelia. In epithelia, expression of TCTP varied depending on its type and location. In enteric neurons, TCTP was predominantly expressed in the processes. Translationally controlled tumor protein expression in the liver followed porto-central gradient with higher expression in pericentral hepatocytes. In the pancreas, TCTP was expressed in both acini and islet cells. Our finding of nearly universal localization and expression of TCTP in mouse digestive organs points to the hitherto unrecognized functional importance of TCTP in the digestive system and suggests the need for further studies of the possible role of TCTP in the proliferation, secretion, absorption and neural regulation of the digestive process and its importance in the physiology and pathology of digestive process. PMID:23834399

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hipp, Katharina, E-mail: katharina.hipp@bio.uni-st

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

Managing clinical failure: a complex adaptive system perspective.

PubMed

Matthews, Jean I; Thomas, Paul T

2007-01-01

The purpose of this article is to explore the knowledge capture process at the clinical level. It aims to identify factors that enable or constrain learning. The study applies complex adaptive system thinking principles to reconcile learning within the NHS. The paper uses a qualitative exploratory study with an interpretative methodological stance set in a secondary care NHS Trust. Semi-structured interviews were conducted with healthcare practitioners and managers involved at both strategic and operational risk management processes. A network structure is revealed that exhibits the communication and interdependent working practices to support knowledge capture and adaptive learning. Collaborative multidisciplinary communities, whose values reflect local priorities and promote open dialogue and reflection, are featured. The main concern is that the characteristics of bureaucracy; rational-legal authority, a rule-based culture, hierarchical lines of communication and a centralised governance focus, are hindering clinical learning by generating barriers. Locally emergent collaborative processes are a key strategic resource to capture knowledge, potentially fostering an environment that could learn from failure and translate lessons between contexts. What must be addressed is that reporting mechanisms serve not only the governance objectives, but also supplement learning by highlighting the potential lessons in context. Managers must nurture a collaborative infrastructure using networks in a co-evolutionary manner. Their role is not to direct and design processes but to influence, support and create effective knowledge capture. Although the study only investigated one site the findings and conclusions may well translate to other trusts--such as the risk of not enabling a learning environment at clinical levels.

Molecular determinants of Cytochrome C oxidase IV mRNA axonal trafficking

PubMed Central

Kar, Amar N.; Vargas, Jose Norberto S.; Chen, Cai-Yun; Kowalak, Jeffrey A; Gioio, Anthony E.; Kaplan, Barry B.

2017-01-01

In previous studies, we identified a putative 38-nucleotide stem-loop structure (zipcode) in the 3′ untranslated region of the cytochrome c oxidase subunit IV (COXIV) mRNA that was necessary and sufficient for the axonal localization of the message in primary superior cervical ganglion (SCG) neurons. However, little is known about the proteins that interact with the COXIV-zipcode and regulate the axonal trafficking and local translation of the COXIV message. To identify proteins involved in the axonal transport of the COXIV mRNA, we used the biotinylated 38-nucleotide COXIV RNA zipcode as bait in the affinity purification of COXIV zipcode binding proteins. Gel-shift assays of the biotinylated COXIV zipcode indicated that the putative stem-loop structure functions as a nucleation site for the formation of ribonucleoprotein complexes. Mass spectrometric analysis of the COXIV zipcode ribonucleoprotein complex led to the identification of a large number RNA binding proteins, including fused in sarcoma/translated in liposarcoma (FUS/TLS), and Y-box protein 1 (YB-1). Validation experiments, using western analyses, confirmed the presence of the candidate proteins in the COXIV zipcode affinity purified complexes obtained from SCG axons. Immunohistochemical studies show that FUS, and YB-1 are present in SCG axons. Importantly, RNA immunoprecipitation studies show that FUS, and YB-1 interact with endogenous axonal COXIV transcripts. siRNA-mediated downregulation of the candidate proteins FUS and YB-1 expression in the cell-bodies diminishes the levels of COXIV mRNA in the axon, suggesting functional roles for these proteins in the axonal trafficking of COXIV mRNA. PMID:28161363

A protocol for the development of Mediterranean climate services based on the experiences of the CLIM-RUN case studies

NASA Astrophysics Data System (ADS)

Goodess, Clare; Ruti, Paolo; Rousset, Nathalie

2014-05-01

During the closing stages of the CLIM-RUN EU FP7 project on Climate Local Information in the Mediterranean region Responding to User Needs, the real-world experiences encountered by the case-study teams are being assessed and synthesised to identify examples of good practice and, in particular, to produce the CLIM-RUN protocol for the development of Mediterranean climate services. The specific case studies have focused on renewable energy (Morocco, Spain, Croatia, Cyprus), tourism (Savoie, Tunisia, Croatia, Cyprus) and wild fires (Greece) as well as one cross-cutting case study (Veneto region). They have been implemented following a common programme of local workshops, questionnaires and interviews, with Climate Expert Team and Stakeholder Expert Team members collaborating to identify and translate user needs and subsequently develop climate products and information. Feedback from stakeholders has been essential in assessing and refining these products. The protocol covers the following issues: the overall process and methodological key stages; identification and selection of stakeholders; communication with stakeholders; identification of user needs; translation of needs; producing products; assessing and refining products; methodologies for evaluating the economic value of climate services; and beyond CLIM-RUN - the lessons learnt. Particular emphasis is given to stakeholder analysis in the context of the participatory, bottom-up approach promoted by CLIM-RUN and to the iterative approach taken in the development of climate products. Recommendations are also made for an envisioned three-tier business model for the development of climate services involving climate, intermediary and stakeholder tiers.

A methodology for successfully producing global translations of patient reported outcome measures for use in multiple countries.

PubMed

Two, Rebecca; Verjee-Lorenz, Aneesa; Clayson, Darren; Dalal, Mehul; Grotzinger, Kelly; Younossi, Zobair M

2010-01-01

The production of accurate and culturally relevant translations of patient reported outcome (PRO) measures is essential for the success of international clinical trials. Although there are many reports in publication regarding the translation of PRO measures, the techniques used to produce single translations for use in multiple countries (global translations) are not well documented. This article addresses this apparent lack of documentation and presents the methodology used to create global translations of the Chronic Liver Disease Questionnaire-Hepatitis C Virus (CLDQ-HCV). The challenges of creating a translation for use in multiple countries are discussed, and the criteria for a global translation project explained. Based on a thorough translation and linguistic validation methodology including a concept elaboration, multiple forward translations, two back translations, reviews by in-country clinicians and the instrument developer, pilot testing in each target country and multiple sets of proofreading, the key concept of the global translation methodology is consistent international harmonization, achieved through the involvement of linguists from each target country at every stage of the process. This methodology enabled the successful resolution of the translation issues encountered, and resulted in consistent translations of the CLDQ-HCV that were linguistically and culturally appropriate for all target countries.

Situated learning in translation research training: academic research as a reflection of practice

PubMed Central

Risku, Hanna

2016-01-01

ABSTRACT Situated learning has become a dominant goal in the translation classroom: translation didactics is being developed in a learner-, situation- and experience-based direction, following constructivist and participatory teaching philosophies. However, the explicit use of situated approaches has, so far, not been the centre of attention in translation theory teaching and research training. As a consequence, translation theory often remains unconnected to the skills learned and topics tackled in language-specific translation teaching and the challenges experienced in real-life translation practice. This article reports on the results of an exploratory action research project into the teaching of academic research skills in translation studies at Master’s level. The goal of the project is to develop and test possibilities for employing situated learning in translation research training. The situatedness perspective has a double relevance for the teaching project: the students are involved in an authentic, ongoing research project, and the object of the research project itself deals with authentic translation processes at the workplace. Thus, the project has the potential to improve the expertise of the students as both researchers and reflective practitioners. PMID:27499805

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sasakura, Naoki

The tensor model is discussed as theory of dynamical fuzzy spaces in order to formulate gravity on fuzzy spaces. The numerical analyses of the tensor models possessing Gaussian background solutions have shown that the low-lying long-wavelength fluctuations around the backgrounds are in remarkable agreement with the geometric fluctuations on flat spaces in the general relativity. It has also been shown that part of the orthogonal symmetry of the tensor model spontaneously broken by the backgrounds agrees with the local translation symmetry of the general relativity. Thus the tensor model provides an interesting model of simultaneous emergence of space, the generalmore » relativity, and its local translation symmetry.« less

Many-body self-localization in a translation-invariant Hamiltonian

NASA Astrophysics Data System (ADS)

Mondaini, Rubem; Cai, Zi

2017-07-01

We study the statistical and dynamical aspects of a translation-invariant Hamiltonian, without quench disorder, as an example of the manifestation of the phenomenon of many-body localization. This is characterized by the breakdown of thermalization and by information preservation of initial preparations at long times. To realize this, we use quasiperiodic long-range interactions, which are now achievable in high-finesse cavity experiments, to find evidence suggestive of a divergent time-scale in which charge inhomogeneities in the initial state survive asymptotically. This is reminiscent of a glassy behavior, which appears in the ground state of this system, being also present at infinite temperatures.

Growth Cone MKK7 mRNA Targeting Regulates MAP1b-Dependent Microtubule Bundling to Control Neurite Elongation

PubMed Central

Feltrin, Daniel; Fusco, Ludovico; Witte, Harald; Moretti, Francesca; Martin, Katrin; Letzelter, Michel; Fluri, Erika; Scheiffele, Peter; Pertz, Olivier

2012-01-01

Local mRNA translation in neurons has been mostly studied during axon guidance and synapse formation but not during initial neurite outgrowth. We performed a genome-wide screen for neurite-enriched mRNAs and identified an mRNA that encodes mitogen-activated protein kinase kinase 7 (MKK7), a MAP kinase kinase (MAPKK) for Jun kinase (JNK). We show that MKK7 mRNA localizes to the growth cone where it has the potential to be translated. MKK7 is then specifically phosphorylated in the neurite shaft, where it is part of a MAP kinase signaling module consisting of dual leucine zipper kinase (DLK), MKK7, and JNK1. This triggers Map1b phosphorylation to regulate microtubule bundling leading to neurite elongation. We propose a model in which MKK7 mRNA localization and translation in the growth cone allows for a mechanism to position JNK signaling in the neurite shaft and to specifically link it to regulation of microtubule bundling. At the same time, this uncouples activated JNK from its functions relevant to nuclear translocation and transcriptional activation. PMID:23226105

Decoupled scheme based on the Hermite expansion to construct lattice Boltzmann models for the compressible Navier-Stokes equations with arbitrary specific heat ratio.

PubMed

Hu, Kainan; Zhang, Hongwu; Geng, Shaojuan

2016-10-01

A decoupled scheme based on the Hermite expansion to construct lattice Boltzmann models for the compressible Navier-Stokes equations with arbitrary specific heat ratio is proposed. The local equilibrium distribution function including the rotational velocity of particle is decoupled into two parts, i.e., the local equilibrium distribution function of the translational velocity of particle and that of the rotational velocity of particle. From these two local equilibrium functions, two lattice Boltzmann models are derived via the Hermite expansion, namely one is in relation to the translational velocity and the other is connected with the rotational velocity. Accordingly, the distribution function is also decoupled. After this, the evolution equation is decoupled into the evolution equation of the translational velocity and that of the rotational velocity. The two evolution equations evolve separately. The lattice Boltzmann models used in the scheme proposed by this work are constructed via the Hermite expansion, so it is easy to construct new schemes of higher-order accuracy. To validate the proposed scheme, a one-dimensional shock tube simulation is performed. The numerical results agree with the analytical solutions very well.

Many-body localization in disorder-free systems: The importance of finite-size constraints

DOE Office of Scientific and Technical Information (OSTI.GOV)

Papić, Z., E-mail: zpapic@perimeterinstitute.ca; Perimeter Institute for Theoretical Physics, Waterloo, ON N2L 2Y5; Stoudenmire, E. Miles

2015-11-15

Recently it has been suggested that many-body localization (MBL) can occur in translation-invariant systems, and candidate 1D models have been proposed. We find that such models, in contrast to MBL systems with quenched disorder, typically exhibit much more severe finite-size effects due to the presence of two or more vastly different energy scales. In a finite system, this can artificially split the density of states (DOS) into bands separated by large gaps. We argue for such models to faithfully represent the thermodynamic limit behavior, the ratio of relevant coupling must exceed a certain system-size depedent cutoff, chosen such that variousmore » bands in the DOS overlap one another. Setting the parameters this way to minimize finite-size effects, we study several translation-invariant MBL candidate models using exact diagonalization. Based on diagnostics including entanglement and local observables, we observe thermal (ergodic), rather than MBL-like behavior. Our results suggest that MBL in translation-invariant systems with two or more very different energy scales is less robust than perturbative arguments suggest, possibly pointing to the importance of non-perturbative effects which induce delocalization in the thermodynamic limit.« less

Choice as a Global Language in Local Practice: A Mixed Model of School Choice in Taiwan

ERIC Educational Resources Information Center

Mao, Chin-Ju

2015-01-01

This paper uses school choice policy as an example to demonstrate how local actors adopt, mediate, translate, and reformulate "choice" as neo-liberal rhetoric informing education reform. Complex processes exist between global policy about school choice and the local practice of school choice. Based on the theoretical sensibility of…

Translation and back-translation in qualitative nursing research: methodological review.

PubMed

Chen, Hsiao-Yu; Boore, Jennifer Rp

2010-01-01

To examine the effects of the procedure of translation and the techniques used on the collection and interpretation of original language qualitative data for English presentation. Nursing and health research increasingly use qualitative research for a broadened perspective on practice and research. In numerous qualitative nursing research papers, data are collected in the original language (example Chinese) and the findings are presented in English. No standardised procedures exist for evaluating the influences of translation on the trustworthiness of qualitative data in nursing research. Translation and back-translation related literature review was conducted. This is a methodological review paper. Discussion. This paper discusses the factors influencing the quality of translation including translator, back-translation, culture and language. Additionally, the translation procedures reported in the literature and the author's experiences are considered. The translation procedures described in qualitative nursing research can be summarised as: 1 Verbatim transcription of the content in original language, and then analysis of content; 2 Two bilingual translators are necessary to translate the emerged concepts and categories; 3 Back translate is employed; 4 An expert panel committee is involved in reaching final agreement on the translation. Development of the translation procedures could provide qualitative nursing researchers with a guide when collecting data in one language and presenting results in another language. In this way, the necessary rigour in qualitative nursing research could be achieved.

Accessing memory

DOEpatents

Yoon, Doe Hyun; Muralimanohar, Naveen; Chang, Jichuan; Ranganthan, Parthasarathy

2017-09-26

A disclosed example method involves performing simultaneous data accesses on at least first and second independently selectable logical sub-ranks to access first data via a wide internal data bus in a memory device. The memory device includes a translation buffer chip, memory chips in independently selectable logical sub-ranks, a narrow external data bus to connect the translation buffer chip to a memory controller, and the wide internal data bus between the translation buffer chip and the memory chips. A data access is performed on only the first independently selectable logical sub-rank to access second data via the wide internal data bus. The example method also involves locating a first portion of the first data, a second portion of the first data, and the second data on the narrow external data bus during separate data transfers.

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

PubMed

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

2017-05-01

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

Adaptation and translation of mental health interventions in Middle Eastern Arab countries: a systematic review of barriers to and strategies for effective treatment implementation.

PubMed

Gearing, Robin E; Schwalbe, Craig S; MacKenzie, Michael J; Brewer, Kathryne B; Ibrahim, Rawan W; Olimat, Hmoud S; Al-Makhamreh, Sahar S; Mian, Irfan; Al-Krenawi, Alean

2013-11-01

All too often, efficacious psychosocial evidence-based interventions fail when adapted from one culture to another. International translation requires a deep understanding of the local culture, nuanced differences within a culture, established service practices, and knowledge of obstacles and promoters to treatment implementation. This research investigated the following objectives to better facilitate cultural adaptation and translation of psychosocial and mental health treatments in Arab countries: (1) identify barriers or obstacles; (2) identify promoting strategies; and (3) provide clinical and research recommendations. This systematic review of 22 psychosocial or mental health studies in Middle East Arab countries identified more barriers (68%) than promoters (32%) to effective translation and adaptation of empirically supported psychosocial interventions. Identified barriers include obstacles related to acceptability of the intervention within the cultural context, community and system difficulties, and problems with clinical engagement processes. Whereas identified promoter strategies centre on the importance of partnering and working within the local and cultural context, the need to engage with acceptable and traditional intervention characteristics, and the development of culturally appropriate treatment strategies and techniques. Although Arab cultures across the Middle East are unique, this article provides a series of core clinical and research recommendations to assist effective treatment adaptation and translation within Arab communities in the Middle East.

Local motion adaptation enhances the representation of spatial structure at EMD arrays

PubMed Central

Lindemann, Jens P.; Egelhaaf, Martin

2017-01-01

Neuronal representation and extraction of spatial information are essential for behavioral control. For flying insects, a plausible way to gain spatial information is to exploit distance-dependent optic flow that is generated during translational self-motion. Optic flow is computed by arrays of local motion detectors retinotopically arranged in the second neuropile layer of the insect visual system. These motion detectors have adaptive response characteristics, i.e. their responses to motion with a constant or only slowly changing velocity decrease, while their sensitivity to rapid velocity changes is maintained or even increases. We analyzed by a modeling approach how motion adaptation affects signal representation at the output of arrays of motion detectors during simulated flight in artificial and natural 3D environments. We focused on translational flight, because spatial information is only contained in the optic flow induced by translational locomotion. Indeed, flies, bees and other insects segregate their flight into relatively long intersaccadic translational flight sections interspersed with brief and rapid saccadic turns, presumably to maximize periods of translation (80% of the flight). With a novel adaptive model of the insect visual motion pathway we could show that the motion detector responses to background structures of cluttered environments are largely attenuated as a consequence of motion adaptation, while responses to foreground objects stay constant or even increase. This conclusion even holds under the dynamic flight conditions of insects. PMID:29281631

The Lexicographic Treatment of Color Terms

ERIC Educational Resources Information Center

Williams, Krista

2014-01-01

This dissertation explores the main question, "What are the issues involved in the definition and translation of color terms in dictionaries?" To answer this question, I examined color term definitions in monolingual dictionaries of French and English, and color term translations in bilingual dictionaries of French paired with nine…

Cultural Differences on Chinese and English Idioms of Diet and the Translation

ERIC Educational Resources Information Center

Yang, Chunli

2010-01-01

Idioms is a special culture which is shaped in the daily lives of the local people, particularly the idioms of diet has a close relation with various elements, such as the eating custom, history, fairy tales, geographic situations. Also, different ways of translation on different diet idioms in English and Chinese will be analyzed in this article.…

Implementing 'translational' biomedical research: convergence and divergence among clinical and basic scientists.

PubMed

Morgan, Myfanwy; Barry, Christine A; Donovan, Jenny L; Sandall, Jane; Wolfe, Charles D A; Boaz, Annette

2011-10-01

Universities are increasingly regarded as key actors in the new 'knowledge economy', with requirements to produce market-oriented knowledge and engage in commercialization. This is of particular significance in the biomedical field, reflecting the perceived gap between success in terms of scientific discoveries and its transformation into products. The dominant discourse attributes this situation to 'blocks' in the translational pathway from 'bench to bedside', leading to policies to 'reengineer' the research enterprise. This study examines a pilot initiative established by the UK's Medical Research Council (MRC). This involved employing a change agent (Research Translator) supported by a small amount of translational funding to promote the culture and practice of translational research at a university/hospital site in England. An ethnographically informed case study involving semi-structured and open exploratory interviews, observation and document review, was conducted in 2008. Analysis and interpretation were informed by Bourdieu's logic of practice applied to science. The requirements of translational research promoted by the Research Translator and its sources of capital (authority, prestige etc) were largely congruent with the 'field' of clinical science. In contrast, translational research diverged from perceptions of 'legitimate' science and requirements for capital accumulation held by the majority of basic scientists who often described this research as 'high risk' and were resistant to the Research Translator's advice. However some differences in motivations and practices were identified within groups of scientists associated with career stage, work environment and specialty. We argue that there are convergent and divergent forces that influence scientists' readiness to adopt a market-oriented translational research model and in turn facilitate or constrain the effectiveness of a knowledge broker. We also identify ways in which current structures and policies continue to promote a continuum of forms of knowledge production, thus challenging notions of a linear shift. Copyright © 2011 Elsevier Ltd. All rights reserved.

Reactivation of stalled polyribosomes in synaptic plasticity

PubMed Central

Graber, Tyson E.; Hébert-Seropian, Sarah; Khoutorsky, Arkady; David, Alexandre; Yewdell, Jonathan W.; Lacaille, Jean-Claude; Sossin, Wayne S.

2013-01-01

Some forms of synaptic plasticity require rapid, local activation of protein synthesis. Although this is thought to reflect recruitment of mRNAs to free ribosomes, this would limit the speed and magnitude of translational activation. Here we provide compelling in situ evidence supporting an alternative model in which synaptic mRNAs are transported as stably paused polyribosomes. Remarkably, we show that metabotropic glutamate receptor activation allows the synthesis of proteins that lead to a functional long-term depression phenotype even when translation initiation has been greatly reduced. Thus, neurons evolved a unique mechanism to swiftly translate synaptic mRNAs into functional protein upon synaptic signaling using stalled polyribosomes to bypass the rate-limiting step of translation initiation. Because dysregulated plasticity is implicated in neurodevelopmental and psychiatric disorders such as fragile X syndrome, this work uncovers a unique translational target for therapies. PMID:24043809

Whi3, an S. cerevisiae RNA-binding protein, is a component of stress granules that regulates levels of its target mRNAs.

PubMed

Holmes, Kristen J; Klass, Daniel M; Guiney, Evan L; Cyert, Martha S

2013-01-01

RNA binding proteins (RBPs) are vital to the regulation of mRNA transcripts, and can alter mRNA localization, degradation, translation, and storage. Whi3 was originally identified in a screen for small cell size mutants, and has since been characterized as an RBP. The identification of Whi3-interacting mRNAs involved in mediating cellular responses to stress suggested that Whi3 might be involved in stress-responsive RNA processing. We show that Whi3 localizes to stress granules in response to glucose deprivation or heat shock. The kinetics and pattern of Whi3 localization in response to a range of temperatures were subtly but distinctly different from those of known components of RNA processing granules. Deletion of Whi3 resulted in an increase in the relative abundance of Whi3 target RNAs, either in the presence or absence of heat shock. Increased levels of the CLN3 mRNA in whi3Δ cells may explain their decreased cell size. Another mRNA target of Whi3 encodes the zinc-responsive transcription factor Zap1, suggesting a role for Whi3 in response to zinc stress. Indeed, we found that whi3Δ cells have enhanced sensitivity to zinc toxicity. Together our results suggest an expanded model for Whi3 function: in addition to its role as a regulator of the cell cycle, Whi3 may have a role in stress-dependent RNA processing and responses to a variety of stress conditions.

