Translational head movements of pigeons in response to a rotating pattern: characteristics and tool to analyse mechanisms underlying detection of rotational and translational optical flow.

PubMed

Nalbach, H O

1992-01-01

Pigeons freely standing in the centre of a two-dimensionally textured cylinder not only rotate but also laterally translate their head in response to the pattern sinusoidally oscillating or unidirectionally rotating around their vertical axis. The translational head movement dominates the response at high oscillation frequencies, whereas in a unidirectionally rotating drum head translation declines at about the same rate as the rotational response increases. It is suggested that this is a consequence of charging the 'velocity storage' in the vestibulo-ocular system. Similar to the rotational head movement (opto-collic reflex), the translational head movement is elicited via a wide-field motion sensitive system. The underlying mechanism can be described as vector integration of movement vectors tangential to the pattern rotation. Stimulation of the frontal visual field elicits largest translational responses while rotational responses can be elicited equally well from any azimuthal position of a moving pattern. Experiments where most of the pattern is occluded by a screen and the pigeon is allowed to view the stimulus through one or two windows demonstrate a short-range inhibition and long-range excitation between movement detectors that feed into the rotational system. Furthermore, the results obtained from such types of experiments suggest that the rotational system inhibits the translational system. These mechanisms may help the pigeon to decompose image flow into its translational and rotational components. Because of their translational response to a rotational stimulus, it is concluded, however, that pigeons either generally cannot perfectly perform the task or they need further visual information, like differential image motion, that was not available to them in the paradigms.

The Community Mentorship Program: Providing Community-Engagement Opportunities for Early-Stage Clinical and Translational Scientists to Facilitate Research Translation

PubMed Central

Patino, Cecilia M.; Kubicek, Katrina; Robles, Marisela; Kiger, Holly; Dzekov, Jeanne

2016-01-01

Problem A goal of the Southern California Clinical and Translational Science Institute (SC-CTSI) at the University of Southern California (USC) and Children's Hospital Los Angeles is to train early-stage clinical translational scientists (CTSs) to conduct research that improves the health of diverse communities. This goal aligns well with the Institute of Medicine's recommendations emphasizing community engagement in biomedical research that facilitates research translation. The Community Mentorship Program (CMP), created to complement community-engaged research (CER) didactics, matches CTSs with community mentors who help CTSs identify and complete community-engaged experiences that inform their research. Approach The CMP was piloted in 2013-2015 by the SC-CTSI Workforce Development and Community-Engagement cores. The CMP team matched three CTSs (assistant professors pursuing mentored career development awards, two with CER experience) with mentors at community-based organizations (CBOs) aligned with their research interests. Each mentor–mentee pair signed a memorandum of understanding. The CMP team checked in regularly, monitoring progress and addressing challenges in CTSs’ completion of their community-engaged experience. Outcomes All pairs completed at least one community-engaged activity informing the CTS's research. In exit interviews, the CTSs and CBO mentors expressed satisfaction with the program and stated they would continue to work together. The CTSs reported the program provided opportunities to develop networks outside academia, build trust within the community, and receive feedback and learn from individuals in communities affected by their research. Next Steps The CMP will be expanded to include all eligible early-career CTSs and promoted for use in similar settings outside the SC-CTSI. PMID:27508342

The Community Mentorship Program: Providing Community-Engagement Opportunities for Early-Stage Clinical and Translational Scientists to Facilitate Research Translation.

PubMed

Patino, Cecilia M; Kubicek, Katrina; Robles, Marisela; Kiger, Holly; Dzekov, Jeanne

2017-02-01

A goal of the Southern California Clinical and Translational Science Institute (SC-CTSI) at the University of Southern California and Children's Hospital Los Angeles is to train early-stage clinical and translational scientists (CTSs) to conduct research that improves the health of diverse communities. This goal aligns well with the Institute of Medicine's recommendations emphasizing community engagement in biomedical research that facilitates research translation. The Community Mentorship Program (CMP), created to complement community-engaged research didactics, matches CTSs with community mentors who help them identify and complete community-engaged experiences that inform their research. The CMP was piloted in 2013-2015 by the SC-CTSI Workforce Development and Community Engagement cores. The CMP team matched three CTSs (assistant professors pursuing mentored career development awards) with mentors at community-based organizations (CBOs) aligned with their research interests. Each mentor-mentee pair signed a memorandum of understanding. The CMP team checked in regularly, monitoring progress and addressing challenges in CTSs' completion of their community-engaged experience. Each pair completed at least one community-engaged activity informing the CTS's research. In exit interviews, the CTSs and CBO mentors expressed satisfaction with the program and stated that they would continue to work together. The CTSs reported that the program provided opportunities to develop networks outside academia, build trust within the community, and receive feedback and learn from individuals in communities affected by their research. The CMP will be expanded to include all eligible early-career CTSs and promoted for use in similar settings outside the SC-CTSI.

Proteomic identification of early salicylate- and flg22-responsive redox-sensitive proteins in Arabidopsis

PubMed Central

Liu, Pei; Zhang, Huoming; Yu, Boying; Xiong, Liming; Xia, Yiji

2015-01-01

Accumulation of reactive oxygen species (ROS) is one of the early defense responses against pathogen infection in plants. The mechanism about the initial and direct regulation of the defense signaling pathway by ROS remains elusive. Perturbation of cellular redox homeostasis by ROS is believed to alter functions of redox-sensitive proteins through their oxidative modifications. Here we report an OxiTRAQ-based proteomic study in identifying proteins whose cysteines underwent oxidative modifications in Arabidopsis cells during the early response to salicylate or flg22, two defense pathway elicitors that are known to disturb cellular redox homeostasis. Among the salicylate- and/or flg22-responsive redox-sensitive proteins are those involved in transcriptional regulation, chromatin remodeling, RNA processing, post-translational modifications, and nucleocytoplasmic shuttling. The identification of the salicylate-/flg22-responsive redox-sensitive proteins provides a foundation from which further study can be conducted toward understanding biological significance of their oxidative modifications during the plant defense response. PMID:25720653

Mitochondrial unfolded protein response controls matrix pre-RNA processing and translation.

PubMed

Münch, Christian; Harper, J Wade

2016-06-30

The mitochondrial matrix is unique in that it must integrate the folding and assembly of proteins derived from the nuclear and mitochondrial genomes. In Caenorhabditis elegans, the mitochondrial unfolded protein response (UPRmt) senses matrix protein misfolding and induces a program of nuclear gene expression, including mitochondrial chaperonins, to promote mitochondrial proteostasis. While misfolded mitochondrial-matrix-localized ornithine transcarbamylase induces chaperonin expression, our understanding of mammalian UPRmt is rudimentary, reflecting a lack of acute triggers for UPRmt activation. This limitation has prevented analysis of the cellular responses to matrix protein misfolding and the effects of UPRmt on mitochondrial translation to control protein folding loads. Here we combine pharmacological inhibitors of matrix-localized HSP90/TRAP1 (ref. 8) or LON protease, which promote chaperonin expression, with global transcriptional and proteomic analysis to reveal an extensive and acute response of human cells to UPRmt. This response encompasses widespread induction of nuclear genes, including matrix-localized proteins involved in folding, pre-RNA processing and translation. Functional studies revealed rapid but reversible translation inhibition in mitochondria occurring concurrently with defects in pre-RNA processing caused by transcriptional repression and LON-dependent turnover of the mitochondrial pre-RNA processing nuclease MRPP3 (ref. 10). This study reveals that acute mitochondrial protein folding stress activates both increased chaperone availability within the matrix and reduced matrix-localized protein synthesis through translational inhibition, and provides a framework for further dissection of mammalian UPRmt.

Translation repression via modulation of the cytoplasmic poly(A)-binding protein in the inflammatory response

PubMed Central

Zhang, Xu; Chen, Xiaoli; Liu, Qiuying; Zhang, Shaojie; Hu, Wenqian

2017-01-01

Gene expression is precisely regulated during the inflammatory response to control infection and limit the detrimental effects of inflammation. Here, we profiled global mRNA translation dynamics in the mouse primary macrophage-mediated inflammatory response and identified hundreds of differentially translated mRNAs. These mRNAs’ 3’UTRs have enriched binding motifs for several RNA-binding proteins, which implies extensive translational regulatory networks. We characterized one such protein, Zfp36, as a translation repressor. Using primary macrophages from a Zfp36-V5 epitope tagged knock-in mouse generated by CRISPR/Cas9-mediated genome editing, we found that the endogenous Zfp36 directly interacts with the cytoplasmic poly(A)-binding protein. Importantly, this interaction is required for the translational repression of Zfp36’s target mRNAs in resolving inflammation. Altogether, these results uncovered critical roles of translational regulations in controlling appropriate gene expression during the inflammatory response and revealed a new biologically relevant molecular mechanism of translational repression via modulating the cytoplasmic poly(A)-binding protein. DOI: http://dx.doi.org/10.7554/eLife.27786.001 PMID:28635594

Three-dimensional organization of otolith-ocular reflexes in rhesus monkeys. III. Responses To translation

NASA Technical Reports Server (NTRS)

Angelaki, D. E.

1998-01-01

The three-dimensional (3-D) properties of the translational vestibulo-ocular reflexes (translational VORs) during lateral and fore-aft oscillations in complete darkness were studied in rhesus monkeys at frequencies between 0.16 and 25 Hz. In addition, constant velocity off-vertical axis rotations extended the frequency range to 0.02 Hz. During lateral motion, horizontal responses were in phase with linear velocity in the frequency range of 2-10 Hz. At both lower and higher frequencies, phase lags were introduced. Torsional response phase changed more than 180 degrees in the tested frequency range such that torsional eye movements, which could be regarded as compensatory to "an apparent roll tilt" at the lowest frequencies, became anticompensatory at all frequencies above approximately 1 Hz. These results suggest two functionally different frequency bandwidths for the translational VORs. In the low-frequency spectrum (<<0.5 Hz), horizontal responses compensatory to translation are small and high-pass-filtered whereas torsional response sensitivity is relatively frequency independent. At higher frequencies however, both horizontal and torsional response sensitivity and phase exhibit a similar frequency dependence, suggesting a common role during head translation. During up-down motion, vertical responses were in phase with translational velocity at 3-5 Hz but phase leads progressively increased for lower frequencies (>90 degrees at frequencies <0.2 Hz). No consistent dependence on static head orientation was observed for the vertical response components during up-down motion and the horizontal and torsional response components during lateral translation. The frequency response characteristics of the translational VORs were fitted by "periphery/brain stem" functions that related the linear acceleration input, transduced by primary otolith afferents, to the velocity signals providing the input to the velocity-to-position neural integrator and the oculomotor plant. The

Response of Pendulums to Translational and Rotational Components of Ground Motion

NASA Astrophysics Data System (ADS)

Graizer, V.; Kalkan, E.

2008-12-01

Dynamic response of most seismological instruments and many engineering structures to ground shaking can be represented via response of a pendulum (single-degree-of-freedom oscillator). Pendulum response is usually simplified by considering the input from uni-axial translational motion only. Complete ground motion however, includes not only translational components but also rotations (tilt and torsion). We consider complete equations of motion for three following types of pendulum: (i) conventional mass-on-rod, (ii) mass- on-spring type, and (iii) inverted (astatic), then their response sensitivities to each component of complex ground motion are examined. Inverted pendulums are used in seismology for more than 100 years, for example, classical Wiechert's horizontal seismograph built around 1905 and still used at some seismological observatories, and recent Guralp's horizontal seismometers CMG-40T and CMG-3T. Inverted pendulums also have significant importance for engineering applications where they are often used to simulate the dynamic response of various structural systems. The results of this study show that a horizontal pendulum similar to a modern accelerometer used in strong motion measurements is practically sensitive to translational motion and tilt only, while inverted pendulum is sensitive not only to translational components, but also to angular accelerations and tilt. For better understanding of the inverted pendulum's dynamic behavior under complex ground excitation, relative contribution of each component of motion on response variants is carefully isolated. The responses of pendulums are calculated in time-domain using close-form solution Duhamel's integral with complex input forcing functions. As compared to a common horizontal pendulum, response of an inverted pendulum is sensitive to acceleration of gravity and vertical acceleration when it reaches the level close to 1.0 g. Gravity effect introduces nonlinearity into the differential equation of

Post-recombination early Universe cooling by translation-internal inter-conversion: The role of minor constituents.

PubMed

McCaffery, Anthony J

2015-09-14

Little is known of the mechanism by which H and H2, the principal constituents of the post-re-combination early Universe, cooled sufficiently to permit cluster formation, nucleosynthesis, and, eventually, the formation of structured objects. Radiative decay primarily cools the internal modes of H2, as Δj = - 2 jumps accompany quadrupolar emission. This, however, would be a self-limiting mechanism. In this work, a translational energy cooling mechanism based on collision-induced, translation-to-internal mode conversion, is extended, following an earlier study [A. J. McCaffery and R. J. Marsh, J. Chem. Phys. 139, 234310 (2013)] of ensembles comprising H2 in a H atom bath gas. Here, the possible influence of minor species, such as HD, on this cooling mechanism is investigated. Results suggest that the influence of HD is small but not insignificant. Conversion is very rapid and an overall translation-to-internal energy conversion efficiency of some 5% could be expected. This finding may be of use in the further development of models of this complex phase of early Universe evolution. An unexpected finding in this study was that H2 + HD ensembles are capable of very rapid translation-to-internal conversion with efficiencies of >40% and relaxation rates that appear to be relatively slow. This may have potential as an energy storage mechanism.

NCI–RTOG Translational Program Strategic Guidelines for the Early-Stage Development of Radiosensitizers

PubMed Central

2013-01-01

The addition of chemotherapeutic agents to ionizing radiation has improved survival in many malignancies. Cure rates may be further improved by adding novel targeted agents to current radiotherapy or radiochemotherapy regimens. Despite promising laboratory data, progress in the clinical development of new drugs with radiation has been limited. To define and address the problems involved, a collaborative effort between individuals within the translational research program of the Radiation Oncology Therapy Group and the National Cancer Institute was established. We discerned challenges to drug development with radiation including: 1) the limited relevance of preclinical work, 2) the pharmaceutical industry’s diminished interest, and 3) the important individual skills and institutional commitments required to ensure a successful program. The differences between early-phase trial designs with and without radiation are noted as substantial. The traditional endpoints for early-phase clinical trials—acute toxicity and maximum-tolerated dose—are of limited value when combining targeted agents with radiation. Furthermore, response rate is not a useful surrogate marker of activity in radiation combination trials.Consequently, a risk-stratified model for drug-dose escalation with radiation is proposed, based upon the known and estimated adverse effects. The guidelines discuss new clinical trial designs, such as the time-to-event continual reassessment method design for phase I trials, randomized phase II “screening” trials, and the use of surrogate endpoints, such as pathological response. It is hoped that by providing a clear pathway, this article will accelerate the rate of drug development with radiation. PMID:23231975

Inhibition of host cell translation elongation by Legionella pneumophila blocks the host cell unfolded protein response.

PubMed

Hempstead, Andrew D; Isberg, Ralph R

2015-12-08

Cells of the innate immune system recognize bacterial pathogens by detecting common microbial patterns as well as pathogen-specific activities. One system that responds to these stimuli is the IRE1 branch of the unfolded protein response (UPR), a sensor of endoplasmic reticulum (ER) stress. Activation of IRE1, in the context of Toll-like receptor (TLR) signaling, induces strong proinflammatory cytokine induction. We show here that Legionella pneumophila, an intravacuolar pathogen that replicates in an ER-associated compartment, blocks activation of the IRE1 pathway despite presenting pathogen products that stimulate this response. L. pneumophila TLR ligands induced the splicing of mRNA encoding XBP1s, the main target of IRE1 activity. L. pneumophila was able to inhibit both chemical and bacterial induction of XBP1 splicing via bacterial translocated proteins that interfere with host protein translation. A strain lacking five translocated translation elongation inhibitors was unable to block XBP1 splicing, but this could be rescued by expression of a single such inhibitor, consistent with limitation of the response by translation elongation inhibitors. Chemical inhibition of translation elongation blocked pattern recognition receptor-mediated XBP1 splicing, mimicking the effects of the bacterial translation inhibitors. In contrast, host cell-promoted inhibition of translation initiation in response to the pathogen was ineffective in blocking XBP1 splicing, demonstrating the need for the elongation inhibitors for protection from the UPR. The inhibition of host translation elongation may be a common strategy used by pathogens to limit the innate immune response by interfering with signaling via the UPR.

(Very) Early technology assessment and translation of predictive biomarkers in breast cancer.

PubMed

Miquel-Cases, Anna; Schouten, Philip C; Steuten, Lotte M G; Retèl, Valesca P; Linn, Sabine C; van Harten, Wim H

2017-01-01

Predictive biomarkers can guide treatment decisions in breast cancer. Many studies are undertaken to discover and translate these biomarkers, yet few biomarkers make it to practice. Before use in clinical decision making, predictive biomarkers need to demonstrate analytical validity, clinical validity and clinical utility. While attaining analytical and clinical validity is relatively straightforward, by following methodological recommendations, the achievement of clinical utility is extremely challenging. It requires demonstrating three associations: the biomarker with the outcome (prognostic association), the effect of treatment independent of the biomarker, and the differential treatment effect between the prognostic and the predictive biomarker (predictive association). In addition, economical, ethical, regulatory, organizational and patient/doctor-related aspects are hampering the translational process. Traditionally, these aspects do not receive much attention until formal approval or reimbursement of a biomarker test (informed by Health Technology Assessment (HTA)) is at stake, at which point the clinical utility and sometimes price of the test can hardly be influenced anymore. When HTA analyses are performed earlier, during biomarker research and development, they may prevent further development of those biomarkers unlikely to ever provide sufficient added value to society, and rather facilitate translation of the promising ones. Early HTA is particularly relevant for the predictive biomarker field, as expensive medicines are under pressure and the need for biomarkers to guide their appropriate use is huge. Closer interaction between clinical researchers and HTA experts throughout the translational research process will ensure that available data and methodologies will be used most efficiently to facilitate biomarker translation. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Quantitative Nucleotide Level Analysis of Regulation of Translation in Response to Depolarization of Cultured Neural Cells

PubMed Central

Dalal, Jasbir S.; Yang, Chengran; Sapkota, Darshan; Lake, Allison M.; O'Brien, David R.; Dougherty, Joseph D.

2017-01-01

Studies on regulation of gene expression have contributed substantially to understanding mechanisms for the long-term activity-dependent alterations in neural connectivity that are thought to mediate learning and memory. Most of these studies, however, have focused on the regulation of mRNA transcription. Here, we utilized high-throughput sequencing coupled with ribosome footprinting to globally characterize the regulation of translation in primary mixed neuronal-glial cultures in response to sustained depolarization. We identified substantial and complex regulation of translation, with many transcripts demonstrating changes in ribosomal occupancy independent of transcriptional changes. We also examined sequence-based mechanisms that might regulate changes in translation in response to depolarization. We found that these are partially mediated by features in the mRNA sequence—notably upstream open reading frames and secondary structure in the 5′ untranslated region—both of which predict downregulation in response to depolarization. Translationally regulated transcripts are also more likely to be targets of FMRP and include genes implicated in autism in humans. Our findings support the idea that control of mRNA translation plays an important role in response to neural activity across the genome. PMID:28190998

tRNA thiolation links translation to stress responses in Saccharomyces cerevisiae.

PubMed

Damon, Jadyn R; Pincus, David; Ploegh, Hidde L

2015-01-15

Although tRNA modifications have been well catalogued, the precise functions of many modifications and their roles in mediating gene expression are still being elucidated. Whereas tRNA modifications were long assumed to be constitutive, it is now apparent that the modification status of tRNAs changes in response to different environmental conditions. The URM1 pathway is required for thiolation of the cytoplasmic tRNAs tGlu(UUC), tGln(UUG), and tLys(UUU) in Saccharomyces cerevisiae. We demonstrate that URM1 pathway mutants have impaired translation, which results in increased basal activation of the Hsf1-mediated heat shock response; we also find that tRNA thiolation levels in wild-type cells decrease when cells are grown at elevated temperature. We show that defects in tRNA thiolation can be conditionally advantageous, conferring resistance to endoplasmic reticulum stress. URM1 pathway proteins are unstable and hence are more sensitive to changes in the translational capacity of cells, which is decreased in cells experiencing stresses. We propose a model in which a stress-induced decrease in translation results in decreased levels of URM1 pathway components, which results in decreased tRNA thiolation levels, which further serves to decrease translation. This mechanism ensures that tRNA thiolation and translation are tightly coupled and coregulated according to need. © 2015 Damon et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Early caregiving and physiological stress responses.

PubMed

Luecken, Linda J; Lemery, Kathryn S

2004-05-01

Inadequate early caregiving has been associated with risks of stress-related psychological and physical illness over the life span. Dysregulated physiological stress responses may represent a mechanism linking early caregiving to health outcomes. This paper reviews evidence linking early caregiving to physiological responses that can increase vulnerability to stress-related illness. A number of high-risk family characteristics, including high conflict, divorce, abuse, and parental psychopathology, are considered in the development of stress vulnerability. Three theoretical pathways linking caregiving to physiological stress responses are outlined: genetic, psychosocial, and cognitive-affective. Exciting preliminary evidence suggests that early caregiving can impact long-term physiological stress responses. Directions for future research in this area are suggested.

Enhanced transcription and translation in clay hydrogel and implications for early life evolution

PubMed Central

Yang, Dayong; Peng, Songming; Hartman, Mark R.; Gupton-Campolongo, Tiffany; Rice, Edward J.; Chang, Anna Kathryn; Gu, Zi; Lu, G. Q. (Max); Luo, Dan

2013-01-01

In most contemporary life forms, the confinement of cell membranes provides localized concentration and protection for biomolecules, leading to efficient biochemical reactions. Similarly, confinement may have also played an important role for prebiotic compartmentalization in early life evolution when the cell membrane had not yet formed. It remains an open question how biochemical reactions developed without the confinement of cell membranes. Here we mimic the confinement function of cells by creating a hydrogel made from geological clay minerals, which provides an efficient confinement environment for biomolecules. We also show that nucleic acids were concentrated in the clay hydrogel and were protected against nuclease, and that transcription and translation reactions were consistently enhanced. Taken together, our results support the importance of localized concentration and protection of biomolecules in early life evolution, and also implicate a clay hydrogel environment for biochemical reactions during early life evolution. PMID:24196527

Big data from electronic health records for early and late translational cardiovascular research: challenges and potential.

PubMed

Hemingway, Harry; Asselbergs, Folkert W; Danesh, John; Dobson, Richard; Maniadakis, Nikolaos; Maggioni, Aldo; van Thiel, Ghislaine J M; Cronin, Maureen; Brobert, Gunnar; Vardas, Panos; Anker, Stefan D; Grobbee, Diederick E; Denaxas, Spiros

2018-04-21

Cohorts of millions of people's health records, whole genome sequencing, imaging, sensor, societal and publicly available data present a rapidly expanding digital trace of health. We aimed to critically review, for the first time, the challenges and potential of big data across early and late stages of translational cardiovascular disease research. We sought exemplars based on literature reviews and expertise across the BigData@Heart Consortium. We identified formidable challenges including: data quality, knowing what data exist, the legal and ethical framework for their use, data sharing, building and maintaining public trust, developing standards for defining disease, developing tools for scalable, replicable science and equipping the clinical and scientific work force with new inter-disciplinary skills. Opportunities claimed for big health record data include: richer profiles of health and disease from birth to death and from the molecular to the societal scale; accelerated understanding of disease causation and progression, discovery of new mechanisms and treatment-relevant disease sub-phenotypes, understanding health and diseases in whole populations and whole health systems and returning actionable feedback loops to improve (and potentially disrupt) existing models of research and care, with greater efficiency. In early translational research we identified exemplars including: discovery of fundamental biological processes e.g. linking exome sequences to lifelong electronic health records (EHR) (e.g. human knockout experiments); drug development: genomic approaches to drug target validation; precision medicine: e.g. DNA integrated into hospital EHR for pre-emptive pharmacogenomics. In late translational research we identified exemplars including: learning health systems with outcome trials integrated into clinical care; citizen driven health with 24/7 multi-parameter patient monitoring to improve outcomes and population-based linkages of multiple EHR sources

Early-Life Nutrition and Neurodevelopment: Use of the Piglet as a Translational Model12

PubMed Central

Mudd, Austin T

2017-01-01

Optimal nutrition early in life is critical to ensure proper structural and functional development of infant organ systems. Although pediatric nutrition historically has emphasized research on the relation between nutrition, growth rates, and gastrointestinal maturation, efforts increasingly have focused on how nutrition influences neurodevelopment. The provision of human milk is considered the gold standard in pediatric nutrition; thus, there is interest in understanding how functional nutrients and bioactive components in milk may modulate developmental processes. The piglet has emerged as an important translational model for studying neurodevelopmental outcomes influenced by pediatric nutrition. Given the comparable nutritional requirements and strikingly similar brain developmental patterns between young pigs and humans, the piglet is being used increasingly in developmental nutritional neuroscience studies. The piglet primarily has been used to assess the effects of dietary fatty acids and their accretion in the brain throughout neurodevelopment. However, recent research indicates that other dietary components, including choline, iron, cholesterol, gangliosides, and sialic acid, among other compounds, also affect neurodevelopment in the pig model. Moreover, novel analytical techniques, including but not limited to MRI, behavioral assessments, and molecular quantification, allow for a more holistic understanding of how nutrition affects neurodevelopmental patterns. By combining early-life nutritional interventions with innovative analytical approaches, opportunities abound to quantify factors affecting neurodevelopmental trajectories in the neonate. This review discusses research using the translational pig model with primary emphasis on early-life nutrition interventions assessing neurodevelopment outcomes, while also discussing nutritionally-sensitive methods to characterize brain maturation. PMID:28096130

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.

The translation elongation factor eEF1A1 couples transcription to translation during heat shock response

PubMed Central

Vera, Maria; Pani, Bibhusita; Griffiths, Lowri A; Muchardt, Christian; Abbott, Catherine M; Singer, Robert H; Nudler, Evgeny

2014-01-01

Translation elongation factor eEF1A has a well-defined role in protein synthesis. In this study, we demonstrate a new role for eEF1A: it participates in the entire process of the heat shock response (HSR) in mammalian cells from transcription through translation. Upon stress, isoform 1 of eEF1A rapidly activates transcription of HSP70 by recruiting the master regulator HSF1 to its promoter. eEF1A1 then associates with elongating RNA polymerase II and the 3′UTR of HSP70 mRNA, stabilizing it and facilitating its transport from the nucleus to active ribosomes. eEF1A1-depleted cells exhibit severely impaired HSR and compromised thermotolerance. In contrast, tissue-specific isoform 2 of eEF1A does not support HSR. By adjusting transcriptional yield to translational needs, eEF1A1 renders HSR rapid, robust, and highly selective; thus, representing an attractive therapeutic target for numerous conditions associated with disrupted protein homeostasis, ranging from neurodegeneration to cancer. DOI: http://dx.doi.org/10.7554/eLife.03164.001 PMID:25233275

Dynamic m(6)A mRNA methylation directs translational control of heat shock response.

PubMed

Zhou, Jun; Wan, Ji; Gao, Xiangwei; Zhang, Xingqian; Jaffrey, Samie R; Qian, Shu-Bing

2015-10-22

The most abundant mRNA post-transcriptional modification is N(6)-methyladenosine (m(6)A), which has broad roles in RNA biology. In mammalian cells, the asymmetric distribution of m(6)A along mRNAs results in relatively less methylation in the 5' untranslated region (5'UTR) compared to other regions. However, whether and how 5'UTR methylation is regulated is poorly understood. Despite the crucial role of the 5'UTR in translation initiation, very little is known about whether m(6)A modification influences mRNA translation. Here we show that in response to heat shock stress, certain adenosines within the 5'UTR of newly transcribed mRNAs are preferentially methylated. We find that the dynamic 5'UTR methylation is a result of stress-induced nuclear localization of YTHDF2, a well-characterized m(6)A 'reader'. Upon heat shock stress, the nuclear YTHDF2 preserves 5'UTR methylation of stress-induced transcripts by limiting the m(6)A 'eraser' FTO from demethylation. Remarkably, the increased 5'UTR methylation in the form of m(6)A promotes cap-independent translation initiation, providing a mechanism for selective mRNA translation under heat shock stress. Using Hsp70 mRNA as an example, we demonstrate that a single m(6)A modification site in the 5'UTR enables translation initiation independent of the 5' end N(7)-methylguanosine cap. The elucidation of the dynamic features of 5'UTR methylation and its critical role in cap-independent translation not only expands the breadth of physiological roles of m(6)A, but also uncovers a previously unappreciated translational control mechanism in heat shock response.

Translating a US Early Palliative Care Model for Turkey and Singapore.

PubMed

Akyar, Imatullah; Dionne-Odom, James N; Yang, Grace Meijuan; Bakitas, Marie A

2018-01-01

The field of palliative care is growing in acceptance and sophistication globally. No longer considered just for patients at end-of-life, palliative care is now being incorporated early in the disease trajectory. Despite professional guidelines supporting early palliative care, there are few models that have been created that can be translated into practice cross-culturally. In the United States, the Educate, Nurture, Advise, Before, Life Ends (ENABLE) early palliative care telehealth model has demonstrated effectiveness in improving quality of life, mood, symptom relief, and survival for patients with cancer and is now being tested in patients with heart failure. Family caregivers of patients who have received ENABLE concurrent with their care recipients have also demonstrated positive outcomes in quality of life and caregiver burden. Internationally, a number of investigators are culturally adapting ENABLE for patients and family caregivers. While some elements of ENABLE, such as symptom management and self-care, and the caregiving role are relevant cross-culturally, others have been built on Western principles of self-determination or represent concepts such as advance care planning which will require more cultural adaptation. In addition, ENABLE was initially an in-person approach that was converted to telehealth to accommodate a rural population-it will be important to understand cultural norms related to receiving care by phone or if an in-person approach will be more culturally acceptable. This paper describes efforts in Turkey and Singapore to culturally adapt the ENABLE early palliative care principles for their countries.

Responses of neurons in the medial column of the inferior olive in pigeons to translational and rotational optic flowfields.

PubMed

Winship, I R; Wylie, D R

2001-11-01

The responses of neurons in the medial column of the inferior olive to translational and rotational optic flow were recorded from anaesthetized pigeons. Panoramic translational or rotational flowfields were produced by mechanical devices that projected optic flow patterns onto the walls, ceiling and floor of the room. The axis of rotation/translation could be positioned to any orientation in three-dimensional space such that axis tuning could be determined. Each neuron was assigned a vector representing the axis about/along which the animal would rotate/translate to produce the flowfield that elicited maximal modulation. Both translation-sensitive and rotation-sensitive neurons were found. For neurons responsive to translational optic flow, the preferred axis is described with reference to a standard right-handed coordinate system, where +x, +y and +z represent rightward, upward and forward translation of the animal, respectively (assuming that all recordings were from the right side of the brain). t(+y) neurons were maximally excited in response to a translational optic flowfield that results from self-translation upward along the vertical (y) axis. t(-y) neurons also responded best to translational optic flow along the vertical axis but showed the opposite direction preference. The two remaining groups, t(-x+z) and t(-x-z) neurons, responded best to translational optic flow along horizontal axes that were oriented 45 degrees to the midline. There were two types of neurons responsive to rotational optic flow: rVA neurons preferred rotation about the vertical axis, and rH135c neurons preferred rotation about a horizontal axis at 135 degrees contralateral azimuth. The locations of marking lesions indicated a clear topographical organization of the six response types. In summary, our results reinforce that the olivo-cerebellar system dedicated to the analysis of optic flow is organized according to a reference frame consisting of three approximately orthogonal axes

Translating a US Early Palliative Care Model for Turkey and Singapore

PubMed Central

Akyar, Imatullah; Dionne-Odom, James N.; Yang, Grace Meijuan; Bakitas, Marie A.

2018-01-01

The field of palliative care is growing in acceptance and sophistication globally. No longer considered just for patients at end-of-life, palliative care is now being incorporated early in the disease trajectory. Despite professional guidelines supporting early palliative care, there are few models that have been created that can be translated into practice cross-culturally. In the United States, the Educate, Nurture, Advise, Before, Life Ends (ENABLE) early palliative care telehealth model has demonstrated effectiveness in improving quality of life, mood, symptom relief, and survival for patients with cancer and is now being tested in patients with heart failure. Family caregivers of patients who have received ENABLE concurrent with their care recipients have also demonstrated positive outcomes in quality of life and caregiver burden. Internationally, a number of investigators are culturally adapting ENABLE for patients and family caregivers. While some elements of ENABLE, such as symptom management and self-care, and the caregiving role are relevant cross-culturally, others have been built on Western principles of self-determination or represent concepts such as advance care planning which will require more cultural adaptation. In addition, ENABLE was initially an in-person approach that was converted to telehealth to accommodate a rural population-it will be important to understand cultural norms related to receiving care by phone or if an in-person approach will be more culturally acceptable. This paper describes efforts in Turkey and Singapore to culturally adapt the ENABLE early palliative care principles for their countries. PMID:29379831

Automatic translation among spoken languages

NASA Technical Reports Server (NTRS)

Walter, Sharon M.; Costigan, Kelly

1994-01-01

The Machine Aided Voice Translation (MAVT) system was developed in response to the shortage of experienced military field interrogators with both foreign language proficiency and interrogation skills. Combining speech recognition, machine translation, and speech generation technologies, the MAVT accepts an interrogator's spoken English question and translates it into spoken Spanish. The spoken Spanish response of the potential informant can then be translated into spoken English. Potential military and civilian applications for automatic spoken language translation technology are discussed in this paper.

tRNA-mediated codon-biased translation in mycobacterial hypoxic persistence

NASA Astrophysics Data System (ADS)

Chionh, Yok Hian; McBee, Megan; Babu, I. Ramesh; Hia, Fabian; Lin, Wenwei; Zhao, Wei; Cao, Jianshu; Dziergowska, Agnieszka; Malkiewicz, Andrzej; Begley, Thomas J.; Alonso, Sylvie; Dedon, Peter C.

2016-11-01

Microbial pathogens adapt to the stress of infection by regulating transcription, translation and protein modification. We report that changes in gene expression in hypoxia-induced non-replicating persistence in mycobacteria--which models tuberculous granulomas--are partly determined by a mechanism of tRNA reprogramming and codon-biased translation. Mycobacterium bovis BCG responded to each stage of hypoxia and aerobic resuscitation by uniquely reprogramming 40 modified ribonucleosides in tRNA, which correlate with selective translation of mRNAs from families of codon-biased persistence genes. For example, early hypoxia increases wobble cmo5U in tRNAThr(UGU), which parallels translation of transcripts enriched in its cognate codon, ACG, including the DosR master regulator of hypoxic bacteriostasis. Codon re-engineering of dosR exaggerates hypoxia-induced changes in codon-biased DosR translation, with altered dosR expression revealing unanticipated effects on bacterial survival during hypoxia. These results reveal a coordinated system of tRNA modifications and translation of codon-biased transcripts that enhance expression of stress response proteins in mycobacteria.

tRNA-mediated codon-biased translation in mycobacterial hypoxic persistence

PubMed Central

Chionh, Yok Hian; McBee, Megan; Babu, I. Ramesh; Hia, Fabian; Lin, Wenwei; Zhao, Wei; Cao, Jianshu; Dziergowska, Agnieszka; Malkiewicz, Andrzej; Begley, Thomas J.; Alonso, Sylvie; Dedon, Peter C.