Breaking Through Barriers for Participatory Marine Conservation

NASA Astrophysics Data System (ADS)

Dustan, P.; Wheeler, L.

2016-02-01

Marine scientists and influential members of the diving community are realizing that ecology, like politics, is local and we need to be more proactive to promote conservation where we live and wherever we go in the marine world. Scientists can no longer simply pursue pure "loading dock" science because ocean degradation is accelerating and soon there may be little or nothing to study. This is especially acute in the tropics where fragile terrestrial and marine landscapes are coming under increasing anthropogenic pressures. Clearly it is in everyone's best interests to do what we can to protect and restore tropical ecosystems. We work to create a growing community of eco-divers and land-based members who are actively involved in local watershed and coral reef cleanup dives, international outreach expeditions, and watershed awareness. Our operating principle is based on the concept that people feel connected when they get involved in a cause they are passionate about. The transcending simplicity of active participation, working together for a cause beyond an immediate goal, empowers people to change the world. Our activities strive to inspire K-12 and beyond to become stewards of the ocean, which translates to the planet. We will describe three active projects in Bali, Belize, and Hawaii that blend science and sociology. This fusion of scientific and sport diving for reef conservation based on the tenets that: 1. Local actions can help prevent losses from local threats, which builds resilience to larger scale stress. 2. The action plan must be guided by good scientific knowledge and the Precautionary Principle. 3. There must be clear solutions that are economically viable without depleting the "resource". 4. The knowledge must be shared with locals who can effect real sociological changes. 5. Cultural sustainability means that "progress" cannot destroy culture and intergenerational equity. 6. Allow the ecological infrastructure to function in a near-intact condition.

Translation initiation mediated by nuclear cap-binding protein complex.

PubMed

Ryu, Incheol; Kim, Yoon Ki

2017-04-01

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

Genome-wide assessment of differential translations with ribosome profiling data

PubMed Central

Xiao, Zhengtao; Zou, Qin; Liu, Yu; Yang, Xuerui

2016-01-01

The closely regulated process of mRNA translation is crucial for precise control of protein abundance and quality. Ribosome profiling, a combination of ribosome foot-printing and RNA deep sequencing, has been used in a large variety of studies to quantify genome-wide mRNA translation. Here, we developed Xtail, an analysis pipeline tailored for ribosome profiling data that comprehensively and accurately identifies differentially translated genes in pairwise comparisons. Applied on simulated and real datasets, Xtail exhibits high sensitivity with minimal false-positive rates, outperforming existing methods in the accuracy of quantifying differential translations. With published ribosome profiling datasets, Xtail does not only reveal differentially translated genes that make biological sense, but also uncovers new events of differential translation in human cancer cells on mTOR signalling perturbation and in human primary macrophages on interferon gamma (IFN-γ) treatment. This demonstrates the value of Xtail in providing novel insights into the molecular mechanisms that involve translational dysregulations. PMID:27041671

French translation and cross-cultural adaptation of The Myotonic Dystrophy Health Index.

PubMed

Gagnon, Cynthia; Tremblay, Marjolaine; CôTé, Isabelle; Heatwole, Chad

2018-04-01

Validation studies of disease-specific instruments for myotonic dystrophy type-1 (DM1) are required prior to their global use in clinical trials involving different cultures and countries. Here we translate and culturally adapt the Myotonic Dystrophy Health Index (MDHI), a disease-specific patient-reported outcome (PRO) measure, for a French DM1 population. Using the International Society for Pharmacoeconomics and Outcomes Research Task Force method for translation and adaptation of PRO questionnaires, we created a French translation of the MDHI. We subsequently tested this instrument in a cohort of French-speaking patients with DM1. The MDHI was forward and back translated and modified by consensus to create the most compatible translation. Cognitive interviews were conducted with 5 patients with DM1 to ensure the usability and understanding of the translation. The French version of the MDHI is an optimal translation of the original instrument that is acceptable to native patients and ready for clinical trial use. Muscle Nerve 57: 686-689, 2018. © 2017 Wiley Periodicals, Inc.

Behavioral and electrophysiological signatures of word translation processes.

PubMed

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

2018-01-31

Translation is a demanding process during which a message is analyzed, translated and communicated from one language to another. Despite numerous studies on translation mechanisms, the electrophysiological processes underlying translation with overt production remain largely unexplored. Here, we investigated how behavioral response patterns and spatial-temporal brain dynamics differ in a translation compared to a control within-language word-generation task. We also investigated how forward and backward translation differs on the behavioral and electrophysiological level. To address these questions, healthy late bilingual subjects performed a translation and a within-language control task while a 128-channel EEG was recorded. Behavioral data showed faster responses for translation compared to within-language word generation and faster responses for backward than forward translation. The ERP-analysis revealed stronger early ( < 200ms) preparatory and attentional processes for between than within word generation. Later (424-630ms) differences were characterized by distinct engagement of domain-general control networks, namely self-monitoring and lexical access interference. Language asymmetry effects occurred at a later stage (600ms), reflecting differences in conceptual processing characterized by a larger involvement of areas implicated in attention, arousal and awareness for forward versus backward translation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cell-adhesion molecules in memory formation.

PubMed

Schmidt, R

1995-01-23

After learning events the CNS of higher organisms selects, which acquired informations are permanently stored as a memory trace. This period of memory consolidation is susceptible to interference by biochemical inhibitors of transcription and translation. Ependymin is a specific CNS glycoprotein functionally involved in memory consolidation in goldfish: after active shock-avoidance conditioning ependymin mRNA is rapidly induced in meningeal fibroblasts followed by enhanced synthesis and secretion of several closely related forms of the protein. Intracranial injections of anti-ependymin antisera or antisense oligodeoxynucleotides interfere specifically with memory consolidation, indicating that only de novo synthesized ependymin molecules are involved. Ependymin is capable of directing the growth of central axons in vitro and participates in neuronal regeneration in situ, presumably by its HNK-1 cell-adhesion epitope. Experiments reviewed in this article suggest a model that involves two regulation mechanisms for the function of ependymin in behavioural plasticity: while hormones appear to determine, how much of this cell adhesion molecule is synthesized after learning, local changes of metal cation concentrations in the micro-environment of activated neurons may polymerize ependymin at those synapses, that have to be consolidated to improve their efficacy for future use.

Genome Cyclization as Strategy for Flavivirus RNA Replication

PubMed Central

Villordo, Sergio M.; Gamarnik, Andrea V.

2017-01-01

Long-range and local RNA-RNA contacts in viral RNA genomes result in tertiary structures that modulate the function of enhancers, promoters, and silencers during translation, RNA replication, and encapsidation. In the case of flaviviruses, the presence of inverted complementary sequences at the 5′ and 3′ ends of the genome mediate long-range RNA interactions and RNA cyclization. The circular conformation of flavivirus genomes was demonstrated to be essential for RNA amplification. New ideas about the mechanisms by which circular genomes participate in flavivirus replication have emerged in the last few years. Here, we will describe the latest information about cis-acting elements involved in flavivirus genome cyclization, RNA promoter elements required for viral polymerase recognition, and how these elements together coordinate viral RNA synthesis. PMID:18703097

Lighting a path: genetic studies pinpoint neurodevelopmental mechanisms in autism and related disorders.

PubMed

Pescosolido, Matthew F; Yang, Unikora; Sabbagh, Mark; Morrow, Eric M

2012-09-01

In this review, we outline critical molecular processes that have been implicated by discovery of genetic mutations in autism. These mechanisms need to be mapped onto the neurodevelopment step(s) gone awry that may be associated with cause in autism. Molecular mechanisms include: (i) regulation of gene expression; (ii) pre-mRNA splicing; (iii) protein localization, translation, and turnover; (iv) synaptic transmission; (v) cell signaling; (vi) the functions of cytoskeletal and scaffolding proteins; and (vii) the function of neuronal cell adhesion molecules. While the molecular mechanisms appear broad, they may converge on only one of a few steps during neurodevelopment that perturbs the structure, function, and/or plasticity of neuronal circuitry. While there are many genetic mutations involved, novel treatments may need to target only one of few developmental mechanisms.

A new MIF4G domain-containing protein, CTIF, directs nuclear cap-binding protein CBP80/20-dependent translation

PubMed Central

Kim, Kyoung Mi; Cho, Hana; Choi, Kobong; Kim, Jaedong; Kim, Bong-Woo; Ko, Young-Gyu; Jang, Sung Key; Kim, Yoon Ki

2009-01-01

During or right after mRNA export via the nuclear pore complex (NPC) in mammalian cells, mRNAs undergo translation mediated by nuclear cap-binding proteins 80 and 20 (CBP80/20). After CBP80/20-dependent translation, CBP80/20 is replaced by cytoplasmic cap-binding protein eIF4E, which directs steady-state translation. Nonsense-mediated mRNA decay (NMD), one of the best-characterized mRNA surveillance mechanisms, has been shown to occur on CBP80/20-bound mRNAs. However, despite the tight link between CBP80/20-dependent translation and NMD, the underlying molecular mechanism and cellular factors that mediate CBP80/20-dependent translation remain obscure. Here, we identify a new MIF4G domain-containing protein, CTIF (CBP80/20-dependent translation initiation factor). CTIF interacts directly with CBP80 and is part of the CBP80/20-dependent translation initiation complex. Depletion of endogenous CTIF from an in vitro translation system selectively blocks the translation of CBP80-bound mRNAs, while addition of purified CTIF restores it. Accordingly, down-regulation of endogenous CTIF abrogates NMD. Confocal microscopy shows that CTIF is localized to the perinuclear region. Our observations demonstrate the existence of CBP80/20-dependent translation and support the idea that CBP80/20-dependent translation is mechanistically different from steady-state translation through identification of a specific cellular protein, CTIF. PMID:19648179

Projector Center: Replication, Transcription, and Translation.

ERIC Educational Resources Information Center

Ruth, Edward B.

1984-01-01

Describes the use of a chart that systematically summarizes three basic steps that involve DNA and its decoding in both eukaryotic and prokaryotic cells: replication; transcription, and translation. Indicates that the chart (mounted on a tranparency) does an adequate job of conveying basic information about nucleic acids to students. (DH)

Frames of Reference in the Classroom

ERIC Educational Resources Information Center

Grossman, Joshua

2012-01-01

The classic film "Frames of Reference" effectively illustrates concepts involved with inertial and non-inertial reference frames. In it, Donald G. Ivey and Patterson Hume use the cameras perspective to allow the viewer to see motion in reference frames translating with a constant velocity, translating while accelerating, and rotating--all with…

Time Translation of Quantum Properties

NASA Astrophysics Data System (ADS)

Laura, Roberto; Vanni, Leonardo

2009-02-01

Based on the notion of time translation, we develop a formalism to deal with the logic of quantum properties at different times. In our formalism it is possible to enlarge the usual notion of context to include composed properties involving properties at different times. We compare our results with the theory of consistent histories.

14 CFR Section 14 - Objective Classification-Nonoperating Income and Expense

Code of Federal Regulations, 2013 CFR

2013-01-01

... under account 82 Other Interest. [ER-1401, 50 FR 245, Jan. 3, 1985] 85Foreign exchange gains and losses. Record here gains and losses from transactions involving currency translations resulting from nonroutine abnormal changes in rates of foreign exchange and gains or losses which arise from translations of long...

14 CFR Section 14 - Objective Classification-Nonoperating Income and Expense

Code of Federal Regulations, 2014 CFR

2014-01-01

... under account 82 Other Interest. [ER-1401, 50 FR 245, Jan. 3, 1985] 85Foreign exchange gains and losses. Record here gains and losses from transactions involving currency translations resulting from nonroutine abnormal changes in rates of foreign exchange and gains or losses which arise from translations of long...

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

ERIC Educational Resources Information Center

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

2014-01-01

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

Mental Health Risk Factors Associated with Childhood Language Brokering

ERIC Educational Resources Information Center

Rainey, Vanessa R.; Flores, Valerie; Morrison, Robert G.; David, E. J. R.; Silton, Rebecca L.

2014-01-01

Serving as a language translator (broker) for family members during childhood can affect cognitive and emotional functions in both beneficial and detrimental ways. Child language brokers translate in a variety of contexts including conversations between their parents and financial, legal and medical professionals. Pressure to be involved in these…

Literature in Translation for Secondary Students.

ERIC Educational Resources Information Center

Jobe, Ronald A.

Literature in translation can provide English speaking secondary school students with a sensitive glimpse into life in other areas of the world and can be a contributor to international understanding. In such stories as Anne Holm's "I Am David," or "The Hostage," the characters become involved in webs of adventure and play…

Beyond Monolingualism: Philosophy as Translation and the Understanding of "Other" Cultures

ERIC Educational Resources Information Center

Saito, Naoko

2009-01-01

Beyond a monolingual mentality and beyond the language that is typically observed in the prevalent discourse of education for understanding other cultures, this article tries to present another approach: Stanley Cavell's idea of "philosophy as translation." This Cavellian approach shows that understanding foreign cultures involves a relation to…

The Productive Difficulty of Untranslatables in Qualitative Research

ERIC Educational Resources Information Center

Ruitenberg, Claudia W.; Knowlton, Autumn; Li, Gang

2016-01-01

The paper highlights the role of translation in qualitative research that involves multiple languages. Its particular focus is on untranslatables, that is, those words or phrases in a source language that pose challenges to translators because no direct equivalent is available in the target language. "Untranslatables" create moments of…

Interactome analysis reveals ZNF804A, a schizophrenia risk gene, as a novel component of protein translational machinery critical for embryonic neurodevelopment

PubMed Central

Zhou, Y; Dong, F; Lanz, T A; Reinhart, V; Li, M; Liu, L; Zou, J; Xi, H S; Mao, Y

2018-01-01

Recent genome-wide association studies identified over 100 genetic loci that significantly associate with schizophrenia (SZ). A top candidate gene, ZNF804A, was robustly replicated in different populations. However, its neural functions are largely unknown. Here we show in mouse that ZFP804A, the homolog of ZNF804A, is required for normal progenitor proliferation and neuronal migration. Using a yeast two-hybrid genome-wide screen, we identified novel interacting proteins of ZNF804A. Rather than transcriptional factors, genes involved in mRNA translation are highly represented in our interactome result. ZNF804A co-fractionates with translational machinery and modulates the translational efficiency as well as the mTOR pathway. The ribosomal protein RPSA interacts with ZNF804A and rescues the migration and translational defects caused by ZNF804A knockdown. RNA immunoprecipitation–RNAseq (RIP-Seq) identified transcripts bound to ZFP804A. Consistently, ZFP804A associates with many short transcripts involved in translational and mitochondrial regulation. Moreover, among the transcripts associated with ZFP804A, a SZ risk gene, neurogranin (NRGN), is one of ZFP804A targets. Interestingly, downregulation of ZFP804A decreases NRGN expression and overexpression of NRGN can ameliorate ZFP804A-mediated migration defect. To verify the downstream targets of ZNF804A, a Duolink in situ interaction assay confirmed genes from our RIP-Seq data as the ZNF804A targets. Thus, our work uncovered a novel mechanistic link of a SZ risk gene to neurodevelopment and translational control. The interactome-driven approach here is an effective way for translating genome-wide association findings into novel biological insights of human diseases. PMID:28924186

Stability of a stem-loop involving the initiator AUG controls the efficiency of internal initiation of translation on hepatitis C virus RNA.

PubMed Central

Honda, M; Brown, E A; Lemon, S M

1996-01-01

The initiation of translation on the positive-sense RNA genome of hepatitis C virus (HCV) is directed by an internal ribosomal entry site (IRES) that occupies most of the 341-nt 5' nontranslated RNA (5'NTR). Previous studies indicate that this IRES differs from picornaviral IRESs in that its activity is dependent upon RNA sequence downstream of the initiator AUG. Here, we demonstrate that the initiator AUG of HCV is located within a stem-loop (stem-loop IV) involving nt -12 to +12 (with reference to the AUG). This structure is conserved among HCV strains, and is present in the 5'NTR of the phylogenetically distant GB virus B. Mutant, nearly genome-length RNAs containing nucleotide substitutions predicted to enhance the stability of stem-loop IV were generally deficient in cap-independent translation both in vitro and in vivo. Additional mutations that destabilize the stem-loop restored translation to normal. Thus, the stability of the stem-loop is strongly but inversely correlated with the efficiency of internal initiation of translation. In contrast, mutations that stabilize this stem-loop had comparatively little effect on translation of 5' truncated RNAs by scanning ribosomes, suggesting that internal initiation of translation follows binding of the 40S ribosome directly at the site of stem-loop IV. Because stem-loop IV is not required for internal entry of ribosomes but is able to regulate this process, we speculate that it may be stabilized by interactions with a viral protein, providing a mechanism for feedback regulation of translation, which may be important for viral persistence. PMID:8849773

Anthropology, brokerage, and collaboration in the development of a Tongan public psychiatry: Local lessons for global mental health.

PubMed

Poltorak, Mike

2016-12-01

The Global Mental Health (GMH) movement has raised questions of the translatability of psychiatric concepts and the challenges of community engagement. In Tonga, the local psychiatrist Dr Puloka successfully established a publicly accessible psychiatry that has improved admission rates for serious mental illnesses and addressed some of the stigma attached to diagnosis. On the basis of historical analysis and ethnographic fieldwork with healers, doctors, and patients since 1998, this article offers an ethnographic contextualization of the development and reception of Puloka's three key interventions during the 1990s: (a) collaboration with traditional healers; (b) translation of psychiatric diagnoses into local cultural concepts; and (c) encouraging freedom of movement and legal appeal to involuntary admission. Dr Puloka's use of medical anthropological and transcultural psychiatry research informed a community-engaged brokerage between the implications of psychiatric nosologies and local needs that can address some of the challenges of the Global Mental Health movement.

Biomedical informatics and translational medicine.

PubMed

Sarkar, Indra Neil

2010-02-26

Biomedical informatics involves a core set of methodologies that can provide a foundation for crossing the "translational barriers" associated with translational medicine. To this end, the fundamental aspects of biomedical informatics (e.g., bioinformatics, imaging informatics, clinical informatics, and public health informatics) may be essential in helping improve the ability to bring basic research findings to the bedside, evaluate the efficacy of interventions across communities, and enable the assessment of the eventual impact of translational medicine innovations on health policies. Here, a brief description is provided for a selection of key biomedical informatics topics (Decision Support, Natural Language Processing, Standards, Information Retrieval, and Electronic Health Records) and their relevance to translational medicine. Based on contributions and advancements in each of these topic areas, the article proposes that biomedical informatics practitioners ("biomedical informaticians") can be essential members of translational medicine teams.

Automatic elastic image registration by interpolation of 3D rotations and translations from discrete rigid-body transformations.

PubMed

Walimbe, Vivek; Shekhar, Raj

2006-12-01

We present an algorithm for automatic elastic registration of three-dimensional (3D) medical images. Our algorithm initially recovers the global spatial mismatch between the reference and floating images, followed by hierarchical octree-based subdivision of the reference image and independent registration of the floating image with the individual subvolumes of the reference image at each hierarchical level. Global as well as local registrations use the six-parameter full rigid-body transformation model and are based on maximization of normalized mutual information (NMI). To ensure robustness of the subvolume registration with low voxel counts, we calculate NMI using a combination of current and prior mutual histograms. To generate a smooth deformation field, we perform direct interpolation of six-parameter rigid-body subvolume transformations obtained at the last subdivision level. Our interpolation scheme involves scalar interpolation of the 3D translations and quaternion interpolation of the 3D rotational pose. We analyzed the performance of our algorithm through experiments involving registration of synthetically deformed computed tomography (CT) images. Our algorithm is general and can be applied to image pairs of any two modalities of most organs. We have demonstrated successful registration of clinical whole-body CT and positron emission tomography (PET) images using this algorithm. The registration accuracy for this application was evaluated, based on validation using expert-identified anatomical landmarks in 15 CT-PET image pairs. The algorithm's performance was comparable to the average accuracy observed for three expert-determined registrations in the same 15 image pairs.

Burden of illness and research investments in translational sciences for pharmaceuticals in metastatic cancers.

PubMed

Wang, Wei-Jhih; Robertson, Justin C; Basu, Anirban

2017-01-01

To explore whether investments in translational sciences for six metastatic cancers follow idiosyncratic returns to those investments rather than levels of burden of illness (BI). Associate the number of translational clinical trials in the USA involving oncolytic drugs approved during 2008-2013 and the level (in 2008) and changes (2002-2008 and 2008-2014) in cancer-specific years of life lost. Investments in trials were positively associated only with contemporary changes in BI (2008-2014). The relationship was stronger for government-sponsored comparative-effectiveness trials than for industry. Translational research investments follow anticipated changes to BI levels. Systematic quantification of these expected returns from specific investments can help guide investment decisions in translational health sciences and generate productive dialogue across stakeholders.

Interprofessional collaborative practice within cancer teams: Translating evidence into action. A mixed methods study protocol

PubMed Central

2010-01-01

Background A regional integrated cancer network has implemented a program (educational workshops, reflective and mentoring activities) designed to support the uptake of evidence-informed interprofessional collaborative practices (referred to in this text as EIPCP) within cancer teams. This research project, which relates to the Registered Nurses' Association of Ontario (RNAO) Best Practice Guidelines and other sources of research evidence, represents a unique opportunity to learn more about the factors and processes involved in the translation of evidence-based recommendations into professional practices. The planned study seeks to address context-specific challenges and the concerns of nurses and other stakeholders regarding the uptake of evidence-based recommendations to effectively promote and support interprofessional collaborative practices. Aim This study aims to examine the uptake of evidence-based recommendations from best practice guidelines intended to enhance interprofessional collaborative practices within cancer teams. Design The planned study constitutes a practical trial, defined as a trial designed to provide comprehensive information that is grounded in real-world healthcare dynamics. An exploratory mixed methods study design will be used. It will involve collecting quantitative data to assess professionals' knowledge and attitudes, as well as practice environment factors associated with effective uptake of evidence-based recommendations. Semi-structured interviews will be conducted concurrently with care providers to gather qualitative data for describing the processes involved in the translation of evidence into action from both the users' (n = 12) and providers' (n = 24) perspectives. The Graham et al. Ottawa Model of Research Use will serve to construct operational definitions of concepts, and to establish the initial coding labels to be used in the thematic analysis of the qualitative data. Quantitative and qualitative results will be merged during interpretation to provide complementary perspectives of interrelated contextual factors that enhance the uptake of EIPCP and changes in professional practices. Discussion The information obtained from the study will produce new knowledge on the interventions and sources of support most conducive to the uptake of evidence and building of capacity to sustain new interprofessional collaborative practice patterns. It will provide new information on strategies for overcoming barriers to evidence-informed interventions. The findings will also pinpoint critical determinants of 'what works and why' taking into account the interplay between evidence, operational, relational micro-processes of care, uniqueness of patients' needs and preferences, and the local context. PMID:20626858

Overview of Three-Dimensional Atomic-Resolution Holography and Imaging Techniques: Recent Advances in Local-Structure Science

NASA Astrophysics Data System (ADS)

Daimon, Hiroshi

2018-06-01

Local three-dimensional (3D) atomic arrangements without periodicity have not been able to be studied until recently. Recently, several holographies and related techniques have been developed to reveal the 3D atomic arrangement around specific atoms with no translational symmetry. This review gives an overview of these new local 3D atomic imaging techniques.

Deformation analysis of the unified lunar control networks

NASA Astrophysics Data System (ADS)

Iz, H. Bâki; Chen, Yong Qi; King, Bruce Anthony; Ding, Xiaoli; Wu, Chen

2009-12-01

This study compares the latest Unified Lunar Control Network, ULCN 2005, solution with the earlier ULCN 1994 solution at global and local scales. At the global scale, the relative rotation, translation, and deformation (normal strains and shears) parameters between the two networks are estimated as a whole using their colocated station Cartesian coordinate differences. At the local scale, the network station coordinate differences are examined in local topocentric coordinate systems whose origins are located at the geometric center of quadrangles and tetrahedrons. This study identified that the omission of the topography in the old ULCN solutions shifted the geometric center of the lunar figure up to 5 km in the lunar equatorial plane and induced a few hundred-meter level global rotations of the ULCN 1994 reference frame with respect to ULCN 2005. The displacements between the old and new control networks are less than ± 2 km on the average at the local scale, which behave like translations, caused by the omission of lunar topography in the earlier solution. The contribution of local rigid body rotations and dilatational and compressional components to the local displacements are approximately ± 100 m for a quadrangle/tetrahedron of an average side length of 10 km.

Comparative expression profiling of AtRAD5B and AtNDL1: Hints towards a role in G protein mediated signaling.

PubMed

Khatri, Nisha; Singh, Swati; Hakim, Nasmeen; Mudgil, Yashwanti

2017-11-01

Arabidopsis AtRAD5B encodes for a putative helicase of the class SWItch/Sucrose Non-Fermentable (SWI/SNF) ATPases. We identified AtRAD5B as an interactor of N-MYC DOWNREGULATED-LIKE1 (AtNDL1) in a yeast two-hybrid screen. AtNDL1 is a G protein signaling component which regulates auxin transport and gradients together with GTP binding protein beta 1 (AGB1). Auxin gradients are known to recruit SWI/SNF remodeling complexes to the chromatin and regulate expression of genes involved in flower and leaf formation. In current study, a comparative spatial and temporal co-expression/localization analysis of AtNDL1, AGB1 with AtRAD5B was carried out in order to explore the possibility of their coexistence in a common signaling network. Translational fusion (GUS) of AtNDL1 and AtRAD5B in seedlings and reproductive organs revealed that both shared similar expression patterns with the highest expression observed in male reproductive organs. Moreover, they shared similar domains of localization in roots, suggesting their potential functioning together in reproductive and root development processes. This study predicts the existence of a signaling network involving AtNDL1, AGB1 with AtRAD5B. Copyright © 2017 Elsevier B.V. All rights reserved.

SMN regulates axonal local translation via miR-183/mTOR pathway

PubMed Central

Kye, Min Jeong; Niederst, Emily D.; Wertz, Mary H.; Gonçalves, Inês do Carmo G.; Akten, Bikem; Dover, Katarzyna Z.; Peters, Miriam; Riessland, Markus; Neveu, Pierre; Wirth, Brunhilde; Kosik, Kenneth S.; Sardi, S. Pablo; Monani, Umrao R.; Passini, Marco A.; Sahin, Mustafa

2014-01-01

Reduced expression of SMN protein causes spinal muscular atrophy (SMA), a neurodegenerative disorder leading to motor neuron dysfunction and loss. However, the molecular mechanisms by which SMN regulates neuronal dysfunction are not fully understood. Here, we report that reduced SMN protein level alters miRNA expression and distribution in neurons. In particular, miR-183 levels are increased in neurites of SMN-deficient neurons. We demonstrate that miR-183 regulates translation of mTor via direct binding to its 3′ UTR. Interestingly, local axonal translation of mTor is reduced in SMN-deficient neurons, and this can be recovered by miR-183 inhibition. Finally, inhibition of miR-183 expression in the spinal cord of an SMA mouse model prolongs survival and improves motor function of Smn-mutant mice. Together, these observations suggest that axonal miRNAs and the mTOR pathway are previously unidentified molecular mechanisms contributing to SMA pathology. PMID:25055867

Resuscitation Education Science: Educational Strategies to Improve Outcomes From Cardiac Arrest: A Scientific Statement From the American Heart Association.

PubMed

Cheng, Adam; Nadkarni, Vinay M; Mancini, Mary Beth; Hunt, Elizabeth A; Sinz, Elizabeth H; Merchant, Raina M; Donoghue, Aaron; Duff, Jonathan P; Eppich, Walter; Auerbach, Marc; Bigham, Blair L; Blewer, Audrey L; Chan, Paul S; Bhanji, Farhan

2018-06-21

The formula for survival in resuscitation describes educational efficiency and local implementation as key determinants in survival after cardiac arrest. Current educational offerings in the form of standardized online and face-to-face courses are falling short, with providers demonstrating a decay of skills over time. This translates to suboptimal clinical care and poor survival outcomes from cardiac arrest. In many institutions, guidelines taught in courses are not thoughtfully implemented in the clinical environment. A current synthesis of the evidence supporting best educational and knowledge translation strategies in resuscitation is lacking. In this American Heart Association scientific statement, we provide a review of the literature describing key elements of educational efficiency and local implementation, including mastery learning and deliberate practice, spaced practice, contextual learning, feedback and debriefing, assessment, innovative educational strategies, faculty development, and knowledge translation and implementation. For each topic, we provide suggestions for improving provider performance that may ultimately optimize patient outcomes from cardiac arrest. © 2018 American Heart Association, Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, M.; Al-Dayeh, L.; Patel, P.

It is well known that even small movements of the head can lead to artifacts in fMRI. Corrections for these movements are usually made by a registration algorithm which accounts for translational and rotational motion of the head under a rigid body assumption. The brain, however, is not entirely rigid and images are prone to local deformations due to CSF motion, susceptibility effects, local changes in blood flow and inhomogeneities in the magnetic and gradient fields. Since nonrigid body motion is not adequately corrected by approaches relying on simple rotational and translational corrections, we have investigated a general approach wheremore » an n{sup th} order polynomial is used to map all images onto a common reference image. The coefficients of the polynomial transformation were determined through minimization of the ratio of the variance to the mean of each pixel. Simulation studies were conducted to validate the technique. Results of experimental studies using polynomial transformation for 2D and 3D registration show lower variance to mean ratio compared to simple rotational and translational corrections.« less

Cross-cultural adaptation and translation of a quality of life tool for new mothers: a methodological and experiential account from six countries.

PubMed

Symon, Andrew; Nagpal, Jitender; Maniecka-Bryła, Irena; Nowakowska-Głąb, Agata; Rashidian, Arash; Khabiri, Roghayeh; Mendes, Isabel; Pinheiro, Ana Karina Bezerra; de Oliveira, Mirna Fontenele; Wu, Liping

2013-04-01

To examine the challenges and solutions encountered in the translation and cross-cultural adaptation of an English language quality of life tool in India, China, Iran, Portugal, Brazil, and Poland. Those embarking on research involving translation and cross-cultural adaptation must address certain practical and conceptual issues. These include instrument choice, linguistic factors, and cultural or philosophical differences, which may render an instrument inappropriate, even when expertly translated. Publication bias arises when studies encountering difficulties do not admit to these, or are not published at all. As an educative guide to the potential pitfalls involved in the cross-cultural adaptation process, this article reports the conceptual, linguistic, and methodological experiences of researchers in six countries, who translated and adapted the Mother-Generated Index, a quality of life tool originally developed in English. Principal investigator experience from six stand-alone studies (two published) ranging from postgraduate research to citywide surveys. DISCUSSION/IMPLICATIONS FOR NURSING: This analysis of a series of stand-alone cross-cultural studies provides lessons about how conceptual issues, such as the uniqueness of perceived quality of life and the experience of new motherhood, can be addressed. This original international approach highlights practical lessons relating to instrument choice, and the resources available to researchers with different levels of experience. Although researchers may be confident of effective translation, conceptual and practical difficulties may be more problematic. Instrument choice is crucial. Researchers must negotiate adequate resources for cross-cultural research, including time, translation facilities, and expert advice about conceptual issues. © 2012 Blackwell Publishing Ltd.

The expression analysis of Sfrs10 and Celf4 during mouse retinal development

PubMed Central

Karunakaran, Devi Krishna Priya; Congdon, Sean; Guerrette, Thomas; Banday, Abdul Rouf; Lemoine, Christopher; Chhaya, Nisarg; Kanadia, Rahul

2013-01-01

Processing of mRNAs including, alternative splicing (AS), mRNA transport and translation regulation are crucial to eukaryotic gene expression. For example, >90% of the gene in the human genome are known to undergo alternative splicing thereby expanding the proteome production capacity of a limited number of genes. Similarly, mRNA export and translation regulation plays a vital role in regulating protein production. Thus, it is important to understand how these RNA binding proteins including alternative splicing factors (ASFs) and mRNA transport and translation factors regulate these processes. Here we report the expression of an ASF, Serine-arginine rich splicing factor 10 (Sfrs10) and a mRNA translation regulation factor, CUGBP, elav like family member 4 (Celf4) in the developing mouse retina. Sfrs10 was expressed throughout postnatal (P) retinal development and was observed progressively in newly differentiating neurons. Immunofluorescence (IF) showed Sfrs10 in retinal ganglion cells (RGCs) at P0, followed by amacrine and bipolar cells, and at P8 it was enriched in red/green cone photoreceptor cells. By P22, Sfrs10 was observed in rod photoreceptors in a peri-nuclear pattern. Like Sfrs10, Celf4 was also observed in the developing retina, but with two distinct retinal isoforms. In situ hybridization (ISH) showed progressive expression of Celf4 in differentiating neurons, which was confirmed by IF that showed a dynamic shift in Celf4 localization. Early in development Celf4 expression was restricted to the nuclei of newly differentiating RGCs and later (E16 onwards) it was observed in the initial segments of RGC axons. Later, during postnatal development, Celf4 was observed in amacrine and bipolar cells, but here it was predominantly cytoplasmic and enriched in the two synaptic layers. Specifically, at P14, Celf4 was observed in the synaptic boutons of rod bipolar cells marked by Pkc-α. Thus, Celf4 might be regulating AS early in development besides its known role of regulating mRNA localization/translation. In all, our data suggests an important role for AS and mRNA localization/translation in retinal neuron differentiation. PMID:23932931

The role of tRNA and ribosome competition in coupling the expression of different mRNAs in Saccharomyces cerevisiae

PubMed Central

Chu, Dominique; Barnes, David J.; von der Haar, Tobias

2011-01-01

Protein synthesis translates information from messenger RNAs into functional proteomes. Because of the finite nature of the resources required by the translational machinery, both the overall protein synthesis activity of a cell and activity on individual mRNAs are controlled by the allocation of limiting resources. Upon introduction of heterologous sequences into an organism—for example for the purposes of bioprocessing or synthetic biology—limiting resources may also become overstretched, thus negatively affecting both endogenous and heterologous gene expression. In this study, we present a mean-field model of translation in Saccharomyces cerevisiae for the investigation of two particular translational resources, namely ribosomes and aminoacylated tRNAs. We firstly use comparisons of experiments with heterologous sequences and simulations of the same conditions to calibrate our model, and then analyse the behaviour of the translational system in yeast upon introduction of different types of heterologous sequences. Our main findings are that: competition for ribosomes, rather than tRNAs, limits global translation in this organism; that tRNA aminoacylation levels exert, at most, weak control over translational activity; and that decoding speeds and codon adaptation exert strong control over local (mRNA specific) translation rates. PMID:21558172

An efficient blocking M2L translation for low-frequency fast multipole method in three dimensions

NASA Astrophysics Data System (ADS)

Takahashi, Toru; Shimba, Yuta; Isakari, Hiroshi; Matsumoto, Toshiro

2016-05-01

We propose an efficient scheme to perform the multipole-to-local (M2L) translation in the three-dimensional low-frequency fast multipole method (LFFMM). Our strategy is to combine a group of matrix-vector products associated with M2L translation into a matrix-matrix product in order to diminish the memory traffic. For this purpose, we first developed a grouping method (termed as internal blocking) based on the congruent transformations (rotational and reflectional symmetries) of M2L-translators for each target box in the FMM hierarchy (adaptive octree). Next, we considered another method of grouping (termed as external blocking) that was able to handle M2L translations for multiple target boxes collectively by using the translational invariance of the M2L translation. By combining these internal and external blockings, the M2L translation can be performed efficiently whilst preservingthe numerical accuracy exactly. We assessed the proposed blocking scheme numerically and applied it to the boundary integral equation method to solve electromagnetic scattering problems for perfectly electrical conductor. From the numerical results, it was found that the proposed M2L scheme achieved a few times speedup compared to the non-blocking scheme.

Community-Based Environmental Monitoring Goes to School: Translations, Detours and Escapes

ERIC Educational Resources Information Center

Lynch, Julianne; Eilam, Efrat; Fluker, Martin; Augar, Naomi

2017-01-01

Community-school partnerships are an established practice within environmental science education, where a focus on how local phenomena articulate with broader environmental issues and concerns brings potential benefits for schools, community organisations and local communities. This paper contributes to our understanding of such educational…

Optical superheterodyne receiver uses laser for local oscillator

NASA Technical Reports Server (NTRS)

Lucy, R. F.

1966-01-01

Optical superheterodyne receiver uses a laser coupled to a frequency translator to supply both the incident signal and local oscillator signal and thus permit reception of amplitude modulated video bandwidth signals through the atmosphere. This receiver is useful in scientific propagation experiments, tracking experiments, and communication experiments.

Critical excitation spectrum of a quantum chain with a local three-spin coupling.

PubMed

McCabe, John F; Wydro, Tomasz

2011-09-01

Using the phenomenological renormalization group (PRG), we evaluate the low-energy excitation spectrum along the critical line of a quantum spin chain having a local interaction between three Ising spins and longitudinal and transverse magnetic fields, i.e., a Turban model. The low-energy excitation spectrum found with the PRG agrees with the spectrum predicted for the (D(4),A(4)) conformal minimal model under a nontrivial correspondence between translations at the critical line and discrete lattice translations. Under this correspondence, the measurements confirm a prediction that the critical line of this quantum spin chain and the critical point of the two-dimensional three-state Potts model are in the same universality class.

Translation of Polioviral mRNA Is Inhibited by Cleavage of Polypyrimidine Tract-Binding Proteins Executed by Polioviral 3Cpro

PubMed Central

Back, Sung Hoon; Kim, Yoon Ki; Kim, Woo Jae; Cho, Sungchan; Oh, Hoe Rang; Kim, Jung-Eun; Jang, Sung Key

2002-01-01

The translation of polioviral mRNA occurs through an internal ribosomal entry site (IRES). Several RNA-binding proteins, such as polypyrimidine tract-binding protein (PTB) and poly(rC)-binding protein (PCBP), are required for the poliovirus IRES-dependent translation. Here we report that a poliovirus protein, 3Cpro (and/or 3CDpro), cleaves PTB isoforms (PTB1, PTB2, and PTB4). Three 3Cpro target sites (one major target site and two minor target sites) exist in PTBs. PTB fragments generated by poliovirus infection are redistributed to the cytoplasm from the nucleus, where most of the intact PTBs are localized. Moreover, these PTB fragments inhibit polioviral IRES-dependent translation in a cell-based assay system. We speculate that the proteolytic cleavage of PTBs may contribute to the molecular switching from translation to replication of polioviral RNA. PMID:11836431

Co-translational protein targeting facilitates centrosomal recruitment of PCNT during centrosome maturation in vertebrates

PubMed Central

Mahe, Karan; Ou, Tingyoung; Castro, Noemi M; Christensen, Lana N; Cheung, Lee; Jiang, Xueer; Yoon, Daniel; Huang, Bo

2018-01-01

As microtubule-organizing centers of animal cells, centrosomes guide the formation of the bipolar spindle that segregates chromosomes during mitosis. At mitosis onset, centrosomes maximize microtubule-organizing activity by rapidly expanding the pericentriolar material (PCM). This process is in part driven by the large PCM protein pericentrin (PCNT), as its level increases at the PCM and helps recruit additional PCM components. However, the mechanism underlying the timely centrosomal enrichment of PCNT remains unclear. Here, we show that PCNT is delivered co-translationally to centrosomes during early mitosis by cytoplasmic dynein, as evidenced by centrosomal enrichment of PCNT mRNA, its translation near centrosomes, and requirement of intact polysomes for PCNT mRNA localization. Additionally, the microtubule minus-end regulator, ASPM, is also targeted co-translationally to mitotic spindle poles. Together, these findings suggest that co-translational targeting of cytoplasmic proteins to specific subcellular destinations may be a generalized protein targeting mechanism. PMID:29708497

Sociolinguistic reflection on neuropsychological assessment: an insight into selected culturally adapted battery of Lebanese Arabic cognitive testing.

PubMed

Abou-Mrad, Fadi; Tarabey, Lubna; Zamrini, Edward; Pasquier, Florence; Chelune, Gordon; Fadel, Patricia; Hayek, Maryse

2015-10-01

Neuropsychological tests (NPTs) are highly dependent on education, culture differences as well as age and sex. It is therefore essential to take these factors into consideration when translating NPTs to be used in screening for cognitive impairment. Translations into Arabic must respect the principles of linguistic relativity and cultural specificity of the population under study. The objective is to assess feasibility and outcome of translating neuropsychological tests to Arabic. A team of Lebanese professionals selected a battery of screening NPTs. These tests were translated into Arabic and independently back translated by a team of sociolinguists and cultural specialists. The translations were adapted to suit the Lebanese culture. The final NPT translated versions were reached by consensus of an expert panel and tested on a group of independently living community-dwelling elderly. Translated items had to be modified when: (1) terms could not be translated using one word as required by the test; (2) Concepts were foreign to the culture; (3) Translated words carried multiple meanings; (4) Words were rarely used in Lebanon; (5) Sentences did not have an equivalent; and (6) Words had letters pronounced differently by subgroups in Lebanon. Despite all measures to maintain cultural sensitivity in translations, non-linguistic challenges remained. A battery of cognitive screening tests were translated into Arabic and adapted for the Lebanese population. These adaptations allow for a better assessment of cognitive abilities since they reflect the thought patterns of the population. The challenge is to establish local normative data.

Gene expression profile differences in left and right liver lobes from mid-gestation fetal baboons: a cautionary tale

PubMed Central

Cox, Laura A; Schlabritz-Loutsevitch, Natalia; Hubbard, Gene B; Nijland, Mark J; McDonald, Thomas J; Nathanielsz, Peter W

2006-01-01

Interpretation of gene array data presents many potential pitfalls in adult tissues. Gene array techniques applied to fetal tissues present additional confounding pitfalls. The left lobe of the fetal liver is supplied with blood containing more oxygen than the right lobe. Since synthetic activity and cell function are oxygen dependent, we hypothesized major differences in mRNA expression between the fetal right and left liver lobes. Our aim was to demonstrate the need to evaluate RNA samples from both lobes. We performed whole genome expression profiling on left and right liver lobe RNA from six 90-day gestation baboon fetuses (term 180 days). Comparing right with left, we found 875 differentially expressed genes – 312 genes were up-regulated and 563 down-regulated. Pathways for damaged DNA binding, endonuclease activity, interleukin binding and receptor activity were up-regulated in right lobe; ontological pathways related to cell signalling, cell organization, cell biogenesis, development, intracellular transport, phospholipid metabolism, protein biosynthesis, protein localization, protein metabolism, translational regulation and vesicle mediated transport were down-regulated in right lobe. Molecular pathway analysis showed down-regulation of pathways related to heat shock protein binding, ion channel and transporter activities, oxygen binding and transporter activities, translation initiation and translation regulator activities. Genes involved in amino acid biosynthesis, lipid biosynthesis and oxygen transport were also differentially expressed. This is the first demonstration of RNA differences between the two lobes of the fetal liver. The data support the argument that a complete interpretation of gene expression in the developing liver requires data from both lobes. PMID:16484296

Achieving Health Equity Through Community Engagement in Translating Evidence to Policy: The San Francisco Health Improvement Partnership, 2010-2016.

PubMed

Grumbach, Kevin; Vargas, Roberto A; Fleisher, Paula; Aragón, Tomás J; Chung, Lisa; Chawla, Colleen; Yant, Abbie; Garcia, Estela R; Santiago, Amor; Lang, Perry L; Jones, Paula; Liu, Wylie; Schmidt, Laura A

2017-03-23

The San Francisco Health Improvement Partnership (SFHIP) promotes health equity by using a novel collective impact model that blends community engagement with evidence-to-policy translational science. The model involves diverse stakeholders, including ethnic-based community health equity coalitions, the local public health department, hospitals and health systems, a health sciences university, a school district, the faith community, and others sectors. We report on 3 SFHIP prevention initiatives: reducing consumption of sugar sweetened beverages (SSBs), regulating retail alcohol sales, and eliminating disparities in children's oral health. SFHIP is governed by a steering committee. Partnership working groups for each initiative collaborate to 1) develop and implement action plans emphasizing feasible, scalable, translational-science-informed interventions and 2) consider sustainability early in the planning process by including policy and structural interventions. Through SFHIP's efforts, San Francisco enacted ordinances regulating sale and advertising of SSBs and a ballot measure establishing a soda tax. Most San Francisco hospitals implemented or committed to implementing healthy-beverage policies that prohibited serving or selling SSBs. SFHIP helped prevent Starbucks and Taco Bell from receiving alcohol licenses in San Francisco and helped prevent state authorization of sale of powdered alcohol. SFHIP increased the number of primary care clinics providing fluoride varnish at routine well-child visits from 3 to 14 and acquired a state waiver to allow dental clinics to be paid for dental services delivered in schools. The SFHIP model of collective impact emphasizing community engagement and policy change accomplished many of its intermediate goals to create an environment promoting health and health equity.