2016-01-01

Microbial pathogens adapt to the stress of infection by regulating transcription, translation and protein modification. We report that changes in gene expression in hypoxia-induced non-replicating persistence in mycobacteria—which models tuberculous granulomas—are partly determined by a mechanism of tRNA reprogramming and codon-biased translation. Mycobacterium bovis BCG responded to each stage of hypoxia and aerobic resuscitation by uniquely reprogramming 40 modified ribonucleosides in tRNA, which correlate with selective translation of mRNAs from families of codon-biased persistence genes. For example, early hypoxia increases wobble cmo5U in tRNAThr(UGU), which parallels translation of transcripts enriched in its cognate codon, ACG, including the DosR master regulator of hypoxic bacteriostasis. Codon re-engineering of dosR exaggerates hypoxia-induced changes in codon-biased DosR translation, with altered dosR expression revealing unanticipated effects on bacterial survival during hypoxia. These results reveal a coordinated system of tRNA modifications and translation of codon-biased transcripts that enhance expression of stress response proteins in mycobacteria. PMID:27834374

Response to Sakurai: The Influence of Translation on Reading Amount, Proficiency and Speed in Extensive Reading

ERIC Educational Resources Information Center

Stephens, Meredith

2016-01-01

In this response to Sakurai, Meredith Stephens agrees that Sakurai (2015) raises an important issue of which native English speaking teachers may be unaware; Japanese learners of English typically translate into Japanese while reading English. Sakurai explained, "It is speculated that Japanese students naturally translate English into…

Translation Control: A Multifaceted Regulator of Inflammatory Response

PubMed Central

Mazumder, Barsanjit; Li, Xiaoxia; Barik, Sailen

2010-01-01

A robust innate immune response is essential to the protection of all vertebrates from infection, but it often comes with the price tag of acute inflammation. If unchecked, a runaway inflammatory response can cause significant tissue damage, resulting in myriad disorders, such as dermatitis, toxicshock, cardiovascular disease, acute pelvic and arthritic inflammatory diseases, and various infections. To prevent such pathologies, cells have evolved mechanisms to rapidly and specifically shut off these beneficial inflammatory activities before they become detrimental. Our review of recent literature, including our own work, reveals that the most dominant and common mechanism is translational silencing, in which specific regulatory proteins or complexes are recruited to cis-acting RNA structures in the untranslated regions of single or multiple mRNAs that code for the inflammatory protein(s). Enhancement of the silencing function may constitute a novel pharmacological approach to prevent immunity-related inflammation. PMID:20304832

Translation control: a multifaceted regulator of inflammatory response.

PubMed

Mazumder, Barsanjit; Li, Xiaoxia; Barik, Sailen

2010-04-01

A robust innate immune response is essential to the protection of all vertebrates from infection, but it often comes with the price tag of acute inflammation. If unchecked, a runaway inflammatory response can cause significant tissue damage, resulting in myriad disorders, such as dermatitis, toxic shock, cardiovascular disease, acute pelvic and arthritic inflammatory diseases, and various infections. To prevent such pathologies, cells have evolved mechanisms to rapidly and specifically shut off these beneficial inflammatory activities before they become detrimental. Our review of recent literature, including our own work, reveals that the most dominant and common mechanism is translational silencing, in which specific regulatory proteins or complexes are recruited to cis-acting RNA structures in the untranslated regions of single or multiple mRNAs that code for the inflammatory protein(s). Enhancement of the silencing function may constitute a novel pharmacological approach to prevent immunity-related inflammation.

Translational Response of Toe-Restrained Retaining Walls to Earthquake Ground Motions Using CorpsWallSlip (CWSlip)

DTIC Science & Technology

2007-06-01

corresponding software developed for the translational response of rock- founded retaining walls buttressed at their toe by a reinforced concrete slab...by a Reinforced Concrete Slab ...........................................................................................................32 2.1...2.5 New translational analysis model of a wall retaining a partially submerged backfill and buttressed by a reinforced concrete slab

Primate translational vestibuloocular reflexes. II. Version and vergence responses to fore-aft motion

NASA Technical Reports Server (NTRS)

McHenry, M. Q.; Angelaki, D. E.

2000-01-01

To maintain binocular fixation on near targets during fore-aft translational disturbances, largely disjunctive eye movements are elicited the amplitude and direction of which should be tuned to the horizontal and vertical eccentricities of the target. The eye movements generated during this task have been investigated here as trained rhesus monkeys fixated isovergence targets at different horizontal and vertical eccentricities during 10 Hz fore-aft oscillations. The elicited eye movements complied with the geometric requirements for binocular fixation, although not ideally. First, the corresponding vergence angle for which the movement of each eye would be compensatory was consistently less than that dictated by the actual fixation parameters. Second, the eye position with zero sensitivity to translation was not straight ahead, as geometrically required, but rather exhibited a systematic dependence on viewing distance and vergence angle. Third, responses were asymmetric, with gains being larger for abducting and downward compared with adducting and upward gaze directions, respectively. As frequency was varied between 4 and 12 Hz, responses exhibited high-pass filter properties with significant differences between abduction and adduction responses. As a result of these differences, vergence sensitivity increased as a function of frequency with a steeper slope than that of version. Despite largely undercompensatory version responses, vergence sensitivity was closer to ideal. Moreover, the observed dependence of vergence sensitivity on vergence angle, which was varied between 2.5 and 10 MA, was largely linear rather than quadratic (as geometrically predicted). We conclude that the spatial tuning of eye velocity sensitivity as a function of gaze and viewing distance follows the general geometric dependencies required for the maintenance of foveal visual acuity. However, systematic deviations from ideal behavior exist that might reflect asymmetric processing of

Ultra-deep sequencing of ribosome-associated poly-adenylated RNA in early Drosophila embryos reveals hundreds of conserved translated sORFs.

PubMed

Li, Hongmei; Hu, Chuansheng; Bai, Ling; Li, Hua; Li, Mingfa; Zhao, Xiaodong; Czajkowsky, Daniel M; Shao, Zhifeng

2016-12-01

There is growing recognition that small open reading frames (sORFs) encoding peptides shorter than 100 amino acids are an important class of functional elements in the eukaryotic genome, with several already identified to play critical roles in growth, development, and disease. However, our understanding of their biological importance has been hindered owing to the significant technical challenges limiting their annotation. Here we combined ultra-deep sequencing of ribosome-associated poly-adenylated RNAs with rigorous conservation analysis to identify a comprehensive population of translated sORFs during early Drosophila embryogenesis. In total, we identify 399 sORFs, including those previously annotated but without evidence of translational capacity, those found within transcripts previously classified as non-coding, and those not previously known to be transcribed. Further, we find, for the first time, evidence for translation of many sORFs with different isoforms, suggesting their regulation is as complex as longer ORFs. Furthermore, many sORFs are found not associated with ribosomes in late-stage Drosophila S2 cells, suggesting that many of the translated sORFs may have stage-specific functions during embryogenesis. These results thus provide the first comprehensive annotation of the sORFs present during early Drosophila embryogenesis, a necessary basis for a detailed delineation of their function in embryogenesis and other biological processes. © The Author 2016. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

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

PubMed Central

García, Adolfo M.; Ibáñez, Agustín; Huepe, David; Houck, Alexander L.; Michon, Maëva; Lezama, Carlos G.; Chadha, Sumeer; Rivera-Rei, Álvaro

2014-01-01

Studies on bilingual word reading and translation have examined the effects of lexical variables (e.g., concreteness, cognate status) by comparing groups of non-translators with varying levels of L2 proficiency. However, little attention has been paid to another relevant factor: translation expertise (TI). To explore this issue, we administered word reading and translation tasks to two groups of non-translators possessing different levels of informal TI (Experiment 1), and to three groups of bilinguals possessing different levels of translation training (Experiment 2). Reaction-time recordings showed that in all groups reading was faster than translation and unaffected by concreteness and cognate effects. Conversely, in both experiments, all groups translated concrete and cognate words faster than abstract and non-cognate words, respectively. Notably, an advantage of backward over forward translation was observed only for low-proficiency non-translators (in Experiment 1). Also, in Experiment 2, the modifications induced by translation expertise were more marked in the early than in the late stages of training and practice. The results suggest that TI contributes to modulating inter-equivalent connections in bilingual memory. PMID:25429279

Enterovirus Control of Translation and RNA Granule Stress Responses.

PubMed

Lloyd, Richard E

2016-03-30

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

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

PubMed

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

2017-02-08

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

Translational signaling responses preceding resistance training-mediated myofiber hypertrophy in young and old humans

PubMed Central

Mayhew, David L.; Kim, Jeong-su; Cross, James M.; Ferrando, Arny A.

2009-01-01

While skeletal muscle protein accretion during resistance training (RT)-mediated myofiber hypertrophy is thought to result from upregulated translation initiation signaling, this concept is based on responses to a single bout of unaccustomed resistance exercise (RE) with no measure of hypertrophy across RT. Further, aging appears to affect acute responses to RE, but whether age differences in responsiveness persist during RT leading to impaired RT adaptation is unclear. We therefore tested whether muscle protein fractional synthesis rate (FSR) and Akt/mammalian target of rapamycin (mTOR) signaling in response to unaccustomed RE differed in old vs. young adults, and whether age differences in acute responsiveness were associated with differences in muscle hypertrophy after 16 wk of RT. Fifteen old and 21 young adult subjects completed the 16-wk study. The phosphorylation states of Akt, S6K1, ribosomal protein S6 (RPS6), eukaryotic initiation factor 4E (eIF4E) binding protein (4EBP1), eIF4E, and eIF4G were all elevated (23–199%) 24 h after a bout of unaccustomed RE. A concomitant 62% increase in FSR was found in a subset (6 old, 8 young). Age × time interaction was found only for RPS6 phosphorylation (+335% in old subjects only), while there was an interaction trend (P = 0.084) for FSR (+96% in young subjects only). After 16 wk of RT, gains in muscle mass, type II myofiber size, and voluntary strength were similar in young and old subjects. In conclusion, at the level of translational signaling, we found no evidence of impaired responsiveness among older adults, and for the first time, we show that changes in translational signaling after unaccustomed RE were associated with substantial muscle protein accretion (hypertrophy) during continued RT. PMID:19589955

[Early mobilization. Competencies, responsibilities, milestones].

PubMed

Nydahl, P; Dewes, M; Dubb, R; Filipovic, S; Hermes, C; Jüttner, F; Kaltwasser, A; Klarmann, S; Klas, K; Mende, H; Rothaug, O; Schuchhardt, D

2016-03-01

Early mobilization is an evident, interprofessional concept to improve the outcome of intensive care patients. It reduces psychocognitive deficits and delirium and attenuates a general deconditioning, including atrophy of the respiratory pump and skeletal muscles. In this regard the interdisciplinary approach of early mobilization, taking into account different levels of mobilization, appears to be beneficial. The purpose of this study was to explore opinions on collaboration and tasks between different professional groups. During the 25th Bremen Conference on Intensive Medicine and Nursing on 20 February 2015, a questionnaire survey was carried out among the 120 participants of the German Early Mobilization Network meeting. In all, 102 questionnaires were analyzed. Most participants reported on the interdisciplinarity of the approach, but none of the tasks and responsibilities concerning early mobilization can be assigned to a single professional group. The practical implementation of mobilizing orally intubated patients may require two registered nurses as well as a physical therapist. Implementation in daily practice seems to be heterogeneous. There is no consensus regarding collaboration, competencies, and responsibilities with respect to early mobilization of intensive care patients. The approach to date has been characterized by a lack of interprofessional communication, which may lead to an inefficient use of the broad and varied base of knowledge and experienceof the different professions.

Designing Interventions Informed by Scientific Knowledge About Effects of Early Adversity: A Translational Neuroscience Agenda for Next Generation Addictions Research

PubMed Central

Fisher, Philip A.; Berkman, Elliot T.

2015-01-01

In spite of extensive scientific knowledge about the neurobiological systems and neural pathways underlying addictions, only limited progress has been made to reduce the population-level incidence of addictions by using prevention and treatment programs. In this area of research the translation of basic neuroscience of causal mechanisms to effective interventions has not been fully realized. In this article we describe how an understanding of the effects of early adverse experiences on brain and biological development may provide new opportunities to achieve impact at scale with respect to reduction of addictions. We propose four categories of new knowledge that translational neuroscience investigations of addictions should incorporate to be successful. We then describe a translational neuroscience-informed smoking cessation intervention based on this model. PMID:26985399

Translation suppression promotes stress granule formation and cell survival in response to cold shock

PubMed Central

Hofmann, Sarah; Cherkasova, Valeria; Bankhead, Peter; Bukau, Bernd; Stoecklin, Georg

2012-01-01

Cells respond to different types of stress by inhibition of protein synthesis and subsequent assembly of stress granules (SGs), cytoplasmic aggregates that contain stalled translation preinitiation complexes. Global translation is regulated through the translation initiation factor eukaryotic initiation factor 2α (eIF2α) and the mTOR pathway. Here we identify cold shock as a novel trigger of SG assembly in yeast and mammals. Whereas cold shock–induced SGs take hours to form, they dissolve within minutes when cells are returned to optimal growth temperatures. Cold shock causes eIF2α phosphorylation through the kinase PERK in mammalian cells, yet this pathway is not alone responsible for translation arrest and SG formation. In addition, cold shock leads to reduced mitochondrial function, energy depletion, concomitant activation of AMP-activated protein kinase (AMPK), and inhibition of mTOR signaling. Compound C, a pharmacological inhibitor of AMPK, prevents the formation of SGs and strongly reduces cellular survival in a translation-dependent manner. Our results demonstrate that cells actively suppress protein synthesis by parallel pathways, which induce SG formation and ensure cellular survival during hypothermia. PMID:22875991

Translational and structural requirements of the early nodulin gene enod40, a short-open reading frame-containing RNA, for elicitation of a cell-specific growth response in the alfalfa root cortex.

PubMed

Sousa, C; Johansson, C; Charon, C; Manyani, H; Sautter, C; Kondorosi, A; Crespi, M

2001-01-01

A diversity of mRNAs containing only short open reading frames (sORF-RNAs; encoding less than 30 amino acids) have been shown to be induced in growth and differentiation processes. The early nodulin gene enod40, coding for a 0.7-kb sORF-RNA, is expressed in the nodule primordium developing in the root cortex of leguminous plants after infection by symbiotic bacteria. Ballistic microtargeting of this gene into Medicago roots induced division of cortical cells. Translation of two sORFs (I and II, 13 and 27 amino acids, respectively) present in the conserved 5' and 3' regions of enod40 was required for this biological activity. These sORFs may be translated in roots via a reinitiation mechanism. In vitro translation products starting from the ATG of sORF I were detectable by mutating enod40 to yield peptides larger than 38 amino acids. Deletion of a Medicago truncatula enod40 region between the sORFs, spanning a predicted RNA structure, did not affect their translation but resulted in significantly decreased biological activity. Our data reveal a complex regulation of enod40 action, pointing to a role of sORF-encoded peptides and structured RNA signals in developmental processes involving sORF-RNAs.

Early career mentoring for translational researchers: mentee perspectives on challenges and issues.

PubMed

Keller, Thomas E; Collier, Peter J; Blakeslee, Jennifer E; Logan, Kay; McCracken, Karen; Morris, Cynthia

2014-01-01

The education and training of early career biomedical translational researchers often involves formal mentoring by more experienced colleagues. This study investigated the nature of these mentoring relationships from the perspective of mentees. The objective was to understand the challenges and issues encountered by mentees in forming and maintaining productive mentoring relationships. Three focus groups (n=14) were conducted with early career researchers who had mentored career development awards. Thematic analysis identified, categorized, and illustrated the challenges and issues reported by mentees. The range of mentee challenges was reflected in five major categories: (a) network--finding appropriate mentors to meet various needs; (b) access--structuring schedules and opportunities to receive mentoring; (c) expectations--negotiating the mechanics of the mentoring relationship and its purpose; (d) alignment--managing mentor-mentee mismatches regarding interests, priorities, and goals; and (e) skills and supports--developing the institutional supports to be successful. Mentoring relationships created for academic training and career development contend with tasks common to many other relationships, namely, recognizing compatibility, finding time, establishing patterns, agreeing to goals, and achieving aims. Identifying challenges faced by mentees can facilitate the development of appropriate trainings and supports to foster mentoring relationships in academic and career settings.

The Frustrated Host Response to Legionella pneumophila Is Bypassed by MyD88-Dependent Translation of Pro-inflammatory Cytokines

PubMed Central

Asrat, Seblewongel; Dugan, Aisling S.; Isberg, Ralph R.

2014-01-01

Many pathogens, particularly those that require their host for survival, have devised mechanisms to subvert the host immune response in order to survive and replicate intracellularly. Legionella pneumophila, the causative agent of Legionnaires' disease, promotes intracellular growth by translocating proteins into its host cytosol through its type IV protein secretion machinery. At least 5 of the bacterial translocated effectors interfere with the function of host cell elongation factors, blocking translation and causing the induction of a unique host cell transcriptional profile. In addition, L. pneumophila also interferes with translation initiation, by preventing cap-dependent translation in host cells. We demonstrate here that protein translation inhibition by L. pneumophila leads to a frustrated host MAP kinase response, where genes involved in the pathway are transcribed but fail to be translated due to the bacterium-induced protein synthesis inhibition. Surprisingly, few pro-inflammatory cytokines, such as IL-1α and IL-1β, bypass this inhibition and get synthesized in the presence of Legionella effectors. We show that the selective synthesis of these genes requires MyD88 signaling and takes place in both infected cells that harbor bacteria and neighboring bystander cells. Our findings offer a perspective of how host cells are able to cope with pathogen-encoded activities that disrupt normal cellular process and initiate a successful inflammatory response. PMID:25058342

A Clinical Translation of the Article Titled "Evidence for the Implementation of the Early Start Denver Model for Young Children With Autism Spectrum Disorder".

PubMed

Shannon, Robin Adair

2015-01-01

The purpose of this article is to offer a clinical translation of a literature review titled "Evidence for the Implementation of the Early Start Denver Model for Young Children With Autism Spectrum Disorder" by Ryberg (2015). The literature review was conducted to determine the strength of the research evidence regarding the effectiveness of the Early Start Denver Model in improving cognitive, language, and behavioral functioning of children with autism spectrum disorder. In an effort to narrow the gap between evidence and practice, this clinical translation will discuss the components of the literature review in terms of its rationale for and objectives, methods, results, and implications for evidence-based nursing practice. © The Author(s) 2015.

Early Career Mentoring for Translational Researchers: Mentee Perspectives on Challenges and Issues

PubMed Central

Keller, Thomas E.; Collier, Peter J.; Blakeslee, Jennifer E.; Logan, Kay; McCracken, Karen; Morris, Cynthia

2014-01-01

Background and purposes The education and training of early career biomedical translational researchers often involves formal mentoring by more experienced colleagues. This study investigated the nature of these mentoring relationships from the perspective of mentees. The objective was to understand the challenges and issues encountered by mentees in forming and maintaining productive mentoring relationships. Method Three focus groups (n=14) were conducted with early career researchers who had mentored career development awards. Thematic analysis identified, categorized, and illustrated the challenges and issues reported by mentees. Results The range of mentee challenges was reflected in five major categories: 1) network—finding appropriate mentors to meet various needs; 2) access—structuring schedules and opportunities to receive mentoring; 3) expectations—negotiating the mechanics of the mentoring relationship and its purpose; 4) alignment—managing mentor-mentee mismatches regarding interests, priorities, and goals; and 5) skills and supports—developing the institutional supports to be successful. Conclusions Mentoring relationships created for academic training and career development contend with tasks common to many other relationships, namely recognizing compatibility, finding time, establishing patterns, agreeing to goals, and achieving aims. Identifying challenges faced by mentees can facilitate the development of appropriate trainings and supports to foster mentoring relationships in academic and career settings. PMID:25010230

Inspiring hope-A physician's responsibility, translating the science into clinical practice.

PubMed

Temple, Walley J

2018-03-01

Giving hope to patients is our responsibility. It is the essence of a meaningful practice in medicine. Science now allows us to understand this complex and multidimensional human dynamic, and translate it into clinical practice. Quantitative research has shown hope is strong even in terminal illness. Through qualitative methodology hope fostering strategies and hope hindering behaviors have been identified. This exciting new knowledge facilitates the challenging task of disclosure of bad news while enabling hope. © 2017 Wiley Periodicals, Inc.

Translational medicine: science or wishful thinking?

PubMed Central

Wehling, Martin

2008-01-01

"Translational medicine" as a fashionable term is being increasingly used to describe the wish of biomedical researchers to ultimately help patients. Despite increased efforts and investments into R&D, the output of novel medicines has been declining dramatically over the past years. Improvement of translation is thought to become a remedy as one of the reasons for this widening gap between input and output is the difficult transition between preclinical ("basic") and clinical stages in the R&D process. Animal experiments, test tube analyses and early human trials do simply not reflect the patient situation well enough to reliably predict efficacy and safety of a novel compound or device. This goal, however, can only be achieved if the translational processes are scientifically backed up by robust methods some of which still need to be developed. This mainly relates to biomarker development and predictivity assessment, biostatistical methods, smart and accelerated early human study designs and decision algorithms among other features. It is therefore claimed that a new science needs to be developed called 'translational science in medicine'. PMID:18559092

Translational Identification of Transcriptional Signatures of Major Depression and Antidepressant Response

PubMed Central

Hervé, Mylène; Bergon, Aurélie; Le Guisquet, Anne-Marie; Leman, Samuel; Consoloni, Julia-Lou; Fernandez-Nunez, Nicolas; Lefebvre, Marie-Noëlle; El-Hage, Wissam; Belzeaux, Raoul; Belzung, Catherine; Ibrahim, El Chérif

2017-01-01

Major depressive disorder (MDD) is a highly prevalent mental illness whose therapy management remains uncertain, with more than 20% of patients who do not achieve response to antidepressants. Therefore, identification of reliable biomarkers to predict response to treatment will greatly improve MDD patient medical care. Due to the inaccessibility and lack of brain tissues from living MDD patients to study depression, researches using animal models have been useful in improving sensitivity and specificity of identifying biomarkers. In the current study, we used the unpredictable chronic mild stress (UCMS) model and correlated stress-induced depressive-like behavior (n = 8 unstressed vs. 8 stressed mice) as well as the fluoxetine-induced recovery (n = 8 stressed and fluoxetine-treated mice vs. 8 unstressed and fluoxetine-treated mice) with transcriptional signatures obtained by genome-wide microarray profiling from whole blood, dentate gyrus (DG), and the anterior cingulate cortex (ACC). Hierarchical clustering and rank-rank hypergeometric overlap (RRHO) procedures allowed us to identify gene transcripts with variations that correlate with behavioral profiles. As a translational validation, some of those transcripts were assayed by RT-qPCR with blood samples from 10 severe major depressive episode (MDE) patients and 10 healthy controls over the course of 30 weeks and four visits. Repeated-measures ANOVAs revealed candidate trait biomarkers (ARHGEF1, CMAS, IGHMBP2, PABPN1 and TBC1D10C), whereas univariate linear regression analyses uncovered candidates state biomarkers (CENPO, FUS and NUBP1), as well as prediction biomarkers predictive of antidepressant response (CENPO, NUBP1). These data suggest that such a translational approach may offer new leads for clinically valid panels of biomarkers for MDD. PMID:28848385

Development of an Infection-Responsive Fluorescent Sensor for the Early Detection of Urinary Catheter Blockage.

PubMed

Milo, Scarlet; Acosta, Florianne B; Hathaway, Hollie J; Wallace, Laura A; Thet, Naing T; Jenkins, A Toby A

2018-03-23

Formation of crystalline biofilms following infection by Proteus mirabilis can lead to encrustation and blockage of long-term indwelling catheters, with serious clinical consequences. We describe a simple sensor, placed within the catheter drainage bag, to alert of impending blockage via a urinary color change. The pH-responsive sensor is a dual-layered polymeric "lozenge", able to release the self-quenching dye 5(6)-carboxyfluorescein in response to the alkaline urine generated by the expression of bacterial urease. Sensor performance was evaluated within a laboratory model of the catheterized urinary tract, infected with both urease positive and negative bacterial strains under conditions of established infection, achieving an average "early warning" of catheter blockage of 14.5 h. Signaling only occurred following infection with urease positive bacteria. Translation of these sensors into a clinical environment would allow appropriate intervention before the occurrence of catheter blockage, a problem for which there is currently no effective control method.

Characterizing Responses of Translation Invariant Neurons to Natural Stimuli: Maximally Informative Invariant Dimensions

PubMed Central

Eickenberg, Michael; Rowekamp, Ryan J.; Kouh, Minjoon; Sharpee, Tatyana O.

2012-01-01

Our visual system is capable of recognizing complex objects even when their appearances change drastically under various viewing conditions. Especially in the higher cortical areas, the sensory neurons reflect such functional capacity in their selectivity for complex visual features and invariance to certain object transformations, such as image translation. Due to the strong nonlinearities necessary to achieve both the selectivity and invariance, characterizing and predicting the response patterns of these neurons represents a formidable computational challenge. A related problem is that such neurons are poorly driven by randomized inputs, such as white noise, and respond strongly only to stimuli with complex high-order correlations, such as natural stimuli. Here we describe a novel two-step optimization technique that can characterize both the shape selectivity and the range and coarseness of position invariance from neural responses to natural stimuli. One step in the optimization involves finding the template as the maximally informative dimension given the estimated spatial location where the response could have been triggered within each image. The estimates of the locations that triggered the response are subsequently updated in the next step. Under the assumption of a monotonic relationship between the firing rate and stimulus projections on the template at a given position, the most likely location is the one that has the largest projection on the estimate of the template. The algorithm shows quick convergence during optimization, and the estimation results are reliable even in the regime of small signal-to-noise ratios. When we apply the algorithm to responses of complex cells in the primary visual cortex (V1) to natural movies, we find that responses of the majority of cells were significantly better described by translation invariant models based on one template compared with position-specific models with several relevant features. PMID:22734487

Responses of non-eye movement central vestibular neurons to sinusoidal horizontal translation in compensated macaques after unilateral labyrinthectomy

PubMed Central

Lin, Nan; Wei, Min

2014-01-01

After vestibular labyrinth injury, behavioral deficits partially recover through the process of vestibular compensation. The present study was performed to improve our understanding of the physiology of the macaque vestibular system in the compensated state (>7 wk) after unilateral labyrinthectomy (UL). Three groups of vestibular nucleus neurons were included: pre-UL control neurons, neurons ipsilateral to the lesion, and neurons contralateral to the lesion. The firing responses of neurons sensitive to linear acceleration in the horizontal plane were recorded during sinusoidal horizontal translation directed along six different orientations (30° apart) at 0.5 Hz and 0.2 g peak acceleration (196 cm/s2). This data defined the vector of best response for each neuron in the horizontal plane, along which sensitivity, symmetry, detection threshold, and variability of firing were determined. Additionally, the responses of the same cells to translation over a series of frequencies (0.25–5.0 Hz) either in the interaural or naso-occipital orientation were obtained to define the frequency response characteristics in each group. We found a decrease in sensitivity, increase in threshold, and alteration in orientation of best responses in the vestibular nuclei after UL. Additionally, the phase relationship of the best neural response to translational stimulation changed with UL. The symmetry of individual neuron responses in the excitatory and inhibitory directions was unchanged by UL. Bilateral central utricular neurons still demonstrated two-dimension tuning after UL, consistent with spatio-temporal convergence from a single vestibular end-organ. These neuronal data correlate with known behavioral deficits after unilateral vestibular compromise. PMID:24717349

Coordinated post-translational responses of aquaporins to abiotic and nutritional stimuli in Arabidopsis roots.

PubMed

di Pietro, Magali; Vialaret, Jérôme; Li, Guo-Wei; Hem, Sonia; Prado, Karine; Rossignol, Michel; Maurel, Christophe; Santoni, Véronique

2013-12-01

In plants, aquaporins play a crucial role in regulating root water transport in response to environmental and physiological cues. Controls achieved at the post-translational level are thought to be of critical importance for regulating aquaporin function. To investigate the general molecular mechanisms involved, we performed, using the model species Arabidopsis, a comprehensive proteomic analysis of root aquaporins in a large set of physiological contexts. We identified nine physiological treatments that modulate root hydraulics in time frames of minutes (NO and H2O2 treatments), hours (mannitol and NaCl treatments, exposure to darkness and reversal with sucrose, phosphate supply to phosphate-starved roots), or days (phosphate or nitrogen starvation). All treatments induced inhibition of root water transport except for sucrose supply to dark-grown plants and phosphate resupply to phosphate-starved plants, which had opposing effects. Using a robust label-free quantitative proteomic methodology, we identified 12 of 13 plasma membrane intrinsic protein (PIP) aquaporin isoforms, 4 of the 10 tonoplast intrinsic protein isoforms, and a diversity of post-translational modifications including phosphorylation, methylation, deamidation, and acetylation. A total of 55 aquaporin peptides displayed significant changes after treatments and enabled the identification of specific and as yet unknown patterns of response to stimuli. The data show that the regulation of PIP and tonoplast intrinsic protein abundance was involved in response to a few treatments (i.e. NaCl, NO, and nitrate starvation), whereas changes in the phosphorylation status of PIP aquaporins were positively correlated to changes in root hydraulic conductivity in the whole set of treatments. The identification of in vivo deamidated forms of aquaporins and their stimulus-induced changes in abundance may reflect a new mechanism of aquaporin regulation. The overall work provides deep insights into the in vivo post-translational

Sequoyah Foreign Language Translation System - Business Case Analysis

DTIC Science & Technology

2007-12-01

Interactive Natural Dialogue System (S-MINDS)..................................................................20 j. Voice Response Translator ( VRT ...20 Figure 8. U.S. Marine Military Policeman Demonstrating VRT (From: Ref. U.S...www.languagerealm.com/Files/usmc_mt_test_2004.pdf. 21 j. Voice Response Translator ( VRT ) The VRT is a S2S human language translation device that uses

The effects of fixed-time reinforcement schedules on functional response classes: a translational study.

PubMed

Heinicke, Megan R; Carr, James E; LeBlanc, Linda A

2012-01-01

Research on functional response classes has applied significance because less severe forms of problem behavior have been found to co-occur with more severe forms. In addition, the most severe forms of problem behavior are sometimes targeted for intervention without monitoring other less severe forms. In such cases, it is unknown whether and how untreated forms of problem behavior covary with the targeted behaviors. The present study employed a translational procedure (with button presses as the target behavior) to investigate response covariation under noncontingent reinforcement with typically developing preschoolers. The results indicated that noncontingent reinforcement was generally effective in decreasing all response class members when only one member was targeted.

Proteogenomic analysis reveals alternative splicing and translation as part of the abscisic acid response in Arabidopsis seedlings.

PubMed

Zhu, Fu-Yuan; Chen, Mo-Xian; Ye, Neng-Hui; Shi, Lu; Ma, Kai-Long; Yang, Jing-Fang; Cao, Yun-Ying; Zhang, Youjun; Yoshida, Takuya; Fernie, Alisdair R; Fan, Guang-Yi; Wen, Bo; Zhou, Ruo; Liu, Tie-Yuan; Fan, Tao; Gao, Bei; Zhang, Di; Hao, Ge-Fei; Xiao, Shi; Liu, Ying-Gao; Zhang, Jianhua

2017-08-01

In eukaryotes, mechanisms such as alternative splicing (AS) and alternative translation initiation (ATI) contribute to organismal protein diversity. Specifically, splicing factors play crucial roles in responses to environment and development cues; however, the underlying mechanisms are not well investigated in plants. Here, we report the parallel employment of short-read RNA sequencing, single molecule long-read sequencing and proteomic identification to unravel AS isoforms and previously unannotated proteins in response to abscisic acid (ABA) treatment. Combining the data from the two sequencing methods, approximately 83.4% of intron-containing genes were alternatively spliced. Two AS types, which are referred to as alternative first exon (AFE) and alternative last exon (ALE), were more abundant than intron retention (IR); however, by contrast to AS events detected under normal conditions, differentially expressed AS isoforms were more likely to be translated. ABA extensively affects the AS pattern, indicated by the increasing number of non-conventional splicing sites. This work also identified thousands of unannotated peptides and proteins by ATI based on mass spectrometry and a virtual peptide library deduced from both strands of coding regions within the Arabidopsis genome. The results enhance our understanding of AS and alternative translation mechanisms under normal conditions, and in response to ABA treatment. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Translation Fidelity of Psychological Scales: An Item Response Theory Analysis of an Individualism-Collectivism Scale.

ERIC Educational Resources Information Center

Bontempo, Robert

1993-01-01

Describes a method for assessing the quality of translations based on item response theory (IRT). Results from the IRT technique with French and Chinese versions of a scale measuring individualism-collectivism for samples of 250 U.S., 357 French, and 290 Chinese undergraduates show how several biased items are detected. (SLD)

Strategies for Derisking Translational Processes for Biomedical Technologies.

PubMed

Abou-El-Enein, Mohamed; Duda, Georg N; Gruskin, Elliott A; Grainger, David W

2017-02-01

Inefficient translational processes for technology-oriented biomedical research have led to some prominent and frequent failures in the development of many leading drug candidates, several designated investigational drugs, and some medical devices, as well as documented patient harm and postmarket product withdrawals. Derisking this process, particularly in the early stages, should increase translational efficiency and streamline resource utilization, especially in an academic setting. In this opinion article, we identify a 12-step guideline for reducing risks typically associated with translating medical technologies as they move toward prototypes, preclinical proof of concept, and possible clinical testing. Integrating the described 12-step process should prove valuable for improving how early-stage academic biomedical concepts are cultivated, culled, and manicured toward intended clinical applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthetic Biology and the Translational Imperative.

PubMed

Heidari Feidt, Raheleh; Ienca, Marcello; Elger, Bernice Simone; Folcher, Marc

2017-12-18

Advances at the interface between the biological sciences and engineering are giving rise to emerging research fields such as synthetic biology. Harnessing the potential of synthetic biology requires timely and adequate translation into clinical practice. However, the translational research enterprise is currently facing fundamental obstacles that slow down the transition of scientific discoveries from the laboratory to the patient bedside. These obstacles including scarce financial resources and deficiency of organizational and logistic settings are widely discussed as primary impediments to translational research. In addition, a number of socio-ethical considerations inherent in translational research need to be addressed. As the translational capacity of synthetic biology is tightly linked to its social acceptance and ethical approval, ethical limitations may-together with financial and organizational problems-be co-determinants of suboptimal translation. Therefore, an early assessment of such limitations will contribute to proactively favor successful translation and prevent the promising potential of synthetic biology from remaining under-expressed. Through the discussion of two case-specific inventions in synthetic biology and their associated ethical implications, we illustrate the socio-ethical challenges ahead in the process of implementing synthetic biology into clinical practice. Since reducing the translational lag is essential for delivering the benefits of basic biomedical research to society at large and promoting global health, we advocate a moral obligation to accelerating translational research: the "translational imperative."

Talking the Talk: Translating Research to Practice

ERIC Educational Resources Information Center

Grifenhagen, Jill F.; Barnes, Erica M.; Collins, Molly F.; Dickinson, David K.

2017-01-01

Decades of research have identified features of classrooms and teachers' talk that are associated with children's language growth. Unfortunately, much of this work has not yet translated to widespread practice in early childhood classrooms. Given the important contributions that early language development makes to later academic achievement,…

The power of instructions: Proactive configuration of stimulus-response translation.

PubMed

Meiran, Nachshon; Pereg, Maayan; Kessler, Yoav; Cole, Michael W; Braver, Todd S

2015-05-01

Humans are characterized by an especially highly developed ability to use instructions to prepare toward upcoming events; yet, it is unclear just how powerful instructions can be. Although prior work provides evidence that instructions can be sufficiently powerful to proactively program working memory to execute stimulus-response (S-R) translations, in a reflexlike fashion (intention-based reflexivity [IBR]), the results to date have been equivocal. To overcome this shortcoming, we developed, and tested in 4 studies, a novel paradigm (the NEXT paradigm) that isolates IBR effects even prior to first task execution. In each miniblock, participants received S-R mapping instructions for a new task. Prior to implementing this mapping, responses were required to advance through screens during a preparatory (NEXT) phase. When the NEXT response was incompatible with the instructed S-R mapping, interference (IBR effect) was observed. This NEXT compatibility effect and performance in the implementation (GO) trials barely changed when prior practice of a few trials was provided. Finally, a manipulation that encouraged preparation resulted in relatively durable NEXT compatibility effects (indicating durable preparatory efforts) coupled with improved GO performance (indicating the success of these efforts). Together, these findings establish IBR as a marker of instructed proactive control. (c) 2015 APA, all rights reserved).