Ischaemia–reperfusion injury in liver transplantation—from bench to bedside

PubMed Central

Zhai, Yuan; Petrowsky, Henrik; Hong, Johnny C.; Busuttil, Ronald W.; Kupiec-Weglinski, Jerzy W.

2013-01-01

Ischaemia–reperfusion injury (IRI) in the liver, a major complication of haemorrhagic shock, resection and transplantation, is a dynamic process that involves the two interrelated phases of local ischaemic insult and inflammation-mediated reperfusion injury. This Review highlights the latest mechanistic insights into innate–adaptive immune crosstalk and cell activation cascades that lead to inflammation-mediated injury in livers stressed by ischaemia–reperfusion, discusses progress in large animal experiments and examines efforts to minimize liver IRI in patients who have received a liver transplant. The interlinked signalling pathways in multiple hepatic cell types, the IRI kinetics and positive versus negative regulatory loops at the innate–adaptive immune interface are discussed. The current gaps in our knowledge and the pathophysiology aspects of IRI in which basic and translational research is still required are stressed. An improved appreciation of cellular immune events that trigger and sustain local inflammatory responses, which are ultimately responsible for organ injury, is fundamental to developing innovative strategies for treating patients who have received a liver transplant and developed ischaemia–reperfusion inflammation and organ dysfunction. PMID:23229329

Specification of Dendritogenesis Site in Drosophila aCC Motoneuron by Membrane Enrichment of Pak1 through Dscam1.

PubMed

Kamiyama, Daichi; McGorty, Ryan; Kamiyama, Rie; Kim, Michael D; Chiba, Akira; Huang, Bo

2015-10-12

Precise positioning of dendritic branches is a critical step in the establishment of neuronal circuitry. However, there is limited knowledge on how environmental cues translate into dendrite initiation or branching at a specific position. Here, through a combination of mutation, RNAi, and imaging experiments, we found that a Dscam-Dock-Pak1 hierarchical interaction defines the stereotypical dendrite growth site in the Drosophila aCC motoneuron. This interaction localizes the Cdc42 effector Pak1 to the plasma membrane at the dendrite initiation site before the activation of Cdc42. Ectopic expression of membrane-anchored Pak1 overrides this spatial specification of dendritogenesis, confirming its function in guiding Cdc42 signaling. We further discovered that Dscam1 localization in aCC occurs through an inter-neuronal contact that involves Dscam1 in the partner MP1 neuron. These findings elucidate a mechanism by which Dscam1 controls neuronal morphogenesis through spatial regulation of Cdc42 signaling and, subsequently, cytoskeletal remodeling. Copyright © 2015 Elsevier Inc. All rights reserved.

Instrumentation for measurement of aircraft noise and sonic boom

NASA Technical Reports Server (NTRS)

Zuckerwar, A. J. (Inventor)

1975-01-01

A jet aircraft noise and sonic boom measuring device which converts sound pressure into electric current is described. An electric current proportional to the sound pressure level at a condenser microphone is produced and transmitted over a cable, amplified by a zero drive amplifier and recorded on magnetic tape. The converter is comprised of a local oscillator, a dual-gate field-effect transistor (FET) mixer and a voltage regulator/impedance translator. A carrier voltage that is applied to one of the gates of the FET mixer is generated by the local oscillator. The microphone signal is mixed with the carrier to produce an electrical current at the frequency of vibration of the microphone diaphragm by the FET mixer. The voltage of the local oscillator and mixer stages is regulated, the carrier at the output is eliminated, and a low output impedance at the cable terminals is provided by the voltage regulator/impedance translator.

First Translation Equivalents in Bilingual Toddlers' Expressive Vocabulary: Does Form Similarity Matter?

ERIC Educational Resources Information Center

Bosch, Laura; Ramon-Casas, Marta

2014-01-01

Translation equivalents (TEs) characterize the lexicon of bilinguals from the early stages of acquisition, as reported in studies involving English and other languages in which most cross-language synonyms are dissimilar in phonological form. This research explores the emergence of TEs in Spanish-Catalan bilinguals who are acquiring two languages…

"The Simpsons": Translation and Language Teaching in an EFL Class

ERIC Educational Resources Information Center

Pavan, Elisabetta

2013-01-01

My point of departure for this paper is that translation, so long neglected in foreign language teaching, can not only improve students' linguistic competences in both a foreign language and their mother tongue, but also their awareness of cultural and intercultural elements. It is a widespread popular assumption, among those not involved in…

ABCE1 is essential for S phase progression in human cells

PubMed Central

Toompuu, Marina; Kärblane, Kairi; Pata, Pille; Truve, Erkki; Sarmiento, Cecilia

2016-01-01

ABSTRACT ABCE1 is a highly conserved protein universally present in eukaryotes and archaea, which is crucial for the viability of different organisms. First identified as RNase L inhibitor, ABCE1 is currently recognized as an essential translation factor involved in several stages of eukaryotic translation and ribosome biogenesis. The nature of vital functions of ABCE1, however, remains unexplained. Here, we study the role of ABCE1 in human cell proliferation and its possible connection to translation. We show that ABCE1 depletion by siRNA results in a decreased rate of cell growth due to accumulation of cells in S phase, which is accompanied by inefficient DNA synthesis and reduced histone mRNA and protein levels. We infer that in addition to the role in general translation, ABCE1 is involved in histone biosynthesis and DNA replication and therefore is essential for normal S phase progression. In addition, we analyze whether ABCE1 is implicated in transcript-specific translation via its association with the eIF3 complex subunits known to control the synthesis of cell proliferation-related proteins. The expression levels of a few such targets regulated by eIF3A, however, were not consistently affected by ABCE1 depletion. PMID:26985706

Six-degree-of-freedom local seismic records from micro-earthquakes and anthropogenic events

NASA Astrophysics Data System (ADS)

Brokešová, J.; Málek, J.

2012-04-01

Full ground motion description, including both translational and rotational components, attracts still more attention in modern seismology. There is a need for portable rotational sensors, easily installed and operated in the field, sensitive enough to provide 6DOF records in a wide range of amplitudes excited not only by strong but also weak motion events. A new prototype of our rotational seismic sensor system (Rotaphone) designed to measure three rotation rate and three ground velocity components is presented. Our method is based on measurements of the differential motions between paired low-frequency geophones attached to a rigid skeleton, the size of which is much smaller than the wavelength of interest. This approach is conditioned by a precise calibration of each paired geophone in the system. A method of our in-situ calibration is explained and demonstrated. The device was thoroughly tested at the Albuquerque Seismological Laboratory, U.S. Geological Survey, with focus on linearity and cross-axis errors. Results of these tests confirm its proper function. The Rotaphone operates in the frequency range 2-40 Hz and its dynamic range is at least 120 dB. It was successfully applied to measure 6DOF ground motions from local shallow micro-earthquakes in the West Bohemia swarm area (Czech Republic), at Hronov-Pozíčí fault zone in East Bohemia (Czech Republic), and in the vicinity of the salt-works of Provadia (Bulgaria). It was also used to obtain records from anthropogenic sources (blasts, rockbursts). Three-axial rotation rate records for these types of events are shown and discussed. Their peak amplitudes reach values from 10-7 rad/s to 10-4 rad/s. To characterize the significance of rotation we define the rotation to translation ratio (RTR) relating peak amplitudes of rotation rate and translational velocity. The RTR factor for different types of local events is discussed in view of its dependence on hypocentral distance, source type and probably on radiation pattern and geological structure along the wavepaths. Thanks to our method of retrieving rotation rates, their records are not contaminated by translational motions. Opposite is not true. Special attention is devoted to the problem of contamination of translational records by rotations. Our approach enables to compensate for this contamination. This procedure is especially important for horizontal translational components that contain a non-negligible contribution from gravity in the case of tilting of the instrument. Possible application of Rotaphones in local seismic networks and seismic prospecting is discussed.

Multidetector Scattering as a Probe of Local Structure in Disordered Phases

NASA Astrophysics Data System (ADS)

Clark, Noel A.; Ackerson, Bruce J.; Hurd, Alan J.

1983-05-01

The local translational structure of a two-dimensional colloidal liquid is observed by use of cross correlation of the intensity fluctuations of light scattered by the liquid through two different wave vectors. The utility of multidetector scattering in probing multipoint correlations in disordered phases is thereby demonstrated unambiguously.

47 CFR 74.783 - Station identification.

Code of Federal Regulations, 2011 CFR

2011-10-01

... originating local programming as defined by § 74.701(h) operating over 0.001 kw peak visual power (0.002 kw... visual presentation or a clearly understandable aural presentation of the translator station's call... identification procedures given in § 73.1201 when locally originating programming, as defined by § 74.701(h). The...

TRANSLATION TO PORTUGUESE LANGUAGE AND CROSS-CULTURAL ADAPTATION OF THE MODIFIED ROWE SCORE FOR OVERHEAD ATHLETES

PubMed Central

Marcondes, Freddy Beretta; de Vasconcelos, Rodrigo Antunes; Marchetto, Adriano; de Andrade, André Luis Lugnani; Filho, Américo Zoppi; Etchebehere, Maurício

2015-01-01

Objetctive: Study was to translate and culturally adapt the modified Rowe score for overhead athletes. Methods: The translation and cultural adaptation process initially involved the stages of translation, synthesis, back-translation, and revision by the Translation Group. It was than created the pre-final version of the questionnaire, being the areas “function” and “pain” applied to 20 athletes that perform overhead movements and that suffered SLAP lesions in the dominant shoulder and the areas “active compression test and anterior apprehension test” and “motion” were applied to 15 health professionals. Results: During the translation process there were made little modifications in the questionnaire in order to adapt it to Brazilian culture, without changing the semantics and the idiomatic concept originally described. Conclusion: The questionnaire was easily understood by the subjects of the study, being possible to obtain the Brazilian version of the modified Rowe score for overhead athletes that underwent surgical treatment of the SLAP lesion. PMID:27047903

MTO1 mediates tissue specificity of OXPHOS defects via tRNA modification and translation optimization, which can be bypassed by dietary intervention

PubMed Central

Tischner, Christin; Hofer, Annette; Wulff, Veronika; Stepek, Joanna; Dumitru, Iulia; Becker, Lore; Haack, Tobias; Kremer, Laura; Datta, Alexandre N.; Sperl, Wolfgang; Floss, Thomas; Wurst, Wolfgang; Chrzanowska-Lightowlers, Zofia; De Angelis, Martin Hrabe; Klopstock, Thomas; Prokisch, Holger; Wenz, Tina

2015-01-01

Mitochondrial diseases often exhibit tissue-specific pathologies, but this phenomenon is poorly understood. Here we present regulation of mitochondrial translation by the Mitochondrial Translation Optimization Factor 1, MTO1, as a novel player in this scenario. We demonstrate that MTO1 mediates tRNA modification and controls mitochondrial translation rate in a highly tissue-specific manner associated with tissue-specific OXPHOS defects. Activation of mitochondrial proteases, aberrant translation products, as well as defects in OXPHOS complex assembly observed in MTO1 deficient mice further imply that MTO1 impacts translation fidelity. In our mouse model, MTO1-related OXPHOS deficiency can be bypassed by feeding a ketogenic diet. This therapeutic intervention is independent of the MTO1-mediated tRNA modification and involves balancing of mitochondrial and cellular secondary stress responses. Our results thereby establish mammalian MTO1 as a novel factor in the tissue-specific regulation of OXPHOS and fine tuning of mitochondrial translation accuracy. PMID:25552653

Translational Genomics in Low and Middle Income Countries: Opportunities and Challenges

PubMed Central

Tekola-Ayele, Fasil; Rotimi, Charles N.

2015-01-01

Translation of genomic discoveries into patient care is slowly becoming a reality in developed economies around the world. In contrast, low and middle income countries (LMIC) have participated minimally in genomic research for several reasons including lack of coherent national policies, limited number of well-trained genomic scientists, poor research infrastructure, and local economic and cultural challenges. Recent initiatives such as the Human Heredity and Health in Africa (H3Africa), the Qatar Genome Project and the Mexico National Institute of Genomic Medicine (INMEGEN) that aim to address these problems through capacity building and empowerment of local researchers have sparked a paradigm shift. In this short communication, we describe experiences of small-scale medical genetics and translational genomics research programs in LMIC. The lessons drawn from these programs drive home the importance of addressing resource, policy, and socio-cultural dynamics to realize the promise of precision medicine driven by genomic science globally. By echoing lessons from a bench-to-community translational genomics research, we advocate that large-scale genomics research projects can be successfully linked with health care programs. To harness the benefits of genomics-led health care, LMIC governments should begin to develop national genomics policies that will address human and technology capacity development within the context of their national economic and socio-cultural uniqueness. These policies should encourage international collaboration and promote link between the public health program and genomics researchers. Finally, we highlight the potential catalytic roles of the global community to foster translational genomics in LMIC. PMID:26138992

Linguistic validation of translation of the self-assessment goal achievement (saga) questionnaire from English

PubMed Central

2012-01-01

Background A linguistic validation of the Self-Assessment Goal Achievement (SAGA) questionnaire was conducted for 12 European languages, documenting that each translation adequately captures the concepts of the original English-language version of the questionnaire and is readily understood by subjects in the target population. Methods Native-speaking residents of the target countries who reported urinary problems/lower urinary tract problems were asked to review a translation of the SAGA questionnaire, which was harmonized among 12 languages: Danish, Dutch, English (UK), Finnish, French, German, Greek, Icelandic, Italian, Norwegian, Spanish, and Swedish. During a cognitive debriefing interview, participants were asked to identify any words that were difficult to understand and explain in their own words the meaning of each sentence in the questionnaire. The qualitative analysis was conducted by local linguistic validation teams (original translators, back translator, project manager, interviewer, and survey research expert). Results Translations of the SAGA questionnaire from English to 12 European languages were well understood by the participants with an overall comprehension rate across language of 98.9%. In addition, the translations retained the original meaning of the SAGA items and instructions. Comprehension difficulties were identified, and after review by the translation team, minor changes were made to 7 of the 12 translations to improve clarity and comprehension. Conclusions Conceptual, semantic, and cultural equivalence of each translation of the SAGA questionnaire was achieved thus confirming linguistic validation. PMID:22525050

Linguistic validation of translation of the Self-Assessment Goal Achievement (SAGA) questionnaire from English.

PubMed

Piault, Elisabeth; Doshi, Sameepa; Brandt, Barbara A; Angün, Çolpan; Evans, Christopher J; Bergqvist, Agneta; Trocio, Jeffrey

2012-04-23

A linguistic validation of the Self-Assessment Goal Achievement (SAGA) questionnaire was conducted for 12 European languages, documenting that each translation adequately captures the concepts of the original English-language version of the questionnaire and is readily understood by subjects in the target population. Native-speaking residents of the target countries who reported urinary problems/lower urinary tract problems were asked to review a translation of the SAGA questionnaire, which was harmonized among 12 languages: Danish, Dutch, English (UK), Finnish, French, German, Greek, Icelandic, Italian, Norwegian, Spanish, and Swedish. During a cognitive debriefing interview, participants were asked to identify any words that were difficult to understand and explain in their own words the meaning of each sentence in the questionnaire. The qualitative analysis was conducted by local linguistic validation teams (original translators, back translator, project manager, interviewer, and survey research expert). Translations of the SAGA questionnaire from English to 12 European languages were well understood by the participants with an overall comprehension rate across language of 98.9%. In addition, the translations retained the original meaning of the SAGA items and instructions. Comprehension difficulties were identified, and after review by the translation team, minor changes were made to 7 of the 12 translations to improve clarity and comprehension. Conceptual, semantic, and cultural equivalence of each translation of the SAGA questionnaire was achieved thus confirming linguistic validation.

Global Forum 2015 dialogue on "From evidence to policy - thinking outside the box": perspectives to improve evidence uptake and good practices in the African Region.

PubMed

Kirigia, Joses Muthuri; Pannenborg, Charles Ok; Amore, Luis Gabriel Cuervo; Ghannem, Hassen; IJsselmuiden, Carel; Nabyonga-Orem, Juliet

2016-07-18

The Global Forum 2015 panel session dialogue entitled "From evidence to policy - thinking outside the box" was held on 26 August 2015 in the Philippines to debate why evidence was not fully translated into policy and practice and what could be done to increase its uptake. This paper reports the reasons and possible actions for increasing the uptake of evidence, and highlights the actions partners could take to increase the use of evidence in the African Region. The Global Forum 2015 debate attributed African Region's low uptake of evidence to the big gap in incentives and interests between research for health researchers and public health policy-makers; limited appreciation on the side of researchers that public health decisions are based on multiple and complex considerations; perception among users that research evidence is not relevant to local contexts; absence of knowledge translation platforms; sub-optimal collaboration and engagement between industry and research institutions; lack of involvement of civil society organizations; lack of engagement of communities in the research process; failure to engage the media; limited awareness and debate in national and local parliaments on the importance of investing in research and innovation; and dearth of research and innovation parks in the African Region. The actions needed in the Region to increase the uptake of evidence in policy and practice include strengthening NHRS governance; bridging the motivation gap between researchers and health policy-makers; restoring trust between researchers and decision-makers; ensuring close and continuous intellectual intercourse among researchers, ministry of health policy-makers and technocrats during the life course of research projects or programmes; proactive collaboration between academia and industry; regular briefings of civil society, media, relevant parliamentary committees and development partners; development of vibrant knowledge translation platforms; development of action plans for implementing research recommendations, preferably in the context of the Sustainable Development Goals; and encouragement of competition on NHRS strengthening and research output and uptake among the countries using a barometer or scorecard to review their performance at various regional ministerial forums and taking into account the lessons learned from the MDG period.

Differential Subcellular Localization of Leishmania Alba-Domain Proteins throughout the Parasite Development.

PubMed

Dupé, Aurélien; Dumas, Carole; Papadopoulou, Barbara

2015-01-01

Alba-domain proteins are RNA-binding proteins found in archaea and eukaryotes and recently studied in protozoan parasites where they play a role in the regulation of virulence factors and stage-specific proteins. This work describes in silico structural characterization, cellular localization and biochemical analyses of Alba-domain proteins in Leishmania infantum. We show that in contrast to other protozoa, Leishmania have two Alba-domain proteins, LiAlba1 and LiAlba3, representative of the Rpp20- and the Rpp25-like eukaryotic subfamilies, respectively, which share several sequence and structural similarities but also important differences with orthologs in other protozoa, especially in sequences targeted for post-translational modifications. LiAlba1 and LiAlba3 proteins form a complex interacting with other RNA-binding proteins, ribosomal subunits, and translation factors as supported by co-immunoprecipitation and sucrose gradient sedimentation analysis. A higher co-sedimentation of Alba proteins with ribosomal subunits was seen upon conditions of decreased translation, suggesting a role of these proteins in translational repression. The Leishmania Alba-domain proteins display differential cellular localization throughout the parasite development. In the insect promastigote stage, Alba proteins co-localize predominantly to the cytoplasm but they translocate to the nucleolus and the flagellum upon amastigote differentiation in the mammalian host and are found back to the cytoplasm once amastigote differentiation is completed. Heat-shock, a major signal of amastigote differentiation, triggers Alba translocation to the nucleolus and the flagellum. Purification of the Leishmania flagellum confirmed LiAlba3 enrichment in this organelle during amastigote differentiation. Moreover, partial characterization of the Leishmania flagellum proteome of promastigotes and differentiating amastigotes revealed the presence of other RNA-binding proteins, as well as differences in the flagellum composition between these two parasite lifestages. Shuttling of Alba-domain proteins between the cytoplasm and the nucleolus or the flagellum throughout the parasite life cycle suggests that these RNA-binding proteins participate in several distinct regulatory pathways controlling developmental gene expression in Leishmania.

Differential Subcellular Localization of Leishmania Alba-Domain Proteins throughout the Parasite Development

PubMed Central

Dupé, Aurélien; Dumas, Carole; Papadopoulou, Barbara

2015-01-01

Alba-domain proteins are RNA-binding proteins found in archaea and eukaryotes and recently studied in protozoan parasites where they play a role in the regulation of virulence factors and stage-specific proteins. This work describes in silico structural characterization, cellular localization and biochemical analyses of Alba-domain proteins in Leishmania infantum. We show that in contrast to other protozoa, Leishmania have two Alba-domain proteins, LiAlba1 and LiAlba3, representative of the Rpp20- and the Rpp25-like eukaryotic subfamilies, respectively, which share several sequence and structural similarities but also important differences with orthologs in other protozoa, especially in sequences targeted for post-translational modifications. LiAlba1 and LiAlba3 proteins form a complex interacting with other RNA-binding proteins, ribosomal subunits, and translation factors as supported by co-immunoprecipitation and sucrose gradient sedimentation analysis. A higher co-sedimentation of Alba proteins with ribosomal subunits was seen upon conditions of decreased translation, suggesting a role of these proteins in translational repression. The Leishmania Alba-domain proteins display differential cellular localization throughout the parasite development. In the insect promastigote stage, Alba proteins co-localize predominantly to the cytoplasm but they translocate to the nucleolus and the flagellum upon amastigote differentiation in the mammalian host and are found back to the cytoplasm once amastigote differentiation is completed. Heat-shock, a major signal of amastigote differentiation, triggers Alba translocation to the nucleolus and the flagellum. Purification of the Leishmania flagellum confirmed LiAlba3 enrichment in this organelle during amastigote differentiation. Moreover, partial characterization of the Leishmania flagellum proteome of promastigotes and differentiating amastigotes revealed the presence of other RNA-binding proteins, as well as differences in the flagellum composition between these two parasite lifestages. Shuttling of Alba-domain proteins between the cytoplasm and the nucleolus or the flagellum throughout the parasite life cycle suggests that these RNA-binding proteins participate in several distinct regulatory pathways controlling developmental gene expression in Leishmania. PMID:26334886

Sonic Hedgehog Guides Axons via Zipcode Binding Protein 1-Mediated Local Translation.