The Multidisciplinary Translational Team (MTT) Model for Training and Development of Translational Research Investigators

PubMed Central

Hellmich, Mark R.; Cestone, Christina M.; Wooten, Kevin C.; Ottenbacher, Kenneth J.; Chonmaitree, Tasnee; Anderson, Karl E.; Brasier, Allan R.

2015-01-01

ABSTRACT Multiinstitutional research collaborations now form the most rapid and productive project execution structures in the health sciences. Effective adoption of a multidisciplinary team research approach is widely accepted as one mechanism enabling rapid translation of new discoveries into interventions in human health. Although the impact of successful team‐based approaches facilitating innovation has been well‐documented, its utility for training a new generation of scientists has not been thoroughly investigated. We describe the characteristics of how multidisciplinary translational teams (MTTs) promote career development of translational research scholars through competency building, interprofessional integration, and team‐based mentoring approaches. Exploratory longitudinal and outcome assessments from our experience show that MTT membership had a positive effect on the development of translational research competencies, as determined by a self‐report survey of 32 scholars. We also observed that all trainees produced a large number of collaborative publications that appeared to be associated with their CTSA association and participation with MTTs. We conclude that the MTT model provides a unique training environment for translational and team‐based learning activities, for investigators at early stages of career development. PMID:26010046

The Multidisciplinary Translational Team (MTT) Model for Training and Development of Translational Research Investigators.

PubMed

Ameredes, Bill T; Hellmich, Mark R; Cestone, Christina M; Wooten, Kevin C; Ottenbacher, Kenneth J; Chonmaitree, Tasnee; Anderson, Karl E; Brasier, Allan R

2015-10-01

Multiinstitutional research collaborations now form the most rapid and productive project execution structures in the health sciences. Effective adoption of a multidisciplinary team research approach is widely accepted as one mechanism enabling rapid translation of new discoveries into interventions in human health. Although the impact of successful team-based approaches facilitating innovation has been well-documented, its utility for training a new generation of scientists has not been thoroughly investigated. We describe the characteristics of how multidisciplinary translational teams (MTTs) promote career development of translational research scholars through competency building, interprofessional integration, and team-based mentoring approaches. Exploratory longitudinal and outcome assessments from our experience show that MTT membership had a positive effect on the development of translational research competencies, as determined by a self-report survey of 32 scholars. We also observed that all trainees produced a large number of collaborative publications that appeared to be associated with their CTSA association and participation with MTTs. We conclude that the MTT model provides a unique training environment for translational and team-based learning activities, for investigators at early stages of career development. © 2015 Wiley Periodicals, Inc.

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.

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.

Translating Alcohol Research

PubMed Central

Batman, Angela M.; Miles, Michael F.

2015-01-01

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

Translational Regulation in Nutrigenomics12

PubMed Central

Liu, Botao; Qian, Shu-Bing

2011-01-01

The emergence of genome-wide analysis to interrogate cellular DNA, RNA, and protein content has revolutionized the study of the control network that mediates cellular homeostasis. Nutrigenomics addresses the effect of nutrients on gene expression, which provides a basis for understanding the biological activity of dietary components. Translation of mRNAs represents the last step of genetic flow and primarily defines the proteome. Translational regulation is thus critical for gene expression, in particular, under nutrient excess or deficiency. Until recently, it was unclear how the global effects of translational control are influenced by nutrient signaling. An emerging concept of translational reprogramming addresses how to maintain the expression of specific proteins during pathophysiological conditions by translation of selective mRNAs. Here we describe recent advances in our understanding of translational control, nutrient signaling, and their dysregulation in aging and cancer. The mechanistic understanding of translational regulation in response to different nutrient conditions may help identify potential dietary and therapeutic targets to improve human health. PMID:22332093

Translational informatics: an industry perspective.

PubMed

Cantor, Michael N

2012-01-01

Translational informatics (TI) is extremely important for the pharmaceutical industry, especially as the bar for regulatory approval of new medications is set higher and higher. This paper will explore three specific areas in the drug development lifecycle, from tools developed by precompetitive consortia to standardized clinical data collection to the effective delivery of medications using clinical decision support, in which TI has a major role to play. Advancing TI will require investment in new tools and algorithms, as well as ensuring that translational issues are addressed early in the design process of informatics projects, and also given higher weight in funding or publication decisions. Ultimately, the source of translational tools and differences between academia and industry are secondary, as long as they move towards the shared goal of improving health.

mEBT: multiple-matching Evidence-based Translator of Murine Genomic Responses for Human Immunity Studies.

PubMed

Tae, Donghyun; Seok, Junhee

2018-05-29

In this paper, we introduce multiple-matching Evidence-based Translator (mEBT) to discover genomic responses from murine expression data for human immune studies, which are significant in the given condition of mice and likely have similar responses in the corresponding condition of human. mEBT is evaluated over multiple data sets and shows improved inter-species agreement. mEBT is expected to be useful for research groups who use murine models to study human immunity. http://cdal.korea.ac.kr/mebt/. jseok14@korea.ac.kr. Supplementary data are available at Bioinformatics online.

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

The Impact of Machine Translation and Computer-aided Translation on Translators

NASA Astrophysics Data System (ADS)

Peng, Hao

2018-03-01

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

Hepatitis C Virus Reveals a Novel Early Control in Acute Immune Response

PubMed Central

Arnaud, Noëlla; Dabo, Stéphanie; Akazawa, Daisuke; Fukasawa, Masayoshi; Shinkai-Ouchi, Fumiko; Hugon, Jacques; Wakita, Takaji; Meurs, Eliane F.

2011-01-01

Recognition of viral RNA structures by the intracytosolic RNA helicase RIG-I triggers induction of innate immunity. Efficient induction requires RIG-I ubiquitination by the E3 ligase TRIM25, its interaction with the mitochondria-bound MAVS protein, recruitment of TRAF3, IRF3- and NF-κB-kinases and transcription of Interferon (IFN). In addition, IRF3 alone induces some of the Interferon-Stimulated Genes (ISGs), referred to as early ISGs. Infection of hepatocytes with Hepatitis C virus (HCV) results in poor production of IFN despite recognition of the viral RNA by RIG-I but can lead to induction of early ISGs. HCV was shown to inhibit IFN production by cleaving MAVS through its NS3/4A protease and by controlling cellular translation through activation of PKR, an eIF2α-kinase containing dsRNA-binding domains (DRBD). Here, we have identified a third mode of control of IFN induction by HCV. Using HCVcc and the Huh7.25.CD81 cells, we found that HCV controls RIG-I ubiquitination through the di-ubiquitine-like protein ISG15, one of the early ISGs. A transcriptome analysis performed on Huh7.25.CD81 cells silenced or not for PKR and infected with JFH1 revealed that HCV infection leads to induction of 49 PKR-dependent genes, including ISG15 and several early ISGs. Silencing experiments revealed that this novel PKR-dependent pathway involves MAVS, TRAF3 and IRF3 but not RIG-I, and that it does not induce IFN. Use of PKR inhibitors showed that this pathway requires the DRBD but not the kinase activity of PKR. We then demonstrated that PKR interacts with HCV RNA and MAVS prior to RIG-I. In conclusion, HCV recruits PKR early in infection as a sensor to trigger induction of several IRF3-dependent genes. Among those, ISG15 acts to negatively control the RIG-I/MAVS pathway, at the level of RIG-I ubiquitination.These data give novel insights in the machinery involved in the early events of innate immune response. PMID:22022264

[Molecular mechanisms of protein biosynthesis initiation--biochemical and biomedical implications of a new model of translation enhanced by the RNA hypoxia response element (rHRE)].

PubMed

Master, Adam; Nauman, Alicja

2014-01-01

Translation initiation is a key rate-limiting step in cellular protein synthesis. A cap-dependent initiation is the most effective mechanism of the translation. However, some physiological (mitosis) and pathological (oxidative stress) processes may switch the classic mechanism to an alternative one that is regulated by an mRNA element such as IRES, uORF, IRE, CPE, DICE, AURE or CITE. A recently discovered mechanism of RNA hypoxia response element (rHRE)-dependent translation initiation, may change the view of oxygen-regulated translation and give a new insight into unexplained biochemical processes. Hypoxia is one of the better-known factors that may trigger an alternative mechanism of the translation initiation. Temporal events of oxygen deficiency within tissues and organs may activate processes such as angiogenesis, myogenesis, regeneration, wound healing, and may promote an adaptive response in cardiovascular and neurodegenerative diseases. On the other hand, growth of solid tumors may be accompanied by cyclic hypoxia, allowing for synthesis of proteins required for further progression of cancer cells. This paper provides a review of current knowledge on translational control in the context of alternative models of translation initiation.

Pharmacogenetics and Imaging-Pharmacogenetics of Antidepressant Response: Towards Translational Strategies.

PubMed

Lett, Tristram A; Walter, Henrik; Brandl, Eva J

2016-12-01

Genetic variation underlies both the response to antidepressant treatment and the occurrence of side effects. Over the past two decades, a number of pharmacogenetic variants, among these the SCL6A4, BDNF, FKBP5, GNB3, GRIK4, and ABCB1 genes, have come to the forefront in this regard. However, small effects sizes, mixed results in independent samples, and conflicting meta-analyses results led to inherent difficulties in the field of pharmacogenetics translating these findings into clinical practice. Nearly all antidepressant pharmacogenetic variants have potentially pleiotropic effects in which they are associated with major depressive disorder, intermediate phenotypes involved in emotional processes, and brain areas affected by antidepressant treatment. The purpose of this article is to provide a comprehensive review of the advances made in the field of pharmacogenetics of antidepressant efficacy and side effects, imaging findings of antidepressant response, and the latest results in the expanding field of imaging-pharmacogenetics studies. We suggest there is mounting evidence that genetic factors exert their impact on treatment response by influencing brain structural and functional changes during antidepressant treatment, and combining neuroimaging and genetic methods may be a more powerful way to detect biological mechanisms of response than either method alone. The most promising imaging-pharmacogenetics findings exist for the SCL6A4 gene, with converging associations with antidepressant response, frontolimbic predictors of affective symptoms, and normalization of frontolimbic activity following antidepressant treatment. More research is required before imaging-pharmacogenetics informed personalized medicine can be applied to antidepressant treatment; nevertheless, inroads have been made towards assessing genetic and neuroanatomical liability and potential clinical application.

Reactive Oxygen Species-Mediated Loss of Synaptic Akt1 Signaling Leads to Deficient Activity-Dependent Protein Translation Early in Alzheimer's Disease.

PubMed

Ahmad, Faraz; Singh, Kunal; Das, Debajyoti; Gowaikar, Ruturaj; Shaw, Eisha; Ramachandran, Arathy; Rupanagudi, Khader Valli; Kommaddi, Reddy Peera; Bennett, David A; Ravindranath, Vijayalakshmi

2017-12-01

Synaptic deficits are known to underlie the cognitive dysfunction seen in Alzheimer's disease (AD). Generation of reactive oxygen species (ROS) by β-amyloid has also been implicated in AD pathogenesis. However, it is unclear whether ROS contributes to synaptic dysfunction seen in AD pathogenesis and, therefore, we examined whether altered redox signaling could contribute to synaptic deficits in AD. Activity dependent but not basal translation was impaired in synaptoneurosomes from 1-month old presymptomatic APP Swe /PS1ΔE9 (APP/PS1) mice, and this deficit was sustained till middle age (MA, 9-10 months). ROS generation leads to oxidative modification of Akt1 in the synapse and consequent reduction in Akt1-mechanistic target of rapamycin (mTOR) signaling, leading to deficiency in activity-dependent protein translation. Moreover, we found a similar loss of activity-dependent protein translation in synaptoneurosomes from postmortem AD brains. Loss of activity-dependent protein translation occurs presymptomatically early in the pathogenesis of AD. This is caused by ROS-mediated loss of pAkt1, leading to reduced synaptic Akt1-mTOR signaling and is rescued by overexpression of Akt1. ROS-mediated damage is restricted to the synaptosomes, indicating selectivity. We demonstrate that ROS-mediated oxidative modification of Akt1 contributes to synaptic dysfunction in AD, seen as loss of activity-dependent protein translation that is essential for synaptic plasticity and maintenance. Therapeutic strategies promoting Akt1-mTOR signaling at synapses may provide novel target(s) for disease-modifying therapy in AD. Antioxid. Redox Signal. 27, 1269-1280.

Binary translation using peephole translation rules

DOEpatents

Bansal, Sorav; Aiken, Alex

2010-05-04

An efficient binary translator uses peephole translation rules to directly translate executable code from one instruction set to another. In a preferred embodiment, the translation rules are generated using superoptimization techniques that enable the translator to automatically learn translation rules for translating code from the source to target instruction set architecture.

Development of Translational Methods in Spectral Analysis of Human Infant Crying and Rat Pup Ultrasonic Vocalizations for Early Neurobehavioral Assessment

PubMed Central

Zeskind, Philip Sanford; McMurray, Matthew S.; Garber, Kristin A.; Neuspiel, Juliana M.; Cox, Elizabeth T.; Grewen, Karen M.; Mayes, Linda C.; Johns, Josephine M.

2011-01-01

The purpose of this article is to describe the development of translational methods by which spectrum analysis of human infant crying and rat pup ultrasonic vocalizations (USVs) can be used to assess potentially adverse effects of various prenatal conditions on early neurobehavioral development. The study of human infant crying has resulted in a rich set of measures that has long been used to assess early neurobehavioral insult due to non-optimal prenatal environments, even among seemingly healthy newborn and young infants. In another domain of study, the analysis of rat put USVs has been conducted via paradigms that allow for better experimental control over correlated prenatal conditions that may confound findings and conclusions regarding the effects of specific prenatal experiences. The development of translational methods by which cry vocalizations of both species can be analyzed may provide the opportunity for findings from the two approaches of inquiry to inform one another through their respective strengths. To this end, we present an enhanced taxonomy of a novel set of common measures of cry vocalizations of both human infants and rat pups based on a conceptual framework that emphasizes infant crying as a graded and dynamic acoustic signal. This set includes latency to vocalization onset, duration and repetition rate of expiratory components, duration of inter-vocalization-intervals and spectral features of the sound, including the frequency and amplitude of the fundamental and dominant frequencies. We also present a new set of classifications of rat pup USV waveforms that include qualitative shifts in fundamental frequency, similar to the presence of qualitative shifts in fundamental frequency that have previously been related to insults to neurobehavioral integrity in human infants. Challenges to the development of translational analyses, including the use of different terminologies, methods of recording, and spectral analyses are discussed, as well as

Blood gene expression profiling of an early acetaminophen response.

PubMed

Bushel, P R; Fannin, R D; Gerrish, K; Watkins, P B; Paules, R S

2017-06-01

Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4 g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing, and 12 genes were detected with expression profiles significantly altered within 24 h. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure, and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration.

Blood Gene Expression Profiling of an Early Acetaminophen Response

PubMed Central

Bushel, Pierre R.; Fannin, Rick D.; Gerrish, Kevin; Watkins, Paul B.; Paules, Richard S.

2018-01-01

Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing and 12 genes were detected with expression profiles significantly altered within 24 hrs. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration. PMID:26927286

Reduction of protein translation and activation of autophagy protect against PINK1 pathogenesis in Drosophila melanogaster.

PubMed

Liu, Song; Lu, Bingwei

2010-12-09

Mutations in PINK1 and Parkin cause familial, early onset Parkinson's disease. In Drosophila melanogaster, PINK1 and Parkin mutants show similar phenotypes, such as swollen and dysfunctional mitochondria, muscle degeneration, energy depletion, and dopaminergic (DA) neuron loss. We previously showed that PINK1 and Parkin genetically interact with the mitochondrial fusion/fission pathway, and PINK1 and Parkin were recently proposed to form a mitochondrial quality control system that involves mitophagy. However, the in vivo relationships among PINK1/Parkin function, mitochondrial fission/fusion, and autophagy remain unclear; and other cellular events critical for PINK1 pathogenesis remain to be identified. Here we show that PINK1 genetically interacted with the protein translation pathway. Enhanced translation through S6K activation significantly exacerbated PINK1 mutant phenotypes, whereas reduction of translation showed suppression. Induction of autophagy by Atg1 overexpression also rescued PINK1 mutant phenotypes, even in the presence of activated S6K. Downregulation of translation and activation of autophagy were already manifested in PINK1 mutant, suggesting that they represent compensatory cellular responses to mitochondrial dysfunction caused by PINK1 inactivation, presumably serving to conserve energy. Interestingly, the enhanced PINK1 mutant phenotype in the presence of activated S6K could be fully rescued by Parkin, apparently in an autophagy-independent manner. Our results reveal complex cellular responses to PINK1 inactivation and suggest novel therapeutic strategies through manipulation of the compensatory responses.

Reduction of Protein Translation and Activation of Autophagy Protect against PINK1 Pathogenesis in Drosophila melanogaster

PubMed Central

Liu, Song; Lu, Bingwei

2010-01-01

Mutations in PINK1 and Parkin cause familial, early onset Parkinson's disease. In Drosophila melanogaster, PINK1 and Parkin mutants show similar phenotypes, such as swollen and dysfunctional mitochondria, muscle degeneration, energy depletion, and dopaminergic (DA) neuron loss. We previously showed that PINK1 and Parkin genetically interact with the mitochondrial fusion/fission pathway, and PINK1 and Parkin were recently proposed to form a mitochondrial quality control system that involves mitophagy. However, the in vivo relationships among PINK1/Parkin function, mitochondrial fission/fusion, and autophagy remain unclear; and other cellular events critical for PINK1 pathogenesis remain to be identified. Here we show that PINK1 genetically interacted with the protein translation pathway. Enhanced translation through S6K activation significantly exacerbated PINK1 mutant phenotypes, whereas reduction of translation showed suppression. Induction of autophagy by Atg1 overexpression also rescued PINK1 mutant phenotypes, even in the presence of activated S6K. Downregulation of translation and activation of autophagy were already manifested in PINK1 mutant, suggesting that they represent compensatory cellular responses to mitochondrial dysfunction caused by PINK1 inactivation, presumably serving to conserve energy. Interestingly, the enhanced PINK1 mutant phenotype in the presence of activated S6K could be fully rescued by Parkin, apparently in an autophagy-independent manner. Our results reveal complex cellular responses to PINK1 inactivation and suggest novel therapeutic strategies through manipulation of the compensatory responses. PMID:21151574

The Human Vertical Translation Vestibulo-ocular Reflex (tVOR): Normal and Abnormal Responses

PubMed Central

Liao, Ke; Walker, Mark F.; Joshi, Anand; Reschke, Millard; Strupp, Michael; Leigh, R. John

2010-01-01

Geometric considerations indicate that the human translational vestibulo-ocular reflex (tVOR) should have substantially different properties than the angular vestibulo-ocular reflex (aVOR). Specifically, tVOR cannot simultaneously stabilize images of distant and near objects on the retina. Most studies make the tacit assumption that tVOR acts to stabilize foveal images even though, in humans, tVOR is reported to compensate for less than 60% of foveal image motion. We have determined that the compensation gain (eye rotational velocity / required eye rotational velocity to maintain foveal target fixation) of tVOR is held steady at ~ 0.6 during viewing of either near or distant targets during vertical (bob) translations in ambient illumination. We postulate that tVOR evolved not to stabilize the image of the target on the fovea, but rather to minimize retinal image motion between objects lying in different depth planes, in order to optimize motion parallax information. Such behavior is optimized when binocular visual cues of both far and distant targets are available in ambient light. Patients with progressive supranuclear palsy or cerebellar ataxia show impaired ability to increase tVOR responses appropriately when they view near targets. In cerebellar patients, impaired ability to adjust tVOR responses to viewing conditions occurs despite intact ability to converge at near. Loss of the ability to adjust tVOR according to viewing conditions appears to represent a distinct disorder of vestibular function. PMID:19645882

Early response to psychological trauma--what GPs can do.

PubMed

Wade, Darryl; Howard, Alexandra; Fletcher, Susan; Cooper, John; Forbes, David

2013-09-01

There is a high prevalence of psychological trauma exposure among primary care patients. General practitioners are well placed to provide appropriate support for patients coping with trauma. This article outlines an evidence-based early response to psychological trauma. Psychological first aid is the preferred approach in providing early assistance to patients who have experienced a traumatic event. General practitioners can be guided by five empirically derived principles in their early response: promoting a sense of safety, calming, self efficacy, connectedness and hope. Structured psychological interventions, including psychological debriefing, are not routinely recommended in the first few weeks following trauma exposure. General practitioner self care is an important aspect of providing post-trauma patient care.

Tilt and Translation Motion Perception during Pitch Tilt with Visual Surround Translation

NASA Technical Reports Server (NTRS)

O'Sullivan, Brita M.; Harm, Deborah L.; Reschke, Millard F.; Wood, Scott J.

2006-01-01

The central nervous system must resolve the ambiguity of inertial motion sensory cues in order to derive an accurate representation of spatial orientation. Previous studies suggest that multisensory integration is critical for discriminating linear accelerations arising from tilt and translation head motion. Visual input is especially important at low frequencies where canal input is declining. The NASA Tilt Translation Device (TTD) was designed to recreate postflight orientation disturbances by exposing subjects to matching tilt self motion with conflicting visual surround translation. Previous studies have demonstrated that brief exposures to pitch tilt with foreaft visual surround translation produced changes in compensatory vertical eye movement responses, postural equilibrium, and motion sickness symptoms. Adaptation appeared greatest with visual scene motion leading (versus lagging) the tilt motion, and the adaptation time constant appeared to be approximately 30 min. The purpose of this study was to compare motion perception when the visual surround translation was inphase versus outofphase with pitch tilt. The inphase stimulus presented visual surround motion one would experience if the linear acceleration was due to foreaft self translation within a stationary surround, while the outofphase stimulus had the visual scene motion leading the tilt by 90 deg as previously used. The tilt stimuli in these conditions were asymmetrical, ranging from an upright orientation to 10 deg pitch back. Another objective of the study was to compare motion perception with the inphase stimulus when the tilts were asymmetrical relative to upright (0 to 10 deg back) versus symmetrical (10 deg forward to 10 deg back). Twelve subjects (6M, 6F, 22-55 yrs) were tested during 3 sessions separated by at least one week. During each of the three sessions (out-of-phase asymmetrical, in-phase asymmetrical, inphase symmetrical), subjects were exposed to visual surround translation

Machine Translation and Other Translation Technologies.

ERIC Educational Resources Information Center

Melby, Alan

1996-01-01

Examines the application of linguistic theory to machine translation and translator tools, discusses the use of machine translation and translator tools in the real world of translation, and addresses the impact of translation technology on conceptions of language and other issues. Findings indicate that the human mind is flexible and linguistic…

Translational control of aberrant stress responses as a hallmark of cancer.

PubMed

El-Naggar, Amal M; Sorensen, Poul H

2018-04-01

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

Stress-mediated translational control in cancer cells.

PubMed

Leprivier, Gabriel; Rotblat, Barak; Khan, Debjit; Jan, Eric; Sorensen, Poul H

2015-07-01

Tumor cells are continually subjected to diverse stress conditions of the tumor microenvironment, including hypoxia, nutrient deprivation, and oxidative or genotoxic stress. Tumor cells must evolve adaptive mechanisms to survive these conditions to ultimately drive tumor progression. Tight control of mRNA translation is critical for this response and the adaptation of tumor cells to such stress forms. This proceeds though a translational reprogramming process which restrains overall translation activity to preserve energy and nutrients, but which also stimulates the selective synthesis of major stress adaptor proteins. Here we present the different regulatory signaling pathways which coordinate mRNA translation in the response to different stress forms, including those regulating eIF2α, mTORC1 and eEF2K, and we explain how tumor cells hijack these pathways for survival under stress. Finally, mechanisms for selective mRNA translation under stress, including the utilization of upstream open reading frames (uORFs) and internal ribosome entry sites (IRESes) are discussed in the context of cell stress. This article is part of a Special Issue entitled: Translation and Cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

Reactive Oxygen Species-Mediated Loss of Synaptic Akt1 Signaling Leads to Deficient Activity-Dependent Protein Translation Early in Alzheimer's Disease

PubMed Central

Ahmad, Faraz; Singh, Kunal; Das, Debajyoti; Gowaikar, Ruturaj; Shaw, Eisha; Ramachandran, Arathy; Rupanagudi, Khader Valli; Kommaddi, Reddy Peera; Bennett, David A.

2017-01-01

Abstract Aims: Synaptic deficits are known to underlie the cognitive dysfunction seen in Alzheimer's disease (AD). Generation of reactive oxygen species (ROS) by β-amyloid has also been implicated in AD pathogenesis. However, it is unclear whether ROS contributes to synaptic dysfunction seen in AD pathogenesis and, therefore, we examined whether altered redox signaling could contribute to synaptic deficits in AD. Results: Activity dependent but not basal translation was impaired in synaptoneurosomes from 1-month old presymptomatic APPSwe/PS1ΔE9 (APP/PS1) mice, and this deficit was sustained till middle age (MA, 9–10 months). ROS generation leads to oxidative modification of Akt1 in the synapse and consequent reduction in Akt1-mechanistic target of rapamycin (mTOR) signaling, leading to deficiency in activity-dependent protein translation. Moreover, we found a similar loss of activity-dependent protein translation in synaptoneurosomes from postmortem AD brains. Innovation: Loss of activity-dependent protein translation occurs presymptomatically early in the pathogenesis of AD. This is caused by ROS-mediated loss of pAkt1, leading to reduced synaptic Akt1-mTOR signaling and is rescued by overexpression of Akt1. ROS-mediated damage is restricted to the synaptosomes, indicating selectivity. Conclusions: We demonstrate that ROS-mediated oxidative modification of Akt1 contributes to synaptic dysfunction in AD, seen as loss of activity-dependent protein translation that is essential for synaptic plasticity and maintenance. Therapeutic strategies promoting Akt1-mTOR signaling at synapses may provide novel target(s) for disease-modifying therapy in AD. Antioxid. Redox Signal. 27, 1269–1280. PMID:28264587

Plant Translation Factors and Virus Resistance

PubMed Central

Sanfaçon, Hélène

2015-01-01

Plant viruses recruit cellular translation factors not only to translate their viral RNAs but also to regulate their replication and potentiate their local and systemic movement. Because of the virus dependence on cellular translation factors, it is perhaps not surprising that many natural plant recessive resistance genes have been mapped to mutations of translation initiation factors eIF4E and eIF4G or their isoforms, eIFiso4E and eIFiso4G. The partial functional redundancy of these isoforms allows specific mutation or knock-down of one isoform to provide virus resistance without hindering the general health of the plant. New possible targets for antiviral strategies have also been identified following the characterization of other plant translation factors (eIF4A-like helicases, eIF3, eEF1A and eEF1B) that specifically interact with viral RNAs and proteins and regulate various aspects of the infection cycle. Emerging evidence that translation repression operates as an alternative antiviral RNA silencing mechanism is also discussed. Understanding the mechanisms that control the development of natural viral resistance and the emergence of virulent isolates in response to these plant defense responses will provide the basis for the selection of new sources of resistance and for the intelligent design of engineered resistance that is broad-spectrum and durable. PMID:26114476

Health responsibility and workplace health promotion among women: early detection of cancer.

PubMed

Kushnir, T; Rabinowitz, S; Melamed, S; Weisberg, E; Ribak, J

1995-01-01

The importance of health responsibility as one aspect of a health-promoting lifestyle has been emphasized repeatedly. Yet there are only a few empirical studies of its role in preventive behavior. We examined the relationship between health responsibility and early-detection practices for breast and cervical cancer. A group of 253 women employees of a large industrial company participated in a cancer screening program subsidized by the employer. They completed questionnaires assessing health responsibility and reported early-detection practices: frequency of breast self-examination and physician breast examinations, frequency of Pap tests, and time lapsed since last Pap test and breast examinations. Health responsibility was a significant independent predictor of breast examination indicators but not of Pap tests. Education level was an important predictor for Pap tests, and age predicted most early-detection practices. The findings lend some support to the role of health responsibility in initiating breast examinations. Better prediction of early-detection practices could be achieved by adding cognitive and emotional components to the existing responsibility scale and by distinguishing between retrospective and prospective responsibility.

Early childhood adversity, toxic stress, and the role of the pediatrician: translating developmental science into lifelong health.

PubMed

Garner, Andrew S; Shonkoff, Jack P

2012-01-01

Advances in a wide range of biological, behavioral, and social sciences are expanding our understanding of how early environmental influences (the ecology) and genetic predispositions (the biologic program) affect learning capacities, adaptive behaviors, lifelong physical and mental health, and adult productivity. A supporting technical report from the American Academy of Pediatrics (AAP) presents an integrated ecobiodevelopmental framework to assist in translating these dramatic advances in developmental science into improved health across the life span. Pediatricians are now armed with new information about the adverse effects of toxic stress on brain development, as well as a deeper understanding of the early life origins of many adult diseases. As trusted authorities in child health and development, pediatric providers must now complement the early identification of developmental concerns with a greater focus on those interventions and community investments that reduce external threats to healthy brain growth. To this end, AAP endorses a developing leadership role for the entire pediatric community-one that mobilizes the scientific expertise of both basic and clinical researchers, the family-centered care of the pediatric medical home, and the public influence of AAP and its state chapters-to catalyze fundamental change in early childhood policy and services. AAP is committed to leveraging science to inform the development of innovative strategies to reduce the precipitants of toxic stress in young children and to mitigate their negative effects on the course of development and health across the life span.

Presence of early stage cancer does not impair the early protein metabolic response to major surgery

PubMed Central

Klimberg, V. Suzanne; Allasia, Arianna; Deutz, Nicolaas EP

2017-01-01

Abstract Background Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. Methods In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post‐absorptive state and net protein anabolic response to a meal. Results Major surgery resulted in an up‐regulation of post‐absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2 = 0.85, P < 0.001) was independent of the presence of non‐cachectic early stage breast cancer or surgery. Conclusions The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the

Presence of early stage cancer does not impair the early protein metabolic response to major surgery.

PubMed

Engelen, Mariëlle P K J; Klimberg, V Suzanne; Allasia, Arianna; Deutz, Nicolaas Ep

2017-06-01

Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post-absorptive state and net protein anabolic response to a meal. Major surgery resulted in an up-regulation of post-absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2  = 0.85, P < 0.001) was independent of the presence of non-cachectic early stage breast cancer or surgery. The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the anabolic response to meal intake within 24 h after

Translational control plays an important role in the adaptive heat-shock response of Streptomyces coelicolor

PubMed Central

Pothi, Radhika; Hesketh, Andrew; Möller-Levet, Carla; Hodgson, David A; Laing, Emma E; Stewart, Graham R; Smith, Colin P

2018-01-01

Abstract Stress-induced adaptations require multiple levels of regulation in all organisms to repair cellular damage. In the present study we evaluated the genome-wide transcriptional and translational changes following heat stress exposure in the soil-dwelling model actinomycete bacterium, Streptomyces coelicolor. The combined analysis revealed an unprecedented level of translational control of gene expression, deduced through polysome profiling, in addition to transcriptional changes. Our data show little correlation between the transcriptome and ‘translatome’; while an obvious downward trend in genome wide transcription was observed, polysome associated transcripts following heat-shock showed an opposite upward trend. A handful of key protein players, including the major molecular chaperones and proteases were highly induced at both the transcriptional and translational level following heat-shock, a phenomenon known as ‘potentiation’. Many other transcripts encoding cold-shock proteins, ABC-transporter systems, multiple transcription factors were more highly polysome-associated following heat stress; interestingly, these protein families were not induced at the transcriptional level and therefore were not previously identified as part of the stress response. Thus, stress coping mechanisms at the level of gene expression in this bacterium go well beyond the induction of a relatively small number of molecular chaperones and proteases in order to ensure cellular survival at non-physiological temperatures. PMID:29746664

Translational control plays an important role in the adaptive heat-shock response of Streptomyces coelicolor.

PubMed

Bucca, Giselda; Pothi, Radhika; Hesketh, Andrew; Möller-Levet, Carla; Hodgson, David A; Laing, Emma E; Stewart, Graham R; Smith, Colin P

2018-05-09

Stress-induced adaptations require multiple levels of regulation in all organisms to repair cellular damage. In the present study we evaluated the genome-wide transcriptional and translational changes following heat stress exposure in the soil-dwelling model actinomycete bacterium, Streptomyces coelicolor. The combined analysis revealed an unprecedented level of translational control of gene expression, deduced through polysome profiling, in addition to transcriptional changes. Our data show little correlation between the transcriptome and 'translatome'; while an obvious downward trend in genome wide transcription was observed, polysome associated transcripts following heat-shock showed an opposite upward trend. A handful of key protein players, including the major molecular chaperones and proteases were highly induced at both the transcriptional and translational level following heat-shock, a phenomenon known as 'potentiation'. Many other transcripts encoding cold-shock proteins, ABC-transporter systems, multiple transcription factors were more highly polysome-associated following heat stress; interestingly, these protein families were not induced at the transcriptional level and therefore were not previously identified as part of the stress response. Thus, stress coping mechanisms at the level of gene expression in this bacterium go well beyond the induction of a relatively small number of molecular chaperones and proteases in order to ensure cellular survival at non-physiological temperatures.

Pichia pastoris regulates its gene-specific response to different carbon sources at the transcriptional, rather than the translational, level.

PubMed

Prielhofer, Roland; Cartwright, Stephanie P; Graf, Alexandra B; Valli, Minoska; Bill, Roslyn M; Mattanovich, Diethard; Gasser, Brigitte

2015-03-11

The methylotrophic, Crabtree-negative yeast Pichia pastoris is widely used as a heterologous protein production host. Strong inducible promoters derived from methanol utilization genes or constitutive glycolytic promoters are typically used to drive gene expression. Notably, genes involved in methanol utilization are not only repressed by the presence of glucose, but also by glycerol. This unusual regulatory behavior prompted us to study the regulation of carbon substrate utilization in different bioprocess conditions on a genome wide scale. We performed microarray analysis on the total mRNA population as well as mRNA that had been fractionated according to ribosome occupancy. Translationally quiescent mRNAs were defined as being associated with single ribosomes (monosomes) and highly-translated mRNAs with multiple ribosomes (polysomes). We found that despite their lower growth rates, global translation was most active in methanol-grown P. pastoris cells, followed by excess glycerol- or glucose-grown cells. Transcript-specific translational responses were found to be minimal, while extensive transcriptional regulation was observed for cells grown on different carbon sources. Due to their respiratory metabolism, cells grown in excess glucose or glycerol had very similar expression profiles. Genes subject to glucose repression were mainly involved in the metabolism of alternative carbon sources including the control of glycerol uptake and metabolism. Peroxisomal and methanol utilization genes were confirmed to be subject to carbon substrate repression in excess glucose or glycerol, but were found to be strongly de-repressed in limiting glucose-conditions (as are often applied in fed batch cultivations) in addition to induction by methanol. P. pastoris cells grown in excess glycerol or glucose have similar transcript profiles in contrast to S. cerevisiae cells, in which the transcriptional response to these carbon sources is very different. The main response to

The Translational Science Training Program at NIH: Introducing Early Career Researchers to the Science and Operation of Translation of Basic Research to Medical Interventions

PubMed Central

Gilliland, C. Taylor; Sittampalam, G. Sitta; Wang, Philip Y.; Ryan, Philip E.

2016-01-01

Translational science is an emerging field that holds great promise to accelerate the development of novel medical interventions. As the field grows, so does the demand for highly trained biomedical scientists to fill the positions that are being created. Many graduate and postdoctorate training programs do not provide their trainees with sufficient education to take advantage of this growing employment sector. To help better prepare the trainees at the National Institutes of Health for possible careers in translation, we have created the Translational Science Training Program (TSTP)1. The TSTP is an intensive 2–3 day training program that introduces NIH postdoctoral trainees and graduate students to the science and operation of turning basic research discoveries into a medical therapeutic, device or diagnostic, and also exposes them to the variety of career options in translational science. Through a combination of classroom teaching from practicing experts in the various disciplines of translation and small group interactions with pre-clinical development teams, participants in the TSTP gain knowledge that will aid them in obtaining a career in translational science and building a network to make the transition to the field. PMID:27231204

Early life socioeconomic position and immune response to persistent infections among elderly Latinos.

PubMed

Meier, Helen C S; Haan, Mary N; Mendes de Leon, Carlos F; Simanek, Amanda M; Dowd, Jennifer B; Aiello, Allison E

2016-10-01

Persistent infections, such as cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), Helicobacter pylori (H. pylori), and Toxoplasma gondii (T. gondii), are common in the U.S. but their prevalence varies by socioeconomic status. It is unclear if early or later life socioeconomic position (SEP) is a more salient driver of disparities in immune control of these infections. Using data from the Sacramento Area Latino Study on Aging, we examined whether early or later life SEP was the strongest predictor of immune control later in life by contrasting two life course models, the critical period model and the chain of risk model. Early life SEP was measured as a latent variable, derived from parental education and occupation, and food availability. Indicators for SEP in later life included education level and occupation. Individuals were categorized by immune response to each pathogen (seronegative, low, medium and high) with increasing immune response representing poorer immune control. Cumulative immune response was estimated using a latent profile analysis with higher total immune response representing poorer immune control. Structural equation models were used to examine direct, indirect and total effects of early life SEP on each infection and cumulative immune response, controlling for age and gender. The direct effect of early life SEP on immune response was not statistically significant for the infections or cumulative immune response. Higher early life SEP was associated with lower immune response for T. gondii, H. pylori and cumulative immune response through pathways mediated by later life SEP. For CMV, higher early life SEP was both directly associated and partially mediated by later life SEP. No association was found between SEP and HSV-1. Findings from this study support a chain of risk model, whereby early life SEP acts through later life SEP to affect immune response to persistent infections in older age. Copyright © 2016 Elsevier Ltd. All rights

Masked translation priming effects with low proficient bilinguals.

PubMed

Dimitropoulou, Maria; Duñabeitia, Jon Andoni; Carreiras, Manuel

2011-02-01

Non-cognate masked translation priming lexical decision studies with unbalanced bilinguals suggest that masked translation priming effects are asymmetric as a function of the translation direction (significant effects only in the dominant [L1] to nondominant [L2] language translation direction). However, in contrast to the predictions of most current accounts of masked translation priming effects, bidirectional effects have recently been reported with a group of low proficient bilinguals Duyck & Warlop 2009 (Experimental Psychology 56:173-179). In a series of masked translation priming lexical decision experiments we examined whether the same pattern of effects would emerge with late and low proficient Greek (L1)-Spanish (L2) bilinguals. Contrary to the results obtained by Duyck and Warlop, and in line with the results found in most studies in the masked priming literature, significant translation priming effects emerged only when the bilinguals performed the task with L1 primes and L2 targets. The existence of the masked translation priming asymmetry with low proficient bilinguals suggests that cross-linguistic automatic lexico-semantic links may be established very early in the process of L2 acquisition. These findings could help to define models of bilingualism that consider L2 proficiency level to be a determining factor.

The translational science training program at NIH: Introducing early career researchers to the science and operation of translation of basic research to medical interventions.

PubMed

Gilliland, C Taylor; Sittampalam, G Sitta; Wang, Philip Y; Ryan, Philip E

2017-01-02

Translational science is an emerging field that holds great promise to accelerate the development of novel medical interventions. As the field grows, so does the demand for highly trained biomedical scientists to fill the positions that are being created. Many graduate and postdoctorate training programs do not provide their trainees with sufficient education to take advantage of this growing employment sector. To help better prepare the trainees at the National Institutes of Health for possible careers in translation, we have created the Translational Science Training Program (TSTP). The TSTP is an intensive 2- to 3-day training program that introduces NIH postdoctoral trainees and graduate students to the science and operation of turning basic research discoveries into a medical therapeutic, device or diagnostic, and also exposes them to the variety of career options in translational science. Through a combination of classroom teaching from practicing experts in the various disciplines of translation and small group interactions with pre-clinical development teams, participants in the TSTP gain knowledge that will aid them in obtaining a career in translational science and building a network to make the transition to the field. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):13-24, 2017. © 2016 The International Union of Biochemistry and Molecular Biology.

National Institutes of Health Update: Translating Basic Behavioral Science into New Pediatric Obesity Interventions.

PubMed

Czajkowski, Susan M

2016-06-01

Pediatric obesity increases the risk of later-life obesity and chronic diseases. Basic research to better understand factors associated with excessive weight gain in early life and studies translating research findings into preventive and therapeutic strategies are essential to our ability to better prevent and treat childhood obesity. This overview describes several National Institutes of Health efforts designed to stimulate basic and translational research in childhood obesity prevention and treatment. These examples demonstrate the value of research in early phase translational pediatric obesity research and highlight some promising directions for this important area of research. Published by Elsevier Inc.

Developing a translational ecology workforce

USGS Publications Warehouse

Schwartz, Mark W.; Hiers, J. Kevin; Davis, Frank W.; Garfin, Gregg; Jackson, Stephen T.; Terando, Adam J.; Woodhouse, Connie A.; Morelli, Toni; Williamson, Matthew A.; Brunson, Mark W.

2017-01-01

We define a translational ecologist as a professional ecologist with diverse disciplinary expertise and skill sets, as well as a suitable personal disposition, who engages across social, professional, and disciplinary boundaries to partner with decision makers to achieve practical environmental solutions. Becoming a translational ecologist requires specific attention to obtaining critical non‐scientific disciplinary breadth and skills that are not typically gained through graduate‐level education. Here, we outline a need for individuals with broad training in interdisciplinary skills, use our personal experiences as a basis for assessing the types of interdisciplinary skills that would benefit potential translational ecologists, and present steps that interested ecologists may take toward becoming translational. Skills relevant to translational ecologists may be garnered through personal experiences, informal training, short courses, fellowships, and graduate programs, among others. We argue that a translational ecology workforce is needed to bridge the gap between science and natural resource decisions. Furthermore, we argue that this task is a cooperative responsibility of individuals interested in pursuing these careers, educational institutions interested in training scientists for professional roles outside of academia, and employers seeking to hire skilled workers who can foster stakeholder‐engaged decision making.

Early-life inflammation, immune response and ageing.

PubMed

Khan, Imroze; Agashe, Deepa; Rolff, Jens

2017-03-15

Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response. © 2017 The Author(s).

Early-life inflammation, immune response and ageing

PubMed Central

2017-01-01

Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response. PMID:28275145

Translating Theoretical Principles to Classroom Practice

ERIC Educational Resources Information Center

Robbins, Sheri

2017-01-01

This study followed two teacher candidates from the Communities as Resources in Early Childhood Teacher Education (CREATE) project into their first year classrooms to determine whether they were able to translate the theoretical principles from their teacher preparation program into practice during their first year of teaching. It also examined…

Ethical Considerations in Tissue Engineering Research: Case Studies in Translation

PubMed Central

Baker, Hannah B.; McQuilling, John P.

2016-01-01

Tissue engineering research is a complex process that requires investigators to focus on the relationship between their research and anticipated gains in both knowledge and treatment improvements. The ethical considerations arising from tissue engineering research are similarly complex when addressing the translational progression from bench to bedside, and investigators in the field of tissue engineering act as moral agents at each step of their research along the translational pathway, from early benchwork and preclinical studies to clinical research. This review highlights the ethical considerations and challenges at each stage of research, by comparing issues surrounding two translational tissue engineering technologies: the bioartificial pancreas and a tissue engineered skeletal muscle construct. We present relevant ethical issues and questions to consider at each step along the translational pathway, from the basic science bench to preclinical research to first-in-human clinical trials. Topics at the bench level include maintaining data integrity, appropriate reporting and dissemination of results, and ensuring that studies are designed to yield results suitable for advancing research. Topics in preclinical research include the principle of “modest translational distance” and appropriate animal models. Topics in clinical research include key issues that arise in early-stage clinical trials, including selection of patient-subjects, disclosure of uncertainty, and defining success. The comparison of these two technologies and their ethical issues brings to light many challenges for translational tissue engineering research and provides guidance for investigators engaged in development of any tissue engineering technology. PMID:26282436

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

PubMed

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

2012-01-01

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

Early skin toxicity predicts better outcomes, and early tumor shrinkage predicts better response after cetuximab treatment in advanced colorectal cancer.

PubMed

Kogawa, T; Doi, A; Shimokawa, M; Fouad, T M; Osuga, T; Tamura, F; Mizushima, T; Kimura, T; Abe, S; Ihara, H; Kukitsu, T; Sumiyoshi, T; Yoshizaki, N; Hirayama, M; Sasaki, T; Kawarada, Y; Kitashiro, S; Okushiba, S; Kondo, H; Tsuji, Y

2015-03-01

Cetuximab-containing treatments for metastatic colorectal cancer have been shown to have higher overall response rates and longer progression-free and overall survival than other systemic therapies. Cetuximab-related manifestations, including severe skin toxicity and early tumor shrinkage, have been shown to be predictors of response to cetuximab. We hypothesized that early skin toxicity is a predictor of response and better outcomes in patients with advanced colorectal carcinoma. We retrospectively evaluated 62 patients with colorectal adenocarcinoma who had unresectable tumors and were treated with cetuximab in our institution. Skin toxicity grade was evaluated on each treatment day. Tumor size was evaluated using computed tomography prior to treatment and 4-8 weeks after the start of treatment with cetuximab.Patients with early tumor shrinkage after starting treatment with cetuximab had a significantly higher overall response rate (P = 0.0001). Patients with early skin toxicity showed significantly longer overall survival (P = 0.0305), and patients with higher skin toxicity grades had longer progression-free survival (P = 0.0168).We have shown that early tumor shrinkage, early onset of skin toxicity, and high skin toxicity grade are predictors of treatment efficacy and/or outcome in patients with advanced colorectal carcinoma treated with cetuximab.

Translational reciprocity: bridging the gap between preclinical studies and clinical treatment of stress effects on the adolescent brain.

PubMed

Neigh, G N; Ritschel, L A; Kilpela, L S; Harrell, C S; Bourke, C H

2013-09-26

The genetic, biological, and environmental backgrounds of an organism fundamentally influence the balance between risk and resilience to stress. Sex, age, and environment transact with responses to trauma in ways that can mitigate or exacerbate the likelihood that post-traumatic stress disorder will develop. Translational approaches to modeling affective disorders in animals will ultimately provide novel treatments and a better understanding of the neurobiological underpinnings behind these debilitating disorders. The extant literature on trauma/stress has focused predominately on limbic and cortical structures that innervate the hypothalamic-pituitary-adrenal axis and influence glucocorticoid-mediated negative feedback. It is through these neuroendocrine pathways that a self-perpetuating fear memory can propagate the long-term effects of early life trauma. Recent work incorporating translational approaches has provided novel pathways that can be influenced by early life stress, such as the glucocorticoid receptor chaperones, including FKBP51. Animal models of stress have differing effects on behavior and endocrine pathways; however, complete models replicating clinical characteristics of risk and resilience have not been rigorously studied. This review discusses a four-factor model that considers the importance of studying both risk and resilience in understanding the developmental response to trauma/stress. Consideration of the multifactorial nature of clinical populations in the design of preclinical models and the application of preclinical findings to clinical treatment approaches comprise the core of translational reciprocity, which is discussed in the context of the four-factor model. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Istanbul Earthquake Early Warning and Rapid Response System

NASA Astrophysics Data System (ADS)

Erdik, M. O.; Fahjan, Y.; Ozel, O.; Alcik, H.; Aydin, M.; Gul, M.

2003-12-01

As part of the preparations for the future earthquake in Istanbul a Rapid Response and Early Warning system in the metropolitan area is in operation. For the Early Warning system ten strong motion stations were installed as close as possible to the fault zone. Continuous on-line data from these stations via digital radio modem provide early warning for potentially disastrous earthquakes. Considering the complexity of fault rupture and the short fault distances involved, a simple and robust Early Warning algorithm, based on the exceedance of specified threshold time domain amplitude levels is implemented. The band-pass filtered accelerations and the cumulative absolute velocity (CAV) are compared with specified threshold levels. When any acceleration or CAV (on any channel) in a given station exceeds specific threshold values it is considered a vote. Whenever we have 2 station votes within selectable time interval, after the first vote, the first alarm is declared. In order to specify the appropriate threshold levels a data set of near field strong ground motions records form Turkey and the world has been analyzed. Correlations among these thresholds in terms of the epicenter distance the magnitude of the earthquake have been studied. The encrypted early warning signals will be communicated to the respective end users by UHF systems through a "service provider" company. The users of the early warning signal will be power and gas companies, nuclear research facilities, critical chemical factories, subway system and several high-rise buildings. Depending on the location of the earthquake (initiation of fault rupture) and the recipient facility the alarm time can be as high as about 8s. For the rapid response system one hundred 18 bit-resolution strong motion accelerometers were placed in quasi-free field locations (basement of small buildings) in the populated areas of the city, within an area of approximately 50x30km, to constitute a network that will enable early

Tubulin post-translational modifications in the primitive protist Trichomonas vaginalis.

PubMed

Delgado-Viscogliosi, P; Brugerolle, G; Viscogliosi, E

1996-01-01

Using several specific monoclonal antibodies, we investigated the occurrence and distribution of different post-translationally modified tubulin during interphase and division of the primitive flagellated protist Trichomonas vaginalis. Immunoblotting and immunofluorescence experiments revealed that interphasic microtubular structures of T. vaginalis contained acetylated and glutamylated but non-tyrosinated and non-glycylated [Brugerolle and Adoutte, 1988: Bio Systems 21: 255-268] tubulin. Immunofluorescence studies performed on dividing cells showed that the extranuclear mitotic spindle (or paradesmosis) was acetylated and glutamylated, which contrast with the ephemeral nature of this structure. Newly formed short axostyles also contained acetylated and glutamylated tubulin suggesting that both post-translational modifications might take place very early after assembly of microtubular structures. Our results indicate that acetylation and glutamylation of tubulin appeared early in the history of eukaryotes and could reflect the occurrence of post-translational modifications of tubulin in the primitive eukaryotic cells. These cells probably had a highly ordered cross-linked microtubular cytoskeleton in which microtubules showed a low level of subunit exchange dynamics.

mTORC1-dependent translation of collapsin response mediator protein-2 drives neuroadaptations underlying excessive alcohol-drinking behaviors

PubMed Central

Liu, F; Laguesse, S; Legastelois, R; Morisot, N; Ben Hamida, S; Ron, D

2017-01-01

Mammalian target of rapamycin complex 1 (mTORC1) has an essential role in dendritic mRNA translation and participates in mechanisms underlying alcohol-drinking and reconsolidation of alcohol-related memories. Here, we report that excessive alcohol consumption increases the translation of downstream targets of mTORC1, including collapsin response mediator protein-2 (CRMP-2), in the nucleus accumbens (NAc) of rodents. We show that alcohol-mediated induction of CRMP-2 translation is mTORC1-dependent, leading to increased CRMP-2 protein levels. Furthermore, we demonstrate that alcohol intake also blocks glycogen synthase kinase-3β (GSK-3β)-phosphorylation of CRMP-2, which results in elevated binding of CRMP-2 to microtubules and a concomitant increase in microtubule content. Finally, we show that systemic administration of the CRMP-2 inhibitor lacosamide, or knockdown of CRMP-2 in the NAc decreases excessive alcohol intake. These results suggest that CRMP-2 in the NAc is a convergent point that receives inputs from two signaling pathways, mTORC1 and GSK-3β, that in turn drives excessive alcohol-drinking behaviors. PMID:26952865

Post-translational regulation of plant immunity.

PubMed

Withers, John; Dong, Xinnian

2017-08-01

Plants have evolved multi-layered molecular defense strategies to protect against pathogens. Plant immune signaling largely relies on post-translational modifications (PTMs) to induce rapid alterations of signaling pathways to achieve a response that is appropriate to the type of pathogen and infection pressure. In host cells, dynamic PTMs have emerged as powerful regulatory mechanisms that cells use to adjust their immune response. PTM is also a virulence strategy used by pathogens to subvert host immunity through the activities of effector proteins secreted into the host cell. Recent studies focusing on deciphering post-translational mechanisms underlying plant immunity have offered an in-depth view of how PTMs facilitate efficient immune responses and have provided a more dynamic and holistic view of plant immunity. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Translational science: past, present, and future.

PubMed

Curry, Stephen H

2008-02-01

The concept of translational science is at least 15 years old. However, in its most recent incarnation, it represents the identification of a funding category designed to encourage academic participation in a critical stage of the drug discovery and product development process. It is hoped that this will make the process both shorter and more efficient. In this review, the author first considers the historical development of the pharmaceutical R&D process. The place of translational science in the process, the scientific techniques involved, and aspects of the business environment necessary for its success are then considered. Translational science does not displace preclinical development. Both concepts are relevant to the paramount importance of successfully and expeditiously bridging the gap between preclinical science and clinical testing, "from bench to bedside." Translational science is particularly likely to stimulate biomarker research in the universities and related business community and will probably give a modest boost to early clinical testing and commercialization of discoveries within the academic setting. Whether there will be a consequent improvement in the quality and efficiency of the overall process remains to be seen.

Early feeding and early life housing conditions influence the response towards a noninfectious lung challenge in broilers.

PubMed

Simon, K; de Vries Reilingh, G; Bolhuis, J E; Kemp, B; Lammers, A

2015-09-01

Early life conditions such as feed and water availability immediately post hatch (PH) and housing conditions may influence immune development and therefore immune reactivity later in life. The current study addressed the consequences of a combination of these 2 early life conditions for immune reactivity, i.e., the specific antibody response towards a non-infectious lung challenge. Broiler chicks received feed and water either immediately p.h. or with a 72 h delay and were either reared in a floor or a cage system. At 4 weeks of age, chicks received either an intra-tracheally administered Escherichia coli lipopolysaccharide (LPS)/Human Serum Albumin (HUSA) challenge or a placebo, and antibody titers were measured up to day 14 after administration of the challenge. Chicks housed on the floor and which had a delayed access to feed p.h. showed the highest antibody titers against HuSA. These chicks also showed the strongest sickness response and poorest performance in response to the challenge, indicating that chicks with delayed access to feed might be more sensitive to an environment with higher antigenic pressure. In conclusion, results from the present study show that early life feeding strategy and housing conditions influence a chick's response to an immune challenge later in life. These 2 early life factors should therefore be taken into account when striving for a balance between disease resistance and performance in poultry. © 2015 Poultry Science Association Inc.

Defining Clinical Response Criteria and Early Response Criteria for Precision Oncology: Current State-of-the-Art and Future Perspectives.

PubMed

Subbiah, Vivek; Chuang, Hubert H; Gambhire, Dhiraj; Kairemo, Kalevi

2017-02-15

In this era of precision oncology, there has been an exponential growth in the armamentarium of genomically targeted therapies and immunotherapies. Evaluating early responses to precision therapy is essential for "go" versus "no go" decisions for these molecularly targeted drugs and agents that arm the immune system. Many different response assessment criteria exist for use in solid tumors and lymphomas. We reviewed the literature using the Medline/PubMed database for keywords "response assessment" and various known response assessment criteria published up to 2016. In this article we review the commonly used response assessment criteria. We present a decision tree to facilitate selection of appropriate criteria. We also suggest methods for standardization of various response assessment criteria. The relevant response assessment criteria were further studied for rational of development, key features, proposed use and acceptance by various entities. We also discuss early response evaluation and provide specific case studies of early response to targeted therapy. With high-throughput, advanced computing programs and digital data-mining it is now possible to acquire vast amount of high quality imaging data opening up a new field of "omics in radiology"-radiomics that complements genomics for personalized medicine. Radiomics is rapidly evolving and is still in the research arena. This cutting-edge technology is poised to move soon to the mainstream clinical arena. Novel agents with new mechanisms of action require advanced molecular imaging as imaging biomarkers. There is an urgent need for development of standardized early response assessment criteria for evaluation of response to precision therapy.

Ethical considerations in tissue engineering research: Case studies in translation.

PubMed

Baker, Hannah B; McQuilling, John P; King, Nancy M P

2016-04-15

Tissue engineering research is a complex process that requires investigators to focus on the relationship between their research and anticipated gains in both knowledge and treatment improvements. The ethical considerations arising from tissue engineering research are similarly complex when addressing the translational progression from bench to bedside, and investigators in the field of tissue engineering act as moral agents at each step of their research along the translational pathway, from early benchwork and preclinical studies to clinical research. This review highlights the ethical considerations and challenges at each stage of research, by comparing issues surrounding two translational tissue engineering technologies: the bioartificial pancreas and a tissue engineered skeletal muscle construct. We present relevant ethical issues and questions to consider at each step along the translational pathway, from the basic science bench to preclinical research to first-in-human clinical trials. Topics at the bench level include maintaining data integrity, appropriate reporting and dissemination of results, and ensuring that studies are designed to yield results suitable for advancing research. Topics in preclinical research include the principle of "modest translational distance" and appropriate animal models. Topics in clinical research include key issues that arise in early-stage clinical trials, including selection of patient-subjects, disclosure of uncertainty, and defining success. The comparison of these two technologies and their ethical issues brings to light many challenges for translational tissue engineering research and provides guidance for investigators engaged in development of any tissue engineering technology. Copyright © 2015 Elsevier Inc. All rights reserved.

Translation norms for English and Spanish: The role of lexical variables, word class, and L2 proficiency in negotiating translation ambiguity

PubMed Central

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

2014-01-01

We present a set of translation norms for 670 English and 760 Spanish nouns, verbs and class ambiguous items that varied in their lexical properties in both languages, collected from 80 bilingual participants. Half of the words in each language received more than a single translation across participants. Cue word frequency and imageability were both negatively correlated with number of translations. Word class predicted number of translations: Nouns had fewer translations than did verbs, which had fewer translations than class-ambiguous items. The translation probability of specific responses was positively correlated with target word frequency and imageability, and with its form overlap with the cue word. Translation choice was modulated by L2 proficiency: Less proficient bilinguals tended to produce lower probability translations than more proficient bilinguals, but only in forward translation, from L1 to L2. These findings highlight the importance of translation ambiguity as a factor influencing bilingual representation and performance. The norms can also provide an important resource to assist researchers in the selection of experimental materials for studies of bilingual and monolingual language performance. These norms may be downloaded from www.psychonomic.org/archive. PMID:18183923

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

PubMed

Baggio, Gustavo Inheta; Hage, Simone Rocha de Vasconcellos

2017-12-07

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

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

The ever-evolving role of mTOR in translation.

PubMed

Fonseca, Bruno D; Smith, Ewan M; Yelle, Nicolas; Alain, Tommy; Bushell, Martin; Pause, Arnim

2014-12-01

Control of translation allows for the production of stoichiometric levels of each protein in the cell. Attaining such a level of fine-tuned regulation of protein production requires the coordinated temporal and spatial control of numerous cellular signalling cascades impinging on the various components of the translational machinery. Foremost among these is the mTOR signalling pathway. The mTOR pathway regulates both the initiation and elongation steps of protein synthesis through the phosphorylation of numerous translation factors, while simultaneously ensuring adequate folding of nascent polypeptides through co-translational degradation of misfolded proteins. Perhaps most remarkably, mTOR is also a key regulator of the synthesis of ribosomal proteins and translation factors themselves. Two seminal studies have recently shown in translatome analysis that the mTOR pathway preferentially regulates the translation of mRNAs encoding ribosomal proteins and translation factors. Therefore, the role of the mTOR pathway in the control of protein synthesis extends far beyond immediate translational control. By controlling ribosome production (and ultimately ribosome availability), mTOR is a master long-term controller of protein synthesis. Herein, we review the literature spanning the early discoveries of mTOR on translation to the latest advances in our understanding of how the mTOR pathway controls the synthesis of ribosomal proteins. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Regulation of host translational machinery by African swine fever virus.

PubMed

Castelló, Alfredo; Quintas, Ana; Sánchez, Elena G; Sabina, Prado; Nogal, Marisa; Carrasco, Luis; Revilla, Yolanda

2009-08-01

African swine fever virus (ASFV), like other complex DNA viruses, deploys a variety of strategies to evade the host's defence systems, such as inflammatory and immune responses and cell death. Here, we analyse the modifications in the translational machinery induced by ASFV. During ASFV infection, eIF4G and eIF4E are phosphorylated (Ser1108 and Ser209, respectively), whereas 4E-BP1 is hyperphosphorylated at early times post infection and hypophosphorylated after 18 h. Indeed, a potent increase in eIF4F assembly is observed in ASFV-infected cells, which is prevented by rapamycin treatment. Phosphorylation of eIF4E, eIF4GI and 4E-BP1 is important to enhance viral protein production, but is not essential for ASFV infection as observed in rapamycin- or CGP57380-treated cells. Nevertheless, eIF4F components are indispensable for ASFV protein synthesis and virus spread, since eIF4E or eIF4G depletion in COS-7 or Vero cells strongly prevents accumulation of viral proteins and decreases virus titre. In addition, eIF4F is not only activated but also redistributed within the viral factories at early times of infection, while eIF4G and eIF4E are surrounding these areas at late times. In fact, other components of translational machinery such as eIF2alpha, eIF3b, eIF4E, eEF2 and ribosomal P protein are enriched in areas surrounding ASFV factories. Notably, the mitochondrial network is polarized in ASFV-infected cells co-localizing with ribosomes. Thus, translation and ATP synthesis seem to be coupled and compartmentalized at the periphery of viral factories. At later times after ASFV infection, polyadenylated mRNAs disappear from the cytoplasm of Vero cells, except within the viral factories. The distribution of these pools of mRNAs is similar to the localization of viral late mRNAs. Therefore, degradation of cellular polyadenylated mRNAs and recruitment of the translation machinery to viral factories may contribute to the inhibition of host protein synthesis, facilitating ASFV

Regulation of Host Translational Machinery by African Swine Fever Virus

PubMed Central

Castelló, Alfredo; Quintas, Ana; Sánchez, Elena G.; Sabina, Prado; Nogal, Marisa; Carrasco, Luis; Revilla, Yolanda

2009-01-01

African swine fever virus (ASFV), like other complex DNA viruses, deploys a variety of strategies to evade the host's defence systems, such as inflammatory and immune responses and cell death. Here, we analyse the modifications in the translational machinery induced by ASFV. During ASFV infection, eIF4G and eIF4E are phosphorylated (Ser1108 and Ser209, respectively), whereas 4E-BP1 is hyperphosphorylated at early times post infection and hypophosphorylated after 18 h. Indeed, a potent increase in eIF4F assembly is observed in ASFV-infected cells, which is prevented by rapamycin treatment. Phosphorylation of eIF4E, eIF4GI and 4E-BP1 is important to enhance viral protein production, but is not essential for ASFV infection as observed in rapamycin- or CGP57380-treated cells. Nevertheless, eIF4F components are indispensable for ASFV protein synthesis and virus spread, since eIF4E or eIF4G depletion in COS-7 or Vero cells strongly prevents accumulation of viral proteins and decreases virus titre. In addition, eIF4F is not only activated but also redistributed within the viral factories at early times of infection, while eIF4G and eIF4E are surrounding these areas at late times. In fact, other components of translational machinery such as eIF2α, eIF3b, eIF4E, eEF2 and ribosomal P protein are enriched in areas surrounding ASFV factories. Notably, the mitochondrial network is polarized in ASFV-infected cells co-localizing with ribosomes. Thus, translation and ATP synthesis seem to be coupled and compartmentalized at the periphery of viral factories. At later times after ASFV infection, polyadenylated mRNAs disappear from the cytoplasm of Vero cells, except within the viral factories. The distribution of these pools of mRNAs is similar to the localization of viral late mRNAs. Therefore, degradation of cellular polyadenylated mRNAs and recruitment of the translation machinery to viral factories may contribute to the inhibition of host protein synthesis, facilitating ASFV

A translational study on looming-evoked defensive response and the underlying subcortical pathway in autism.

PubMed

Hu, Yu; Chen, Zhuoming; Huang, Lu; Xi, Yue; Li, Bingxiao; Wang, Hong; Yan, Jiajian; Lee, Tatia M C; Tao, Qian; So, Kwok-Fai; Ren, Chaoran

2017-11-07

Rapidly approaching objects indicating threats can induce defensive response through activating a subcortical pathway comprising superior colliculus (SC), lateral posterior nucleus (LP), and basolateral amygdala (BLA). Abnormal defensive response has been reported in autism, and impaired synaptic connections could be the underlying mechanism. Whether the SC-LP-BLA pathway processes looming stimuli abnormally in autism is not clear. Here, we found that looming-evoked defensive response is impaired in a subgroup of the valproic acid (VPA) mouse model of autism. By combining the conventional neurotracer and transneuronal rabies virus tracing techniques, we demonstrated that synaptic connections in the SC-LP-BLA pathway were abnormal in VPA mice whose looming-evoked defensive responses were absent. Importantly, we further translated the finding to children with autism and observed that they did not present looming-evoked defensive response. Furthermore, the findings of the DTI with the probabilistic tractography showed that the structural connections of SC-pulvinar-amygdala in autism children were weak. The pulvinar is parallel to the LP in a mouse. Because looming-evoked defensive response is innate in humans and emerges much earlier than do social and language functions, the absence of defensive response could be an earlier sign of autism in children.

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

The WEAVE focus translation system: from design to construction

NASA Astrophysics Data System (ADS)

Canchado, Manuel; Romero, Antonio; Maroto, Óscar; Tomas, Albert; Martín-Nuño, Carlos; Casalta, Joan Manel; Prida, Joaquín.; L. Aguerri, J. Alfonso; Herreros, José Miguel; Delgado, José Miguel; Burgal, José Alonso; Abrams, Don Carlos; Dee, Kevin; Dalton, Gavin; Bonifacio, Piercarlo; Trager, Scott C.; Vallenari, Antonella

2016-07-01

WEAVE is a new wide-field spectroscopy facility proposed for the prime focus of the 4.2m William Herschel Telescope (WHT), placed in La Palma, Canary Islands, Spain. To allow for the compensation of the effects of temperature-induced and gravity-induced image degradation, the WEAVE prime focus assembly will be translated along the telescope optical axis. The assembly comprises the prime focus corrector with integrated ADC, a central mount for the corrector, an instrument rotator and a twin-focal-plane fibre positioner. Translation is accomplished through the use of a set of purpose-built actuators; collectively referred to as the Focus Translation System (FTS), formed by four independently-controlled Focus Translation Units (FTUs), eight vanes connecting the FTUs to a central can, and a central can hosting WEAVE Instrument. Each FTU is capable of providing a maximum stroke of +/-4mm with sufficient, combined force to move the five-tonne assembly with a positional accuracy of +/-20μm at a resolution of 5μm. The coordinated movement of the four FTUs allows +/-3mm WEAVE focus adjustment in the optical axis and +/-0.015° tilt correction in one axis. The control of the FTS is accomplished through a PLC-based subsystem that receives positional demands from the higher-level Instrument Control System. SENER has been responsible for designing, manufacturing and testing the FTS and the equipment required to manipulate and store the FTS together with the instrument. This manuscript describes the final design of the FTS along with the analyses and simulations that were performed, discusses the manufacturing procedures and the results of early verification prior to integration with the telescope. The plans for mounting the whole system on the telescope are also discussed.

Translational leadership: new approaches to team development.

PubMed

Harrigan, Rosanne C; Emery, Lori M

2010-01-01

Little is known about how to develop collaborative multidisciplinary research teams. Following a comprehensive needs assessment, we developed a curriculum-based, multi-disciplinary, didactic and experiential Translational Leadership training program grounded in adult learning theory. In addition, we constructed collaborative clinical/translational research experiences for trainees to enhance clinical/translational research skills. KEY PROGRAMMATIC ELEMENTS AND PRELIMINARY FINDINGS: This 15-week Translational Leadership program was generated based on the following premises. Academic translational leadership teams should partner and collaborate, customize, make the program relevant to the culture, create a common language, use the best resources, and establish measurable goals for success. Development of effective collaborative research teams is essential to the management of successful translational research teams. Development of these skills in addition to cultural humility will provide the best infrastructure and human capital committed to the resolution of health disparities. Effective translational research teams are more comfortable with the component team members and the communities where they implement their protocols. Our participants highly valued the diverse experiences from this program; several have succeeded in leading community-based research teams. Our Translational Leadership program offers essential skills using adult learning theory for translational researchers who become capable of leading and participating in translational research teams. We believe including community members in the training of translational research programs is an important asset. The multidisciplinary approach develops skills that are also of significant use to the community and its acceptance of responsibility for its own health.

Auditory-neurophysiological responses to speech during early childhood: Effects of background noise

PubMed Central

White-Schwoch, Travis; Davies, Evan C.; Thompson, Elaine C.; Carr, Kali Woodruff; Nicol, Trent; Bradlow, Ann R.; Kraus, Nina

2015-01-01

Early childhood is a critical period of auditory learning, during which children are constantly mapping sounds to meaning. But learning rarely occurs under ideal listening conditions—children are forced to listen against a relentless din. This background noise degrades the neural coding of these critical sounds, in turn interfering with auditory learning. Despite the importance of robust and reliable auditory processing during early childhood, little is known about the neurophysiology underlying speech processing in children so young. To better understand the physiological constraints these adverse listening scenarios impose on speech sound coding during early childhood, auditory-neurophysiological responses were elicited to a consonant-vowel syllable in quiet and background noise in a cohort of typically-developing preschoolers (ages 3–5 yr). Overall, responses were degraded in noise: they were smaller, less stable across trials, slower, and there was poorer coding of spectral content and the temporal envelope. These effects were exacerbated in response to the consonant transition relative to the vowel, suggesting that the neural coding of spectrotemporally-dynamic speech features is more tenuous in noise than the coding of static features—even in children this young. Neural coding of speech temporal fine structure, however, was more resilient to the addition of background noise than coding of temporal envelope information. Taken together, these results demonstrate that noise places a neurophysiological constraint on speech processing during early childhood by causing a breakdown in neural processing of speech acoustics. These results may explain why some listeners have inordinate difficulties understanding speech in noise. Speech-elicited auditory-neurophysiological responses offer objective insight into listening skills during early childhood by reflecting the integrity of neural coding in quiet and noise; this paper documents typical response properties

Altered Evoked Gamma-Band Responses Reveal Impaired Early Visual Processing in ADHD Children

ERIC Educational Resources Information Center

Lenz, Daniel; Krauel, Kerstin; Flechtner, Hans-Henning; Schadow, Jeanette; Hinrichs, Hermann; Herrmann, Christoph S.

2010-01-01

Neurophysiological studies yield contrary results whether attentional problems of patients with attention-deficit/hyperactivity disorder (ADHD) are related to early visual processing deficits or not. Evoked gamma-band responses (GBRs), being among the first cortical responses occurring as early as 90 ms after visual stimulation in human EEG, have…

Brd4 modulates the innate immune response through Mnk2-eIF4E pathway-dependent translational control of IκBα.

PubMed

Bao, Yan; Wu, Xuewei; Chen, Jinjing; Hu, Xiangming; Zeng, Fuxing; Cheng, Jianjun; Jin, Hong; Lin, Xin; Chen, Lin-Feng

2017-05-16

Bromodomain-containing factor Brd4 has emerged as an important transcriptional regulator of NF-κB-dependent inflammatory gene expression. However, the in vivo physiological function of Brd4 in the inflammatory response remains poorly defined. We now demonstrate that mice deficient for Brd4 in myeloid-lineage cells are resistant to LPS-induced sepsis but are more susceptible to bacterial infection. Gene-expression microarray analysis of bone marrow-derived macrophages (BMDMs) reveals that deletion of Brd4 decreases the expression of a significant amount of LPS-induced inflammatory genes while reversing the expression of a small subset of LPS-suppressed genes, including MAP kinase-interacting serine/threonine-protein kinase 2 ( Mknk2 ). Brd4 -deficient BMDMs display enhanced Mnk2 expression and the corresponding eukaryotic translation initiation factor 4E (eIF4E) activation after LPS stimulation, leading to an increased translation of IκBα mRNA in polysomes. The enhanced newly synthesized IκBα reduced the binding of NF-κB to the promoters of inflammatory genes, resulting in reduced inflammatory gene expression and cytokine production. By modulating the translation of IκBα via the Mnk2-eIF4E pathway, Brd4 provides an additional layer of control for NF-κB-dependent inflammatory gene expression and inflammatory response.