PubMed

Lepelletier, Léa; Langlois, Sébastien D; Kent, Christopher B; Welshhans, Kristy; Morin, Steves; Bassell, Gary J; Yam, Patricia T; Charron, Frédéric

2017-02-15

Sonic hedgehog (Shh) attracts spinal cord commissural axons toward the floorplate. How Shh elicits changes in the growth cone cytoskeleton that drive growth cone turning is unknown. We find that the turning of rat commissural axons up a Shh gradient requires protein synthesis. In particular, Shh stimulation increases β-actin protein at the growth cone even when the cell bodies have been removed. Therefore, Shh induces the local translation of β-actin at the growth cone. We hypothesized that this requires zipcode binding protein 1 (ZBP1), an mRNA-binding protein that transports β-actin mRNA and releases it for local translation upon phosphorylation. We found that Shh stimulation increases phospho-ZBP1 levels in the growth cone. Disruption of ZBP1 phosphorylation in vitro abolished the turning of commissural axons toward a Shh gradient. Disruption of ZBP1 function in vivo in mouse and chick resulted in commissural axon guidance errors. Therefore, ZBP1 is required for Shh to guide commissural axons. This identifies ZBP1 as a new mediator of noncanonical Shh signaling in axon guidance. SIGNIFICANCE STATEMENT Sonic hedgehog (Shh) guides axons via a noncanonical signaling pathway that is distinct from the canonical Hedgehog signaling pathway that specifies cell fate and morphogenesis. Axon guidance is driven by changes in the growth cone in response to gradients of guidance molecules. Little is known about the molecular mechanism of how Shh orchestrates changes in the growth cone cytoskeleton that are required for growth cone turning. Here, we show that the guidance of axons by Shh requires protein synthesis. Zipcode binding protein 1 (ZBP1) is an mRNA-binding protein that regulates the local translation of proteins, including actin, in the growth cone. We demonstrate that ZBP1 is required for Shh-mediated axon guidance, identifying a new member of the noncanonical Shh signaling pathway. Copyright © 2017 the authors 0270-6474/17/371685-11$15.00/0.

Intra-plastid protein trafficking: how plant cells adapted prokaryotic mechanisms to the eukaryotic condition.

PubMed

Celedon, Jose M; Cline, Kenneth

2013-02-01

Protein trafficking and localization in plastids involve a complex interplay between ancient (prokaryotic) and novel (eukaryotic) translocases and targeting machineries. During evolution, ancient systems acquired new functions and novel translocation machineries were developed to facilitate the correct localization of nuclear encoded proteins targeted to the chloroplast. Because of its post-translational nature, targeting and integration of membrane proteins posed the biggest challenge to the organelle to avoid aggregation in the aqueous compartments. Soluble proteins faced a different kind of problem since some had to be transported across three membranes to reach their destination. Early studies suggested that chloroplasts addressed these issues by adapting ancient-prokaryotic machineries and integrating them with novel-eukaryotic systems, a process called 'conservative sorting'. In the last decade, detailed biochemical, genetic, and structural studies have unraveled the mechanisms of protein targeting and localization in chloroplasts, suggesting a highly integrated scheme where ancient and novel systems collaborate at different stages of the process. In this review we focus on the differences and similarities between chloroplast ancestral translocases and their prokaryotic relatives to highlight known modifications that adapted them to the eukaryotic situation. This article is part of a Special Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids. Copyright © 2012 Elsevier B.V. All rights reserved.

Sub-Cellular Localization and Complex Formation by Aminoacyl-tRNA Synthetases in Cyanobacteria: Evidence for Interaction of Membrane-Anchored ValRS with ATP Synthase.

PubMed

Santamaría-Gómez, Javier; Ochoa de Alda, Jesús A G; Olmedo-Verd, Elvira; Bru-Martínez, Roque; Luque, Ignacio

2016-01-01

tRNAs are charged with cognate amino acids by aminoacyl-tRNA synthetases (aaRSs) and subsequently delivered to the ribosome to be used as substrates for gene translation. Whether aminoacyl-tRNAs are channeled to the ribosome by transit within translational complexes that avoid their diffusion in the cytoplasm is a matter of intense investigation in organisms of the three domains of life. In the cyanobacterium Anabaena sp. PCC 7120, the valyl-tRNA synthetase (ValRS) is anchored to thylakoid membranes by means of the CAAD domain. We have investigated whether in this organism ValRS could act as a hub for the nucleation of a translational complex by attracting other aaRSs to the membranes. Out of the 20 aaRSs, only ValRS was found to localize in thylakoid membranes whereas the other enzymes occupied the soluble portion of the cytoplasm. To investigate the basis for this asymmetric distribution of aaRSs, a global search for proteins interacting with the 20 aaRSs was conducted. The interaction between ValRS and the FoF1 ATP synthase complex here reported is of utmost interest and suggests a functional link between elements of the gene translation and energy production machineries.

Assessment and manifestation of central sensitisation across different chronic pain conditions.

PubMed

Arendt-Nielsen, L; Morlion, B; Perrot, S; Dahan, A; Dickenson, A; Kress, H G; Wells, C; Bouhassira, D; Mohr Drewes, A

2018-02-01

Different neuroplastic processes can occur along the nociceptive pathways and may be important in the transition from acute to chronic pain and for diagnosis and development of optimal management strategies. The neuroplastic processes may result in gain (sensitisation) or loss (desensitisation) of function in relation to the incoming nociceptive signals. Such processes play important roles in chronic pain, and although the clinical manifestations differ across condition processes, they share some common mechanistic features. The fundamental understanding and quantitative assessment of particularly some of the central sensitisation mechanisms can be translated from preclinical studies into the clinic. The clinical perspectives are implementation of such novel information into diagnostics, mechanistic phenotyping, prevention, personalised treatment, and drug development. The aims of this paper are to introduce and discuss (1) some common fundamental central pain mechanisms, (2) how they may translate into the clinical signs and symptoms across different chronic pain conditions, (3) how to evaluate gain and loss of function using quantitative pain assessment tools, and (4) the implications for optimising prevention and management of pain. The chronic pain conditions selected for the paper are neuropathic pain in general, musculoskeletal pain (chronic low back pain and osteoarthritic pain in particular), and visceral pain (irritable bowel syndrome in particular). The translational mechanisms addressed are local and widespread sensitisation, central summation, and descending pain modulation. Central sensitisation is an important manifestation involved in many different chronic pain conditions. Central sensitisation can be different to assess and evaluate as the manifestations vary from pain condition to pain condition. Understanding central sensitisation may promote better profiling and diagnosis of pain patients and development of new regimes for mechanism based therapy. Some of the mechanisms underlying central sensitisation can be translated from animals to humans providing new options in development of therapies and profiling drugs under development. © 2017 European Pain Federation - EFIC®.

Translation and cross-cultural adaptation of a standardized international questionnaire on use of alternative and complementary medicine (I-CAM - Q) for Argentina.

PubMed

Esteban, Santiago; Vázquez Peña, Fernando; Terrasa, Sergio

2016-03-31

The widespread and growing use of alternative and complementary medicine (CAM) worldwide has been thoroughly described. In Argentina the limited information on the use of CAM has been reported between 40 and 55 %. However, the rate of use is extremely variable worldwide. For this purpose the international questionnaire on the use of complementary and alternative medicines (I-CAM - Q), was developed. The implementation of a translated and cross-culturally adapted version of the questionnaire would allow for a reliable and standardized evaluation of the rate of use of CAM in Argentina. It would be a great step towards improving what we know about the healing habits of our population. The forward and back-translation method was used. Four translators were involved. A committee was commissioned to reconcile the different versions. The process of cross-cultural adaptation was made by consulting 17 alternative and complementary medicine experts using the DELPHI method. The retrieved questionnaire was evaluated in 18 patients sampled by convenience (9 men, different educational and self-reported health levels). The interviews consisted of three parts: an initial demographics questionnaire; the administration of the I-CAM-Q and finally the cognitive interview, which included reviewing the questionnaire and reexamining questions that generated doubts during the interview. The comprehension of the questions was also evaluated. As a last step, using the information obtained from the interviews, the final version of the questionnaire was drafted. The questionnaire seems to have been accepted by most patients during the interviews. Conflictive elements that emerged did not seem to have an impact on its administration. The flexibility of the questionnaire allowed to add professionals and practices which contributed to a more accurate local adaptation. Further research should focus on assessing the questionnaire's psychometric performance and validity, which so far has not been done.

Human cytomegalovirus TRS1 protein associates with the 7-methylguanosine mRNA cap and facilitates translation

PubMed Central

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

2015-01-01

Viruses rely on the host translation machinery for the synthesis of viral proteins. Human cells have evolved sensors that recognize viral RNAs and inhibit mRNA translation in order to limit virus replication. Understanding how viruses manipulate the host translation machinery to gain access to ribosomes and disable the antiviral response is therefore a critical aspect of the host:pathogen interface. In this study we used a proteomics approach to identify human cytomegalovirus (HCMV) proteins that might contribute to viral mRNA translation. The HCMV TRS1 protein (pTRS1) associated with the 7-methylguanosine (m7G) mRNA cap, increased the total level of protein synthesis, and co-localized with mRNAs undergoing translation initiation during infection. pTRS1 stimulated translation of a non-viral reporter gene and increased the translation of a reporter containing an HCMV 5’ untranslated region (5’UTR) to a greater extent. The preferential effect of pTRS1 on translation of an mRNA containing a viral 5’UTR required the pTRS1 RNA and PKR binding domains, and was likely the result of PKR inhibition. However pTRS1 also stimulated the total level of protein synthesis and translation directed by an HCMV 5’UTR in cells lacking PKR. Thus our results demonstrate that pTRS1 stimulates translation through both PKR-dependent and PKR-independent mechanisms. PMID:25894605

Quality control procedures for dynamic treatment delivery techniques involving couch motion.

PubMed

Yu, Victoria Y; Fahimian, Benjamin P; Xing, Lei; Hristov, Dimitre H

2014-08-01

In this study, the authors introduce and demonstrate quality control procedures for evaluating the geometric and dosimetric fidelity of dynamic treatment delivery techniques involving treatment couch motion synchronous with gantry and multileaf collimator (MLC). Tests were designed to evaluate positional accuracy, velocity constancy and accuracy for dynamic couch motion under a realistic weight load. A test evaluating the geometric accuracy of the system in delivering treatments over complex dynamic trajectories was also devised. Custom XML scripts that control the Varian TrueBeam™ STx (Serial #3) axes in Developer Mode were written to implement the delivery sequences for the tests. Delivered dose patterns were captured with radiographic film or the electronic portal imaging device. The couch translational accuracy in dynamic treatment mode was 0.01 cm. Rotational accuracy was within 0.3°, with 0.04 cm displacement of the rotational axis. Dose intensity profiles capturing the velocity constancy and accuracy for translations and rotation exhibited standard deviation and maximum deviations below 3%. For complex delivery involving MLC and couch motions, the overall translational accuracy for reproducing programmed patterns was within 0.06 cm. The authors conclude that in Developer Mode, TrueBeam™ is capable of delivering dynamic treatment delivery techniques involving couch motion with good geometric and dosimetric fidelity.

Signal recognition particle assembly in relation to the function of amplified nucleoli of Xenopus oocytes.

PubMed

Sommerville, John; Brumwell, Craig L; Politz, Joan C Ritland; Pederson, Thoru

2005-03-15

The signal recognition particle (SRP) is a ribonucleoprotein machine that controls the translation and intracellular sorting of membrane and secreted proteins. The SRP contains a core RNA subunit with which six proteins are assembled. Recent work in both yeast and mammalian cells has identified the nucleolus as a possible initial site of SRP assembly. In the present study, SRP RNA and protein components were identified in the extrachromosomal, amplified nucleoli of Xenopus laevis oocytes. Fluorescent SRP RNA microinjected into the oocyte nucleus became specifically localized in the nucleoli, and endogenous SRP RNA was also detected in oocyte nucleoli by RNA in situ hybridization. An initial step in the assembly of SRP involves the binding of the SRP19 protein to SRP RNA. When green fluorescent protein (GFP)-tagged SRP19 protein was injected into the oocyte cytoplasm it was imported into the nucleus and became concentrated in the amplified nucleoli. After visiting the amplified nucleoli, GFP-tagged SRP19 protein was detected in the cytoplasm in a ribonucleoprotein complex, having a sedimentation coefficient characteristic of the SRP. These results suggest that the amplified nucleoli of Xenopus oocytes produce maternal stores not only of ribosomes, the classical product of nucleoli, but also of SRP, presumably as a global developmental strategy for stockpiling translational machinery for early embryogenesis.

Post-translational quantitation by SRM/MRM: applications in cardiology.

PubMed

Gianazza, Erica; Banfi, Cristina

2018-06-04

Post-translational modifications (PTMs) have an important role in the regulation of protein function, localization and interaction with other molecules. PTMs apply a dynamic control of proteins both in physiological and pathological conditions. The study of disease-specific PTMs allows identifying potential biomarkers and developing effective drugs. Enrichment techniques combined with high-resolution MS/MS analysis provide attractive results on PTMs characterization. Selected reaction monitoring/multiple reaction monitoring (SRM/MRM) is a powerful targeted assay for the quantitation and validation of PTMs in complex biological samples. Areas covered: The most frequent PTMs are described in terms of biological role and analytical methods commonly used to detect them. The applications of SRM/MRM for the absolute quantitation of PTMs are reported and a specific section is focused on PTMs detection in proteins that are involved in cardiovascular system and heart diseases. Expert commentary: PTMs characterization in relation to disease pathology is still in progress, but targeted proteomics by LC-MS/MS has significantly upgraded the knowledge in the last years. Advances in enrichment strategies and software tools will facilitate the interpretation of high PTMs complexity. Promising studies confirm the great potentiality of SRM/MRM to study PTMs in cardiovascular field and PTMomics could be very useful in a clinical perspective.

Science, Politics, and Communication: The Case of Community Water Fluoridation in the US.

PubMed

Allukian, Myron; Carter-Pokras, Olivia D; Gooch, Barbara F; Horowitz, Alice M; Iida, Hiroko; Jacob, Matt; Kleinman, Dushanka V; Kumar, Jayanth; Maas, William R; Pollick, Howard; Rozier, R Gary

2018-06-01

Community water fluoridation (CWF) and its effect in reducing the burden of dental caries (tooth decay) is considered one of the 10 public health achievements in the 20th century. In the U.S., three-quarters (74.4%) of people on community water supplies have optimally fluoridated water, and each year approximately 90 communities actively consider starting or discontinuing CWF. CWF exists within the policy environment and includes actions taken by local community councils, health and water boards, and groups; state legislatures and health departments; national regulatory and science agencies; independent science entities; and professional and nonprofit organizations. Epidemiologists have been in the forefront of CWF. Experience with the past 70 years reveals that the coming decades will bring additional questions, recommendations, and challenges for CWF. The continued involvement of epidemiologists as part of multidisciplinary teams is needed in research, surveillance, peer review of studies, assessment of systematic review findings, and in the translation and communication of science findings to audiences with limited science/health literacy. This chapter's purpose is to 1) examine how epidemiologic evidence regarding CWF has been translated into practice and policy, 2) examine how recommendations for and challenges to CWF have affected epidemiologic research and community decision-making, and 3) identify lessons learned for epidemiologists. Copyright © 2017 Elsevier Inc. All rights reserved.

The other side of the broken window: a methodology that translates building permits into an ecometric of investment by community members.

PubMed

O'Brien, Daniel Tumminelli; Montgomery, Barrett W

2015-03-01

Much research has focused on physical disorder in urban neighborhoods as evidence that the community does not maintain local norms and spaces. Little attention has been paid to the opposite: indicators of proactive investment in the neighborhood's upkeep. This manuscript presents a methodology that translates a database of approved building permits into an ecometric of investment by community members, establishing basic content, criteria for reliability, and construct validity. A database from Boston, MA contained 150,493 permits spanning 2.5 years, each record including the property to be modified, permit type, and date issued. Investment was operationalized as the proportion of properties in a census block group that underwent an addition or renovation, excluding larger developments involving the demolition or construction of a building. The reliability analysis found that robust measures could be generated every 6 months, and that longitudinal analysis could differentiate between trajectories across neighborhoods. The validity analysis supported two hypotheses: investment was best predicted by homeownership and median income; and maintained an independent relationship with measures of physical disorder despite controlling for demographics, implying that it captures the other end of a spectrum of neighborhood maintenance. Possible uses for the measure in research and policy are discussed.

The enactment of knowledge translation: a study of the Collaborations for Leadership in Applied Health Research and Care initiative within the English National Health Service.

PubMed

D'Andreta, Daniela; Scarbrough, Harry; Evans, Sarah

2013-10-01

We contribute to existing knowledge translation (KT) literature by developing the notion of 'enactment' and illustrate this through an interpretative, comparative case-study analysis of three Collaborations for Leadership in Applied Health Research and Care (CLAHRC) initiatives. We argue for a focus on the way in which the CLAHRC model has been 'enacted' as central to the different KT challenges and capabilities encountered. A comparative, mixed method study created a typology of enactments (Classical, Home-grown and Imported) using qualitative analysis and social network analysis. We identify systematic differences in the enactment of the CLAHRC model. The sources of these different enactments are subsequently related to variation in formative interpretations and leadership styles, the implementation of different governance structures, and the relative epistemic differences between the professional groups involved. Enactment concerns the creative agency of individuals and groups in constituting a particular context for their work through their local interpretation of a particular KT model. Our theory of enactment goes beyond highlighting variation between CLAHRCs, to explore the mechanisms that influence the way a particular model is interpreted and acted upon. We thus encourage less focus on conceptual models and more on the formative role played by leaders of KT initiatives.

The translational landscape of Arabidopsis mitochondria.

PubMed

Planchard, Noelya; Bertin, Pierre; Quadrado, Martine; Dargel-Graffin, Céline; Hatin, Isabelle; Namy, Olivier; Mireau, Hakim

2018-06-05

Messenger RNA translation is a complex process that is still poorly understood in eukaryotic organelles like mitochondria. Growing evidence indicates though that mitochondrial translation differs from its bacterial counterpart in many key aspects. In this analysis, we have used ribosome profiling technology to generate a genome-wide snapshot view of mitochondrial translation in Arabidopsis. We show that, unlike in humans, most Arabidopsis mitochondrial ribosome footprints measure 27 and 28 bases. We also reveal that respiratory subunits encoding mRNAs show much higher ribosome association than other mitochondrial mRNAs, implying that they are translated at higher levels. Homogenous ribosome densities were generally detected within each respiratory complex except for complex V, where higher ribosome coverage corroborated with higher requirements for specific subunits. In complex I respiratory mutants, a reorganization of mitochondrial mRNAs ribosome association was detected involving increased ribosome densities for certain ribosomal protein encoding transcripts and a reduction in translation of a few complex V mRNAs. Taken together, our observations reveal that plant mitochondrial translation is a dynamic process and that translational control is important for gene expression in plant mitochondria. This study paves the way for future advances in the understanding translation in higher plant mitochondria.

Unpacking knowledge translation in participatory research: a micro-level study.

PubMed

Lillehagen, Ida; Heggen, Kristin; Engebretsen, Eivind

2016-10-01

Funding bodies, policy makers, researchers and clinicians are seeking strategies to increase the translation of knowledge between research and practice. Participatory research encompasses a range of approaches for clinicians' involvement in research in the hope of increasing the relevance and usability of research. Our aim was to explore how knowledge is translated and integrated in participants' presentations and negotiations about knowledge. Twelve collaboration meetings were observed, and discussions between researchers and clinicians were recorded. The material was examined using the following analytical terms: knowledge object, knowledge form, knowledge position and knowledge tasks. We identified a recurring rhetorical pattern in translational processes that we call 'relevance testing': a strategy by which the participants attempt to create coherence and identify relevance across different contexts. The limitation of this translational strategy was a tendency to reinforce a 'two-communities' logic: re-establishing the separated worlds and rationales between clinicians and researchers. The 'translational work' that unfolds during discussions remains implicit. It may be that participants are unable to explicitly address and identify the knowledge translation processes because they lack necessary conceptual tools. Our results contribute to increased awareness about translational processes and provide a language through which barriers to translation can be addressed. © The Author(s) 2016.

Insights on the evolution of metabolic networks of unicellular translationally biased organisms from transcriptomic data and sequence analysis.

PubMed

Carbone, Alessandra; Madden, Richard

2005-10-01

Codon bias is related to metabolic functions in translationally biased organisms, and two facts are argued about. First, genes with high codon bias describe in meaningful ways the metabolic characteristics of the organism; important metabolic pathways corresponding to crucial characteristics of the lifestyle of an organism, such as photosynthesis, nitrification, anaerobic versus aerobic respiration, sulfate reduction, methanogenesis, and others, happen to involve especially biased genes. Second, gene transcriptional levels of sets of experiments representing a significant variation of biological conditions strikingly confirm, in the case of Saccharomyces cerevisiae, that metabolic preferences are detectable by purely statistical analysis: the high metabolic activity of yeast during fermentation is encoded in the high bias of enzymes involved in the associated pathways, suggesting that this genome was affected by a strong evolutionary pressure that favored a predominantly fermentative metabolism of yeast in the wild. The ensemble of metabolic pathways involving enzymes with high codon bias is rather well defined and remains consistent across many species, even those that have not been considered as translationally biased, such as Helicobacter pylori, for instance, reveal some weak form of translational bias for this genome. We provide numerical evidence, supported by experimental data, of these facts and conclude that the metabolic networks of translationally biased genomes, observable today as projections of eons of evolutionary pressure, can be analyzed numerically and predictions of the role of specific pathways during evolution can be derived. The new concepts of Comparative Pathway Index, used to compare organisms with respect to their metabolic networks, and Evolutionary Pathway Index, used to detect evolutionarily meaningful bias in the genetic code from transcriptional data, are introduced.