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.

Translation of globin messenger RNA by the mouse ovum

PubMed Central

Brinster, R. L.; Chen, H. Y.; Trumbauer, M. E.; Avarbock, M. R.

2016-01-01

It has been demonstrated that the Xenopus oocyte can translate rabbit haemoglobin messenger RNA (mRNA) following microinjection of the message into the cell1. The Xenopus oocyte has since been shown to be capable of translating a variety of messenger RNAs from different species2–4. This system has proved useful in understanding the mechanism of message translation and has also provided information about the translation capability of the Xenopus oocyte5,6. Several other cell types, including HeLa cells and fibroblasts, can also translate exogenous message injected into the cell7,8. However, there have been no reports of injection of mRNA into oocytes or fertilised one-cell ova of mammalian species. Nevertheless, the latter system could be of considerable use in studying the processing of exogenous messages in a mammalian system undergoing development, as well as providing insight into the way the early embryo processes injected messages and the protein products of such messages. We report here the results of injecting message into the fertilised one-cell mouse ovum and show that both mouse and rabbit globin mRNA are translated in this system. PMID:7352032

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.

Culture in Translation and Translation Studies.

ERIC Educational Resources Information Center

Schaffner, Christina

1994-01-01

Reviews the evolution of translation from an exchange of information within and across cultural boundaries to its current status as a scholarly endeavor. Translations may have far-reaching effects in the target and source culture. Translators should be cognizant of the foreign language and culture in order to successfully realize their role as…

Early Change in Stroke Size Performs Best in Predicting Response to Therapy.

PubMed

Simpkins, Alexis Nétis; Dias, Christian; Norato, Gina; Kim, Eunhee; Leigh, Richard

2017-01-01

Reliable imaging biomarkers of response to therapy in acute stroke are needed. The final infarct volume and percent of early reperfusion have been used for this purpose. Early fluctuation in stroke size is a recognized phenomenon, but its utility as a biomarker for response to therapy has not been established. This study examined the clinical relevance of early change in stroke volume and compared it with the final infarct volume and percent of early reperfusion in identifying early neurologic improvement (ENI). Acute stroke patients, enrolled between 2013 and 2014 with serial magnetic resonance imaging (MRI) scans (pretreatment baseline, 2 h post, and 24 h post), who received thrombolysis were included in the analysis. Early change in stroke volume, infarct volume at 24 h on diffusion, and percent of early reperfusion were calculated from the baseline and 2 h MRI scans were compared. ENI was defined as ≥4 point decrease in National Institutes of Health Stroke Scales within 24 h. Logistic regression models and receiver operator characteristics analysis were used to compare the efficacy of 3 imaging biomarkers. Serial MRIs of 58 acute stroke patients were analyzed. Early change in stroke volume was significantly associated with ENI by logistic regression analysis (OR 0.93, p = 0.048) and remained significant after controlling for stroke size and severity (OR 0.90, p = 0.032). Thus, for every 1 mL increase in stroke volume, there was a 10% decrease in the odds of ENI, while for every 1 mL decrease in stroke volume, there was a 10% increase in the odds of ENI. Neither infarct volume at 24 h nor percent of early reperfusion were significantly associated with ENI by logistic regression. Receiver-operator characteristic analysis identified early change in stroke volume as the only biomarker of the 3 that performed significantly different than chance (p = 0.03). Early fluctuations in stroke size may represent a more reliable biomarker for response to therapy than the

WE-FG-202-02: Exploration of High-Resolution Quantitative Ultrasonic Micro-Vascular Imaging for Early Assessment of Radiotherapy Tumor Response

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

Kasoji, S; Rivera, J; Dayton, P

Purpose: Currently, we cannot predict an individual patient’s response to a given radiotherapy which normally is not detected for weeks to months post-treatment. As a result, precious time is wasted for patients with unresponsive tumors who could have switched to an alternative treatment much earlier. Presently, no early treatment response detection method exists that is effective, low-cost, non-invasive, and safe. We hypothesize that changes in tumor microvasculature predict tumor response to radiotherapy earlier than tumor volume changes. Recent radiobiology research suggests tumors undergo vascular remodeling in response to radiation well before manifesting changes in tumor volume. We propose monitoring tumormore » microvasculature post-radiation using Acoustic Angiography (AA), a novel ultrasound imaging modality developed and patented in-house. In this study, we investigate whether changes in tumor microvasculature, measured using AA, can be an early indicator of high-dose radiotherapy success, compared to changes in tumor volume. Methods: Fibrosarcoma xenograft tumor tissue was subcutaneously implanted into rodent flanks (N=10). Animal tumors (N=8) were irradiated with a single treatment of 15Gy using a clinical LINAC at 100SSD and 2×2cm field size. Two untreated rats were left as tumor controls. AA imaging was performed immediately posttreatment and every third day thereafter for 30 days, or until tumors disappeared. Tumor volumes and vascular densities were measured from anatomical b-mode ultrasound and AA images, respectively. Results: Statistical differences in vascular density between treatment responders and non-responders were observed on Day 10 (p=0.005), whereas statistical differences in tumor volume were not observed until Day 19 (p=0.02). Conclusions: Tumor vascularity differences may be observed substantially earlier than differences in tumor size. In addition, significant early increases in vascular density were observed in non

Topical Review: Translating Translational Research in Behavioral Science.

PubMed

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

2015-01-01

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

In Vivo Senescence in the Sbds-Deficient Murine Pancreas: Cell-Type Specific Consequences of Translation Insufficiency

PubMed Central

Tourlakis, Marina E.; Zhang, Siyi; Ball, Heather L.; Gandhi, Rikesh; Liu, Hongrui; Zhong, Jian; Yuan, Julie S.; Guidos, Cynthia J.; Durie, Peter R.; Rommens, Johanna M.

2015-01-01

Genetic models of ribosome dysfunction show selective organ failure, highlighting a gap in our understanding of cell-type specific responses to translation insufficiency. Translation defects underlie a growing list of inherited and acquired cancer-predisposition syndromes referred to as ribosomopathies. We sought to identify molecular mechanisms underlying organ failure in a recessive ribosomopathy, with particular emphasis on the pancreas, an organ with a high and reiterative requirement for protein synthesis. Biallelic loss of function mutations in SBDS are associated with the ribosomopathy Shwachman-Diamond syndrome, which is typified by pancreatic dysfunction, bone marrow failure, skeletal abnormalities and neurological phenotypes. Targeted disruption of Sbds in the murine pancreas resulted in p53 stabilization early in the postnatal period, specifically in acinar cells. Decreased Myc expression was observed and atrophy of the adult SDS pancreas could be explained by the senescence of acinar cells, characterized by induction of Tgfβ, p15Ink4b and components of the senescence-associated secretory program. This is the first report of senescence, a tumour suppression mechanism, in association with SDS or in response to a ribosomopathy. Genetic ablation of p53 largely resolved digestive enzyme synthesis and acinar compartment hypoplasia, but resulted in decreased cell size, a hallmark of decreased translation capacity. Moreover, p53 ablation resulted in expression of acinar dedifferentiation markers and extensive apoptosis. Our findings indicate a protective role for p53 and senescence in response to Sbds ablation in the pancreas. In contrast to the pancreas, the Tgfβ molecular signature was not detected in fetal bone marrow, liver or brain of mouse models with constitutive Sbds ablation. Nevertheless, as observed with the adult pancreas phenotype, disease phenotypes of embryonic tissues, including marked neuronal cell death due to apoptosis, were determined to

In Vivo Senescence in the Sbds-Deficient Murine Pancreas: Cell-Type Specific Consequences of Translation Insufficiency.

PubMed

Tourlakis, Marina E; Zhang, Siyi; Ball, Heather L; Gandhi, Rikesh; Liu, Hongrui; Zhong, Jian; Yuan, Julie S; Guidos, Cynthia J; Durie, Peter R; Rommens, Johanna M

2015-06-01

Genetic models of ribosome dysfunction show selective organ failure, highlighting a gap in our understanding of cell-type specific responses to translation insufficiency. Translation defects underlie a growing list of inherited and acquired cancer-predisposition syndromes referred to as ribosomopathies. We sought to identify molecular mechanisms underlying organ failure in a recessive ribosomopathy, with particular emphasis on the pancreas, an organ with a high and reiterative requirement for protein synthesis. Biallelic loss of function mutations in SBDS are associated with the ribosomopathy Shwachman-Diamond syndrome, which is typified by pancreatic dysfunction, bone marrow failure, skeletal abnormalities and neurological phenotypes. Targeted disruption of Sbds in the murine pancreas resulted in p53 stabilization early in the postnatal period, specifically in acinar cells. Decreased Myc expression was observed and atrophy of the adult SDS pancreas could be explained by the senescence of acinar cells, characterized by induction of Tgfβ, p15(Ink4b) and components of the senescence-associated secretory program. This is the first report of senescence, a tumour suppression mechanism, in association with SDS or in response to a ribosomopathy. Genetic ablation of p53 largely resolved digestive enzyme synthesis and acinar compartment hypoplasia, but resulted in decreased cell size, a hallmark of decreased translation capacity. Moreover, p53 ablation resulted in expression of acinar dedifferentiation markers and extensive apoptosis. Our findings indicate a protective role for p53 and senescence in response to Sbds ablation in the pancreas. In contrast to the pancreas, the Tgfβ molecular signature was not detected in fetal bone marrow, liver or brain of mouse models with constitutive Sbds ablation. Nevertheless, as observed with the adult pancreas phenotype, disease phenotypes of embryonic tissues, including marked neuronal cell death due to apoptosis, were determined to

Dual function of CD70 in viral infection: modulator of early cytokine responses and activator of adaptive responses1

PubMed Central

Allam, Atef; Swiecki, Melissa; Vermi, William; Ashwell, Jonathan D.; Colonna, Marco

2014-01-01

The role of the tumor necrosis factor family member CD70 in adaptive T cell responses has been intensively studied but its function in innate responses is still under investigation. Here we show that CD70 inhibits the early innate response to murine cytomegalovirus (MCMV) but is essential for the optimal generation of virus-specific CD8 T cells. CD70-/- mice reacted to MCMV infection with a robust type I interferon and proinflammatory cytokine response. This response was sufficient for initial control of MCMV, although at later time points, CD70-/- mice became more susceptible to MCMV infection. The heightened cytokine response during the early phase of MCMV infection in CD70-/- mice was paralleled by a reduction in regulatory T cells (Treg). Treg from naïve CD70-/- mice were not as efficient at suppressing T cell proliferation compared to Treg from naïve WT mice and depletion of Treg during MCMV infection in Foxp3-DTR mice or in WT mice recapitulated the phenotype observed in CD70-/- mice. Our study demonstrates that while CD70 is required for the activation of the antiviral adaptive response, it has a regulatory role in early cytokine responses to viruses such as MCMV, possibly through maintenance of Treg survival and function. PMID:24913981

Children's cortisol responses to a social evaluative laboratory stressor from early to middle childhood.

PubMed

Leppert, Katherine A; Kushner, Marissa; Smith, Victoria C; Lemay, Edward P; Dougherty, Lea R

2016-12-01

This study examined the stability of children's cortisol responses to a social evaluative laboratory stressor from early to middle childhood. Ninety-six children (51 males) completed stress-inducing laboratory tasks and provided five salivary cortisol samples in early (W1) and middle (W2) childhood. Although W1 cortisol responses did not predict W2 cortisol responses, children's cortisol responses demonstrated change: compared to their W1 cortisol responses, children's W2 cortisol responses demonstrated an increased slope and more negative quadratic curvature. Furthermore, child psychiatric symptoms at W1 moderated the stability of children's cortisol responses. Children with fewer preschool psychiatric symptoms demonstrated greater inter-individual and intra-individual stability, whereas children with higher preschool psychiatric symptoms and comorbidity demonstrated systematic inter-individual and intra-individual instability in cortisol responses over time. Findings suggest a developmental shift toward increasing cortisol stress responses from early to middle childhood and highlight preschool psychopathology as a moderator of stability in children's cortisol responses over time. © 2016 Wiley Periodicals, Inc.

Translating Alcohol Research: Opportunities and Challenges.

PubMed

Batman, Angela M; Miles, Michael F

2015-01-01

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

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

PubMed

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

2013-05-01

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

Examining English-German Translation Ambiguity Using Primed Translation Recognition

ERIC Educational Resources Information Center

Eddington, Chelsea M.; Tokowicz, Natasha

2013-01-01

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

Translation Ambiguity but Not Word Class Predicts Translation Performance

ERIC Educational Resources Information Center

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

2013-01-01

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

Translation Activities in Bilingual Early Childhood Education: Children's Perspectives and Teachers' Scaffolding

ERIC Educational Resources Information Center

Kultti, Anne; Pramling, Niklas

2017-01-01

In the present study we investigate empirically how six to seven-year-old children with their teachers take on the challenge of translating the lyrics of a children's song from Finnish to English, analyzing how translation is collaboratively constituted by the participants. The study is informed by translanguaging theory and a sociocultural…

Lipid signalling couples translational surveillance to systemic detoxification in Caenorhabditis elegans

PubMed Central

Govindan, J. Amaranath; Jayamani, Elamparithi; Zhang, Xinrui; Breen, Peter; Larkins-Ford, Jonah; Mylonakis, Eleftherios

2015-01-01

Translation in eukaryotes is surveilled to detect toxins and virulence factors and coupled to the induction of defense pathways. C. elegans germline-specific mutations in translation components are detected by this system to induce detoxification and immune responses in distinct somatic cells. An RNAi screen revealed gene inactivations that act at multiple steps in lipid biosynthetic and kinase pathways that act upstream of MAP kinase to mediate the systemic communication of translation-defects to induce detoxification genes. Mammalian bile acids can rescue the defect in detoxification gene induction caused by C. elegans lipid biosynthetic gene inactivations. Extracts prepared from C. elegans with translation deficits but not from wild type can also rescue detoxification gene induction in lipid biosynthetic defective strains. These eukaryotic antibacterial countermeasures are not ignored by bacteria: particular bacterial species suppress normal C. elegans detoxification responses to mutations in translation factors. PMID:26322678

Frameworks for Response to Intervention in Early Childhood: Description and Implications

ERIC Educational Resources Information Center

Communication Disorders Quarterly, 2014

2014-01-01

In February, 2013, the Division of Early Childhood, the National Association for the Education of Young Children, and the National Head Start Association released a collaborative paper to provide clarification and assistance regarding the relationship of response to intervention (RTI) with the field of early childhood (EC). In addition to…

Animal models in translational studies of PTSD.

PubMed

Daskalakis, Nikolaos P; Yehuda, Rachel; Diamond, David M

2013-09-01

Understanding the neurobiological mechanisms of post-traumatic stress disorder (PTSD) is of vital importance for developing biomarkers and more effective pharmacotherapy for this disorder. The design of bidirectional translational studies addressing all facets of PTSD is needed. Animal models of PTSD are needed not only to capture the complexity of PTSD behavioral characteristics, but also to address experimentally the influence of variety of factors which might determine an individual's vulnerability or resilience to trauma, e.g., genetic predisposition, early-life experience and social support. The current review covers recent translational approaches to bridge the gap between human and animal PTSD research and to create a framework for discovery of biomarkers and novel therapeutics. Published by Elsevier Ltd.

Translation failure and medical reversal: Two sides to the same coin.

PubMed

Prasad, Vinay

2016-01-01

Translation failure occurs when the results of preclinical, observational and/or early phase studies fail to predict the results of well done (i.e. appropriately controlled, adequately powered, and properly conducted) phase III or randomised clinical trials. Some failures occur when promising basic science findings fail to replicate in human studies, while others happen when promising uncontrolled trial data show an exaggerated effect that vanishes in the setting of a randomised trial. Medical reversals occur when the results of preclinical, observational and/or early phase studies fail to predict the results of subsequent randomized clinical trials, but the practice has already gained widespread acceptance. Oncologic examples include bevacizumab and the use of autologous stem cell transplant in metastatic breast cancer. In a well-intentioned effort to reduce the rate of translation failure, oncologists must be careful that changes to regulatory processes and clinical trial design do not actually work to increase the approval of ineffective compounds. By trying to cure translation failure, we should be careful to avoid medical reversal. The rise of surrogate end-points and role of hard-wired bias in oncology trials suggest that we may be currently ignoring the simple fact that translation failure and medical reversal are two sides to the same coin. Published by Elsevier Ltd.

Early improvements in anxiety, depression, and anger/hostility symptoms and response to antidepressant treatment.

PubMed

Farabaugh, Amy; Sonawalla, Shamsah; Johnson, Daniel P; Witte, Janet; Papakostas, George I; Goodness, Tracie; Clain, Alisabet; Baer, Lee; Mischoulon, David; Fava, Maurizio; Harley, Rebecca

2010-08-01

The purpose of this study was to examine whether treatment response to fluoxetine by depressed outpatients was predicted by early improvement on any of 3 subscales (Anxiety, Depression, and Anger/Hostility) of the Symptom Questionnaire (SQ). We evaluated 169 depressed outpatients (52.6% female) between ages 18 and 65 (mean age, 40.3 +/- 10.6 years) meeting DSM-IIIR criteria for major depressive disorder (MDD). All patients completed the SQ at baseline (week 0) and at weeks 2, 4, and 8 of treatment with fluoxetine 20 mg/d. We defined treatment response as a > or= 50% reduction in score on the 17-item Hamilton Rating Scale for Depression, and early improvement on 3 SQ subscales (Anxiety, Depression, and Anger/Hostility) as a >30% reduction in score by week 2. The percentage of patients with significant early improvement in anger was significantly greater than the percentage of those with early improvements in anxiety or depression. When early improvement on the Anxiety, Depression, and Anger/Hostility subscales of the SQ were assessed independently by logistic regression, all 3 subscales were predictors of response to treatment. Early improvement in anger, anxiety, and depressive symptoms may predict response to antidepressant treatment among outpatients with MDD.

Early Twentieth Century Responses to the Drug Problem.

ERIC Educational Resources Information Center

Pfennig, Dennis Joseph

1991-01-01

Describes early twentieth-century responses to the drug problem in the United States. Discusses pressure from the media and reformers to control the availability of drugs such as opium and cocaine that were widely available in over-the-counter medications. Focuses on New York State, which took the lead in enacting drug control legislation. (DK)

Transient translational quiescence in primordial germ cells

PubMed Central

Oulhen, Nathalie; Swartz, S. Zachary; Laird, Jessica; Mascaro, Alexandra

2017-01-01

Stem cells in animals often exhibit a slow cell cycle and/or low transcriptional activity referred to as quiescence. Here, we report that the translational activity in the primordial germ cells (PGCs) of the sea urchin embryo (Strongylocentrotus purpuratus) is quiescent. We measured new protein synthesis with O-propargyl-puromycin and L-homopropargylglycine Click-iT technologies, and determined that these cells synthesize protein at only 6% the level of their adjacent somatic cells. Knockdown of translation of the RNA-binding protein Nanos2 by morpholino antisense oligonucleotides, or knockout of the Nanos2 gene by CRISPR/Cas9 resulted in a significant, but partial, increase (47%) in general translation specifically in the PGCs. We found that the mRNA of the translation factor eEF1A is excluded from the PGCs in a Nanos2-dependent manner, a consequence of a Nanos/Pumilio response element (PRE) in its 3′UTR. In addition to eEF1A, the cytoplasmic pH of the PGCs appears to repress translation and simply increasing the pH also significantly restores translation selectively in the PGCs. We conclude that the PGCs of this sea urchin institute parallel pathways to quiesce translation thoroughly but transiently. PMID:28235822

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

ERIC Educational Resources Information Center

Laxen, Jannika; Lavaur, Jean-Marc

2010-01-01

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

Development of a Drug-Response Modeling Framework to Identify Cell Line Derived Translational Biomarkers That Can Predict Treatment Outcome to Erlotinib or Sorafenib.

PubMed

Li, Bin; Shin, Hyunjin; Gulbekyan, Georgy; Pustovalova, Olga; Nikolsky, Yuri; Hope, Andrew; Bessarabova, Marina; Schu, Matthew; Kolpakova-Hart, Elona; Merberg, David; Dorner, Andrew; Trepicchio, William L

2015-01-01

Development of drug responsive biomarkers from pre-clinical data is a critical step in drug discovery, as it enables patient stratification in clinical trial design. Such translational biomarkers can be validated in early clinical trial phases and utilized as a patient inclusion parameter in later stage trials. Here we present a study on building accurate and selective drug sensitivity models for Erlotinib or Sorafenib from pre-clinical in vitro data, followed by validation of individual models on corresponding treatment arms from patient data generated in the BATTLE clinical trial. A Partial Least Squares Regression (PLSR) based modeling framework was designed and implemented, using a special splitting strategy and canonical pathways to capture robust information for model building. Erlotinib and Sorafenib predictive models could be used to identify a sub-group of patients that respond better to the corresponding treatment, and these models are specific to the corresponding drugs. The model derived signature genes reflect each drug's known mechanism of action. Also, the models predict each drug's potential cancer indications consistent with clinical trial results from a selection of globally normalized GEO expression datasets.

A Research Consortium That's All Over the Map--That's Our Strength, if We Use Translation to Teach Each Other: A Response to Janis Forman's ABC Outstanding Researcher Lecture.

ERIC Educational Resources Information Center

Kostelnick, Charles

1998-01-01

Responds to an article in the same issue of this journal by considering several issues: whether pure research in business communication is possible; why business communication translates ideas and methods from other disciplines; and responsibilities of translators. Argues that the breadth of this research consortium should not be seen as a…

Academic Perspectives and Experiences of Knowledge Translation: A Qualitative Study of Public Health Researchers

ERIC Educational Resources Information Center

Collie, Alex; Zardo, Pauline; McKenzie, Donna Margaret; Ellis, Niki

2016-01-01

This study explores the views and experiences of knowledge translation of 14 Australian public health academics. Capacity to engage in knowledge translation is influenced by factors within the academic context and the interaction of the academic and policy environments. Early and mid-career researchers reported a different set of experiences and…

Early response in cognitive-behavior therapy for syndromes of medically unexplained symptoms.

PubMed

Kleinstäuber, Maria; Lambert, Michael J; Hiller, Wolfgang

2017-05-25

Early dramatic treatment response suggests a subset of patients who respond to treatment before most of it has been offered. These early responders tend to be over represented among those who are well at termination and at follow-up. Early response patterns in psychotherapy have been investigated only for a few of mental disorders so far. The main aim of the current study was to examine early response after five therapy-preparing sessions of a cognitive behavior therapy (CBT) for syndromes of medically unexplained symptoms (MUS). In the context of a randomized, waiting-list controlled trial 48 patients who suffered from ≥3 MUS over ≥6 months received 5 therapy-preparing sessions and 20 sessions of CBT for somatoform disorders. They completed self-report scales of somatic symptom severity (SOMS-7 T), depression (BDI-II), anxiety (BSI), illness anxiety and behavior (IAS) at pre-treatment, after 5 therapy-preparing sessions (FU-5P) and at therapy termination (FU-20 T). The current analyses are based on data from the treatment arm only. Repeated measure ANOVAs revealed a significant decrease of depression (d = 0.34), anxiety (d = 0.60), illness anxiety (d = 0.38) and illness behavior (d = 0.42), but no change of somatic symptom severity (d = -0.03) between pre-treatment and FU-5P. Hierarchical linear multiple regression analyses showed that symptom improvements between pre-treatment and FU-5P predict a better outcome at therapy termination for depression and illness anxiety, after controlling for pre-treatment scores. Mixed-effect ANOVAs revealed significant group*time interaction effects indicating differences in the course of symptom improvement over the therapy between patients who fulfilled a reliable change (i.e., early response) during the 5 therapy-preparing sessions and patients who did not reach an early reliable change. Demographic or clinical variables at pre-treatment were not significantly correlated with differential scores between pre

Interrelations between translation and general mRNA degradation in yeast.

PubMed

Huch, Susanne; Nissan, Tracy

2014-01-01

Messenger RNA (mRNA) degradation is an important element of gene expression that can be modulated by alterations in translation, such as reductions in initiation or elongation rates. Reducing translation initiation strongly affects mRNA degradation by driving mRNA toward the assembly of a decapping complex, leading to decapping. While mRNA stability decreases as a consequence of translational inhibition, in apparent contradiction several external stresses both inhibit translation initiation and stabilize mRNA. A key difference in these processes is that stresses induce multiple responses, one of which stabilizes mRNAs at the initial and rate-limiting step of general mRNA decay. Because this increase in mRNA stability is directly induced by stress, it is independent of the translational effects of stress, which provide the cell with an opportunity to assess its response to changing environmental conditions. After assessment, the cell can store mRNAs, reinitiate their translation or, alternatively, embark on a program of enhanced mRNA decay en masse. Finally, recent results suggest that mRNA decay is not limited to non-translating messages and can occur when ribosomes are not initiating but are still elongating on mRNA. This review will discuss the models for the mechanisms of these processes and recent developments in understanding the relationship between translation and general mRNA degradation, with a focus on yeast as a model system. © 2014 The Authors. WIREs RNA published by John Wiley & Sons, Ltd.

Dual-mass vibratory rate gyroscope with suppressed translational acceleration response and quadrature-error correction capability

NASA Technical Reports Server (NTRS)

Clark, William A. (Inventor); Juneau, Thor N. (Inventor); Lemkin, Mark A. (Inventor); Roessig, Allen W. (Inventor)

2001-01-01

A microfabricated vibratory rate gyroscope to measure rotation includes two proof-masses mounted in a suspension system anchored to a substrate. The suspension has two principal modes of compliance, one of which is driven into oscillation. The driven oscillation combined with rotation of the substrate about an axis perpendicular to the substrate results in Coriolis acceleration along the other mode of compliance, the sense-mode. The sense-mode is designed to respond to Coriolis accelerationwhile suppressing the response to translational acceleration. This is accomplished using one or more rigid levers connecting the two proof-masses. The lever allows the proof-masses to move in opposite directions in response to Coriolis acceleration. The invention includes a means for canceling errors, termed quadrature error, due to imperfections in implementation of the sensor. Quadrature-error cancellation utilizes electrostatic forces to cancel out undesired sense-axis motion in phase with drive-mode position.

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.

Evidence-Based Early Reading Practices within a Response to Intervention System

ERIC Educational Resources Information Center

Bursuck, Bill; Blanks, Brooke

2010-01-01

Many students who experience reading failure are inappropriately placed in special education. A promising response to reducing reading failure and the overidentification of students for special education is Response to Intervention (RTI), a comprehensive early detection and prevention system that allows teachers to identify and support struggling…

Poly(ADP-Ribosyl)ation of hnRNP A1 Protein Controls Translational Repression in Drosophila.

PubMed

Ji, Yingbiao; Tulin, Alexei V

2016-10-01

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. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

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

Developing the Translational Research Workforce: A Pilot Study of Common Metrics for Evaluating the Clinical and Translational Award KL2 Program

PubMed Central

Guerrero, Lourdes; Jones, Lisa B.; Tong, Greg; Ireland, Christine; Dumbauld, Jill; Rainwater, Julie

2015-01-01

Abstract Purpose This pilot study describes the career development programs (i.e., NIH KL2 awards) across five Clinical and Translational Science Award (CTSA) institutions within the University of California (UC) system, and examines the feasibility of a set of common metrics for evaluating early outcomes. Methods A survey of program administrators provided data related to the institutional environment within which each KL2 program was implemented. Application and progress report data yielded a combined data set that characterized KL2 awardees, their initial productivity, and early career outcomes. Results The pilot project demonstrated the feasibility of aggregating common metrics data across multiple institutions. The data indicated that KL2 awardees were an accomplished set of investigators, both before and after the award period, representing a wide variety of disciplines. Awardees that had completed their trainee period overwhelmingly remained active in translational research conducted within an academic setting. Early indications also suggest high rates of success with obtaining research funding subsequent to the KL2 award. Conclusion This project offers a model for how to collect and analyze common metrics related to the education and training function of the CTSA Consortium. Next steps call for expanding participation to other CTSA sites outside of the University of California system. PMID:26602332

Dom34 Links Translation to Protein O-mannosylation.

PubMed

van Wijlick, Lasse; Geissen, René; Hilbig, Jessica S; Lagadec, Quentin; Cantero, Pilar D; Pfeifer, Eugen; Juchimiuk, Mateusz; Kluge, Sven; Wickert, Stephan; Alepuz, Paula; Ernst, Joachim F

2016-10-01

In eukaryotes, Dom34 upregulates translation by securing levels of activatable ribosomal subunits. We found that in the yeast Saccharomyces cerevisiae and the human fungal pathogen Candida albicans, Dom34 interacts genetically with Pmt1, a major isoform of protein O-mannosyltransferase. In C. albicans, lack of Dom34 exacerbated defective phenotypes of pmt1 mutants, while they were ameliorated by Dom34 overproduction that enhanced Pmt1 protein but not PMT1 transcript levels. Translational effects of Dom34 required the 5'-UTR of the PMT1 transcript, which bound recombinant Dom34 directly at a CA/AC-rich sequence and regulated in vitro translation. Polysomal profiling revealed that Dom34 stimulates general translation moderately, but that it is especially required for translation of transcripts encoding Pmt isoforms 1, 4 and 6. Because defective protein N- or O-glycosylation upregulates transcription of PMT genes, it appears that Dom34-mediated specific translational upregulation of the PMT transcripts optimizes cellular responses to glycostress. Its translational function as an RNA binding protein acting at the 5'-UTR of specific transcripts adds another facet to the known ribosome-releasing functions of Dom34 at the 3'-UTR of transcripts.

Cortisol Response to Psychosocial Stress in Chinese Early Puberty Girls: Possible Role of Depressive Symptoms.

PubMed

Sun, Ying; Deng, Fang; Liu, Yang; Tao, Fang-Biao

2015-01-01

Objective. The present study aimed at investigating unique patterns of salivary cortisol reactivity and recovery in response to a social stressor among girls with early puberty and exploring possible role of depressive symptom in this association. Design. Case-control study. Patients. Fifty-six girls with early puberty and age- and body mass index- (BMI-) matched normal puberty controls (n = 56) were selected. Measurements. Salivary cortisol was measured in response to the Groningen Social Stress Test for Children. Results. Girls with early puberty had higher cortisol concentration at the end of the GSST (C3), cortisol concentration 20 min after the end of the GSST (C4), and AUC increment (AUCi) compared to non-early puberty girls. Depressive symptoms correlated with blunted HPA reactivity among girls with early puberty. Conclusion. This study demonstrated the disturbance effect of objectively examined early pubertal timing on HPA axis responses. It also suggested that stress reactivity might be blunted for individuals with depressive symptoms.

Predictors of Responsiveness to Early Literacy Intervention: A 10-Year Update

ERIC Educational Resources Information Center

Lam, Elizabeth A.; McMaster, Kristen L.

2014-01-01

The purpose of this review was to update previous reviews on factors related to students' responsiveness to early literacy intervention. The 14 studies in this synthesis used experimental designs, provided small-group or one-on-one reading interventions, and analyzed factors related to responsiveness to those interventions. Participants were…

Interrelations between translation and general mRNA degradation in yeast

PubMed Central

Huch, Susanne; Nissan, Tracy

2014-01-01

Messenger RNA (mRNA) degradation is an important element of gene expression that can be modulated by alterations in translation, such as reductions in initiation or elongation rates. Reducing translation initiation strongly affects mRNA degradation by driving mRNA toward the assembly of a decapping complex, leading to decapping. While mRNA stability decreases as a consequence of translational inhibition, in apparent contradiction several external stresses both inhibit translation initiation and stabilize mRNA. A key difference in these processes is that stresses induce multiple responses, one of which stabilizes mRNAs at the initial and rate-limiting step of general mRNA decay. Because this increase in mRNA stability is directly induced by stress, it is independent of the translational effects of stress, which provide the cell with an opportunity to assess its response to changing environmental conditions. After assessment, the cell can store mRNAs, reinitiate their translation or, alternatively, embark on a program of enhanced mRNA decay en masse. Finally, recent results suggest that mRNA decay is not limited to non-translating messages and can occur when ribosomes are not initiating but are still elongating on mRNA. This review will discuss the models for the mechanisms of these processes and recent developments in understanding the relationship between translation and general mRNA degradation, with a focus on yeast as a model system. How to cite this article: WIREs RNA 2014, 5:747–763. doi: 10.1002/wrna.1244 PMID:24944158

Cortisol Stress Response Variability in Early Adolescence Attachment, Affect and Sex

PubMed Central

Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J.; Wynne-Edwards, Katherine; Wright, Joan M.; Weinberg, Joanne

2017-01-01

Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic–pituitary–adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents. PMID:27468997

Cortisol Stress Response Variability in Early Adolescence: Attachment, Affect and Sex.

PubMed

Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J; Wynne-Edwards, Katherine; Wright, Joan M; Weinberg, Joanne

2017-01-01

Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic-pituitary-adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents.

Chronic early life stress induced by limited bedding and nesting (LBN) material in rodents: critical considerations of methodology, outcomes and translational potential.

PubMed

Walker, Claire-Dominique; Bath, Kevin G; Joels, Marian; Korosi, Aniko; Larauche, Muriel; Lucassen, Paul J; Morris, Margaret J; Raineki, Charlis; Roth, Tania L; Sullivan, Regina M; Taché, Yvette; Baram, Tallie Z

2017-09-01

The immediate and long-term effects of exposure to early life stress (ELS) have been documented in humans and animal models. Even relatively brief periods of stress during the first 10 days of life in rodents can impact later behavioral regulation and the vulnerability to develop adult pathologies, in particular an impairment of cognitive functions and neurogenesis, but also modified social, emotional, and conditioned fear responses. The development of preclinical models of ELS exposure allows the examination of mechanisms and testing of therapeutic approaches that are not possible in humans. Here, we describe limited bedding and nesting (LBN) procedures, with models that produce altered maternal behavior ranging from fragmentation of care to maltreatment of infants. The purpose of this paper is to discuss important issues related to the implementation of this chronic ELS procedure and to describe some of the most prominent endpoints and consequences, focusing on areas of convergence between laboratories. Effects on the hypothalamic-pituitary adrenal (HPA) axis, gut axis and metabolism are presented in addition to changes in cognitive and emotional functions. Interestingly, recent data have suggested a strong sex difference in some of the reported consequences of the LBN paradigm, with females being more resilient in general than males. As both the chronic and intermittent variants of the LBN procedure have profound consequences on the offspring with minimal external intervention from the investigator, this model is advantageous ecologically and has a large translational potential. In addition to the direct effect of ELS on neurodevelopmental outcomes, exposure to adverse early environments can also have intergenerational impacts on mental health and function in subsequent generation offspring. Thus, advancing our understanding of the effect of ELS on brain and behavioral development is of critical concern for the health and wellbeing of both the current

Early stage response problem for post-disaster incidents

NASA Astrophysics Data System (ADS)

Kim, Sungwoo; Shin, Youngchul; Lee, Gyu M.; Moon, Ilkyeong

2018-07-01

Research on evacuation plans for reducing damages and casualties has been conducted to advise defenders against threats. However, despite the attention given to the research in the past, emergency response management, designed to neutralize hazards, has been undermined since planners frequently fail to apprehend the complexities and contexts of the emergency situation. Therefore, this study considers a response problem with unique characteristics for the duration of the emergency. An early stage response problem is identified to find the optimal routing and scheduling plan for responders to prevent further hazards. Due to the complexity of the proposed mathematical model, two algorithms are developed. Data from a high-rise building, called Central City in Seoul, Korea, are used to evaluate the algorithms. Results show that the proposed algorithms can procure near-optimal solutions within a reasonable time.

Lost in Translation? "Bildung" between Ideological Debate and Pragmatism: A Response to Julia Campos

ERIC Educational Resources Information Center

Roche, Jorg

2015-01-01

The term "Bildung" is notoriously difficult to translate. Though it is often translated as "education," this does not entirely convey its meaning nor entirely explain its use in a myriad compounds such as "Bildungssprache" (language of/for education), "Bildungsweg" (path to education),…

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].