Proteomic snapshot of the EGF-induced ubiquitin network

PubMed Central

Argenzio, Elisabetta; Bange, Tanja; Oldrini, Barbara; Bianchi, Fabrizio; Peesari, Raghunath; Mari, Sara; Di Fiore, Pier Paolo; Mann, Matthias; Polo, Simona

2011-01-01

The activity, localization and fate of many cellular proteins are regulated through ubiquitination, a process whereby one or more ubiquitin (Ub) monomers or chains are covalently attached to target proteins. While Ub-conjugated and Ub-associated proteomes have been described, we lack a high-resolution picture of the dynamics of ubiquitination in response to signaling. In this study, we describe the epidermal growth factor (EGF)-regulated Ubiproteome, as obtained by two complementary purification strategies coupled to quantitative proteomics. Our results unveil the complex impact of growth factor signaling on Ub-based intracellular networks to levels that extend well beyond what might have been expected. In addition to endocytic proteins, the EGF-regulated Ubiproteome includes a large number of signaling proteins, ubiquitinating and deubiquitinating enzymes, transporters and proteins involved in translation and transcription. The Ub-based signaling network appears to intersect both housekeeping and regulatory circuitries of cellular physiology. Finally, as proof of principle of the biological relevance of the EGF-Ubiproteome, we demonstrated that EphA2 is a novel, downstream ubiquitinated target of epidermal growth factor receptor (EGFR), critically involved in EGFR biological responses. PMID:21245847

Proteome analysis of yeast response to various nutrient limitations

PubMed Central

Kolkman, Annemieke; Daran-Lapujade, Pascale; Fullaondo, Asier; Olsthoorn, Maurien M A; Pronk, Jack T; Slijper, Monique; Heck, Albert J R

2006-01-01

We compared the response of Saccharomyces cerevisiae to carbon (glucose) and nitrogen (ammonia) limitation in chemostat cultivation at the proteome level. Protein levels were differentially quantified using unlabeled and 15N metabolically labeled yeast cultures. A total of 928 proteins covering a wide range of isoelectric points, molecular weights and subcellular localizations were identified. Stringent statistical analysis identified 51 proteins upregulated in response to glucose limitation and 51 upregulated in response to ammonia limitation. Under glucose limitation, typical glucose-repressed genes encoding proteins involved in alternative carbon source utilization, fatty acids β-oxidation and oxidative phosphorylation displayed an increased protein level. Proteins upregulated in response to nitrogen limitation were mostly involved in scavenging of alternative nitrogen sources and protein degradation. Comparison of transcript and protein levels clearly showed that upregulation in response to glucose limitation was mainly transcriptionally controlled, whereas upregulation in response to nitrogen limitation was essentially controlled at the post-transcriptional level by increased translational efficiency and/or decreased protein degradation. These observations underline the need for multilevel analysis in yeast systems biology. PMID:16738570

Nuclear factors involved in mitochondrial translation cause a subgroup of combined respiratory chain deficiency.

PubMed

Kemp, John P; Smith, Paul M; Pyle, Angela; Neeve, Vivienne C M; Tuppen, Helen A L; Schara, Ulrike; Talim, Beril; Topaloglu, Haluk; Holinski-Feder, Elke; Abicht, Angela; Czermin, Birgit; Lochmüller, Hanns; McFarland, Robert; Chinnery, Patrick F; Chrzanowska-Lightowlers, Zofia M A; Lightowlers, Robert N; Taylor, Robert W; Horvath, Rita

2011-01-01

Mutations in several mitochondrial DNA and nuclear genes involved in mitochondrial protein synthesis have recently been reported in combined respiratory chain deficiency, indicating a generalized defect in mitochondrial translation. However, the number of patients with pathogenic mutations is small, implying that nuclear defects of mitochondrial translation are either underdiagnosed or intrauterine lethal. No comprehensive studies have been reported on large cohorts of patients with combined respiratory chain deficiency addressing the role of nuclear genes affecting mitochondrial protein synthesis to date. We investigated a cohort of 52 patients with combined respiratory chain deficiency without causative mitochondrial DNA mutations, rearrangements or depletion, to determine whether a defect in mitochondrial translation defines the pathomechanism of their clinical disease. We followed a combined approach of sequencing known nuclear genes involved in mitochondrial protein synthesis (EFG1, EFTu, EFTs, MRPS16, TRMU), as well as performing in vitro functional studies in 22 patient cell lines. The majority of our patients were children (<15 years), with an early onset of symptoms <1 year of age (65%). The most frequent clinical presentation was mitochondrial encephalomyopathy (63%); however, a number of patients showed cardiomyopathy (33%), isolated myopathy (15%) or hepatopathy (13%). Genomic sequencing revealed compound heterozygous mutations in the mitochondrial transfer ribonucleic acid modifying factor (TRMU) in a single patient only, presenting with early onset, reversible liver disease. No pathogenic mutation was detected in any of the remaining 51 patients in the other genes analysed. In vivo labelling of mitochondrial polypeptides in 22 patient cell lines showed overall (three patients) or selective (four patients) defects of mitochondrial translation. Immunoblotting for mitochondrial proteins revealed decreased steady state levels of proteins in some patients, but normal or increased levels in others, indicating a possible compensatory mechanism. In summary, candidate gene sequencing in this group of patients has a very low detection rate (1/52), although in vivo labelling of mitochondrial translation in 22 patient cell lines indicate that a nuclear defect affecting mitochondrial protein synthesis is responsible for about one-third of combined respiratory chain deficiencies (7/22). In the remaining patients, the impaired respiratory chain activity is most likely the consequence of several different events downstream of mitochondrial translation. Clinical classification of patients with biochemical analysis, genetic testing and, more importantly, in vivo labelling and immunoblotting of mitochondrial proteins show incoherent results, but a systematic review of these data in more patients may reveal underlying mechanisms, and facilitate the identification of novel factors involved in combined respiratory chain deficiency.

Transdisciplinary translational behavioral (TDTB) research: opportunities, barriers, and innovations.

PubMed

Czajkowski, Susan M; Lynch, Minda R; Hall, Kara L; Stipelman, Brooke A; Haverkos, Lynne; Perl, Harold; Scott, Marcia S; Shirley, Mariela C

2016-03-01

The translation of basic behavioral science discoveries into practical strategies represents a promising approach to developing more effective preventive interventions to improve health. Since translational research inevitably involves making use of diverse perspectives from multiple disciplines, it is best conducted as a transdisciplinary enterprise. In this paper, we discuss current strategies used by NIH to support transdisciplinary translational behavioral (TDTB) research, summarize successful efforts, and highlight challenges encountered in conducting such work (ranging from conceptual to organizational to methodological). Using examples from NIH-funded projects we illustrate the potential benefits of, and barriers to, pursuing this type of research and discuss next steps and potential future directions for NIH-supported TDTB research.

Using Problem-Based Case Studies to Learn about Knowledge Translation Interventions: An Inside Perspective

ERIC Educational Resources Information Center

Bhogal, Sanjit K.; Murray, Mary Ann; McLeod, Katherine M.; Bergen, Anne; Bath, Brenna; Menon, Anita; Kho, Michelle E.; Stacey, Dawn

2011-01-01

Knowledge translation (KT) interventions can facilitate the successful implementation of best practices by engaging and actively involving various stakeholders in the change process. However, for novices, the design of KT interventions can be overwhelming. In this article, we describe our experience as participants in a problem-based case study on…

Studies on Sam68 a cell factor involved in the life cycle of foot-and-mouth disease virus

USDA-ARS?s Scientific Manuscript database

As with other RNA viruses, Foot-and-Mouth Disease Virus (FMDV) recruits various host cell factors to assist in translation and replication of the virus genome. While FMDV translation has been thoroughly investigated, much remains unknown regarding replication of the positive-sense RNA genome. In th...

A Proposed Model of Self-Generated Analogical Reasoning for the Concept of Translation in Protein Synthesis

ERIC Educational Resources Information Center

Salih, Maria

2008-01-01

This paper explored and described the analogical reasoning occurring in the minds of different science achievement groups for the concept of translation in protein synthesis. "What is the process of self-generated analogical reasoning?", "What types of matching was involved?" and "What are the consequences of the matching…

Reduce, Reuse, Recycle: An ESL Textbook/Workbook [In Four Volumes]: (1) Teaching Guide; (2) Edition A. Key Vocabulary Words Translated into 6 Languages: Hmong, Laotian, Korean, Cambodian, Vietnamese, Chinese; (3) Edition B. Key Vocabulary Words Translated into 6 Languages: Spanish, Somali, Russian, Farsi, Bosnian, Arabic; (4) Edition C. Key Vocabulary Words Translated in 6 Languages: Spanish, Russian, Bosnian, Somali, Vietnamese, Hmong.

ERIC Educational Resources Information Center

LaRue, Charles

Each of these three separately-published textbook/workbook editions on the topic of recycling presents key vocabulary words relating to this topic for English as a Second Language students in six languages. These books are designed to increase students' understanding of what the most typical local recycling rules are, why complying with them is…

"Keeping our mission, changing our system": translation and organizational change in natural foods co-ops.

PubMed

Haedicke, Michael A

2012-01-01

Institutional theory has played a central role in the study of organizations for over half a century, but it often overlooks the actions of the people who bring organizations to life. This article advances an inhabited approach to institutional analysis that foregrounds the creativity of organizational members. It argues that people use local cultures to translate and respond to institutional pressures. The article analyzes qualitative data from countercultural co-op stores that have been pushed to conform to mainstream forms of business organization by a competitive market and demonstrates that translation explains why outcomes that institutional theory would not predict have come to pass.

Unilateral dampening of Bmp activity by nodal generates cardiac left-right asymmetry.

PubMed

Veerkamp, Justus; Rudolph, Franziska; Cseresnyes, Zoltan; Priller, Florian; Otten, Cécile; Renz, Marc; Schaefer, Liliana; Abdelilah-Seyfried, Salim

2013-03-25

Signaling by Nodal and Bmp is essential for cardiac laterality. How activities of these pathways translate into left-right asymmetric organ morphogenesis is largely unknown. We show that, in zebrafish, Nodal locally reduces Bmp activity on the left side of the cardiac field. This effect is mediated by the extracellular matrix enzyme Hyaluronan synthase 2, expression of which is induced by Nodal. Unilateral reduction of Bmp signaling results in lower expression of nonmuscle myosin II and higher cell motility on the left, driving asymmetric displacement of the entire cardiac field. In silico modeling shows that left-right differences in cell motility are sufficient to induce a robust, directional migration of cardiac tissue. Thus, the mechanism underlying the formation of cardiac left-right asymmetry involves Nodal modulating an antimotogenic Bmp activity. Copyright © 2013 Elsevier Inc. All rights reserved.

Frontal eye field, where art thou? Anatomy, function, and non-invasive manipulation of frontal regions involved in eye movements and associated cognitive operations

PubMed Central

Vernet, Marine; Quentin, Romain; Chanes, Lorena; Mitsumasu, Andres; Valero-Cabré, Antoni

2014-01-01

The planning, control and execution of eye movements in 3D space relies on a distributed system of cortical and subcortical brain regions. Within this network, the Eye Fields have been described in animals as cortical regions in which electrical stimulation is able to trigger eye movements and influence their latency or accuracy. This review focuses on the Frontal Eye Field (FEF) a “hub” region located in Humans in the vicinity of the pre-central sulcus and the dorsal-most portion of the superior frontal sulcus. The straightforward localization of the FEF through electrical stimulation in animals is difficult to translate to the healthy human brain, particularly with non-invasive neuroimaging techniques. Hence, in the first part of this review, we describe attempts made to characterize the anatomical localization of this area in the human brain. The outcome of functional Magnetic Resonance Imaging (fMRI), Magneto-encephalography (MEG) and particularly, non-invasive mapping methods such a Transcranial Magnetic Stimulation (TMS) are described and the variability of FEF localization across individuals and mapping techniques are discussed. In the second part of this review, we will address the role of the FEF. We explore its involvement both in the physiology of fixation, saccade, pursuit, and vergence movements and in associated cognitive processes such as attentional orienting, visual awareness and perceptual modulation. Finally in the third part, we review recent evidence suggesting the high level of malleability and plasticity of these regions and associated networks to non-invasive stimulation. The exploratory, diagnostic, and therapeutic interest of such interventions for the modulation and improvement of perception in 3D space are discussed. PMID:25202241

A modified Delphi translation strategy and challenges of International Classification for Nursing Practice (ICNP®).

PubMed

Hou, I-Ching; Chang, Polun; Chan, Hui-Ya; Dykes, Patricia C

2013-05-01

Standardized terminology is an important infrastructure component of the electronic health record. ICNP(®) is a systemic coding system that can support the development of nursing information systems. Translation of the standardized terminology preferred terms into local terms is an important first step in the translation process. The purpose of this case report is to describe the translation strategy used and challenges faced in translating ICNP(®) Version 2 preferred terms from English to traditional Chinese. A modified Delphi strategy using forward translation and expert consensus was conducted to facilitate semantic and cultural translation and validation of the ICNP(®) and to make the process generalizable. A nursing informatics expert completed the initial forward translation. Five nursing experts with rich clinical and academic experiences joined this process and validated the initial translation. The nursing experts' consensus was then used to finalize the traditional Chinese terms. A total of 1863 preferred terms from the ICNP(®) Version 2 were translated from English into traditional Chinese. Majority agreement from two or more nursing experts was achieved for 98.3% (n=1832) of the preferred term translations. Less than 2% (n=31) of terms had no majority agreement. Translation challenges include the following: (1) changes in code structure of preferred terms from the ICNP(®) β2 version to Verson 2, (2) inability to identify resources to complete the translation that fully met ICNP recommendations for terminology translators, (3) ambiguous preferred term descriptions, and (4) ambiguous preferred term names. Most of the ICNP(®) Version 2 preferred terms were translated from English into traditional Chinese with majority consensus. For the terms without consensus, we recommend that all synonyms be included in the ICNP(®) translation. In countries like Taiwan where nursing education occurs in English, it is recommended that English terms are displayed along with the translated official language to help nurses to interpret and use the terminology correctly. Crown Copyright © 2012. Published by Elsevier Ireland Ltd. All rights reserved.

A Systematic Translation and Cultural Adaptation Process for Three-Factor Eating Questionnaire (TFEQ-R21).

PubMed

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

2013-10-01

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

Poly(ADP-Ribosyl)ation of hnRNP A1 Protein Controls Translational Repression in Drosophila

PubMed Central

Ji, Yingbiao

2016-01-01

Poly(ADP-ribosyl)ation of heterogeneous nuclear ribonucleoproteins (hnRNPs) regulates the posttranscriptional fate of RNA during development. Drosophila hnRNP A1, Hrp38, is required for germ line stem cell maintenance and oocyte localization. The mRNA targets regulated by Hrp38 are mostly unknown. We identified 428 Hrp38-associated gene transcripts in the fly ovary, including mRNA of the translational repressor Nanos. We found that Hrp38 binds to the 3′ untranslated region (UTR) of Nanos mRNA, which contains a translation control element. We have demonstrated that translation of the luciferase reporter bearing the Nanos 3′ UTR is enhanced by dsRNA-mediated Hrp38 knockdown as well as by mutating potential Hrp38-binding sites. Our data show that poly(ADP-ribosyl)ation inhibits Hrp38 binding to the Nanos 3′ UTR, increasing the translation in vivo and in vitro. hrp38 and Parg null mutants showed an increased ectopic Nanos translation early in the embryo. We conclude that Hrp38 represses Nanos translation, whereas its poly(ADP-ribosyl)ation relieves the repression effect, allowing restricted Nanos expression in the posterior germ plasm during oogenesis and early embryogenesis. PMID:27402862

The molecular mechanisms of plant plasma membrane intrinsic proteins trafficking and stress response.

PubMed

Wang, Xing; Zhang, Ji-long; Feng, Xiu-xiu; Li, Hong-jie; Zhang, Gen-fa

2017-04-20

Plasma membrane intrinsic proteins (PIPs) are plant channel proteins located on the plasma membrane. PIPs transfer water, CO 2 and small uncharged solutes through the plasma membrane. PIPs have high selectivity to substrates, suggestive of a central role in maintaining cellular water balance. The expression, activity and localization of PIPs are regulated at the transcriptional and post-translational levels, and also affected by environmental factors. Numerous studies indicate that the expression patterns and localizations of PIPs can change in response to abiotic stresses. In this review, we summarize the mechanisms of PIP trafficking, transcriptional and post-translational regulations, and abiotic stress responses. Moreover, we also discuss the current research trends and future directions on PIPs.

Translational research: understanding the continuum from bench to bedside.

PubMed

Drolet, Brian C; Lorenzi, Nancy M

2011-01-01

The process of translating basic scientific discoveries to clinical applications, and ultimately to public health improvements, has emerged as an important, but difficult, objective in biomedical research. The process is best described as a "translation continuum" because various resources and actions are involved in this progression of knowledge, which advances discoveries from the bench to the bedside. The current model of this continuum focuses primarily on translational research, which is merely one component of the overall translation process. This approach is ineffective. A revised model to address the entire continuum would provide a methodology to identify and describe all translational activities (eg, implementation, adoption translational research, etc) as well their place within the continuum. This manuscript reviews and synthesizes the literature to provide an overview of the current terminology and model for translation. A modification of the existing model is proposed to create a framework called the Biomedical Research Translation Continuum, which defines the translation process and describes the progression of knowledge from laboratory to health gains. This framework clarifies translation for readers who have not followed the evolving and complicated models currently described. Authors and researchers may use the continuum to understand and describe their research better as well as the translational activities within a conceptual framework. Additionally, the framework may increase the advancement of knowledge by refining discussions of translation and allowing more precise identification of barriers to progress. Copyright © 2011 Mosby, Inc. All rights reserved.

Developing rural community health risk assessments for climate change: a Tasmanian pilot study.

PubMed

Bell, Erica J; Turner, Paul; Meinke, Holger; Holbrook, Neil J

2015-01-01

This article examines the development and pilot implementation of an approach to support local community decision-makers to plan health adaptation responses to climate change. The approach involves health and wellbeing risk assessment supported through the use of an electronic tool. While climate change is a major foreseeable public health threat, the extent to which health services are prepared for, or able to adequately respond to, climate change impact-related risks remains unclear. Building health decision-support mechanisms in order to involve and empower local stakeholders to help create the basis for agreement on these adaptive actions is an important first step. The primary research question was 'What can be learned from pilot implementation of a community health and well-being risk assessment (CHWRA) information technology-based tool designed to support understanding of, and decision-making on, local community challenges and opportunities associated with health risks posed by climate change? The article examines the complexity of climate change science to adaptation translational processes, with reference to existing research literature on community development. This is done in the context of addressing human health risks for rural and remote communities in Tasmania, Australia. This process is further examined through the pilot implementation of an electronic tool designed to support the translation of physically based climate change impact information into community-level assessments of health risks and adaptation priorities. The procedural and technical nature of the CHWRA tool is described, and the implications of the data gathered from stakeholder workshops held at three rural Tasmanian local government sites are considered and discussed. Bushfire, depression and waterborne diseases were identified by community stakeholders as being potentially 'catastrophic' health effects 'likely' to 'almost certain' to occur at one or more Tasmanian rural sites - based on an Intergovernmental Panel on Climate Change style of assessment. Consensus statements from stakeholders also suggested concern with health sector adaptation capacity and community resilience, and what community stakeholders defined as 'last straw' climate effects in already stressed communities. Preventative action and community engagement were also seen as important, especially with regard to managing the ways that climate change can multiply socioeconomic and health outcome inequality. Above all, stakeholder responses emphasised the importance of an applied, complexity-oriented understanding of how climate and climate change impacts affect local communities and local services to compromise the overall quality of human health in these communities. Complex community-level assessments about climate change and related health risks and responses can be captured electronically in ways that offer potentially actionable information about priorities for health sector adaptation, as a first step in planning. What is valuable about these community judgements is the creation of shared values and commitments. Future iteration of the IT tool could include decision-support modules to support best practice health sector adaptation scenarios, providing participants with opportunities to develop their know-how about health sector adaptation to climate change. If managed carefully, such tools could work within a balanced portfolio of measures to help reduce the rising health burden from climate change.

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

Code of Federal Regulations, 2011 CFR

2011-10-01

... locally originated visual and/or aural messages limited to emergency warnings of imminent danger, to local... following modes of service: (1) For the retransmission of programming of a TV broadcast or DTV broadcast... the origination of programming and commercial matter as defined in § 74.701(l). (3) Whenever operating...

Technologies for Controlled, Local Delivery of siRNA

PubMed Central

Sarett, Samantha M.; Nelson, Christopher E.; Duvall, Craig L.

2015-01-01

The discovery of RNAi in the late 1990s unlocked a new realm of therapeutic possibilities by enabling potent and specific silencing of theoretically any desired genetic target. Better elucidation of the mechanism of action, the impact of chemical modifications that stabilize and reduce nonspecific effects of siRNA molecules, and the key design considerations for effective delivery systems has spurred progress toward developing clinically-successful siRNA therapies. A logical aim for initial siRNA translation is local therapies, as delivering siRNA directly to its site of action helps to ensure that a sufficient dose reaches the target tissue, lessens the potential for off-target side effects, and circumvents the substantial systemic delivery barriers. While topical siRNA delivery has progressed into numerous clinical trials, an enormous opportunity also exists to develop sustained-release, local delivery systems that enable both spatial and temporal control of gene silencing. This review focuses on material platforms that establish both localized and controlled gene silencing, with emphasis on the systems that show most promise for clinical translation. PMID:26476177

The Yeast Eukaryotic Translation Initiation Factor 2B Translation Initiation Complex Interacts with the Fatty Acid Synthesis Enzyme YBR159W and Endoplasmic Reticulum Membranes

PubMed Central

Browne, Christopher M.; Samir, Parimal; Fites, J. Scott; Villarreal, Seth A.

2013-01-01

Using affinity purifications coupled with mass spectrometry and yeast two-hybrid assays, we show the Saccharomyces cerevisiae translation initiation factor complex eukaryotic translation initiation factor 2B (eIF2B) and the very-long-chain fatty acid (VLCFA) synthesis keto-reductase enzyme YBR159W physically interact. The data show that the interaction is specifically between YBR159W and eIF2B and not between other members of the translation initiation or VLCFA pathways. A ybr159wΔ null strain has a slow-growth phenotype and a reduced translation rate but a normal GCN4 response to amino acid starvation. Although YBR159W localizes to the endoplasmic reticulum membrane, subcellular fractionation experiments show that a fraction of eIF2B cofractionates with lipid membranes in a YBR159W-independent manner. We show that a ybr159wΔ yeast strain and other strains with null mutations in the VLCFA pathway cause eIF2B to appear as numerous foci throughout the cytoplasm. PMID:23263984

From technical jargon to plain English for application.

PubMed Central

Lindsley, O R

1991-01-01

These examples of translating technical jargon into plain English application words, acronyms, letter codes, and simple tests were necessary as we developed Precision Teaching. I hope our experience is useful to others facing the problems of applying technology in practical settings. At the least, our experience should give you an idea of the work and time involved in making your own translations. Above all, be patient. Accurate plain English translations do not come easily. They cannot be made at your desk. A search often takes years to produce one new accurate plain English translation. Rapid publication pressures, journal editorial policies, and investments in materials, books, and computer programs all combine to hamper these translations. It's possible that you will find some of our plain English equivalents useful in your own applied behavior analysis applications. PMID:1752836

Burden of illness and research investments in translational sciences for pharmaceuticals in metastatic cancers

PubMed Central

Wang, Wei-Jhih; Robertson, Justin C; Basu, Anirban

2017-01-01

Aim: To explore whether investments in translational sciences for six metastatic cancers follow idiosyncratic returns to those investments rather than levels of burden of illness (BI). Methods: Associate the number of translational clinical trials in the USA involving oncolytic drugs approved during 2008–2013 and the level (in 2008) and changes (2002–2008 and 2008–2014) in cancer-specific years of life lost. Results: Investments in trials were positively associated only with contemporary changes in BI (2008–2014). The relationship was stronger for government-sponsored comparative-effectiveness trials than for industry. Conclusion: Translational research investments follow anticipated changes to BI levels. Systematic quantification of these expected returns from specific investments can help guide investment decisions in translational health sciences and generate productive dialogue across stakeholders. PMID:27934549

A murine retrovirus co-Opts YB-1, a translational regulator and stress granule-associated protein, to facilitate virus assembly.