Arsenic and Immune Response to Infection During Pregnancy and Early Life.

PubMed

Attreed, Sarah E; Navas-Acien, Ana; Heaney, Christopher D

2017-06-01

Arsenic, a known carcinogen and developmental toxicant, is a major threat to global health. While the contribution of arsenic exposure to chronic diseases and adverse pregnancy and birth outcomes is recognized, its ability to impair critical functions of humoral and cell-mediated immunity-including the specific mechanisms in humans-is not well understood. Arsenic has been shown to increase risk of infectious diseases that have significant health implications during pregnancy and early life. Here, we review the latest research on the mechanisms of arsenic-related immune response alterations that could underlie arsenic-associated increased risk of infection during the vulnerable periods of pregnancy and early life. The latest evidence points to alteration of antibody production and transplacental transfer as well as failure of T helper cells to produce IL-2 and proliferate. Critical areas for future research include the effects of arsenic exposure during pregnancy and early life on immune responses to natural infection and the immunogenicity and efficacy of vaccines.

Can early host responses to mycobacterial infection predict eventual disease outcomes?

PubMed

de Silva, Kumudika; Begg, Douglas J; Plain, Karren M; Purdie, Auriol C; Kawaji, Satoko; Dhand, Navneet K; Whittington, Richard J

2013-11-01

Diagnostic tests used for Johne's disease in sheep either have poor sensitivity and specificity or only detect disease in later stages of infection. Predicting which of the infected sheep are likely to become infectious later in life is currently not feasible and continues to be a major hindrance in disease control. We conducted this longitudinal study to investigate if a suite of diagnostic tests conducted in Mycobacterium avium subspecies paratuberculosis (MAP) exposed lambs at 4 months post infection can accurately predict their clinical status at 12 months post infection. We tracked cellular and humoral responses and quantity of MAP shedding for up to 12 months post challenge in 20 controls and 37 exposed sheep. Infection was defined at necropsy by tissue culture and disease spectrum by lesion type. Data were analysed using univariable and multivariable logistic regression models and a subset of variables from the earliest period post inoculation (4 months) was selected for predicting disease outcomes later on (12 months). Sensitivity and specificity of tests and their combinations in series and parallel were determined. Early elevation in faecal MAP DNA quantity and a lower interferon gamma (IFNγ) response were significantly associated with sheep becoming infectious as well as progressing to severe disease. Conversely, early low faecal MAP DNA and higher interleukin-10 responses were significantly associated with an exposed animal developing protective immunity. Combination of early elevated faecal MAP DNA or lower IFNγ response had the highest sensitivity (75%) and specificity (81%) for identifying sheep that would become infectious. Collectively, these results highlight the potential for combined test interpretation to aid in the early prediction of sheep susceptibility to MAP infection. Copyright © 2013 Elsevier B.V. All rights reserved.

Magnetic translator bearings

NASA Technical Reports Server (NTRS)

Hockney, Richard L. (Inventor); Downer, James R. (Inventor); Eisenhaure, David B. (Inventor); Hawkey, Timothy J. (Inventor); Johnson, Bruce G. (Inventor)

1990-01-01

A magnetic bearing system for enabling translational motion includes a carriage and a shaft for movably supporting the carriage; a first magnetic bearing fixed to one of the carriage and shaft and slidably received in a first channel of the other of the carriage and shaft. The first channel is generally U shaped with two side walls and a back wall. The magnetic bearing includes a pair of spaced magnetic pole pieces, each pole piece having a pair of electromagnetic coils mounted on poles on opposite ends of the pole piece proximate the side walls, and a third electromagnetic coil mounted on a pole of the pole piece proximate the backwall; a motion sensor for sensing translational motion along two axes and rotationally about three axes of the carriage and shaft relative to each other; and a correction circuit responsive to the sensor for generating a correction signal to drive the coils to compensate for any misalignment sensed between the carriage and the shaft.

Negative affective spillover from daily events predicts early response to cognitive therapy for depression.

PubMed

Cohen, Lawrence H; Gunthert, Kathleen C; Butler, Andrew C; Parrish, Brendt P; Wenze, Susan J; Beck, Judith S

2008-12-01

This study evaluated the predictive role of depressed outpatients' (N = 62) affective reactivity to daily stressors in their rates of improvement in cognitive therapy (CT). For 1 week before treatment, patients completed nightly electronic diaries that assessed daily stressors and negative affect (NA). The authors used multilevel modeling to compute each patient's within-day relationship between daily stressors and daily NA (within-day reactivity), as well as the relationship between daily stressors and next-day NA (next-day reactivity; affective spillover). In growth model analyses, the authors evaluated the predictive role of patients' NA reactivity in their early (Sessions 1-4) and late (Sessions 5-12) response to CT. Within-day NA reactivity did not predict early or late response to CT. However, next-day reactivity predicted early response to CT, such that patients who had greater NA spillover in response to negative events had a slower rate of symptom change during the first 4 sessions. Affective spillover did not influence later response to CT. The findings suggest that depressed patients who have difficulty bouncing back the next day from their NA reactions to a relative increase in daily negative events will respond less quickly to the early sessions of CT.

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

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

Standing in the gap: ref lections on translating the Jung-Neumann correspondence.

PubMed

McCartney, Heather

2016-04-01

This paper considers the experience of translating the correspondence between C.G. Jung and Erich Neumann as part of the Philemon series. The translator explores the similarities between analytical work and the task of translation by means of the concepts of the dialectical third and the interactional field. The history and politics of the translation of analytic writing and their consequences for the lingua franca of analysis are discussed. Key themes within the correspondence are outlined, including Jung and Neumann's pre-war exploration of Judaism and the unconscious, the post-war difficulties around the publication of Neumann's Depth Psychology and a New Ethic set against the early years of the C.G. Jung Institute in Zurich, and the development of the correspondents' relationship over time. © 2016, The Society of Analytical Psychology.

Dom34 Links Translation to Protein O-mannosylation

PubMed Central

van Wijlick, Lasse; Geissen, René; Hilbig, Jessica S.; Lagadec, Quentin; Cantero, Pilar D.; Juchimiuk, Mateusz; Kluge, Sven; Wickert, Stephan; Alepuz, Paula; Ernst, Joachim F.

2016-01-01

In eukaryotes, Dom34 upregulates translation by securing levels of activatable ribosomal subunits. We found that in the yeast Saccharomyces cerevisiae and the human fungal pathogen Candida albicans, Dom34 interacts genetically with Pmt1, a major isoform of protein O-mannosyltransferase. In C. albicans, lack of Dom34 exacerbated defective phenotypes of pmt1 mutants, while they were ameliorated by Dom34 overproduction that enhanced Pmt1 protein but not PMT1 transcript levels. Translational effects of Dom34 required the 5′-UTR of the PMT1 transcript, which bound recombinant Dom34 directly at a CA/AC-rich sequence and regulated in vitro translation. Polysomal profiling revealed that Dom34 stimulates general translation moderately, but that it is especially required for translation of transcripts encoding Pmt isoforms 1, 4 and 6. Because defective protein N- or O-glycosylation upregulates transcription of PMT genes, it appears that Dom34-mediated specific translational upregulation of the PMT transcripts optimizes cellular responses to glycostress. Its translational function as an RNA binding protein acting at the 5′-UTR of specific transcripts adds another facet to the known ribosome-releasing functions of Dom34 at the 3′-UTR of transcripts. PMID:27768707

On the nature and consequences of early loss.

PubMed

Hofer, M A

1996-01-01

To describe how an animal model system can be used to explore basic questions about the nature of loss and the effects of early loss on later vulnerability to disease. The physiological and behavioral responses of infant rats to separation from their mothers are first described and then analyzed experimentally into component mechanisms. These studies have revealed an extensive layer of processes underlying the psychological constructs generally used to understand the response to loss. Hidden within the observable interactions of parent and offspring, we found a number of discrete sensorimotor, thermal, and nutrient-based events that have unexpected long-term regulatory effects on specific components of infant physiology and behavior. Release from all of these inhibitory and excitatory regulators together during maternal separation constitutes a novel mechanism by which the experience of loss can be translated into a complex patterned response. Evidence for early regulatory processes has also been found in monkey and human mother-infant interactions. Here they may well constitute the building blocks from which attachment and object representations develop. We and others have found long-term effects of loss, and of selective replacement of regulators, on behavioral development and on later vulnerability to disease. The results give us a new understanding of early attachment as a developmental force and of human grief as a risk to health.

Stem cell hype: media portrayal of therapy translation.

PubMed

Kamenova, Kalina; Caulfield, Timothy

2015-03-11

In this Perspective, we examine the portrayal of translational stem cell research in major daily newspapers in Canada, the United States, and the United Kingdom between 2010 and 2013, focusing on how timelines for stem cell therapies were represented before and after Geron terminated its pioneering stem cell program. Our content analysis reveals that press coverage has shifted from ethical, legal, and social issues to clinical translation issues, and highly optimistic timelines were provided with no substantial change in representation over time. Scientists were the dominant voice with respect to translation timelines. The findings raise questions about the degree to which the media's overly optimistic slant fosters unrealistic expectations regarding the speed of clinical translation and highlight the ethical responsibility of stem cell researchers as public communicators. Copyright © 2015, American Association for the Advancement of Science.

Human ocular responses to translation of the observer and of the scene: dependence on viewing distance.

PubMed

Busettini, C; Miles, F A; Schwarz, U; Carl, J R

1994-01-01

Recent experiments on monkeys have indicated that the eye movements induced by brief translation of either the observer or the visual scene are a linear function of the inverse of the viewing distance. For the movements of the observer, the room was dark and responses were attributed to a translational vestibulo-ocular reflex (TVOR) that senses the motion through the otolith organs; for the movements of the scene, which elicit ocular following, the scene was projected and adjusted in size and speed so that the retinal stimulation was the same at all distances. The shared dependence on viewing distance was consistent with the hypothesis that the TVOR and ocular following are synergistic and share central pathways. The present experiments looked for such dependencies on viewing distance in human subjects. When briefly accelerated along the interaural axis in the dark, human subjects generated compensatory eye movements that were also a linear function of the inverse of the viewing distance to a previously fixated target. These responses, which were attributed to the TVOR, were somewhat weaker than those previously recorded from monkeys using similar methods. When human subjects faced a tangent screen onto which patterned images were projected, brief motion of those images evoked ocular following responses that showed statistically significant dependence on viewing distance only with low-speed stimuli (10 degrees/s). This dependence was at best weak and in the reverse direction of that seen with the TVOR, i.e., responses increased as viewing distance increased. We suggest that in generating an internal estimate of viewing distance subjects may have used a confounding cue in the ocular-following paradigm--the size of the projected scene--which was varied directly with the viewing distance in these experiments (in order to preserve the size of the retinal image). When movements of the subject were randomly interleaved with the movements of the scene--to encourage the

Translational Control of the SigR-Directed Oxidative Stress Response in Streptomyces via IF3-Mediated Repression of a Noncanonical GTC Start Codon

PubMed Central

Feeney, Morgan A.; Chandra, Govind; Findlay, Kim C.; Paget, Mark S. B.

2017-01-01

ABSTRACT The major oxidative stress response in Streptomyces is controlled by the sigma factor SigR and its cognate antisigma factor RsrA, and SigR activity is tightly controlled through multiple mechanisms at both the transcriptional and posttranslational levels. Here we show that sigR has a highly unusual GTC start codon and that this leads to another level of SigR regulation, in which SigR translation is repressed by translation initiation factor 3 (IF3). Changing the GTC to a canonical start codon causes SigR to be overproduced relative to RsrA, resulting in unregulated and constitutive expression of the SigR regulon. Similarly, introducing IF3* mutations that impair its ability to repress SigR translation has the same effect. Thus, the noncanonical GTC sigR start codon and its repression by IF3 are critical for the correct and proper functioning of the oxidative stress regulatory system. sigR and rsrA are cotranscribed and translationally coupled, and it had therefore been assumed that SigR and RsrA are produced in stoichiometric amounts. Here we show that RsrA can be transcribed and translated independently of SigR, present evidence that RsrA is normally produced in excess of SigR, and describe the factors that determine SigR-RsrA stoichiometry. PMID:28611250

The Effect of Translators' Emotional Intelligence on Their Translation Quality

ERIC Educational Resources Information Center

Varzande, Mohsen; Jadidi, Esmaeil

2015-01-01

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

Translating 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…

Induction of cap-independent BiP (hsp-3) and Bcl-2 (ced-9) translation in response to eIF4G (IFG-1) depletion in C. elegans

PubMed Central

Morrison, J Kaitlin; Friday, Andrew J; Henderson, Melissa A; Hao, Enhui; Keiper, Brett D

2014-01-01

During apoptosis, activated caspases cleave the translation initiation factor eIF4G. This cleavage disrupts cap-dependent mRNA translation initiation within the cell. However, a specific subset of mRNAs can still be recruited for protein synthesis in a cap-independent manner by the residual initiation machinery. Many of these mRNAs, including cell death related mRNAs, contain internal ribosome entry sites (IRESes) that promote their enhanced translation during apoptosis. Still other mRNAs have little dependence on the cap recognition mechanism. The expression of the encoded proteins, both anti- and pro-apoptotic, allows for an initial period of attempted cell survival, then commitment to cell death when damage is extensive. In this study we address the translational regulation of the stress and apoptosis-related mRNAs in C. elegans: BiP (hsp-3) (hsp-4), Hif-1 (hif-1), p53 (cep-1), Bcl-2 (ced-9) and Apaf-1 (ced-4). Altered translational efficiency of these messages was observed upon depletion of cap-dependent translation and induction of apoptosis within the C. elegans gonad. Our findings suggest a physiological link between the cap-independent mechanism and the enhanced translation of hsp-3 and ced-9. This increase in the efficiency of translation may be integral to the stress response during the induction of physiological apoptosis. PMID:26779406

Machine-Aided Translation: From Terminology Banks to Interactive Translation Systems.

ERIC Educational Resources Information Center

Greenfield, Concetta C.; Serain, Daniel

The rapid growth of the need for technical translations in recent years has led specialists to utilize computer technology to improve the efficiency and quality of translation. The two approaches considered were automatic translation and terminology banks. Since the results of fully automatic translation were considered unsatisfactory by various…

The Impact of Translators' Academic Experience on Their Translation Quality

ERIC Educational Resources Information Center

Varzande, Mohsen; Jadidi, Esmaeil

2015-01-01

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

Plasma-Sprayed Titanium Patterns for Enhancing Early Cell Responses

NASA Astrophysics Data System (ADS)

Shi, Yunqi; Xie, Youtao; Pan, Houhua; Zheng, Xuebin; Huang, Liping; Ji, Fang; Li, Kai

2016-06-01

Titanium coating has been widely used as a biocompatible metal in biomedical applications. However, the early cell responses and long-term fixation of titanium implants are not satisfied. To obviate these defects, in this paper, micro-post arrays with various widths (150-1000 μm) and intervals (100-300 μm) were fabricated on the titanium substrate by template-assisted plasma spraying technology. In vitro cell culture experiments showed that MC3T3-E1 cells exhibited significantly higher osteogenic differentiation as well as slightly improved adhesion and proliferation on the micro-patterned coatings compared with the traditional one. The cell number on the pattern with 1000 µm width reached 130% after 6 days of incubation, and the expressions of osteopontin (OPN) as well as osteocalcin (OC) were doubled. No obvious difference was found in cell adhesion on various size patterns. The present micro-patterned coatings proposed a new modification method for the traditional plasma spraying technology to enhance the early cell responses and convenience for the bone in-growth.

Vamos a Traducir los MRV (let's translate the VRM): linguistic and cultural inferences drawn from translating a verbal coding system from English into Spanish.

PubMed

Caro, I; Stiles, W B

1997-01-01

Translating a verbal coding system from one language to another can yield unexpected insights into the process of communication in different cultures. This paper describes the problems and understandings we encountered as we translated a verbal response modes (VRM) taxonomy from English into Spanish. Standard translations of text (e.g., psychotherapeutic dialogue) systematically change the form of certain expressions, so supposedly equivalent expressions had different VRM codings in the two languages. Prominent examples of English forms whose translation had different codes in Spanish included tags, question forms, and "let's" expressions. Insofar as participants use such forms to convey nuances of their relationship, standard translations of counseling or psychotherapy sessions or other conversations may systematically misrepresent the relationship between the participants. The differences revealed in translating the VRM system point to subtle but important differences in the degrees of verbal directiveness and inclusion in English versus Spanish, which converge with other observations of differences in individualism and collectivism between Anglo and Hispanic cultures.

Early and long term anamnestic response to HBV booster dose among fully vaccinated Egyptian children during infancy.

PubMed

Salama, Iman I; Sami, Samia M; Said, Zeinab N; Salama, Somaia I; Rabah, Thanaa M; Abdel-Latif, Ghada A; Elmosalami, Dalia M; Saleh, Rehan M; Abdel Mohsin, Aida M; Metwally, Ammal M; Hassanin, Amal I; Emam, Hanaa M; Hemida, Samia A; Elserougy, Safaa M; Shaaban, Fatma A; Fouad, Walaa A; Mohsen, Amira; El-Sayed, Manal H

2018-04-05

To evaluate early and long term anamnestic response to a booster dose of HBV vaccine among non-seroprotected children. A national community based project was carried out on 3600 children aged 9 months to 16 years, fully vaccinated during infancy. They were recruited from 6 governorates representing Egypt. It revealed that 1535 children (42.8%) had non sero-protective anti-HBs (<10 IU/L) and were HBsAg or anti-HBc negative. A challenging dose of 10 μg of mono-valent Euvax HBV vaccine was given to 1121/1535 children. Quantitative assessment of anti-HBs was performed to detect early (2-4 weeks) and long term (one year) anamnestic responses. Early anamnestic response developed among 967/1070 children (90.3%).Children having detectable anti-HBs (1-9 IU/L) significantly developed early anamnestic response (90%) compared to 85% with undetectable anti-HBs (<1 IU/L), P < 0.001. Multiple logistic analysis revealed that undetectable anti-HBs, living in rural residence and children aged 15-16 years were the most significant predicting risk factors for the absence of early anamnestic response (<10 IU/L), with AOR 2.7, 2.7 & 4.7 respectively. After one year, long term anamnestic response was absent among 15% of children who previously showed early response. Poor early anamnestic response and undetectable pre-booster anti-HBs were the significant predicting risk factors for absent long term anamnestic response, with AOR 18.7 & 2.7 respectively. Immunological memory for HBV vaccine outlasts the presence of anti- HBs and HBV vaccination program provides effective long term protection even in children showing waning or undetectable concentrations of anti-HBs. This signifies no need for a booster dose especially to healthy children. Copyright © 2018 Elsevier Ltd. All rights reserved.

Development of a Drug-Response Modeling Framework to Identify Cell Line Derived Translational Biomarkers That Can Predict Treatment Outcome to Erlotinib or Sorafenib

PubMed Central

Li, Bin; Shin, Hyunjin; Gulbekyan, Georgy; Pustovalova, Olga; Nikolsky, Yuri; Hope, Andrew; Bessarabova, Marina; Schu, Matthew; Kolpakova-Hart, Elona; Merberg, David; Dorner, Andrew; Trepicchio, William L.

2015-01-01

Development of drug responsive biomarkers from pre-clinical data is a critical step in drug discovery, as it enables patient stratification in clinical trial design. Such translational biomarkers can be validated in early clinical trial phases and utilized as a patient inclusion parameter in later stage trials. Here we present a study on building accurate and selective drug sensitivity models for Erlotinib or Sorafenib from pre-clinical in vitro data, followed by validation of individual models on corresponding treatment arms from patient data generated in the BATTLE clinical trial. A Partial Least Squares Regression (PLSR) based modeling framework was designed and implemented, using a special splitting strategy and canonical pathways to capture robust information for model building. Erlotinib and Sorafenib predictive models could be used to identify a sub-group of patients that respond better to the corresponding treatment, and these models are specific to the corresponding drugs. The model derived signature genes reflect each drug’s known mechanism of action. Also, the models predict each drug’s potential cancer indications consistent with clinical trial results from a selection of globally normalized GEO expression datasets. PMID:26107615

Translation Analysis on Civil Engineering Text Produced by Machine Translator

NASA Astrophysics Data System (ADS)

Sutopo, Anam

2018-02-01

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

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

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.

The Reasons behind Early Adolescents' Responses to Peer Victimization

ERIC Educational Resources Information Center

Bellmore, Amy; Chen, Wei-Ting; Rischall, Emily

2013-01-01

Victims of school-based peer harassment face a range of risks including psycho-social, physical, and academic harm. The aim of the present study was to examine the behavioral coping responses used by early adolescents when they face peer victimization. To meet this aim, 216 sixth grade students (55% girls) from two urban middle schools and 254…

A Framework for Providing Culturally Responsive Early Intervention Services

ERIC Educational Resources Information Center

Bradshaw, Wendy

2013-01-01

The purpose of this article is to provide a framework that offers a way for early intervention (EI) service providers to better meet the needs of the culturally diverse children and families they serve. This framework was created to organize existing research and literature on cultural responsiveness in a way that fit the unique context of EI. The…

Arsenic and Immune Response to Infection During Pregnancy and Early Life

PubMed Central

Attreed, Sarah E.; Navas-Acien, Ana

2017-01-01

Purpose of Review Arsenic, a known carcinogen and developmental toxicant, is a major threat to global health. While the contribution of arsenic exposure to chronic diseases and adverse pregnancy and birth outcomes is recognized, its ability to impair critical functions of humoral and cell-mediated immunity—including the specific mechanisms in humans—is not well understood. Arsenic has been shown to increase risk of infectious diseases that have significant health implications during pregnancy and early life. Here, we review the latest research on the mechanisms of arsenic-related immune response alterations that could underlie arsenic-associated increased risk of infection during the vulnerable periods of pregnancy and early life. Recent Findings The latest evidence points to alteration of antibody production and transplacental transfer as well as failure of T helper cells to produce IL-2 and proliferate. Summary Critical areas for future research include the effects of arsenic exposure during pregnancy and early life on immune responses to natural infection and the immunogenicity and efficacy of vaccines. PMID:28488132

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

PubMed

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

2010-04-01

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

Translational Research in Alzheimer’s and Prion Diseases

PubMed Central

Di Fede, Giuseppe; Giaccone, Giorgio; Salmona, Mario; Tagliavini, Fabrizio

2017-01-01

Translational neuroscience integrates the knowledge derived by basic neuroscience with the development of new diagnostic and therapeutic tools that may be applied to clinical practice in neurological diseases. This information can be used to improve clinical trial designs and outcomes that will accelerate drug development, and to discover novel biomarkers which can be efficiently employed to early recognize neurological disorders and provide information regarding the effects of drugs on the underlying disease biology. Alzheimer’s disease (AD) and prion disease are two classes of neurodegenerative disorders characterized by incomplete knowledge of the molecular mechanisms underlying their occurrence and the lack of valid biomarkers and effective treatments. For these reasons, the design of therapies that prevent or delay the onset, slow the progression, or improve the symptoms associated to these disorders is urgently needed. During the last few decades, translational research provided a framework for advancing development of new diagnostic devices and promising disease-modifying therapies for patients with prion encephalopathies and AD. In this review, we provide present evidence of how supportive can be the translational approach to the study of dementias and show some results of our preclinical studies which have been translated to the clinical application following the ‘bed-to-bench-and-back’ research model. PMID:29172000

Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals.

PubMed

Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

2017-06-07

Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process.

Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals

PubMed Central

Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

2017-01-01

Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process. PMID:28590456

Consequences of an Early PSA Response to Enzalutamide Treatment for Japanese Patients with Metastatic Castration-resistant Prostate Cancer.

PubMed

Kato, Haruo; Furuya, Yosuke; Miyazawa, Yoshiyuki; Miyao, Takeshi; Syuto, Takahiro; Nomura, Masashi; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Ito, Kazuto; Suzuki, Kazuhiro

2016-11-01

Recent studies have shown that an early prostate-specific antigen (PSA) response to androgen receptor (AR)-targeting agents in metastatic castration-resistant prostate cancer (mCRPC) is associated with a better prognosis. We analyzed early PSA response to enzalutamide and oncological outcomes to study their prognostic significance in the Japanese population. Fifty-one patients with mCRPC (26 of pre-docetaxel and 25 of post-docetaxel status) were treated with enzalutamide. The PSA progression-free survival (PFS), radiographic PFS (rPFS) and overall survival (OS) were assessed. The association of rPFS and OS in patients with an early PSA response at 4 weeks after commencement of enzalutamide was studied. Early PSA responses were significantly associated with a longer rPFS (median of 47.9 vs. 20.1 weeks, p<0.001, in patients exhibiting a 50% PSA response; median of 40.9 vs. 20.1 weeks, p=0.016, in patients exhibiting a 30% PSA response). OS was also significantly associated with an early PSA response (p=0.002 for patients exhibiting a 50% PSA response, p=0.003 for patients exhibiting a 30% PSA response). Multivariate analysis showed that the predictors of a 50% PSA response were an interval to mCRPC and a docetaxel treatment history, while the predictor of a 30% PSA response was a docetaxel treatment history. Furthermore, a 50% PSA response was independently prognostic of rPFS. An early PSA response to enzalutamide was significantly associated with a longer rPFS and OS. This information will aid in the management of patients treated with enzalutamide. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Emotion and style in an English translation of the Quran.

PubMed

Whissell, Cynthia

2004-04-01

An English translation of the Quran was studied in terms of word use patterns, emotionality of words, and style. Variables were assessed with the help of computer programs and the Dictionary of Affect in Language. On the basis of words used at unusually high frequencies, the translation of the Quran was seen to be emphatically about Allah, his Prophets and Message, and believers. The translation of the Quran was slightly less Pleasant and Active in emotional tone than everyday English and also less concrete. It contained an unusual number of negatives and was repetitive but did not contain many rare or long words. Significant differences were noted between chronologically Early and Late suras (chapters) in terms of emotion, style, and word use. An inflection point was identified in the time-line partway through the Meccan suras of the Quran.

Translating Ancient Alchemy: Fragments of Graeco-Egyptian Alchemy in Arabic Compendia.

PubMed

Martelli, Matteo

2017-11-01

Translation played a vital role in the development and transfer of alchemy in Antiquity and the Early Middle Ages. Since its origins in Graeco-Roman Egypt, alchemy was encapsulated in Greek texts which allegedly relied on Persian or Egyptian sources. Later, a variety of Greek and Byzantine writings were translated into Syriac and Arabic, and these translations were in turn fragmented and disseminated in later Arabic compendia. This paper will first review the main phases of this historical process of transmission of alchemy from one language and culture to another. Second, this process will be examined using two significant case studies: a close analysis of various quotations from Graeco-Egyptian authors (Pseudo-Democritus, Zosimus of Panopolis, and Synesius) as presented in two Arabic dialogues on alchemy, The Tome of Images and The Dialogue between Āras and the King Caesar. These sources demonstrate some of the concrete textual realities that underlie general patterns of translation and reception.

Enhancing early child care quality and learning for toddlers at risk: the responsive early childhood program.

PubMed

Landry, Susan H; Zucker, Tricia A; Taylor, Heather B; Swank, Paul R; Williams, Jeffrey M; Assel, Michael; Crawford, April; Huang, Weihua; Clancy-Menchetti, Jeanine; Lonigan, Christopher J; Phillips, Beth M; Eisenberg, Nancy; Spinrad, Tracy L; de Villiers, Jill; de Villiers, Peter; Barnes, Marcia; Starkey, Prentice; Klein, Alice

2014-02-01

Despite reports of positive effects of high-quality child care, few experimental studies have examined the process of improving low-quality center-based care for toddler-age children. In this article, we report intervention effects on child care teachers' behaviors and children's social, emotional, behavioral, early literacy, language, and math outcomes as well as the teacher-child relationship. The intervention targeted the use of a set of responsive teacher practices, derived from attachment and sociocultural theories, and a comprehensive curriculum. Sixty-five childcare classrooms serving low-income 2- and 3-year-old children were randomized into 3 conditions: business-as-usual control, Responsive Early Childhood Curriculum (RECC), and RECC plus explicit social-emotional classroom activities (RECC+). Classroom observations showed greater gains for RECC and RECC+ teachers' responsive practices including helping children manage their behavior, establishing a predictable schedule, and use of cognitively stimulating activities (e.g., shared book reading) compared with controls; however, teacher behaviors did not differ for focal areas such as sensitivity and positive discipline supports. Child assessments demonstrated that children in the interventions outperformed controls in areas of social and emotional development, although children's performance in control and intervention groups was similar for cognitive skills (language, literacy, and math). Results support the positive impact of responsive teachers and environments providing appropriate support for toddlers' social and emotional development. Possible explanations for the absence of systematic differences in children's cognitive skills are considered, including implications for practice and future research targeting low-income toddlers.

Microfluidic-Mass Spectrometry Interfaces for Translational Proteomics.

PubMed

Pedde, R Daniel; Li, Huiyan; Borchers, Christoph H; Akbari, Mohsen

2017-10-01

Interfacing mass spectrometry (MS) with microfluidic chips (μchip-MS) holds considerable potential to transform a clinician's toolbox, providing translatable methods for the early detection, diagnosis, monitoring, and treatment of noncommunicable diseases by streamlining and integrating laborious sample preparation workflows on high-throughput, user-friendly platforms. Overcoming the limitations of competitive immunoassays - currently the gold standard in clinical proteomics - μchip-MS can provide unprecedented access to complex proteomic assays having high sensitivity and specificity, but without the labor, costs, and complexities associated with conventional MS sample processing. This review surveys recent μchip-MS systems for clinical applications and examines their emerging role in streamlining the development and translation of MS-based proteomic assays by alleviating many of the challenges that currently inhibit widespread clinical adoption. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Capturing early signs of deterioration: the dutch-early-nurse-worry-indicator-score and its value in the Rapid Response System.

PubMed

Douw, Gooske; Huisman-de Waal, Getty; van Zanten, Arthur R H; van der Hoeven, Johannes G; Schoonhoven, Lisette

2017-09-01

To determine the predictive value of individual and combined dutch-early-nurse-worry-indicator-score indicators at various Early Warning Score levels, differentiating between Early Warning Scores reaching the trigger threshold to call a rapid response team and Early Warning Score levels not reaching this point. Dutch-early-nurse-worry-indicator-score comprises nine indicators underlying nurses' 'worry' about a patient's condition. All indicators independently show significant association with unplanned intensive care/high dependency unit admission or unexpected mortality. Prediction of this outcome improved by adding the dutch-early-nurse-worry-indicator-score indicators to an Early Warning Score based on vital signs. An observational cohort study was conducted on three surgical wards in a tertiary university-affiliated teaching hospital. Included were surgical, native-speaking, adult patients. Nurses scored presence of 'worry' and/or dutch-early-nurse-worry-indicator-score indicators every shift or when worried. Vital signs were measured according to the prevailing protocol. Unplanned intensive care/high dependency unit admission or unexpected mortality was the composite endpoint. Percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators were calculated at various Early Warning Score levels in control and event groups. Entering all dutch-early-nurse-worry-indicator-score indicators in a multiple logistic regression analysis, we calculated a weighted score and calculated sensitivity, specificity, positive predicted value and negative predicted value for each possible total score. In 3522 patients, 102 (2·9%) had an unplanned intensive care/high dependency unit admissions (n = 97) or unexpected mortality (n = 5). Patients with such events and only slightly changed vital signs had significantly higher percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators expressed than patients in the control group. Increasing number

Neuroimaging in mental health care: voices in translation

PubMed Central

Borgelt, Emily L.; Buchman, Daniel Z.; Illes, Judy

2012-01-01

Images of brain function, popularly called “neuroimages,” have become a mainstay of contemporary communication about neuroscience and mental health. Paralleling media coverage of neuroimaging research and the high visibility of clinics selling scans is pressure from sponsors to move basic research about brain function along the translational pathway. Indeed, neuroimaging may offer benefits to mental health care: early or tailored intervention, opportunities for education and planning, and access to resources afforded by objectification of disorder. However, risks of premature technology transfer, such as misinterpretation, misrepresentation, and increased stigmatization, could compromise patient care. The insights of stakeholder groups about neuroimaging for mental health care are a largely untapped resource of information and guidance for translational efforts. We argue that the insights of key stakeholders—including researchers, healthcare providers, patients, and families—have an essential role to play upstream in professional, critical, and ethical discourse surrounding neuroimaging in mental health. Here we integrate previously orthogonal lines of inquiry involving stakeholder research to describe the translational landscape as well as challenges on its horizon. PMID:23097640

Response to Therapy Following Retreatment of Serofast Early Syphilis Patients With Benzathine Penicillin

PubMed Central

Seña, Arlene C.; Wolff, Mark; Behets, Frieda; Van Damme, Kathleen; Martin, David H.; Leone, Peter; McNeil, Linda; Hook, Edward W.

2013-01-01

Persistent nontreponemal titers after treatment are common among patients with early syphilis. We retreated 82 human immunodeficiency virus–negative early syphilis participants who were serofast at 6 months using benzathine penicillin. Only 27% exhibited serological response after retreatment and after an additional 6 months of follow-up. PMID:23118269

Post-translational derepression of invertase activity in source leaves via down-regulation of invertase inhibitor expression is part of the plant defense response.

PubMed

Bonfig, Katharina B; Gabler, Andrea; Simon, Uwe K; Luschin-Ebengreuth, Nora; Hatz, Martina; Berger, Susanne; Muhammad, Naseem; Zeier, Jürgen; Sinha, Alok K; Roitsch, Thomas

2010-11-01

There is increasing evidence that pathogens do not only elicit direct defense responses, but also cause pronounced changes in primary carbohydrate metabolism. Cell-wall-bound invertases belong to the key regulators of carbohydrate partitioning and source-sink relations. Whereas studies have focused so far only on the transcriptional induction of invertase genes in response to pathogen infection, the role of post-translational regulation of invertase activity has been neglected and was the focus of the present study. Expression analyses revealed that the high mRNA level of one out of three proteinaceous invertase inhibitors in source leaves of Arabidopsis thaliana is strongly repressed upon infection by a virulent strain of Pseudomonas syringae pv. tomato DC3000. This repression is paralleled by a decrease in invertase inhibitor activity. The physiological role of this regulatory mechanism is revealed by the finding that in situ invertase activity was detectable only upon infection by P. syringae. In contrast, a high invertase activity could be measured in vitro in crude and cell wall extracts prepared from both infected and non-infected leaves. The discrepancy between the in situ and in vitro invertase activity of control leaves and the high in situ invertase activity in infected leaves can be explained by the pathogen-dependent repression of invertase inhibitor expression and a concomitant reduction in invertase inhibitor activity. The functional importance of the release of invertase from post-translational inhibition for the defense response was substantiated by the application of the competitive chemical invertase inhibitor acarbose. Post-translational inhibition of extracellular invertase activity by infiltration of acarbose in leaves was shown to increase the susceptibility to P. syringae. The impact of invertase inhibition on spatial and temporal dynamics of the repression of photosynthesis and promotion of bacterial growth during pathogen infection supports

Heterogeneous Nuclear Ribonucleoprotein (hnRNP) E1 Binds to hnRNP A2 and Inhibits Translation of A2 Response Element mRNAs

PubMed Central

Kosturko, Linda D.; Maggipinto, Michael J.; Korza, George; Lee, Joo Won; Carson, John H.