PubMed

Bann, Darrin V; Beyer, Andrea R; Parent, Leslie J

2014-04-01

The Gag protein of the murine retrovirus mouse mammary tumor virus (MMTV) orchestrates the assembly of immature virus particles in the cytoplasm which are subsequently transported to the plasma membrane for release from the cell. The morphogenetic pathway of MMTV assembly is similar to that of Saccharomyces cerevisiae retrotransposons Ty1 and Ty3, which assemble virus-like particles (VLPs) in intracytoplasmic ribonucleoprotein (RNP) complexes. Assembly of Ty1 and Ty3 VLPs depends upon cellular mRNA processing factors, prompting us to examine whether MMTV utilizes a similar set of host proteins to facilitate viral capsid assembly. Our data revealed that MMTV Gag colocalized with YB-1, a translational regulator found in stress granules and P bodies, in intracytoplasmic foci. The association of MMTV Gag and YB-1 in cytoplasmic granules was not disrupted by cycloheximide treatment, suggesting that these sites were not typical stress granules. However, the association of MMTV Gag and YB-1 was RNA dependent, and an MMTV RNA reporter construct colocalized with Gag and YB-1 in cytoplasmic RNP complexes. Knockdown of YB-1 resulted in a significant decrease in MMTV particle production, indicating that YB-1 plays a role in MMTV capsid formation. Analysis by live-cell imaging with fluorescence recovery after photobleaching (FRAP) revealed that the population of Gag proteins localized within YB-1 complexes was relatively immobile, suggesting that Gag forms stable complexes in association with YB-1. Together, our data imply that the formation of intracytoplasmic Gag-RNA complexes is facilitated by YB-1, which promotes MMTV virus assembly. Cellular mRNA processing factors regulate the posttranscriptional fates of mRNAs, affecting localization and utilization of mRNAs under normal conditions and in response to stress. RNA viruses such as retroviruses interact with cellular mRNA processing factors that accumulate in ribonucleoprotein complexes known as P bodies and stress granules. This report shows for the first time that mouse mammary tumor virus (MMTV), a mammalian retrovirus that assembles intracytoplasmic virus particles, commandeers the cellular factor YB-1, a key regulator of translation involved in the cellular stress response. YB-1 is essential for the efficient production of MMTV particles, a process directed by the viral Gag protein. We found that Gag and YB-1 localize together in cytoplasmic granules. Functional studies of Gag/YB-1 granules suggest that they may be sites where virus particles assemble. These studies provide significant insights into the interplay between mRNA processing factors and retroviruses.

Enabling international adoption of LOINC through translation

PubMed Central

Vreeman, Daniel J.; Chiaravalloti, Maria Teresa; Hook, John; McDonald, Clement J.

2012-01-01

Interoperable health information exchange depends on adoption of terminology standards, but international use of such standards can be challenging because of language differences between local concept names and the standard terminology. To address this important barrier, we describe the evolution of an efficient process for constructing translations of LOINC terms names, the foreign language functions in RELMA, and the current state of translations in LOINC. We also present the development of the Italian translation to illustrate how translation is enabling adoption in international contexts. We built a tool that finds the unique list of LOINC Parts that make up a given set of LOINC terms. This list enables translation of smaller pieces like the core component “hepatitis c virus” separately from all the suffixes that could appear with it, such “Ab.IgG”, “DNA”, and “RNA”. We built another tool that generates a translation of a full LOINC name from all of these atomic pieces. As of version 2.36 (June 2011), LOINC terms have been translated into 9 languages from 15 linguistic variants other than its native English. The five largest linguistic variants have all used the Part-based translation mechanism. However, even with efficient tools and processes, translation of standard terminology is a complex undertaking. Two of the prominent linguistic challenges that translators have faced include: the approach to handling acronyms and abbreviations, and the differences in linguistic syntax (e.g. word order) between languages. LOINC’s open and customizable approach has enabled many different groups to create translations that met their needs and matched their resources. Distributing the standard and its many language translations at no cost worldwide accelerates LOINC adoption globally, and is an important enabler of interoperable health information exchange PMID:22285984

Melanocortin 3 Receptor Has a 5′ Exon That Directs Translation of Apically Localized Protein From the Second In-Frame ATG

PubMed Central

Park, Jeenah; Sharma, Neeraj

2014-01-01

Melanocortin-3 receptor (MC3R) is a canonical MSH receptor that plays an essential role in energy homeostasis. Variants in MC3R have been implicated in obesity in humans and mice. However, interpretation of the functional consequences of these variants is challenging because the translational start site of MC3R is unclear. Using 5′ rapid amplification of cDNA ends, we discovered a novel upstream exon that extends the length of the 5′ untranslated region (UTR) in MC3R without changing the open-reading frame. The full-length 5′ UTR directs utilization of an evolutionarily conserved second in-frame ATG as the primary translation start site. MC3R synthesized from the second ATG is localized to apical membranes of polarized Madin-Darby canine kidney cells, consistent with its function as a cell surface mediator of melanocortin signaling. Expression of MC3R causes relocalization of melanocortin receptor accessory protein 2, an accessory factor for melanocortin-2 receptor, to the apical membrane, coincident with the location of MC3R. In contrast, protein synthesized from MC3R cDNAs lacking the 5′ UTR displayed diffuse cytosolic distribution and has no effect on the distribution of melanocortin receptor accessory protein 2. Our findings demonstrate that a previously unannotated 5′ exon directs translation of MC3R protein that localizes to apical membranes of polarized cells. Together, our work provides insight on the structure of human MC3R and reveals a new pathway for regulation of energy metabolism. PMID:25051171

Ejection injury to the spine in small aviators: sled tests of manikins vs. post mortem specimens.

PubMed

Salzar, Robert S; Bolton, James R; Crandall, Jeff R; Paskoff, Glenn R; Shender, Barry S

2009-07-01

This study presents the results of seven aerospace manikin and three post mortem human surrogate (PMHS) horizontal deceleration sled tests. The objective of this study was to establish a body of baseline data that examines the ability of small (fifth percentile) manikins to predict whole-body kinematics associated with aircraft ejection, and whether currently available head and neck injury criteria are applicable in these situations. Subjects were exposed to a short-duration local z-axis sled pulse while horizontally seated and restrained in an ejection seat. Test subjects included instrumented fifth percentile female and male manikins, and two small (163.8 cm, 48.3 kg; 143.5 cm, 48.6 kg) female and one small (166.2 cm, 54.3 kg) male PMHS. The anterior (local x-axis) translations of the PMHS heads were less than those observed in the manikin tests, but the local z-axis translations of the PMHS heads were greater than those of the manikins. Z-axis translations of the manikins' T1 were generally similar to those of the PMHS T1, but the anterior x-axis translations of T1 were greater in the PMHS. The neck injury criterion (Nij) tended to under-predict observed injury (primarily ruptures of the posterior ligaments at C4-5, T2-3), and the Beam Criterion (BC) tended to over-predict observed injury for small occupants. The USN/USAF neck injury criteria (NIC) performed best in predicting the observed injuries. Present manikin designs do not predict the kinematics of PMHS in ejection tests. Further refinement of existing injury criteria is required to accurately predict location and severity of ejection-induced injuries.

Translation, cultural adaption, and test-retest reliability of Chinese versions of the Edinburgh Handedness Inventory and Waterloo Footedness Questionnaire.

PubMed

Yang, Nan; Waddington, Gordon; Adams, Roger; Han, Jia

2018-05-01

Quantitative assessments of handedness and footedness are often required in studies of human cognition and behaviour, yet no reliable Chinese versions of commonly used handedness and footedness questionnaires are available. Accordingly, the objective of the present study was to translate the Edinburgh Handedness Inventory (EHI) and the Waterloo Footedness Questionnaire-Revised (WFQ-R) into Mandarin Chinese and to evaluate the reliability and validity of these translated versions in healthy Chinese people. In the first stage of the study, Chinese versions of the EHI and WFQ-R were produced from a process of translation, back translation and examination, with necessary cultural adaptations. The second stage involved determining the reliability and validity of the translated EHI and WFQ-R for the Chinese population. One hundred and ten Chinese participants were tested online, and the results showed that the Cronbach's alpha coefficient of internal consistency was 0.877 for the translated EHI and 0.855 for the translated WFQ-R. Another 170 Chinese participants were tested and re-tested after a 30-day interval. The intra-class correlation coefficients showed high reliability, 0.898 for the translated EHI and 0.869 for the translated WFQ-R. This preliminary validation study found the translated versions to be reliable and valid tools for assessing handedness and footedness in this population.

Neuropathological biomarker candidates in brain tumors: key issues for translational efficiency.

PubMed

Hainfellner, J A; Heinzl, H

2010-01-01

Brain tumors comprise a large spectrum of rare malignancies in children and adults that are often associated with severe neurological symptoms and fatal outcome. Neuropathological tumor typing provides both prognostic and predictive tissue information which is the basis for optimal postoperative patient management and therapy. Molecular biomarkers may extend and refine prognostic and predictive information in a brain tumor case, providing more individualized and optimized treatment options. In the recent past a few neuropathological brain tumor biomarkers have translated smoothly into clinical use whereas many candidates show protracted translation. We investigated the causes of protracted translation of candidate brain tumor biomarkers. Considering the research environment from personal, social and systemic perspectives we identified eight determinants of translational success: methodology, funding, statistics, organization, phases of research, cooperation, self-reflection, and scientific progeny. Smoothly translating biomarkers are associated with low degrees of translational complexity whereas biomarkers with protracted translation are associated with high degrees. Key issues for translational efficiency of neuropathological brain tumor biomarker research seem to be related to (i) the strict orientation to the mission of medical research, that is the improval of medical practice as primordial purpose of research, (ii) definition of research priorities according to clinical needs, and (iii) absorption of translational complexities by means of operatively beneficial standards. To this end, concrete actions should comprise adequate scientific education of young investigators, and shaping of integrative diagnostics and therapy research both on the local level and the level of influential international brain tumor research platforms.

Human Perception of Ambiguous Inertial Motion Cues

NASA Technical Reports Server (NTRS)

Zhang, Guan-Lu

2010-01-01

Human daily activities on Earth involve motions that elicit both tilt and translation components of the head (i.e. gazing and locomotion). With otolith cues alone, tilt and translation can be ambiguous since both motions can potentially displace the otolithic membrane by the same magnitude and direction. Transitions between gravity environments (i.e. Earth, microgravity and lunar) have demonstrated to alter the functions of the vestibular system and exacerbate the ambiguity between tilt and translational motion cues. Symptoms of motion sickness and spatial disorientation can impair human performances during critical mission phases. Specifically, Space Shuttle landing records show that particular cases of tilt-translation illusions have impaired the performance of seasoned commanders. This sensorimotor condition is one of many operational risks that may have dire implications on future human space exploration missions. The neural strategy with which the human central nervous system distinguishes ambiguous inertial motion cues remains the subject of intense research. A prevailing theory in the neuroscience field proposes that the human brain is able to formulate a neural internal model of ambiguous motion cues such that tilt and translation components can be perceptually decomposed in order to elicit the appropriate bodily response. The present work uses this theory, known as the GIF resolution hypothesis, as the framework for experimental hypothesis. Specifically, two novel motion paradigms are employed to validate the neural capacity of ambiguous inertial motion decomposition in ground-based human subjects. The experimental setup involves the Tilt-Translation Sled at Neuroscience Laboratory of NASA JSC. This two degree-of-freedom motion system is able to tilt subjects in the pitch plane and translate the subject along the fore-aft axis. Perception data will be gathered through subject verbal reports. Preliminary analysis of perceptual data does not indicate that the GIF resolution hypothesis is completely valid for non-rotational periodic motions. Additionally, human perception of translation is impaired without visual or spatial reference. The performance of ground-base subjects in estimating tilt after brief training is comparable with that of crewmembers without training.

Defective cellular trafficking of the bone morphogenetic protein receptor type II by mutations underlying familial pulmonary arterial hypertension.

PubMed

John, Anne; Kizhakkedath, Praseetha; Al-Gazali, Lihadh; Ali, Bassam R

2015-04-25

Familial pulmonary arterial hypertension (FPAH) is a relatively rare but fatal disorder characterized by elevated arterial pressure caused by abnormal proliferation of endothelial cells of the arteries, which eventually leads to heart failure and death. FPAH is inherited as an autosomal dominant trait and is caused by heterozygous mutations in the BMPR2 gene encoding the bone morphogenetic protein type II receptor (BMPR2). BMPR2 belongs to the TGF β/BMP super-family of receptors involved in a signal transduction cascade via the SMAD signaling pathway. The BMPR2 polypeptide is composed of 1038 amino acids and consists of a ligand binding domain, a kinase domain and a cytoplasmic tail. To investigate the cellular and functional consequence of BMPR2 mutations, C-terminally FLAG-tagged constructs of eighteen pathogenic BMPR2 missense mutants were generated by site directed mutagenesis and expressed in HeLa and HEK-293T cell lines. The subcellular localizations of the mutant proteins were investigated using immunostaining and confocal microscopy. Post-translational modifications of the proteins were analyzed by Endoglycosidase H deglycosylation assay. Our results indicated that mutations in the ligand binding domain affecting highly conserved cysteine residues resulted in retention of the mutant proteins in the endoplasmic reticulum (ER), as evident from their co-localization with the ER resident protein calnexin. The kinase domain mutants showed both ER and plasma membrane (PM) distributions, while the cytoplasmic tail domain variants were localized exclusively to the PM. The subcellular localizations of the mutants were further confirmed by their characteristic glycosylation profiles. In conclusion, our results indicate that ER quality control (ERQC) is involved in the pathological mechanism of several BMPR2 receptor missense mutations causing FPAH, which can be explored as a potential therapeutic target in the future. Copyright © 2015. Published by Elsevier B.V.

Activation of writing-specific brain regions when reading Chinese as a second language. Effects of training modality and transfer to novel characters.

PubMed

Lagarrigue, Aurélie; Longcamp, Marieke; Anton, Jean Luc; Nazarian, Bruno; Prévot, Laurent; Velay, Jean-Luc; Cao, Fan; Frenck-Mestre, Cheryl

2017-03-01

We examined the implication of training modality on the cortical representation of Chinese words in adult second language learners of Chinese. In particular, we tested the implication of the neural substrates of writing in a reading task. The brain network sustaining finger writing was defined neuroanatomically based on an independent functional localizer. We examined the brain activations elicited by Chinese words learned via writing vs. pronunciation, and by novel untrained words, within regions of interest (ROIs) defined according to the position of the activation peaks in the localizer, and at the whole brain level. We revealed activations in the reading task that overlapped with several parts of the finger writing network. In addition, our results provide evidence that the neural substrates of writing are differentially involved in reading depending on the stored knowledge for words, as revealed by the fine-grained response of several regions including the left superior parietal lobule and left precentral gyrus / superior frontal sulcus to the experimental manipulations. Training modality and the linguistic properties of the characters also impacted the response of the left mid-fusiform gyrus, confirming its involvement as the brain region where linguistic, visual and sensorimotor information converge during orthographic processing. At the behavioral level, global handwriting quality during the training sessions was positively correlated to the final translation performance. Our results demonstrate substantial overlap in the neural substrates of reading and writing, and indicate that some regions sustaining handwriting are differentially involved in reading depending on the type of knowledge associated with words. Copyright © 2017 Elsevier Ltd. All rights reserved.

Social Priorities as Data

NASA Astrophysics Data System (ADS)

Grubert, E.

2015-12-01

Decision makers' responses to local risks and expected changes to a community from circumstances like natural hazards, human developments, and demographic changes can greatly affect social and environmental outcomes in a community. Translating physical data based in disciplines like engineering and geosciences into positive outcomes for communities can be challenging and often results in conflict that appears to pit "science" against "the public." Scientists can be reluctant to offer recommendations for action based on their work, often (and often correctly) noting that their role is not to make value judgments for a community - particularly for a community that is not their own. Conversely, decision makers can be frustrated by the lack of guidance they receive to help translate data into effective and acceptable action. The solution posed by this submission, given the goal of co-production of knowledge by scientists and decision makers to foster better community outcomes, is to involve the community directly by integrating social scientific methods that address decision making and community engagement to the scientist-decision maker interaction. Specifically, the missing dataset in many scientist-decision maker interactions is the nature of community priorities. Using scientifically valid methods to rigorously collect and characterize community priorities to help recommend tradeoffs between different outcomes indicated by the work of physical and natural scientists can bridge the gap between science and action by involving the community in the process. This submission presents early work on US preferences for different types of social and environmental outcomes designed to integrate directly with engineering and physical science frameworks like Life Cycle Assessment and Environmental Impact Statements. Cardinal preference data are based on surveys of US adults using tools like the Analytical Hierarchy Process, budget allocation, and ranking.

microRNA-122 target sites in the hepatitis C virus RNA NS5B coding region and 3' untranslated region: function in replication and influence of RNA secondary structure.

PubMed

Gerresheim, Gesche K; Dünnes, Nadia; Nieder-Röhrmann, Anika; Shalamova, Lyudmila A; Fricke, Markus; Hofacker, Ivo; Höner Zu Siederdissen, Christian; Marz, Manja; Niepmann, Michael

2017-02-01

We have analyzed the binding of the liver-specific microRNA-122 (miR-122) to three conserved target sites of hepatitis C virus (HCV) RNA, two in the non-structural protein 5B (NS5B) coding region and one in the 3' untranslated region (3'UTR). miR-122 binding efficiency strongly depends on target site accessibility under conditions when the range of flanking sequences available for the formation of local RNA secondary structures changes. Our results indicate that the particular sequence feature that contributes most to the correlation between target site accessibility and binding strength varies between different target sites. This suggests that the dynamics of miRNA/Ago2 binding not only depends on the target site itself but also on flanking sequence context to a considerable extent, in particular in a small viral genome in which strong selection constraints act on coding sequence and overlapping cis-signals and model the accessibility of cis-signals. In full-length genomes, single and combination mutations in the miR-122 target sites reveal that site 5B.2 is positively involved in regulating overall genome replication efficiency, whereas mutation of site 5B.3 showed a weaker effect. Mutation of the 3'UTR site and double or triple mutants showed no significant overall effect on genome replication, whereas in a translation reporter RNA, the 3'UTR target site inhibits translation directed by the HCV 5'UTR. Thus, the miR-122 target sites in the 3'-region of the HCV genome are involved in a complex interplay in regulating different steps of the HCV replication cycle.

Detection Thresholds for Rotation and Translation Gains in 360° Video-Based Telepresence Systems.

PubMed

Zhang, Jingxin; Langbehn, Eike; Krupke, Dennis; Katzakis, Nicholas; Steinicke, Frank

2018-04-01

Telepresence systems have the potential to overcome limits and distance constraints of the real-world by enabling people to remotely visit and interact with each other. However, current telepresence systems usually lack natural ways of supporting interaction and exploration of remote environments (REs). In particular, single webcams for capturing the RE provide only a limited illusion of spatial presence, and movement control of mobile platforms in today's telepresence systems are often restricted to simple interaction devices. One of the main challenges of telepresence systems is to allow users to explore a RE in an immersive, intuitive and natural way, e.g., by real walking in the user's local environment (LE), and thus controlling motions of the robot platform in the RE. However, the LE in which the user's motions are tracked usually provides a much smaller interaction space than the RE. In this context, redirected walking (RDW) is a very suitable approach to solve this problem. However, so far there is no previous work, which explored if and how RDW can be used in video-based 360° telepresence systems. In this article, we conducted two psychophysical experiments in which we have quantified how much humans can be unknowingly redirected on virtual paths in the RE, which are different from the physical paths that they actually walk in the LE. Experiment 1 introduces a discrimination task between local and remote translations, and in Experiment 2 we analyzed the discrimination between local and remote rotations. In Experiment 1 participants performed straightforward translations in the LE that were mapped to straightforward translations in the RE shown as 360° videos, which were manipulated by different gains. Then, participants had to estimate if the remotely perceived translation was faster or slower than the actual physically performed translation. Similarly, in Experiment 2 participants performed rotations in the LE that were mapped to the virtual rotations in a 360° video-based RE to which we applied different gains. Again, participants had to estimate whether the remotely perceived rotation was smaller or larger than the actual physically performed rotation. Our results show that participants are not able to reliably discriminate the difference between physical motion in the LE and the virtual motion from the 360° video RE when virtual translations are down-scaled by 5.8% and up-scaled by 9.7%, and virtual rotations are about 12.3% less or 9.2% more than the corresponding physical rotations in the LE.

Acronyms and effacement: traditional medical practitioners (TMP) in international health development.

PubMed

Pigg, S L

1995-07-01

International development draws on a globalized vision of 'traditional medicine' when constructing country-specific programs that use local practitioners to further health objectives. This paper looks at the tension between this mobile notion of 'the traditional' and the local social ground. Categories such as traditional birth attendant (TBA) and traditional medical practitioner (TMP) emerge from a process of translation that links local realities to development in specific ways. Examination of training programs for two kinds of 'indigenous practitioners' in Nepal--birth attendants and shamans--shows that various Nepalese specialists are constructed as TBAs and TMPs in a discursive process that emphasizes some differences while eliding others. The acronyms TBA and TMP encapsulate numerous acts of translation through which diverse local practices are subsumed into an overarching development framework. The many layers of this process include: how 'traditional healers' are understood in international health policy; how, in national planning, these conceptions are made to fit with existing Nepalese healers; and how research on 'local ideas and practices' becomes authoritative knowledge about 'traditions', which then, in turn, form a basis for the planning and implementation of training programs. The conceptual categories evident in development discourse on 'traditional healers' take concrete, practical form in the design and implementation of training programs. At the same time development attempts to create programs tailored to local conditions, it generates frameworks that efface or exclude much of what local people think, believe and do. Although training programs for TBAs and TMPs have been advocated as a way to 'bridge the gap' between the realities of local peoples lives and development institutions' visions, it is important to realize that, at another level, development discourse produces the very problems it aims to solve. The case study of training programs for TMPs and TBAs in Nepal shows how the universalizing principles inherent in development discourse systematically dismantle and decontextualize different socio-cultural realities in the course of taking them into account. Development institutions are thus positioned as authoritative mediators of all local worlds. Translation is a social act that, through the management of the circulation of discourses, reinforces the particular global-local power relations of international development. Relations of power, as well as states of health, are at stake in health development encounters. This paper questions whether health development can achieve its humanitarian goals within the existing conceptual framework.