2006-01-01

Heterogeneous nuclear ribonucleoprotein (hnRNP) A2 is a trans-acting RNA-binding protein that mediates trafficking of RNAs containing the cis-acting A2 response element (A2RE). Previous work has shown that A2RE RNAs are transported to myelin in oligodendrocytes and to dendrites in neurons. hnRNP E1 is an RNA-binding protein that regulates translation of specific mRNAs. Here, we show by yeast two-hybrid analysis, in vivo and in vitro coimmunoprecipitation, in vitro cross-linking, and fluorescence correlation spectroscopy that hnRNP E1 binds to hnRNP A2 and is recruited to A2RE RNA in an hnRNP A2-dependent manner. hnRNP E1 is colocalized with hnRNP A2 and A2RE mRNA in granules in dendrites of oligodendrocytes. Overexpression of hnRNP E1 or microinjection of exogenous hnRNP E1 in neural cells inhibits translation of A2RE mRNA, but not of non-A2RE RNA. Excess hnRNP E1 added to an in vitro translation system reduces translation efficiency of A2RE mRNA, but not of nonA2RE RNA, in an hnRNP A2-dependent manner. These results are consistent with a model where hnRNP E1 recruited to A2RE RNA granules by binding to hnRNP A2 inhibits translation of A2RE RNA during granule transport. PMID:16775011

Translation between representation languages

NASA Technical Reports Server (NTRS)

Vanbaalen, Jeffrey

1994-01-01

A capability for translating between representation languages is critical for effective knowledge base reuse. A translation technology for knowledge representation languages based on the use of an interlingua for communicating knowledge is described. The interlingua-based translation process consists of three major steps: translation from the source language into a subset of the interlingua, translation between subsets of the interlingua, and translation from a subset of the interlingua into the target language. The first translation step into the interlingua can typically be specified in the form of a grammar that describes how each top-level form in the source language translates into the interlingua. In cases where the source language does not have a declarative semantics, such a grammar is also a specification of a declarative semantics for the language. A methodology for building translators that is currently under development is described. A 'translator shell' based on this methodology is also under development. The shell has been used to build translators for multiple representation languages and those translators have successfully translated nontrivial knowledge bases.

Early Peritoneal Immune Response during Echinococcus granulosus Establishment Displays a Biphasic Behavior

PubMed Central

Mourglia-Ettlin, Gustavo; Marqués, Juan Martín; Chabalgoity, José Alejandro; Dematteis, Sylvia

2011-01-01

Background Cystic echinococcosis is a worldwide distributed helminth zoonosis caused by the larval stage of Echinococcus granulosus. Human secondary cystic echinococcosis is caused by dissemination of protoscoleces after accidental rupture of fertile cysts and is due to protoscoleces ability to develop into new metacestodes. In the experimental model of secondary cystic echinococcosis mice react against protoscoleces producing inefficient immune responses, allowing parasites to develop into cysts. Although the chronic phase of infection has been analyzed in depth, early immune responses at the site of infection establishment, e.g., peritoneal cavity, have not been well studied. Because during early stages of infection parasites are thought to be more susceptible to immune attack, this work focused on the study of cellular and molecular events triggered early in the peritoneal cavity of infected mice. Principal Findings Data obtained showed disparate behaviors among subpopulations within the peritoneal lymphoid compartment. Regarding B cells, there is an active molecular process of plasma cell differentiation accompanied by significant local production of specific IgM and IgG2b antibodies. In addition, peritoneal NK cells showed a rapid increase with a significant percentage of activated cells. Peritoneal T cells showed a substantial increase, with predominance in CD4+ T lymphocytes. There was also a local increase in Treg cells. Finally, cytokine response showed local biphasic kinetics: an early predominant induction of Th1-type cytokines (IFN-γ, IL-2 and IL-15), followed by a shift toward a Th2-type profile (IL-4, IL-5, IL-6, IL-10 and IL-13). Conclusions Results reported here open new ways to investigate the involvement of immune effectors players in E. granulosus establishment, and also in the sequential promotion of Th1- toward Th2-type responses in experimental secondary cystic echinococcosis. These data would be relevant for designing rational therapies

Early life adversity influences stress response association with smoking relapse.

PubMed

al'Absi, Mustafa; Lemieux, Andrine; Westra, Ruth; Allen, Sharon

2017-11-01

We examined the hypothesis that stress-related blunting of cortisol in smokers is particularly pronounced in those with a history of severe life adversity. The two aims of this study were first to examine hormonal, craving, and withdrawal symptoms during ad libitum smoking and after the first 24 h of abstinence in smokers who experienced high or low levels of adversity. Second, we sought to examine the relationship between adversity and hypothalamic-pituitary-adrenal (HPA) hormones to predict relapse during the first month of a smoking cessation attempt. Hormonal and self-report measures were collected from 103 smokers (49 women) during ad libitum smoking and after the first 24 h of abstinence. HPA hormones were measured during baseline rest and in response to acute stress in both conditions. All smokers were interested in smoking cessation, and we prospectively used stress response measures to predict relapse during the first 4 weeks of the smoking cessation attempt. The results showed that high adversity was associated with higher distress and smoking withdrawal symptoms. High level of early life adversity was associated with elevated HPA activity, which was found in both salivary and plasma cortisol. Enhanced adrenocorticotropic hormone (ACTH) stress response was evident in high-adversity but not in low-adversity relapsers. This study demonstrated that early life adversity is associated with stress-related HPA responses. The study also demonstrated that, among smokers who experienced a high level of life adversity, heightened ACTH and cortisol responses were linked with increased risk for smoking relapse.

Early host response in the mammary gland after experimental Streptococcus uberis challenge in heifers.

PubMed

de Greeff, Astrid; Zadoks, Ruth; Ruuls, Lisette; Toussaint, Mathilda; Nguyen, Thi Kim Anh; Downing, Alison; Rebel, Johanna; Stockhofe-Zurwieden, Norbert; Smith, Hilde

2013-06-01

Streptococcus uberis is a highly prevalent causative agent of bovine mastitis, which leads to large economic losses in the dairy industry. The aim of this study was to examine the host response during acute inflammation after experimental challenge with capsulated Strep. uberis. Gene expression in response to Strep. uberis was compared between infected and control quarters in 3 animals. All quarters (n=16) were sampled at 16 different locations. Microarray data showed that 239 genes were differentially expressed between infected and control quarters. No differences in gene expression were observed between the different locations. Microarray data were confirmed for several genes using quantitative PCR analysis. Genes differentially expressed due to early Strep. uberis mastitis represented several stages of the process of infection: (1) pathogen recognition; (2) chemoattraction of neutrophils; (3) tissue repair mechanisms; and (4) bactericidal activity. Three different pathogen recognition genes were induced: ficolins, lipopolysaccharide binding protein, and toll-like receptor 2. Calgranulins were found to be the most strongly upregulated genes during early inflammation. By histology and immunohistochemistry, we demonstrated that changes in gene expression in response to Strep. uberis were induced both in infiltrating somatic milk cells and in mammary epithelial cells, demonstrating that the latter cell type plays a role in milk production as well as immune responsiveness. Given the rapid development of inflammation or mastitis after infection, early diagnosis of (Strep. uberis) mastitis is required for prevention of disease and spread of the pathogen. Insight into host responses could help to design immunomodulatory therapies to dampen inflammation after (early) diagnosis of Strep. uberis mastitis. Future research should focus on development of these early diagnostics and immunomodulatory components for mastitis treatment. Copyright © 2013 American Dairy Science

The Next Step in Understanding Impaired Reactive Balance Control in People With Stroke: The Role of Defective Early Automatic Postural Responses.

PubMed

de Kam, Digna; Roelofs, Jolanda M B; Bruijnes, Amber K B D; Geurts, Alexander C H; Weerdesteyn, Vivian

2017-08-01

Postural muscle responses are often impaired after stroke. We aimed to identify the contribution of deficits in very early postural responses to poorer reactive balance capacity, with a particular focus on reactive stepping as a key strategy for avoiding falls. A total of 34 chronic stroke survivors and 17 controls were subjected to translational balance perturbations in 4 directions. We identified the highest perturbation intensity that could be recovered without stepping (single stepping threshold [SST]) and with maximally 1 step (multiple stepping threshold [MST]). We determined onset latencies and response amplitudes of 7 leg muscles bilaterally and identified associations with balance capacity. People with stroke had a lower MST than controls in all directions. Side steps resulted in a higher lateral MST than crossover steps but were less common toward the paretic side. Postural responses were delayed and smaller in amplitude on the paretic side only. We observed the strongest associations between gluteus medius (GLUT) onset and amplitude and MST toward the paretic side ( R 2 = 0.33). Electromyographic variables were rather weakly associated with forward and backward MSTs ( R 2 = 0.10-0.22) and with SSTs ( R 2 = 0.08-0.15). Delayed and reduced paretic postural responses are associated with impaired reactive stepping after stroke. Particularly, fast and vigorous activity of the GLUT is imperative for overcoming large sideways perturbations, presumably because it facilitates the effective use of side steps. Because people with stroke often fall toward the paretic side, this finding indicates an important target for training.

Stroke preparedness in children: translating knowledge into behavioral intent: a systematic review and meta-analysis.

PubMed

Ottawa, Cassandra; Sposato, Luciano A; Nabbouh, Fadl; Saposnik, Gustavo

2015-10-01

If translated into behavioral intent, improving stroke knowledge may potentially impact on better outcomes. Children are an attractive target population since they can drive familial behavioral changes. However, the impact of interventions on stroke knowledge among children is unclear. We performed a systematic review and meta-analysis to investigate whether educational interventions targeting children improve stroke knowledge and lead to behavioral changes. We searched Ovid, PubMed, and Embase between January 2000 and December 2014. We included studies written in English reporting the number of children aged 6-15 years undergoing educational interventions on stroke and providing the results for baseline and early and late postintervention tests. We compared the proportion of correct answers between baseline, early, and late responses for two endpoints: knowledge and behavioral intent. Of the initial 58 articles found, we included nine that met the inclusion criteria. Compared with baseline tests (51·7%, 95% confidence interval 40·9-62·4), there was improvement in stroke knowledge in early (74·0%, 95% confidence interval 64·4-82·5, P = 0·002) and late (67·3%, 95% confidence interval 55·4-78·2, P = 0·027) responses. There was improvement in the early (92·1%, 95% confidence interval 86·0-96·6, P < 0·001) and late (83·9%, 95% confidence interval 73·5-92·1, P = 0·001) responses for behavioral intent compared with the baseline assessment (63·8%, 95% confidence interval 53·5-73·4). Children are a potentially attractive target population for improvement in stroke knowledge and behavioral intent, both in the short and long term. Our findings may support the implementation of large-scale stroke educational initiatives targeting children. © 2015 World Stroke Organization.

Adding Statistical Machine Translation Adaptation to Computer-Assisted Translation

DTIC Science & Technology

2013-09-01

are automatically searched and used to suggest possible translations; (2) spell-checkers; (3) glossaries; (4) dictionaries ; (5) alignment and...matching against TMs to propose translations; spell-checking, glossary, and dictionary look-up; support for multiple file formats; regular expressions...on Telecommunications. Tehran, 2012, 822–826. Bertoldi, N.; Federico, M. Domain Adaptation for Statistical Machine Translation with Monolingual

Translation in Language Teaching: Insights from Professional Translator Training

ERIC Educational Resources Information Center

Carreres, Angeles; Noriega-Sanchez, Maria

2011-01-01

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

The Impact of Early Substance Use Disorder Treatment Response on Treatment Outcomes Among Pregnant Women With Primary Opioid Use.

PubMed

Tuten, Michelle; Fitzsimons, Heather; Hochheimer, Martin; Jones, Hendree E; Chisolm, Margaret S

2018-03-13

This study examined the impact of early patient response on treatment utilization and substance use among pregnant participants enrolled in substance use disorder (SUD) treatment. Treatment responders (TRs) and treatment nonresponders (TNRs) were compared on pretreatment and treatment measures. Regression models predicted treatment utilization and substance use. TR participants attended more treatment and had lower rates of substance use relative to TNR participants. Regression models for treatment utilization and substance use were significant. Maternal estimated gestational age (EGA) and baseline cocaine use were negatively associated with treatment attendance. Medication-assisted treatment, early treatment response, and baseline SUD treatment were positively associated with treatment attendance. Maternal EGA was negatively associated with counseling attendance; early treatment response was positively associated with counseling attendance. Predictors of any substance use at 1 month were maternal education, EGA, early treatment nonresponse, and baseline cocaine use. The single predictor of any substance use at 2 months was early treatment nonresponse. Predictors of opioid use at 1 month were maternal education, EGA, early treatment nonresponse, and baseline SUD treatment. Predictors of opioid use at 2 months were early treatment nonresponse, and baseline cocaine and marijuana use. Predictors of cocaine use at 1 month were early treatment nonresponse, baseline cocaine use, and baseline SUD treatment. Predictors of cocaine use at 2 months were early treatment nonresponse and baseline cocaine use. Early treatment response predicts more favorable maternal treatment utilization and substance use outcomes. Treatment providers should implement interventions to maximize patient early response to treatment.

A Comparison of Responsive Interventions on Kindergarteners' Early Reading Achievement

ERIC Educational Resources Information Center

Little, Mary E.; Rawlinson, D'Ann; Simmons, Deborah C.; Kim, Minjung; Kwok, Oi-man; Hagan-Burke, Shanna; Simmons, Leslie E.; Fogarty, Melissa; Oslund, Eric; Coyne, Michael D.

2012-01-01

This study compared the effects of Tier 2 reading interventions that operated in response-to-intervention contexts. Kindergarten children (N = 90) who were identified as at risk for reading difficulties were stratified by school and randomly assigned to receive (a) Early Reading Intervention (ERI; Pearson/Scott Foresman, 2004) modified in response…

Personalized medicine: challenges and opportunities for translational bioinformatics

PubMed Central

Overby, Casey Lynnette; Tarczy-Hornoch, Peter

2013-01-01

Personalized medicine can be defined broadly as a model of healthcare that is predictive, personalized, preventive and participatory. Two US President’s Council of Advisors on Science and Technology reports illustrate challenges in personalized medicine (in a 2008 report) and in use of health information technology (in a 2010 report). Translational bioinformatics is a field that can help address these challenges and is defined by the American Medical Informatics Association as “the development of storage, analytic and interpretive methods to optimize the transformation of increasing voluminous biomedical data into proactive, predictive, preventative and participatory health.” This article discusses barriers to implementing genomics applications and current progress toward overcoming barriers, describes lessons learned from early experiences of institutions engaged in personalized medicine and provides example areas for translational bioinformatics research inquiry. PMID:24039624

Vestibulo-Ocular Reflex to Transient Surge Translation: Complex Geometric Response Ablated by Normal Aging

PubMed Central

Tian, Jun-ru; Mokuno, Eriko; Demer, Joseph L.

2007-01-01

The linear vestibulo-ocular reflex (LVOR) to surge (fore-aft) translation has complex kinematics varying with target eccentricity and distance. To determine normal responses and aging changes, 9 younger [age, 28 ± 2 (SE) yr] and 11 older subjects (age, 69 ± 2 yr) underwent 0.5g whole body surge transients while wearing binocular scleral search coils. Linear chair position and head acceleration were measured with a potentiometer and accelerometer. Subjects viewed centered and 10° horizontally and vertically eccentric targets 50, 25, or 15 cm distant before unpredictable onset of randomly directed surge in darkness (LVOR) and light (V-LVOR). Response directions were kinematically appropriate to eccentricity in all subjects, but there were significantly more measurable LVOR and V-LVOR responses (63–79%) in younger than older subjects (38–44%, P < 0.01). Minimal LVOR latency averaged 48 ± 4 ms for younger and significantly longer at 70 ± 6 ms for older subjects. In the interval 200–300 ms after surge onset, horizontal LVOR gain (relative to ideal velocity) of younger subjects averaged over all target distances was 0.55 ± 0.04 and was significantly reduced in older subjects to 0.33 ± 0.04. Horizontal V-LVOR gain was 0.58 ± 0.04 in younger and significantly lower at 0.35 ± 0.06 in older subjects. Vertical gains did not differ significantly between groups. Target visibility had no effect in either group during the initial 200 ms. The LVOR and V-LVOR were augmented by saccades in younger more than older subjects. Aging thus decreases LVOR velocity gain, response rate, and saccade augmentation, but prolongs latency. PMID:16551841

Diffusion MRI in early cancer therapeutic response assessment

PubMed Central

Galbán, C. J.; Hoff, B. A.; Chenevert, T. L.; Ross, B. D.

2016-01-01

Imaging biomarkers for the predictive assessment of treatment response in patients with cancer earlier than standard tumor volumetric metrics would provide new opportunities to individualize therapy. Diffusion-weighted MRI (DW-MRI), highly sensitive to microenvironmental alterations at the cellular level, has been evaluated extensively as a technique for the generation of quantitative and early imaging biomarkers of therapeutic response and clinical outcome. First demonstrated in a rodent tumor model, subsequent studies have shown that DW-MRI can be applied to many different solid tumors for the detection of changes in cellularity as measured indirectly by an increase in the apparent diffusion coefficient (ADC) of water molecules within the lesion. The introduction of quantitative DW-MRI into the treatment management of patients with cancer may aid physicians to individualize therapy, thereby minimizing unnecessary systemic toxicity associated with ineffective therapies, saving valuable time, reducing patient care costs and ultimately improving clinical outcome. This review covers the theoretical basis behind the application of DW-MRI to monitor therapeutic response in cancer, the analytical techniques used and the results obtained from various clinical studies that have demonstrated the efficacy of DW-MRI for the prediction of cancer treatment response. PMID:26773848

Influenza A Virus Host Shutoff Disables Antiviral Stress-Induced Translation Arrest

PubMed Central

Khaperskyy, Denys A.; Emara, Mohamed M.; Johnston, Benjamin P.; Anderson, Paul; Hatchette, Todd F.; McCormick, Craig

2014-01-01

Influenza A virus (IAV) polymerase complexes function in the nucleus of infected cells, generating mRNAs that bear 5′ caps and poly(A) tails, and which are exported to the cytoplasm and translated by host machinery. Host antiviral defences include mechanisms that detect the stress of virus infection and arrest cap-dependent mRNA translation, which normally results in the formation of cytoplasmic aggregates of translationally stalled mRNA-protein complexes known as stress granules (SGs). It remains unclear how IAV ensures preferential translation of viral gene products while evading stress-induced translation arrest. Here, we demonstrate that at early stages of infection both viral and host mRNAs are sensitive to drug-induced translation arrest and SG formation. By contrast, at later stages of infection, IAV becomes partially resistant to stress-induced translation arrest, thereby maintaining ongoing translation of viral gene products. To this end, the virus deploys multiple proteins that block stress-induced SG formation: 1) non-structural protein 1 (NS1) inactivates the antiviral double-stranded RNA (dsRNA)-activated kinase PKR, thereby preventing eIF2α phosphorylation and SG formation; 2) nucleoprotein (NP) inhibits SG formation without affecting eIF2α phosphorylation; 3) host-shutoff protein polymerase-acidic protein-X (PA-X) strongly inhibits SG formation concomitant with dramatic depletion of cytoplasmic poly(A) RNA and nuclear accumulation of poly(A)-binding protein. Recombinant viruses with disrupted PA-X host shutoff function fail to effectively inhibit stress-induced SG formation. The existence of three distinct mechanisms of IAV-mediated SG blockade reveals the magnitude of the threat of stress-induced translation arrest during viral replication. PMID:25010204

Translating questionnaire items for a multi-lingual worker population: the iterative process of translation and cognitive interviews with English-, Spanish-, and Chinese-speaking workers.

PubMed

Fujishiro, Kaori; Gong, Fang; Baron, Sherry; Jacobson, C Jeffery; DeLaney, Sheli; Flynn, Michael; Eggerth, Donald E

2010-02-01

The increasing ethnic diversity of the US workforce has created a need for research tools that can be used with multi-lingual worker populations. Developing multi-language questionnaire items is a complex process; however, very little has been documented in the literature. Commonly used English items from the Job Content Questionnaire and Quality of Work Life Questionnaire were translated by two interdisciplinary bilingual teams and cognitively tested in interviews with English-, Spanish-, and Chinese-speaking workers. Common problems across languages mainly concerned response format. Language-specific problems required more conceptual than literal translations. Some items were better understood by non-English speakers than by English speakers. De-centering (i.e., modifying the English original to correspond with translation) produced better understanding for one item. Translating questionnaire items and achieving equivalence across languages require various kinds of expertise. Backward translation itself is not sufficient. More research efforts should be concentrated on qualitative approaches to developing useful research tools. Published 2009 Wiley-Liss, Inc.

Stomatal Blue Light Response Is Present in Early Vascular Plants.

PubMed

Doi, Michio; Kitagawa, Yuki; Shimazaki, Ken-ichiro

2015-10-01

Light is a major environmental factor required for stomatal opening. Blue light (BL) induces stomatal opening in higher plants as a signal under the photosynthetic active radiation. The stomatal BL response is not present in the fern species of Polypodiopsida. The acquisition of a stomatal BL response might provide competitive advantages in both the uptake of CO2 and prevention of water loss with the ability to rapidly open and close stomata. We surveyed the stomatal opening in response to strong red light (RL) and weak BL under the RL with gas exchange technique in a diverse selection of plant species from euphyllophytes, including spermatophytes and monilophytes, to lycophytes. We showed the presence of RL-induced stomatal opening in most of these species and found that the BL responses operated in all euphyllophytes except Polypodiopsida. We also confirmed that the stomatal opening in lycophytes, the early vascular plants, is driven by plasma membrane proton-translocating adenosine triphosphatase and K(+) accumulation in guard cells, which is the same mechanism operating in stomata of angiosperms. These results suggest that the early vascular plants respond to both RL and BL and actively regulate stomatal aperture. We also found three plant species that absolutely require BL for both stomatal opening and photosynthetic CO2 fixation, including a gymnosperm, C. revoluta, and the ferns Equisetum hyemale and Psilotum nudum. © 2015 American Society of Plant Biologists. All Rights Reserved.

Design, clinical translation and immunological response of biomaterials in regenerative medicine

NASA Astrophysics Data System (ADS)

Sadtler, Kaitlyn; Singh, Anirudha; Wolf, Matthew T.; Wang, Xiaokun; Pardoll, Drew M.; Elisseeff, Jennifer H.

2016-07-01

The field of regenerative medicine aims to replace tissues lost as a consequence of disease, trauma or congenital abnormalities. Biomaterials serve as scaffolds for regenerative medicine to deliver cells, provide biological signals and physical support, and mobilize endogenous cells to repair tissues. Sophisticated chemistries are used to synthesize materials that mimic and modulate native tissue microenvironments, to replace form and to elucidate structure-function relationships of cell-material interactions. The therapeutic relevance of these biomaterial properties can only be studied after clinical translation, whereby key parameters for efficacy can be defined and then used for future design. In this Review, we present the development and translation of biomaterials for two tissue engineering targets, cartilage and cornea, both of which lack the ability to self-repair. Finally, looking to the future, we discuss the role of the immune system in regeneration and the potential for biomaterial scaffolds to modulate immune signalling to create a pro-regenerative environment.

NeuPAT: an intranet database supporting translational research in neuroblastic tumors.

PubMed

Villamón, Eva; Piqueras, Marta; Meseguer, Javier; Blanquer, Ignacio; Berbegall, Ana P; Tadeo, Irene; Hernández, Vicente; Navarro, Samuel; Noguera, Rosa

2013-03-01

Translational research in oncology is directed mainly towards establishing a better risk stratification and searching for appropriate therapeutic targets. This research generates a tremendous amount of complex clinical and biological data needing speedy and effective management. The authors describe the design, implementation and early experiences of a computer-aided system for the integration and management of data for neuroblastoma patients. NeuPAT facilitates clinical and translational research, minimizes the workload in consolidating the information, reduces errors and increases correlation of data through extensive coding. This design can also be applied to other tumor types. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ambiguous Tilt and Translation Motion Cues in Astronauts After Space Flight (ZAG)

NASA Astrophysics Data System (ADS)

Clement, Guilles; Harm, Deborah; Rupert, Angus; Beaton, Kara; Wood, Scott

2008-06-01

Adaptive changes during space flight in how the brain integrates vestibular cues with visual, proprioceptive, and somatosensory information can lead to impaired movement coordination, vertigo, spatial disorientation, and perceptual illusions following transitions between gravity levels. This joint ESA-NASA pre- and post-flight experiment is designed to examine both the physiological basis and operational implications for disorientation and tilt-translation disturbances in astronauts following short-duration space flights. Specifically, this study addresses three questions: (1) What adaptive changes occur in eye movements and motion perception in response to different combinations of tilt and translation motion? (2) Do adaptive changes in tilt-translation responses impair ability to manually control vehicle orientation? (3) Can sensory substitution aids (e.g., tactile) mitigate risks associated with manual control of vehicle orientation?

Early prediction of blonanserin response in Japanese patients with schizophrenia.

PubMed

Kishi, Taro; Matsuda, Yuki; Fujita, Kiyoshi; Iwata, Nakao

2014-01-01

Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia in Japan and Korea. The present study aimed to examine early prediction of blonanserin in patients with schizophrenia. An 8-week, prospective, single-arm, flexible-dose clinical trial of blonanserin in patients with schizophrenia was conducted under real-world conditions. The inclusion criteria were antipsychotic naïve, and first-episode schizophrenia patients or schizophrenia patients with no consumption of any antipsychotic medication for more than 4 weeks before enrollment in this study. The positive predictive value, negative predictive value, sensitivity, specificity, and predictive power were calculated for the response status at week 4 to predict the subsequent response at week 8. Thirty-seven patients were recruited (56.8% of them had first-episode schizophrenia), and 28 (75.7%) completed the trial. At week 8, blonanserin was associated with a significant improvement in the Positive and Negative Syndrome Scale (PANSS) total score (P<0.0001) and in positive (P<0.0001), negative (P<0.0001), and general subscale scores (P<0.0001). In terms of percentage improvement of PANSS total scores from baseline to week 8, 64.9% of patients showed a ≥20% reduction in the PANSS total score and 48.6% showed a ≥30% reduction. However, 8.1% of patients experienced at least one adverse event. Using the 20% reduction in the PANSS total score at week 4 as a definition of an early response, the negative predictive values for later responses (ie, reductions of ≥30 and ≥40 in the PANSS total scores) were 88.9% and 94.1%, respectively. The specificities were 80.0% and 51.6%, respectively. Our results suggest that the blonanserin response at week 4 could predict the later response at week 8.

Early prediction of blonanserin response in Japanese patients with schizophrenia

PubMed Central

Kishi, Taro; Matsuda, Yuki; Fujita, Kiyoshi; Iwata, Nakao

2014-01-01

Background Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia in Japan and Korea. The present study aimed to examine early prediction of blonanserin in patients with schizophrenia. Methods An 8-week, prospective, single-arm, flexible-dose clinical trial of blonanserin in patients with schizophrenia was conducted under real-world conditions. The inclusion criteria were antipsychotic naïve, and first-episode schizophrenia patients or schizophrenia patients with no consumption of any antipsychotic medication for more than 4 weeks before enrollment in this study. The positive predictive value, negative predictive value, sensitivity, specificity, and predictive power were calculated for the response status at week 4 to predict the subsequent response at week 8. Results Thirty-seven patients were recruited (56.8% of them had first-episode schizophrenia), and 28 (75.7%) completed the trial. At week 8, blonanserin was associated with a significant improvement in the Positive and Negative Syndrome Scale (PANSS) total score (P<0.0001) and in positive (P<0.0001), negative (P<0.0001), and general subscale scores (P<0.0001). In terms of percentage improvement of PANSS total scores from baseline to week 8, 64.9% of patients showed a ≥20% reduction in the PANSS total score and 48.6% showed a ≥30% reduction. However, 8.1% of patients experienced at least one adverse event. Using the 20% reduction in the PANSS total score at week 4 as a definition of an early response, the negative predictive values for later responses (ie, reductions of ≥30 and ≥40 in the PANSS total scores) were 88.9% and 94.1%, respectively. The specificities were 80.0% and 51.6%, respectively. Conclusion Our results suggest that the blonanserin response at week 4 could predict the later response at week 8. PMID:25285009

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.

Early Development of Four Cyprinids Native to the Yangtze River, China

USGS Publications Warehouse

Chapman, Duane C.

2006-01-01

Chapter 1 -- Notes on the Translation and Use of "A Study of the Early Development of Grass Carp, Black Carp, Silver Carp, and Bighead Carp in the Yangtze River, China" By Duane C. Chapman and Ning Wang Chapter 2 -- A Study of the Early Development of Grass Carp, Black Carp, Silver Carp, and Bighead Carp in the Yangtze River, China By Bolu Yi, Zhishen Liang, Zhitang Yu, Randuan Lin, and Mingjue HeTranslated by Duane C. Chapman and Ning Wang The document A Study of the Early Development of Grass Carp, Black Carp, Silver Carp, and Bighead Carp in the Yangtze River, China (Chapter 2 of this volume) was translated from the Chinese with the approval and assistance of the living authors of that study. It contains the most detailed description available, and approximately 200 drawings, of the early development of the subject fishes. Chapter 1 provides important instructions on the use of the translation, including a description of the Chinese morphometric conventions, which differ from those used by North American scientists. Chapter 1 also provides the historical context in which Chapter 2 was developed, and information on how the larvae of the subject fishes, which have invaded the Mississippi River basin, may be distinguished from other fishes present in the basin.

New Paradigm for Translational Modeling to Predict Long‐term Tuberculosis Treatment Response

PubMed Central

Bartelink, IH; Zhang, N; Keizer, RJ; Strydom, N; Converse, PJ; Dooley, KE; Nuermberger, EL

2017-01-01

Abstract Disappointing results of recent tuberculosis chemotherapy trials suggest that knowledge gained from preclinical investigations was not utilized to maximal effect. A mouse‐to‐human translational pharmacokinetics (PKs) – pharmacodynamics (PDs) model built on a rich mouse database may improve clinical trial outcome predictions. The model included Mycobacterium tuberculosis growth function in mice, adaptive immune response effect on bacterial growth, relationships among moxifloxacin, rifapentine, and rifampin concentrations accelerating bacterial death, clinical PK data, species‐specific protein binding, drug‐drug interactions, and patient‐specific pathology. Simulations of recent trials testing 4‐month regimens predicted 65% (95% confidence interval [CI], 55–74) relapse‐free patients vs. 80% observed in the REMox‐TB trial, and 79% (95% CI, 72–87) vs. 82% observed in the Rifaquin trial. Simulation of 6‐month regimens predicted 97% (95% CI, 93–99) vs. 92% and 95% observed in 2RHZE/4RH control arms, and 100% predicted and observed in the 35 mg/kg rifampin arm of PanACEA MAMS. These results suggest that the model can inform regimen optimization and predict outcomes of ongoing trials. PMID:28561946

The Nematode Eukaryotic Translation Initiation Factor 4E/G Complex Works with a trans-Spliced Leader Stem-Loop To Enable Efficient Translation of Trimethylguanosine-Capped RNAs ▿ †

PubMed Central

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

2010-01-01

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

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

ERIC Educational Resources Information Center

Ghasemi, Hadis; Hashemian, Mahmood

2016-01-01

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

Les presuppositions du discours: un dilemme pour le traducteur (Presuppositions in Discourse: A Translator's Dilemma).

ERIC Educational Resources Information Center

Ribe, Enriqueta; Olivera, Miguel

1979-01-01

Discusses translation problems resulting from semantic differences in legal and sociopolitical vocabulary, and the translator's responsibility in exposing erroneous or false presuppositions found in the source document. (AM)

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

ERIC Educational Resources Information Center

Mehay, Dennis Nolan

2012-01-01

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

The early response during the interaction of fungal phytopathogen and host plant.

PubMed

Shen, Yilin; Liu, Na; Li, Chuang; Wang, Xin; Xu, Xiaomeng; Chen, Wan; Xing, Guozhen; Zheng, Wenming

2017-05-01

Plants can be infected by a variety of pathogens, most of which can cause severe economic losses. The plants resist the invasion of pathogens via the innate or acquired immune system for surviving biotic stress. The associations between plants and pathogens are sophisticated beyond imaging and the interactions between them can occur at a very early stage after their touching each other. A number of researchers in the past decade have shown that many biochemical events appeared even as early as 5 min after their touching for plant disease resistance response. The early molecular interactions of plants and pathogens are likely to involve protein phosphorylation, ion fluxes, reactive oxygen species (ROS) and other signalling transduction. Here, we reviewed the recent progress in the study for molecular interaction response of fungal pathogens and host plant at the early infection stage, which included many economically important crop fungal pathogens such as cereal rust fungi, tomato Cladosporium fulvum , rice blast and so on. By dissecting the earlier infection stage of the diseases, the avirulent/virulent genes of pathogen or resistance genes of plant could be defined more clearly and accurately, which would undoubtedly facilitate fungal pathogenesis study and resistant crop breeding. © 2017 The Authors.

The early response during the interaction of fungal phytopathogen and host plant

PubMed Central

Shen, Yilin; Liu, Na; Li, Chuang; Wang, Xin; Xu, Xiaomeng; Chen, Wan; Xing, Guozhen

2017-01-01

Plants can be infected by a variety of pathogens, most of which can cause severe economic losses. The plants resist the invasion of pathogens via the innate or acquired immune system for surviving biotic stress. The associations between plants and pathogens are sophisticated beyond imaging and the interactions between them can occur at a very early stage after their touching each other. A number of researchers in the past decade have shown that many biochemical events appeared even as early as 5 min after their touching for plant disease resistance response. The early molecular interactions of plants and pathogens are likely to involve protein phosphorylation, ion fluxes, reactive oxygen species (ROS) and other signalling transduction. Here, we reviewed the recent progress in the study for molecular interaction response of fungal pathogens and host plant at the early infection stage, which included many economically important crop fungal pathogens such as cereal rust fungi, tomato Cladosporium fulvum, rice blast and so on. By dissecting the earlier infection stage of the diseases, the avirulent/virulent genes of pathogen or resistance genes of plant could be defined more clearly and accurately, which would undoubtedly facilitate fungal pathogenesis study and resistant crop breeding. PMID:28469008

Dating Medical Translations.

PubMed

Vagelpohl, Uwe

2015-01-01

The third/ninth-century translator Ḥunayn b. Isḥāq and his associates produced more than a hundred mostly medical translations from Greek into Syriac and then into Arabic. We know little about the chronology of these translations, except for a few scattered remarks in Ḥunayn's Risāla (Epistle). This article attempts to reconstruct the chronology based on Hippocratic quotations in the Arabic translation of Galen's works. Hippocratic writings were usually not translated independently but embedded in Galen's commentaries, so a comparison between this "embedded" Hippocrates and quotations from the same Hippocratic text elsewhere in the Arabic Galen might reveal chronological relationships. The findings of this collation are thought- provoking, but they need to be weighed against the uncertainties surrounding translation methods and potential interference by well-meaning later scholars and scribes.

Challenges in knowledge translation: the early years of Cancer Care Ontario's Program in Evidence-Based Care.

PubMed

Browman, G P

2012-02-01

Cancer Care Ontario's Program in Evidence-Based Care (pebc) was formalized in 1997 to produce clinical practice guidelines for cancer management for the Province of Ontario. At the time, the gap between guideline development and implementation was beginning to be acknowledged. The Program implemented strategies to promote use of guidelines. The program had to overcome numerous social challenges to survive. Prospective strategies useful to practitioners-including participation, transparent communication, a methodological vision, and methodology skills development offerings-were used to create a culture of research-informed oncology practice within a broad community of practitioners.Reactive strategies ensured the survival of the program in the early years, when some within the influential academic community and among decision-makers were skeptical about the feasibility of a rigorous methodologic approach meeting the fast turnaround times necessary for policy. The paper details the pebc strategies within the context of what was known about knowledge translation (kt) at the time, and it tries to identify key success factors. Many of the barriers faced in the implementation of kt-and the strategies for overcoming them-are unavailable in the public domain because the relevant reporting does not fit the traditional paradigm for publication. Telling the "stories behind the story" should be encouraged to enhance the practice of kt beyond the science.

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

PubMed

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

2017-09-01

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

Comparison of Selected Weather Translation Products

NASA Technical Reports Server (NTRS)

Kulkarni, Deepak

2017-01-01

Weather is a primary contributor to the air traffic delays within the National Airspace System (NAS). At present, it is the individual decision makers who use weather information and assess its operational impact in creating effective air traffic management solutions. As a result, the estimation of the impact of forecast weather and the quality of ATM response relies on the skill and experience level of the decision maker. FAA Weather-ATM working groups have developed a Weather-ATM integration framework that consists of weather collection, weather translation, ATM impact conversion and ATM decision support. Some weather translation measures have been developed for hypothetical operations such as decentralized free flight, whereas others are meant to be relevant in current operations. This paper does comparative study of two different weather translation products relevant in current operations and finds that these products have strong correlation with each other. Given inaccuracies in prediction of weather, these differences would not be expected to be of significance in statistical study of a large number of decisions made with a look-ahead time of two hours or more.