Trans‐acting translational regulatory RNA binding proteins

PubMed Central

Harvey, Robert F.; Smith, Tom S.; Mulroney, Thomas; Queiroz, Rayner M. L.; Pizzinga, Mariavittoria; Dezi, Veronica; Villenueva, Eneko; Ramakrishna, Manasa

2018-01-01

The canonical molecular machinery required for global mRNA translation and its control has been well defined, with distinct sets of proteins involved in the processes of translation initiation, elongation and termination. Additionally, noncanonical, trans‐acting regulatory RNA‐binding proteins (RBPs) are necessary to provide mRNA‐specific translation, and these interact with 5′ and 3′ untranslated regions and coding regions of mRNA to regulate ribosome recruitment and transit. Recently it has also been demonstrated that trans‐acting ribosomal proteins direct the translation of specific mRNAs. Importantly, it has been shown that subsets of RBPs often work in concert, forming distinct regulatory complexes upon different cellular perturbation, creating an RBP combinatorial code, which through the translation of specific subsets of mRNAs, dictate cell fate. With the development of new methodologies, a plethora of novel RNA binding proteins have recently been identified, although the function of many of these proteins within mRNA translation is unknown. In this review we will discuss these methodologies and their shortcomings when applied to the study of translation, which need to be addressed to enable a better understanding of trans‐acting translational regulatory proteins. Moreover, we discuss the protein domains that are responsible for RNA binding as well as the RNA motifs to which they bind, and the role of trans‐acting ribosomal proteins in directing the translation of specific mRNAs. This article is categorized under: 1RNA Interactions with Proteins and Other Molecules > RNA–Protein Complexes2Translation > Translation Regulation3Translation > Translation Mechanisms PMID:29341429

Trans-acting translational regulatory RNA binding proteins.

PubMed

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

2018-05-01

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

Is Working Memory Involved in the Transcribing and Editing of Texts?

ERIC Educational Resources Information Center

Hayes, John R.; Chenoweth, N. Ann

2006-01-01

Generally, researchers agree that verbal working memory plays an important role in cognitive processes involved in writing. However, there is disagreement about which cognitive processes make use of working memory. Kellogg has proposed that verbal working memory is involved in translating but not in editing or producing (i.e., typing) text. In…

Automatic detection and recognition of signs from natural scenes.

PubMed

Chen, Xilin; Yang, Jie; Zhang, Jing; Waibel, Alex

2004-01-01

In this paper, we present an approach to automatic detection and recognition of signs from natural scenes, and its application to a sign translation task. The proposed approach embeds multiresolution and multiscale edge detection, adaptive searching, color analysis, and affine rectification in a hierarchical framework for sign detection, with different emphases at each phase to handle the text in different sizes, orientations, color distributions and backgrounds. We use affine rectification to recover deformation of the text regions caused by an inappropriate camera view angle. The procedure can significantly improve text detection rate and optical character recognition (OCR) accuracy. Instead of using binary information for OCR, we extract features from an intensity image directly. We propose a local intensity normalization method to effectively handle lighting variations, followed by a Gabor transform to obtain local features, and finally a linear discriminant analysis (LDA) method for feature selection. We have applied the approach in developing a Chinese sign translation system, which can automatically detect and recognize Chinese signs as input from a camera, and translate the recognized text into English.

Maternal RNA regulates Aurora C kinase during mouse oocyte maturation in a translation-independent fashion.

PubMed

Balboula, Ahmed Z; Blengini, Cecilia S; Gentilello, Amanda S; Takahashi, Masashi; Schindler, Karen

2017-06-01

During oocyte meiotic maturation, Aurora kinase C (AURKC) is required to accomplish many critical functions including destabilizing erroneous kinetochore-microtubule (K-MT)attachments and regulating bipolar spindle assembly. How localized activity of AURKC is regulated in mammalian oocytes, however, is not fully understood. Female gametes from many species, including mouse, contain stores of maternal transcripts that are required for downstream developmental events. We show here that depletion of maternal RNA in mouse oocytes resulted in impaired meiotic progression, increased incidence of chromosome misalignment and abnormal spindle formation at metaphase I (Met I), and cytokinesis defects. Importantly, depletion of maternal RNA perturbed the localization and activity of AURKC within the chromosomal passenger complex (CPC). These perturbations were not observed when translation was inhibited by cycloheximide (CHX) treatment. These results demonstrate a translation-independent function of maternal RNA to regulate AURKC-CPC function in mouse oocytes. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Translational Genomics in Low- and Middle-Income Countries: Opportunities and Challenges.

PubMed

Tekola-Ayele, Fasil; Rotimi, Charles N

2015-01-01

Translation of genomic discoveries into patient care is slowly becoming a reality in developed economies around the world. In contrast, low- and middle-income countries (LMIC) have participated minimally in genomic research for several reasons including the lack of coherent national policies, the limited number of well-trained genomic scientists, poor research infrastructure, and local economic and cultural challenges. Recent initiatives such as the Human Heredity and Health in Africa (H3Africa), the Qatar Genome Project, and the Mexico National Institute of Genomic Medicine (INMEGEN) that aim to address these problems through capacity building and empowerment of local researchers have sparked a paradigm shift. In this short communication, we describe experiences of small-scale medical genetics and translational genomic research programs in LMIC. The lessons drawn from these programs drive home the importance of addressing resource, policy, and sociocultural dynamics to realize the promise of precision medicine driven by genomic science globally. By echoing lessons from a bench-to-community translational genomic research, we advocate that large-scale genomic research projects can be successfully linked with health care programs. To harness the benefits of genomics-led health care, LMIC governments should begin to develop national genomics policies that will address human and technology capacity development within the context of their national economic and sociocultural uniqueness. These policies should encourage international collaboration and promote the link between the public health program and genomics researchers. Finally, we highlight the potential catalytic roles of the global community to foster translational genomics in LMIC. © 2015 S. Karger AG, Basel.

A review of translational medicine. The future paradigm: how can we connect the orthopedic dots better?

PubMed

Mediouni, Mohamed; R Schlatterer, Daniel; Madry, Henning; Cucchiarini, Magali; Rai, Balwant

2017-11-01

Patients with complex medical and surgical problems often travel great distances to prestigious university medical centers in search of solutions and in some cases for nothing more than a diagnosis of their condition. Translational medicine (TM) is an emerging method and process of facilitating medical advances efficiently from the scientist to the clinician. Most established clinicians and those in training know very little about this new discipline. The purpose of this article is to illustrate TM in varied scientific, medical and surgical fields. Anecdotal events in medicine and orthopaedics based upon a practicing orthopaedic surgeon's training and clinical experience are presented. TM is rapidly assuming a greater presence in the medical community. The National Institute of Health (NIH) recognizes this discipline and has funded TM projects. Numerous institutions in Europe and the USA offer advanced degrees in TM. Finally there is a European Society for Translational Medicine (EUTMS), an International Society for Translational Medicine, and an Academy of Translational Medical Professionals (ATMP). The examples of TM presented in this article support the argument for the formation of more TM networks on the local and regional levels. The need for increased participation of researchers and clinicians requires further study to identify the economic and social impact of TM. The examples of TM presented in this article support the argument for the formation of more TM networks on the local and regional levels. Financial constraints for TM can be overcome by pooling government, academic, private, and industry resources in an organized fashion with oversight by a lead TM researcher.

The letter, the dictionary and the laboratory: translating chemistry and mineralogy in eighteenth-century France.

PubMed

Bret, Patrice

2016-04-01

Eighteenth-century scientific translation was not just a linguistic or intellectual affair. It included numerous material aspects requiring a social organization to marshal the indispensable human and non-human actors. Paratexts and actors' correspondences provide a good observatory to get information about aspects such as shipments and routes, processes of translation and language acquisition (dictionaries, grammars and other helpful materials, such as translated works in both languages), texts acquisition and dissemination (including author's additions and corrections, oral presentations in academic meetings and announcements of forthcoming translations). The nature of scientific translation changed in France during the second half of the eighteenth century. Beside solitary translators, it also happened to become a collective enterprise, dedicated to providing abridgements (Collection académique, 1755-79) or enriching the learned journals with full translations of the most recent foreign texts (Guyton de Morveau's 'Bureau de traduction de Dijon', devoted to chemistry and mineralogy, 1781-90). That new trend clearly had a decisive influence on the nature of the scientific press itself. A way to set up science as a social activity in the provincial capital of Dijon, translation required a local and international network for acquiring the linguistic and scientific expertise, along with the original texts, as quickly as possible. Laboratory results and mineralogical observations were used to compare material facts (colour, odour, shape of crystals, etc.) with those described in the original text. By providing a double kind of validation - with both the experiments and the translations - the laboratory thus happened to play a major role in translation.

Poliovirus infection induces the co-localization of cellular protein SRp20 with TIA-1, a cytoplasmic stress granule protein

PubMed Central

Fitzgerald, Kerry D.; Semler, Bert L.

2013-01-01

Different types of environmental stress cause mammalian cells to form cytoplasmic foci, termed stress granules, which contain mRNPs that are translationally silenced. These foci are transient and dynamic, and contain components of the cellular translation machinery as well as certain mRNAs and RNA binding proteins. Stress granules are known to be induced by conditions such as hypoxia, nutrient deprivation, and oxidative stress, and a number of cellular factors have been identified that are commonly associated with these foci. More recently it was discovered that poliovirus infection also induces the formation of stress granules, although these cytoplasmic foci appear to be somewhat compositionally unique. Work described here examined the punctate pattern of SRp20 (a host cell mRNA splicing protein) localization in the cytoplasm of poliovirus-infected cells, demonstrating the partial co-localization of SRp20 with the stress granule marker protein TIA-1. We determined that SRp20 does not co-localize with TIA-1, however, under conditions of oxidative stress, indicating that the close association of these two proteins during poliovirus infection is not representative of a general response to cellular stress. We confirmed that the expression of a dominant negative version of TIA-1 (TIA-1-PRD) results in the dissociation of stress granules. Finally, we demonstrated that expression of wild type TIA-1 or dominant negative TIA-1-PRD in cells during poliovirus infection does not dramatically affect viral translation. Taken together, these studies provide a new example of the unique cytoplasmic foci that form during poliovirus infection. PMID:23830997

Dissemination and implementation of comparative effectiveness evidence: key informant interviews with Clinical and Translational Science Award institutions.

PubMed

Morrato, Elaine H; Concannon, Thomas W; Meissner, Paul; Shah, Nilay D; Turner, Barbara J

2013-03-01

To identify ongoing practices and opportunities for improving national comparative effectiveness research (CER) translation through dissemination and implementation (D&I) via NIH-funded Clinical and Translational Science Award (CTSA) institutions. Key informant interviews were conducted with 18 CTSA grantees sampled to represent a range of D&I efforts. The institutional representatives endorsed fostering CER translation nationally via the CTSA Consortium. However, five themes emerged from the interviews as barriers to CER D&I: lack of institutional awareness, insufficient capacity, lack of established D&I methods, confusion among stakeholders about what CER actually is and limited funding opportunities. Interviewees offered two key recommendations to improve CER translation: development of a centralized clearing house to facilitate the diffusion of CER D&I resources and methods across CTSA institutions; and formalization of the national CTSA network to leverage existing community engagement relationships and resources for the purpose of adapting and disseminating robust CER evidence locally with providers, patients and healthcare systems.

Dissemination and implementation of comparative effectiveness evidence: key informant interviews with Clinical and Translational Science Award institutions

PubMed Central

Morrato, Elaine H; Concannon, Thomas W; Meissner, Paul; Shah, Nilay D; Turner, Barbara J

2014-01-01

Aim To identify ongoing practices and opportunities for improving national comparative effectiveness research (CER) translation through dissemination and implementation (D&I) via NIH-funded Clinical and Translational Science Award (CTSA) institutions. Materials & methods Key informant interviews were conducted with 18 CTSA grantees sampled to represent a range of D&I efforts. Results & conclusions The institutional representatives endorsed fostering CER translation nationally via the CTSA Consortium. However, five themes emerged from the interviews as barriers to CER D&I: lack of institutional awareness, insufficient capacity, lack of established D&I methods, confusion among stakeholders about what CER actually is and limited funding opportunities. Interviewees offered two key recommendations to improve CER translation: development of a centralized clearing house to facilitate the diffusion of CER D&I resources and methods across CTSA institutions; and formalization of the national CTSA network to leverage existing community engagement relationships and resources for the purpose of adapting and disseminating robust CER evidence locally with providers, patients and healthcare systems. PMID:24236560

It's Complicated: Negotiating Between Traditional Research and Community-Based Participatory Research in a Translational Study.

PubMed

Hopkins, Allison L; Moore-Monroy, Martha; Wilkinson-Lee, Ada M; Nuño, Velia Leybas; Armenta, Alexandra; Lopez, Elvia; Vanzzini, Susan; Garcia, Francisco A

2016-01-01

The Interactive Systems Framework (ISF), a guide for translational research, encourages the balancing of traditional research and community-based participatory research (CBPR) approaches. This paper focuses on the challenges, solutions, and lessons learned in applying the ISF to our translational research project. A community-campus partnership translated evidence-based screening guidelines on sexually transmitted infections (STIs) and depression into culturally relevant educational materials. Community health workers (CHWs) disseminated the information through a cross-over design to Hispanic women in Pima County, Arizona. Challenges, solutions, and lessons learned were identified throughout this process. We identified challenges in the areas of research design, and in the ISF systems of prevention synthesis and translation, prevention support, and prevention delivery. We successfully negotiate solutions between the scientific and local community that resulted in acceptable compromises for both groups. The model presented by the ISF is difficult to achieve, but we offer concrete solutions to community members and scientists to move toward that ideal.

Translation and Adaptation of Five English Language Self-Report Health Measures to South Indian Kannada Language

PubMed Central

Thammaiah, Spoorthi; Manchaiah, Vinaya; Easwar, Vijayalakshmi; Krishna, Rajalakshmi

2016-01-01

The objective of this study was to translate and adapt five English self-report health measures to a South Indian language Kannada. Currently, no systematically developed questionnaires assessing hearing rehabilitation outcomes are available for clinical or research use in Kannada. The questionnaires included for translation and adaptation were the hearing handicap questionnaire, the international outcome inventory - hearing aids, the self-assessment of communication, the participation scale, and the assessment of quality of life – 4 dimensions. The questionnaires were translated and adapted using the American Association of Orthopedic Surgeons (AAOS) guidelines. The five stages followed in the study included: i) forward translation; ii) common translation synthesis; iii) backward translation; iv) expert committee review; v) pre-final testing. In this paper, in addition to a description of the process, we also highlight practical issues faced while adopting the procedure with an aim to help readers better understand the intricacies involved in such processes. This can be helpful to researchers and clinicians who are keen to adapt standard self-report questionnaires from other languages to their native language. PMID:27588165

Translational errors as an early event in prion conversion.

PubMed

Hatin, I; Bidou, L; Cullin, C; Rousset, J P

2001-01-01

A prion is an infectious, altered form of a cellular protein which can self-propagate and affect normal phenotype. Prion conversion has been observed for mammalian and yeast proteins but molecular mechanisms that trigger this process remain unclear. Up to now, only post-translational models have been explored. In this work, we tested the hypothesis that co-translational events may be implicated in the conformation changes of the Ure2p protein of Saccharomyces cerevisiae. This protein can adopt a prion conformation leading to an [URE3] phenotype which can be easily assessed and quantified. We analyzed the effect of two antibiotics, known to affect translation, on [URE3] conversion frequency. For cells treated with G418 we observed a parallel increase of translational errors rate and frequency of [URE3] conversion. By contrast, cycloheximide which was not found to affect translational fidelity, has no influence on the induction of [URE3] phenotype. These results raise the possibility that the mechanism of prion conversion might not only involve alternative structures of strictly identical molecules but also aberrant proteins resulting from translational errors.

A Spatio-Temporal Understanding of Growth Regulation during the Salt Stress Response in Arabidopsis[W

PubMed Central

Geng, Yu; Wu, Rui; Wee, Choon Wei; Xie, Fei; Wei, Xueliang; Chan, Penny Mei Yeen; Tham, Cliff; Duan, Lina; Dinneny, José R.

2013-01-01

Plant environmental responses involve dynamic changes in growth and signaling, yet little is understood as to how progress through these events is regulated. Here, we explored the phenotypic and transcriptional events involved in the acclimation of the Arabidopsis thaliana seedling root to a rapid change in salinity. Using live-imaging analysis, we show that growth is dynamically regulated with a period of quiescence followed by recovery then homeostasis. Through the use of a new high-resolution spatio-temporal transcriptional map, we identify the key hormone signaling pathways that regulate specific transcriptional programs, predict their spatial domain of action, and link the activity of these pathways to the regulation of specific phases of growth. We use tissue-specific approaches to suppress the abscisic acid (ABA) signaling pathway and demonstrate that ABA likely acts in select tissue layers to regulate spatially localized transcriptional programs and promote growth recovery. Finally, we show that salt also regulates many tissue-specific and time point–specific transcriptional responses that are expected to modify water transport, Casparian strip formation, and protein translation. Together, our data reveal a sophisticated assortment of regulatory programs acting together to coordinate spatially patterned biological changes involved in the immediate and long-term response to a stressful shift in environment. PMID:23898029

Suppression of the pelo protein by Wolbachia and its effect on dengue virus in Aedes aegypti

PubMed Central

Asad, Sultan; Hussain, Mazhar; Hugo, Leon; Zhang, Guangmei; Watterson, Daniel

2018-01-01

The endosymbiont Wolbachia is known to block replication of several important arboviruses, including dengue virus (DENV), in the mosquito vector Aedes aegypti. So far, the exact mechanism of this viral inhibition is not fully understood. A recent study in Drosophila melanogaster has demonstrated an interaction between the pelo gene and Drosophila C virus. In this study, we explored the possible involvement of the pelo protein, that is involved in protein translation, in Wolbachia-mediated antiviral response and mosquito-DENV interaction. We found that pelo is upregulated during DENV replication and its silencing leads to reduced DENV virion production suggesting that it facilities DENV replication. However, in the presence of Wolbachia, specifically in female mosquitoes, the pelo protein is downregulated and its subcellular localization is altered, which could contribute to reduction in DENV replication in Ae. aegypti. In addition, we show that the microRNA aae-miR-2940-5p, whose abundance is highly enriched in Wolbachia-infected mosquitoes, might mediate regulation of pelo. Our data reveals identification of pelo as a host factor that is positively involved in DENV replication, and its suppression in the presence of Wolbachia may contribute to virus blocking exhibited by the endosymbiont. PMID:29641562

Quantifying translational coupling in E. coli synthetic operons using RBS modulation and fluorescent reporters.

PubMed

Levin-Karp, Ayelet; Barenholz, Uri; Bareia, Tasneem; Dayagi, Michal; Zelcbuch, Lior; Antonovsky, Niv; Noor, Elad; Milo, Ron

2013-06-21

Translational coupling is the interdependence of translation efficiency of neighboring genes encoded within an operon. The degree of coupling may be quantified by measuring how the translation rate of a gene is modulated by the translation rate of its upstream gene. Translational coupling was observed in prokaryotic operons several decades ago, but the quantitative range of modulation translational coupling leads to and the factors governing this modulation were only partially characterized. In this study, we systematically quantify and characterize translational coupling in E. coli synthetic operons using a library of plasmids carrying fluorescent reporter genes that are controlled by a set of different ribosome binding site (RBS) sequences. The downstream gene expression level is found to be enhanced by the upstream gene expression via translational coupling with the enhancement level varying from almost no coupling to over 10-fold depending on the upstream gene's sequence. Additionally, we find that the level of translational coupling in our system is similar between the second and third locations in the operon. The coupling depends on the distance between the stop codon of the upstream gene and the start codon of the downstream gene. This study is the first to systematically and quantitatively characterize translational coupling in a synthetic E. coli operon. Our analysis will be useful in accurate manipulation of gene expression in synthetic biology and serves as a step toward understanding the mechanisms involved in translational expression modulation.

Xu Bing, Ed Pien and Gu Xiong: Lost and Found in Translation

ERIC Educational Resources Information Center

Mahon, Patrick

2008-01-01

The works of contemporary artists Xu Bing, Ed Pien and Gu Xiong are involved in bringing to light some of the factors inherent in social, cultural and linguistic translation. In doing so, each artist is also engaged in the nuanced activity of moving between historical and contemporary aesthetic strategies in order to interrogate the way meaning is…

Reading Strategies in a L2: A Study on Machine Translation

ERIC Educational Resources Information Center

Karnal, Adriana Riess; Pereira, Vera Vanmacher

2015-01-01

This article aims at understanding cognitive strategies which are involved in reading academic texts in English as a L2/FL. Specifically, we focus on reading comprehension when a text is read either using Google translator or not. From this perspective we must consider the reading process in its complexity not only as a decoding process. We follow…

Welcoming Chinese investors in Indonesia: improving the competency of professional Indonesian-Mandarin translator

NASA Astrophysics Data System (ADS)

Ying, Y.; Mursitama, T. N.; Theresia; Mariana

2018-03-01

The study discusses the importance of improving the competency of Indonesian-Mandarin translators to increase economic relations between Indonesia and China. As China’s investment in Indonesia expands in various industry sectors, the need for qualified translators escalates. However, the situation described that Indonesia lacks competent and qualified translators in Mandarin. The study adopts the qualitative approach. Technically, the study utilizes a variety of secondary data consisting of documents, books, publications, and website to collect data based on the needs of qualified translators and how to improve their competency. In addition, primary data collection involves industry and translation service providers, from high schools, vocational schools, colleges, and Chinese language courses through interviews. In this respect, the study contributes to the development of the Mandarin Chinese translator competency through professional translator training programs. The competencies developed include Mandarin language skills in a variety of contexts or themes such as business, industry, accounting, taxation, law, and socio-political issues. The findings of this research indicate the significance to complement the lack of knowledge and skills that are not acquired during the college. Importantly, the authors propose a professional interpreter training model to meet the demand of Chinese investors in Indonesia eventually.