The development of a classification schema for arts-based approaches to knowledge translation.

PubMed

Archibald, Mandy M; Caine, Vera; Scott, Shannon D

2014-10-01

Arts-based approaches to knowledge translation are emerging as powerful interprofessional strategies with potential to facilitate evidence uptake, communication, knowledge, attitude, and behavior change across healthcare provider and consumer groups. These strategies are in the early stages of development. To date, no classification system for arts-based knowledge translation exists, which limits development and understandings of effectiveness in evidence syntheses. We developed a classification schema of arts-based knowledge translation strategies based on two mechanisms by which these approaches function: (a) the degree of precision in key message delivery, and (b) the degree of end-user participation. We demonstrate how this classification is necessary to explore how context, time, and location shape arts-based knowledge translation strategies. Classifying arts-based knowledge translation strategies according to their core attributes extends understandings of the appropriateness of these approaches for various healthcare settings and provider groups. The classification schema developed may enhance understanding of how, where, and for whom arts-based knowledge translation approaches are effective, and enable theorizing of essential knowledge translation constructs, such as the influence of context, time, and location on utilization strategies. The classification schema developed may encourage systematic inquiry into the effectiveness of these approaches in diverse interprofessional contexts. © 2014 Sigma Theta Tau International.

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

PubMed

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

2015-10-01

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

Early life influences on emotional reactivity: evidence that social enrichment has greater effects than handling on anxiety-like behaviors, neuroendocrine responses to stress and central BDNF levels.

PubMed

Cirulli, Francesca; Berry, Alessandra; Bonsignore, Luca Tommaso; Capone, Francesca; D'Andrea, Ivana; Aloe, Luigi; Branchi, Igor; Alleva, Enrico

2010-05-01

During the early post-natal phases the brain is experience-seeking and provided by a considerable plasticity which allows a fine tuning between the external environment and the developing organism. Since the early work of Seymour Levine, an impressive amount of research has clearly shown that stressful experiences exert powerful effects on the brain and body development. These effects can last throughout the entire life span influencing brain function and increasing the risk for depression and anxiety disorders. The mechanisms underlying the effects of early stress on the developing organism have been widely studied in rodents through experimental manipulations of the post-natal environment, such as handling, which have been shown to exert important effects on the emotional phenotype and the response to stress. In the present paper we review the relevant literature and present some original data indicating that, compared to handling, which imposes an external manipulation on the mother-infant relationship, social enrichment, in the form of communal rearing, in mice has very profound effects on animal's emotionality and the response to stress. These effects are also accompanied by important changes in central levels of brain-derived neurotrophic factor. The present data indicate that communal rearing has more pervasive effects than handling, strengthening previous data suggesting that it is a good animal model of reduced susceptibility to depression-like behavior. Overall, the availability of ever more sophisticated animal models represents a fundamental tool to translate basic research data into appropriate interventions for humans raised under traumatic or impoverished situations. (c) 2010 Elsevier Ltd. All rights reserved.

Outcomes-focused knowledge translation: a framework for knowledge translation and patient outcomes improvement.

PubMed

Doran, Diane M; Sidani, Souraya

2007-01-01

Regularly accessing information that is current and reliable continues to be a challenge for front-line staff nurses. Reconceptualizing how nurses access information and designing appropriate decision support systems to facilitate timely access to information may be important for increasing research utilization. An outcomes-focused knowledge translation framework was developed to guide the continuous improvement of patient care through the uptake of research evidence and feedback data about patient outcomes. The framework operationalizes the three elements of the PARIHS framework at the point of care. Outcomes-focused knowledge translation involves four components: (a) patient outcomes measurement and real-time feedback about outcomes achievement; (b) best-practice guidelines, embedded in decision support tools that deliver key messages in response to patient assessment data; (c) clarification of patients' preferences for care; and (d) facilitation by advanced practice nurses and practice leaders. In this paper the framework is described and evidence is provided to support theorized relationships among the concepts in the framework. The framework guided the design of a knowledge translation intervention aimed at continuous improvement of patient care and evidence-based practice, which are fostered through real-time feedback data about patient outcomes, electronic access to evidence-based resources at the point of care, and facilitation by advanced practice nurses. The propositions in the framework need to be empirically tested through future research.

Perceived early-life maternal care and the cortisol response to repeated psychosocial stress.

PubMed

Engert, Veronika; Efanov, Simona I; Dedovic, Katarina; Duchesne, Annie; Dagher, Alain; Pruessner, Jens C

2010-11-01

In the past decade, a body of animal and human research has revealed a profound influence of early-life experiences, ranging from variations in parenting behaviour to severe adversity, on hypothalamic-pituitary-adrenal axis regulation in adulthood. In our own previous studies, we have shown how variations in early-life parental care influence the development of the hippocampus and modify the cortisol awakening response. In the present study, we investigated the influence of early-life maternal care on cortisol, heart rate and subjective psychological responses to the repeated administration of a psychosocial laboratory stressor in a population of 63 healthy young adults. Low, medium and high early-life maternal care groups were identified using the Parental Bonding Instrument. Controlling for the effect of sex, we found an inverted u-shaped relation between increasing levels of maternal care and cortisol stress responsivity. Specifically, overall and stress-induced cortisol levels went from below normal in the low maternal care, to normal in the medium care, back to below normal in the high maternal care groups. We found no group differences with respect to heart rate and subjective psychological stress measures. Whereas low and high maternal care groups exhibited similarly low endocrine stress responses, their psychological profiles were opposed with increased levels of depression and anxiety and decreased self-esteem in the low care group. Sex was unequally distributed among maternal care groups, whereby the number of men with low maternal care was too small to allow introducing sex as a second between-group variable. We discuss the potential significance of this dissociation between endocrine and psychological parameters with respect to stress vulnerability and resistance for each maternal care group.

Dutch translation and cross-cultural validation of the Adult Social Care Outcomes Toolkit (ASCOT).

PubMed

van Leeuwen, Karen M; Bosmans, Judith E; Jansen, Aaltje Pd; Rand, Stacey E; Towers, Ann-Marie; Smith, Nick; Razik, Kamilla; Trukeschitz, Birgit; van Tulder, Maurits W; van der Horst, Henriette E; Ostelo, Raymond W

2015-05-13

The Adult Social Care Outcomes Toolkit was developed to measure outcomes of social care in England. In this study, we translated the four level self-completion version (SCT-4) of the ASCOT for use in the Netherlands and performed a cross-cultural validation. The ASCOT SCT-4 was translated into Dutch following international guidelines, including two forward and back translations. The resulting version was pilot tested among frail older adults using think-aloud interviews. Furthermore, using a subsample of the Dutch ACT-study, we investigated test-retest reliability and construct validity and compared response distributions with data from a comparable English study. The pilot tests showed that translated items were in general understood as intended, that most items were reliable, and that the response distributions of the Dutch translation and associations with other measures were comparable to the original English version. Based on the results of the pilot tests, some small modifications and a revision of the Dignity items were proposed for the final translation, which were approved by the ASCOT development team. The complete original English version and the final Dutch translation can be obtained after registration on the ASCOT website ( http://www.pssru.ac.uk/ascot ). This study provides preliminary evidence that the Dutch translation of the ASCOT is valid, reliable and comparable to the original English version. We recommend further research to confirm the validity of the modified Dutch ASCOT translation.

Effectiveness of Community-Based Early Intervention Based on Pivotal Response Treatment

ERIC Educational Resources Information Center

Smith, Isabel M.; Flanagan, Helen E.; Garon, Nancy; Bryson, Susan E.

2015-01-01

Preschoolers (n = 118) with autism spectrum disorder (ASD) participated in this prospective effectiveness study of an early intervention program. Treatment entailed parent training and therapist-implemented components, incorporating Pivotal Response Treatment and Positive Behaviour Support. Standardized ability and behavioural measures were…

The bradykinin B2 receptor in the early immune response against Listeria infection.

PubMed

Kaman, Wendy E; Wolterink, Arthur F W M; Bader, Michael; Boele, Linda C L; van der Kleij, Desiree

2009-02-01

The endogenous danger signal bradykinin was recently found implicated in the development of immunity against parasites via dendritic cells. We here report an essential role of the B(2) (B(2)R) bradykinin receptor in the early immune response against Listeria infection. Mice deficient in B(2)R (B(2)R(-/-) mice) were shown to suffer from increased hepatic bacterial burden and concomitant dramatic weight loss during infection with Listeria monocytogenes. Levels of cytokines known to play a pivotal role in the early phase immune response against L. monocytogenes, IL-12p70 and IFN-gamma, were reduced in B(2)R(-/-) mice. To extend these findings to the human system, we show that bradykinin potentiates the production of IL-12p70 in human monocyte-derived dendritic cells. Thus, we show that bradykinin and the B(2)R play a role in early innate immune functions during bacterial infection.

Dating Medical Translations

PubMed Central

Vagelpohl, Uwe

2018-01-01

The third/ninth-century translator Ḥunayn b. Isḥāq and his associates produced more than a hundred mostly medical translations from Greek into Syriac and then into Arabic. We know little about the chronology of these translations, except for a few scattered remarks in Ḥunayn’s Risāla (Epistle). This article attempts to reconstruct the chronology based on Hippocratic quotations in the Arabic translation of Galen’s works. Hippocratic writings were usually not translated independently but embedded in Galen’s commentaries, so a comparison between this “embedded” Hippocrates and quotations from the same Hippocratic text elsewhere in the Arabic Galen might reveal chronological relationships. The findings of this collation are thought- provoking, but they need to be weighed against the uncertainties surrounding translation methods and potential interference by well-meaning later scholars and scribes. PMID:29809206

Generalizing Word Lattice Translation

DTIC Science & Technology

2008-02-01

demonstrate substantial gains for Chinese-English and Arabic -English translation. Keywords: word lattice translation, phrase-based and hierarchical...introduce in reordering models. Our experiments evaluating the approach demonstrate substantial gains for Chinese-English and Arabic -English translation. 15...gains for Chinese-English and Arabic -English translation. 1 Introduction When Brown and colleagues introduced statistical machine translation in the

[Inflammasome and its role in immunological and inflammatory response at early stage of burns].

PubMed

Zhang, Fang; Li, Jiahui; Xia, Zhaofan

2014-06-01

Inflammasomes are large multi-protein complexes that serve as a platform for caspase-1 activation, and this process induces subsequent maturation and secretion of the proinflammatory cytokines IL-1β and IL-18, as well as pyroptosis. As an important component of the innate immune system, early activation of inflammasomes in a variety of immune cell subsets can mediate inflammatory response and immunological conditions after burn injury. Here, we review the current knowledge of inflammasomes and its role in immunological and inflammatory response at the early stage of burn injury.

mRNA Translation Gone Awry: Translation Fidelity and Neurological Disease.

PubMed

Kapur, Mridu; Ackerman, Susan L

2018-03-01

Errors during mRNA translation can lead to a reduction in the levels of functional proteins and an increase in deleterious molecules. Advances in next-generation sequencing have led to the discovery of rare genetic disorders, many caused by mutations in genes encoding the mRNA translation machinery, as well as to a better understanding of translational dynamics through ribosome profiling. We discuss here multiple neurological disorders that are linked to errors in tRNA aminoacylation and ribosome decoding. We draw on studies from genetic models, including yeast and mice, to enhance our understanding of the translational defects observed in these diseases. Finally, we emphasize the importance of tRNA, their associated enzymes, and the inextricable link between accuracy and efficiency in the maintenance of translational fidelity. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2014-08-01

The "Beliefs about Medicines Questionnaire" (BMQ) assess balance of necessity and concern of medicines. The BMQ has been translated from English to many languages. However, the original meaning of statements, such as "My medicine is a mystery to me", may be lost in translation. The aim of this study is to compare three Scandinavian translations of the BMQ. (1) How reliable are the translations? (2) Are they still valid after translation? Translated Norwegian, Swedish and Danish versions of the BMQ were scrutinized by three native Scandinavian researchers. Linguistic differences and ambiguities in the 5-point Likert scale and the BMQ statements were compared. In the Scandinavian translations, the Likert scale expanded beyond the original version at one endpoint (Swedish) or both endpoints (Danish). In the BMQ statements, discrepancies ranged from smaller inaccuracies toward completely different meaning. Some dissimilarities reflect different cultural beliefs about medicines. When translating questionnaires, bilingual researchers should scrutinize translations across similar languages to address content validity across different countries and languages. Our findings are of relevance to other BMQ translations in non-English countries, as direct comparisons between different translations might not be reliable or valid. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

PubMed Central

Damgaard, Christian Kroun; Lykke-Andersen, Jens

2011-01-01

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

Human Cytomegalovirus Strategies to Maintain and Promote mRNA Translation

PubMed Central

Vincent, Heather A.; Ziehr, Benjamin; Moorman, Nathaniel J.

2016-01-01

mRNA translation requires the ordered assembly of translation initiation factors and ribosomal subunits on a transcript. Host signaling pathways regulate each step in this process to match levels of protein synthesis to environmental cues. In response to infection, cells activate multiple defenses that limit viral protein synthesis, which viruses must counteract to successfully replicate. Human cytomegalovirus (HCMV) inhibits host defenses that limit viral protein expression and manipulates host signaling pathways to promote the expression of both host and viral proteins necessary for virus replication. Here we review key regulatory steps in mRNA translation, and the strategies used by HCMV to maintain protein synthesis in infected cells. PMID:27089357

Translations on Eastern Europe Scientific Affairs No. 565.

DTIC Science & Technology

1977-11-23

Pages 22. Price PC-/VQ3 FORM NT1S -35 (REV. 3-721 THIS FORM MAY BE REPRODUCED USCOMM-OC M852-P72 JPRS 70215 23 November 1977 TRANSLATIONS...created a method for the investigation of cells , in- tended for early diagnosis of blood disease and tumors. The Central Biophysics Laboratory has...illegible; possibly Botany, or Genetics] has intro- duced new varieties of tomatoes, peppers and tobacco . The economic effect exceeds several hundred

The early economic evaluation of novel biomarkers to accelerate their translation into clinical applications.

PubMed

de Graaf, Gimon; Postmus, Douwe; Westerink, Jan; Buskens, Erik

2018-01-01

Translating prognostic and diagnostic biomarker candidates into clinical applications takes time, is very costly, and many candidates fail. It is therefore crucial to be able to select those biomarker candidates that have the highest chance of successfully being adopted in the clinic. This requires an early estimate of the potential clinical impact and commercial value. In this paper, we aim to demonstratively evaluate a set of novel biomarkers in terms of clinical impact and commercial value, using occurrence of cardiovascular disease (CVD) in type-2 diabetes (DM2) patients as a case study. We defined a clinical application for the novel biomarkers, and subsequently used data from a large cohort study in The Netherlands in a modeling exercise to assess the potential clinical impact and headroom for the biomarkers. The most likely application of the biomarkers would be to identify DM2 patients with a low CVD risk and subsequently withhold statin treatment. As a result, one additional CVD event in every 75 patients may be expected. The expected downstream savings resulted in a headroom for a point-of-care device ranging from €119.09 at a willingness to accept of €0 for one additional CVD event, to €0 at a willingness to accept of €15,614 or more. It is feasible to evaluate novel biomarkers on outcomes directly relevant to technological development and clinical adoption. Importantly, this may be attained at the same point in time and using the same data as used for the evaluation of association with disease and predictive power.

Maternal Dead-end 1 promotes translation of nanos1 by binding the eIF3 complex.

PubMed

Aguero, Tristan; Jin, Zhigang; Chorghade, Sandip; Kalsotra, Auinash; King, Mary Lou; Yang, Jing

2017-10-15

In the developing embryo, primordial germ cells (PGCs) represent the exclusive progenitors of the gametes, and their loss results in adult infertility. During early development, PGCs are exposed to numerous signals that specify somatic cell fates. To prevent somatic differentiation, PGCs must transiently silence their genome, an early developmental process that requires Nanos activity. However, it is unclear how Nanos translation is regulated in developing embryos. We report here that translation of nanos1 after fertilization requires Dead-end 1 (Dnd1), a vertebrate-specific germline RNA-binding protein. We provide evidence that Dnd1 protein, expression of which is low in oocytes, but increases dramatically after fertilization, directly interacts with, and relieves the inhibitory function of eukaryotic initiation factor 3f, a repressive component in the 43S preinitiation complex. This work uncovers a novel translational regulatory mechanism that is fundamentally important for germline development. © 2017. Published by The Company of Biologists Ltd.

The tonic response to the infant knee jerk as an early sign of cerebral palsy.

PubMed

Hamer, Elisa G; La Bastide-Van Gemert, Sacha; Boxum, Anke G; Dijkstra, Linze J; Hielkema, Tjitske; Jeroen Vermeulen, R; Hadders-Algra, Mijna

2018-04-01

Early identification of infants at risk of cerebral palsy (CP) is desirable in order to provide early intervention. We previously demonstrated differences in knee jerk responses between 3-month-old high risk and typically developing infants. To improve early identification by investigating whether the presence of tonic responses (continuous muscle activity occurring after the typical phasic response), clonus or contralateral responses to the knee jerk during infancy is associated with CP. Longitudinal EMG-study. We included 34 high-risk infants (median gestational age 31.9 weeks) who participated in the LEARN2MOVE 0-2 years trial. Video-recorded knee jerk EMG-assessments were performed during infancy (1-4 times). Developmental outcome was assessed at 21 months corrected age (CA). Binomial generalized estimating equations models with repeated measurements were fitted using predictor variables. Infants who later were diagnosed with CP (n = 18) showed more often than infants who were not diagnosed with CP i) tonic responses - from 4 months CA onwards, ii) clonus - from 13 months CA onwards, and iii) contralateral responses - from 15 months CA onwards. The main limitation is the relatively small sample size. The assessment of tonic responses to the knee jerk using EMG may be a valuable add-on tool to appraise a high risk of CP. Copyright © 2018 Elsevier B.V. All rights reserved.

Ribosome profiling reveals changes in translational status of soybean transcripts during immature cotyledon development

PubMed Central

Shamimuzzaman, Md.

2018-01-01

To understand translational capacity on a genome-wide scale across three developmental stages of immature soybean seed cotyledons, ribosome profiling was performed in combination with RNA sequencing and cluster analysis. Transcripts representing 216 unique genes demonstrated a higher level of translational activity in at least one stage by exhibiting higher translational efficiencies (TEs) in which there were relatively more ribosome footprint sequence reads mapping to the transcript than were present in the control total RNA sample. The majority of these transcripts were more translationally active at the early stage of seed development and included 12 unique serine or cysteine proteases and 16 2S albumin and low molecular weight cysteine-rich proteins that may serve as substrates for turnover and mobilization early in seed development. It would appear that the serine proteases and 2S albumins play a vital role in the early stages. In contrast, our investigation of profiles of 19 genes encoding high abundance seed storage proteins, such as glycinins, beta-conglycinins, lectin, and Kunitz trypsin inhibitors, showed that they all had similar patterns in which the TE values started at low levels and increased approximately 2 to 6-fold during development. The highest levels of these seed protein transcripts were found at the mid-developmental stage, whereas the highest ribosome footprint levels of only up to 1.6 TE were found at the late developmental stage. These experimental findings suggest that the major seed storage protein coding genes are primarily regulated at the transcriptional level during normal soybean cotyledon development. Finally, our analyses also identified a total of 370 unique gene models that showed very low TE values including over 48 genes encoding ribosomal family proteins and 95 gene models that are related to energy and photosynthetic functions, many of which have homology to the chloroplast genome. Additionally, we showed that genes of the

Translational control of Nrf2 within the open reading frame

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

Perez-Leal, Oscar, E-mail: operez@temple.edu; Barrero, Carlos A.; Merali, Salim, E-mail: smerali@temple.edu

2013-07-19

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

National Heart, Lung, and Blood Institute and the translation of cardiovascular discoveries into therapeutic approaches.

PubMed

Galis, Zorina S; Black, Jodi B; Skarlatos, Sonia I

2013-04-26

The molecular causes of ≈4000 medical conditions have been described, yet only 5% have associated therapies. For decades, the average time for drug development through approval has taken 10 to 20 years. In recent years, the serious challenges that confront the private sector have made it difficult to capitalize on new opportunities presented by advances in genomics and cellular therapies. Current trends are disturbing. Pharmaceutical companies are reducing their investments in research, and biotechnology companies are struggling to obtain venture funds. To support early-stage translation of the discoveries in basic science, the National Institutes of Health and the National Heart, Lung, and Blood Institute have developed new approaches to facilitating the translation of basic discoveries into clinical applications and will continue to develop a variety of programs that create teams of academic investigators and industry partners. The goal of these programs is to maximize the public benefit of investment of taxpayer dollars in biomedical research and to lessen the risk required for industry partners to make substantial investments. This article highlights several examples of National Heart, Lung, and Blood Institute-initiated translational programs and National Institutes of Health translational resources designed to catalyze and enable the earliest stages of the biomedical product development process. The translation of latest discoveries into therapeutic approaches depends on continued federal funding to enhance the early stages of the product development process and to stimulate and catalyze partnerships between academia, industry, and other sources of capital.

Early Childhood Pedagog"ies": Spaces for Young Children to Flourish

ERIC Educational Resources Information Center

Murray, Jane

2015-01-01

This paper introduces the Special Issue of "Early Child Development and Care" focused on "Early Childhood Pedagogy." It opens by considering past and present discourses concerning early childhood pedagogy, and focus is given to established philosophical underpinnings in the field and their translation to contemporary guidance,…

Hospitalist and Internal Medicine Leaders' Perspectives of Early Discharge Challenges at Academic Medical Centers.

PubMed

Patel, Hemali; Fang, Margaret C; Mourad, Michelle; Green, Adrienne; Wachter, Robert M; Murphy, Ryan D; Harrison, James D

2018-06-01

Improving early discharges may improve patient flow and increase hospital capacity. We conducted a national survey of academic medical centers addressing the prevalence, importance, and effectiveness of early-discharge initiatives. We assembled a list of hospitalist and general internal medicine leaders at 115 US-based academic medical centers. We emailed each institutional representative a 30-item online survey regarding early-discharge initiatives. The survey included questions on discharge prioritization, the prevalence and effectiveness of early-discharge initiatives, and barriers to implementation. We received 61 responses from 115 institutions (53% response rate). Forty-seven (77%) "strongly agreed" or "agreed" that early discharge was a priority. "Discharge by noon" was the most cited goal (n = 23; 38%) followed by "no set time but overall goal for improvement" (n = 13; 21%). The majority of respondents reported early discharge as more important than obtaining translators for non-English-speaking patients and equally important as reducing 30-day readmissions and improving patient satisfaction. The most commonly reported factors delaying discharge were availability of postacute care beds (n = 48; 79%) and patient-related transport complications (n = 44; 72%). The most effective early discharge initiatives reported involved changes to the rounding process, such as preemptive identification and early preparation of discharge paperwork (n = 34; 56%) and communication with patients about anticipated discharge (n = 29; 48%). There is a strong interest in increasing early discharges in an effort to improve hospital throughput and patient flow. © 2017 Society of Hospital Medicine.

Assessment of Translational and Interdisciplinary Clinical Research at an Oklahoma Health Sciences Center

PubMed Central

Dao, Hanh Dung; Kota, Pravina; James, Judith A.; Stoner, Julie A.; Akins, Darrin R.

2015-01-01

Purpose In response to National Institutes of Health initiatives to improve translation of basic science discoveries we surveyed faculty to assess patterns of and barriers to translational research in Oklahoma. Methods An online survey was administered to University of Oklahoma Health Sciences Center, College of Medicine faculty, which included demographic and research questions. Results Responses were received from 126 faculty members (24%). Two-thirds spent ≥20% time on research; among these, 90% conduct clinical and translational research. Identifying funding; recruiting research staff and participants; preparing reports and agreements; and protecting research time were commonly perceived as at least moderate barriers to conducting research. While respondents largely collaborated within their discipline, clinical investigators were more likely than basic science investigators to engage in interdisciplinary research. Conclusion While engagement in translational research is common, specific barriers impact the research process. This could be improved through an expanded interdisciplinary collaboration and research support structure. PMID:26242016

Introduction of translation stop condons into the viral glycoprotein gene in a fish DNA vaccine eliminates induction of protective immunity

USGS Publications Warehouse

Garver, Kyle A.; Conway, Carla M.; Kurath, Gael

2006-01-01

A highly efficacious DNA vaccine against a fish rhabdovirus, infectious hematopoietic necrosis virus (IHNV), was mutated to introduce two stop codons to prevent glycoprotein translation while maintaining the plasmid DNA integrity and RNA transcription ability. The mutated plasmid vaccine, denoted pIHNw-G2stop, when injected intramuscularly into fish at high doses, lacked detectable glycoprotein expression in the injection site muscle, and did not provide protection against lethal virus challenge 7 days post-vaccination. These results suggest that the G-protein itself is required to stimulate the early protective antiviral response observed after vaccination with the nonmutated parental DNA vaccine.

Early Literacy Measures for Improving Student Reading Achievement: Translating Research into Practice

ERIC Educational Resources Information Center

Marston, Doug; Pickart, Mary; Reschly, Amy; Heistad, David; Muyskens, Paul; Tindal, Gerald

2007-01-01

The importance of early literacy instruction and its role in later reading proficiency is well established; however, measures and procedures to screen and monitor proficiency in the area of early literacy are less well researched. The purpose of this study was to (a) examine the technical adequacy and validity of early curriculum-based literacy…

Situationally-Sensitive Knowledge Translation and Relational Decision Making in Hyperacute Stroke: A Qualitative Study

PubMed Central

Murtagh, Madeleine J.; Burges Watson, Duika L.; Jenkings, K. Neil; Lie, Mabel L. S.; Mackintosh, Joan E.; Ford, Gary A.; Thomson, Richard G.

2012-01-01

Stroke is a leading cause of disability. Early treatment of acute ischaemic stroke with rtPA reduces the risk of longer term dependency but carries an increased risk of causing immediate bleeding complications. To understand the challenges of knowledge translation and decision making about treatment with rtPA in hyperacute stroke and hence to inform development of appropriate decision support we interviewed patients, their family and health professionals. The emergency setting and the symptomatic effects of hyper-acute stroke shaped the form, content and manner of knowledge translation to support decision making. Decision making about rtPA in hyperacute stroke presented three conundrums for patients, family and clinicians. 1) How to allow time for reflection in a severely time-limited setting. 2) How to facilitate knowledge translation regarding important treatment risks and benefits when patient and family capacity is blunted by the effects and shock of stroke. 3) How to ensure patient and family views are taken into account when the situation produces reliance on the expertise of clinicians. Strategies adopted to meet these conundrums were fourfold: face to face communication; shaping decisions; incremental provision of information; and communication tailored to the individual patient. Relational forms of interaction were understood to engender trust and allay anxiety. Shaping decisions with patients was understood as an expression of confidence by clinicians that helped alleviate anxiety and offered hope and reassurance to patients and their family experiencing the shock of the stroke event. Neutral presentations of information and treatment options promoted uncertainty and contributed to anxiety. ‘Drip feeding’ information created moments for reflection: clinicians literally made time. Tailoring information to the particular patient and family situation allowed clinicians to account for social and emotional contexts. The principal responses to the

Situationally-sensitive knowledge translation and relational decision making in hyperacute stroke: a qualitative study.

PubMed

Murtagh, Madeleine J; Burges Watson, Duika L; Jenkings, K Neil; Lie, Mabel L S; Mackintosh, Joan E; Ford, Gary A; Thomson, Richard G

2012-01-01

Stroke is a leading cause of disability. Early treatment of acute ischaemic stroke with rtPA reduces the risk of longer term dependency but carries an increased risk of causing immediate bleeding complications. To understand the challenges of knowledge translation and decision making about treatment with rtPA in hyperacute stroke and hence to inform development of appropriate decision support we interviewed patients, their family and health professionals. The emergency setting and the symptomatic effects of hyper-acute stroke shaped the form, content and manner of knowledge translation to support decision making. Decision making about rtPA in hyperacute stroke presented three conundrums for patients, family and clinicians. 1) How to allow time for reflection in a severely time-limited setting. 2) How to facilitate knowledge translation regarding important treatment risks and benefits when patient and family capacity is blunted by the effects and shock of stroke. 3) How to ensure patient and family views are taken into account when the situation produces reliance on the expertise of clinicians. Strategies adopted to meet these conundrums were fourfold: face to face communication; shaping decisions; incremental provision of information; and communication tailored to the individual patient. Relational forms of interaction were understood to engender trust and allay anxiety. Shaping decisions with patients was understood as an expression of confidence by clinicians that helped alleviate anxiety and offered hope and reassurance to patients and their family experiencing the shock of the stroke event. Neutral presentations of information and treatment options promoted uncertainty and contributed to anxiety. 'Drip feeding' information created moments for reflection: clinicians literally made time. Tailoring information to the particular patient and family situation allowed clinicians to account for social and emotional contexts. The principal responses to the challenges of

Vascular-mediated signalling involved in early phosphate stress response in plants.

PubMed

Zhang, Zhaoliang; Zheng, Yi; Ham, Byung-Kook; Chen, Jieyu; Yoshida, Akiko; Kochian, Leon V; Fei, Zhangjun; Lucas, William J

2016-04-04

Depletion of finite global rock phosphate (Pi) reserves will impose major limitations on future agricultural productivity and food security. Hence, modern breeding programmes seek to develop Pi-efficient crops with sustainable yields under reduced Pi fertilizer inputs. In this regard, although the long-term responses of plants to Pi stress are well documented, the early signalling events have yet to be elucidated. Here, we show plant tissue-specific responses to early Pi stress at the transcription level and a predominant role of the plant vascular system in this process. Specifically, imposition of Pi stress induces rapid and major changes in the mRNA population in the phloem translocation stream, and grafting studies have revealed that many hundreds of phloem-mobile mRNAs are delivered to specific sink tissues. We propose that the shoot vascular system acts as the site of root-derived Pi stress perception, and the phloem serves to deliver a cascade of signals to various sinks, presumably to coordinate whole-plant Pi homeostasis.

Extracorporeal Shock Wave Therapy Suppresses the Early Proinflammatory Immune Response to a Severe Cutaneous Burn Injury

DTIC Science & Technology

2009-02-01

Burn wound model Mice were anaesthetised using isoflurane inha- lation. After shaving the dorsum, the exposed skin was washed gently with room...Extracorporeal shock wave therapy suppresses the early proinflammatory immune response to a severe cutaneous burn injury* Thomas A Davis, Alexander...S, Peoples GE, Tadaki D, Elster EA. Extracorporeal shock wave therapy suppresses the early proinflammatory immune response to a severe cutaneous burn

Perceived early-life maternal care and the cortisol response to repeated psychosocial stress

PubMed Central

Engert, Veronika; Efanov, Simona I.; Dedovic, Katarina; Duchesne, Annie; Dagher, Alain; Pruessner, Jens C.

2010-01-01

Background In the past decade, a body of animal and human research has revealed a profound influence of early-life experiences, ranging from variations in parenting behaviour to severe adversity, on hypothalamic–pituitary–adrenal axis regulation in adulthood. In our own previous studies, we have shown how variations in early-life parental care influence the development of the hippocampus and modify the cortisol awakening response. Methods In the present study, we investigated the influence of early-life maternal care on cortisol, heart rate and subjective psychological responses to the repeated administration of a psychosocial laboratory stressor in a population of 63 healthy young adults. Low, medium and high early-life maternal care groups were identified using the Parental Bonding Instrument. Results Controlling for the effect of sex, we found an inverted u-shaped relation between increasing levels of maternal care and cortisol stress responsivity. Specifically, overall and stress-induced cortisol levels went from below normal in the low maternal care, to normal in the medium care, back to below normal in the high maternal care groups. We found no group differences with respect to heart rate and subjective psychological stress measures. Whereas low and high maternal care groups exhibited similarly low endocrine stress responses, their psychological profiles were opposed with increased levels of depression and anxiety and decreased self-esteem in the low care group. Limitations Sex was unequally distributed among maternal care groups, whereby the number of men with low maternal care was too small to allow introducing sex as a second between-group variable. Conclusion We discuss the potential significance of this dissociation between endocrine and psychological parameters with respect to stress vulnerability and resistance for each maternal care group. PMID:20964960

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

ERIC Educational Resources Information Center

Shirinzadeh, Seyed Alireza; Mahadi, Tengku Sepora Tengku

2014-01-01

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

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

ERIC Educational Resources Information Center

Karoly, Adrienn

2012-01-01

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

Early immune responses are independent of RGC dysfunction in glaucoma with complement component C3 being protective.

PubMed

Harder, Jeffrey M; Braine, Catherine E; Williams, Pete A; Zhu, Xianjun; MacNicoll, Katharine H; Sousa, Gregory L; Buchanan, Rebecca A; Smith, Richard S; Libby, Richard T; Howell, Gareth R; John, Simon W M

2017-05-09

Various immune response pathways are altered during early, predegenerative stages of glaucoma; however, whether the early immune responses occur secondarily to or independently of neuronal dysfunction is unclear. To investigate this relationship, we used the Wld s allele, which protects from axon dysfunction. We demonstrate that DBA/2J .Wld s mice develop high intraocular pressure (IOP) but are protected from retinal ganglion cell (RGC) dysfunction and neuroglial changes that otherwise occur early in DBA/2J glaucoma. Despite this, immune pathways are still altered in DBA/2J .Wld s mice. This suggests that immune changes are not secondary to RGC dysfunction or altered neuroglial interactions, but may be directly induced by the increased strain imposed by high IOP. One early immune response following IOP elevation is up-regulation of complement C3 in astrocytes of DBA/2J and DBA/2J. Wld s mice. Unexpectedly, because the disruption of other complement components, such as C1Q, is protective in glaucoma, C3 deficiency significantly increased the number of DBA/2J eyes with nerve damage and RGC loss at an early time point after IOP elevation. Transcriptional profiling of C3-deficient cultured astrocytes implicated EGFR signaling as a hub in C3-dependent responses. Treatment with AG1478, an EGFR inhibitor, also significantly increased the number of DBA/2J eyes with glaucoma at the same early time point. These findings suggest that C3 protects from early glaucomatous damage, a process that may involve EGFR signaling and other immune responses in the optic nerve head. Therefore, therapies that target specific components of the complement cascade, rather than global inhibition, may be more applicable for treating human glaucoma.

Early immune responses are independent of RGC dysfunction in glaucoma with complement component C3 being protective

PubMed Central

Harder, Jeffrey M.; Braine, Catherine E.; Williams, Pete A.; Zhu, Xianjun; MacNicoll, Katharine H.; Sousa, Gregory L.; Buchanan, Rebecca A.; Smith, Richard S.; Howell, Gareth R.; John, Simon W. M.

2017-01-01

Various immune response pathways are altered during early, predegenerative stages of glaucoma; however, whether the early immune responses occur secondarily to or independently of neuronal dysfunction is unclear. To investigate this relationship, we used the Wlds allele, which protects from axon dysfunction. We demonstrate that DBA/2J.Wlds mice develop high intraocular pressure (IOP) but are protected from retinal ganglion cell (RGC) dysfunction and neuroglial changes that otherwise occur early in DBA/2J glaucoma. Despite this, immune pathways are still altered in DBA/2J.Wlds mice. This suggests that immune changes are not secondary to RGC dysfunction or altered neuroglial interactions, but may be directly induced by the increased strain imposed by high IOP. One early immune response following IOP elevation is up-regulation of complement C3 in astrocytes of DBA/2J and DBA/2J.Wlds mice. Unexpectedly, because the disruption of other complement components, such as C1Q, is protective in glaucoma, C3 deficiency significantly increased the number of DBA/2J eyes with nerve damage and RGC loss at an early time point after IOP elevation. Transcriptional profiling of C3-deficient cultured astrocytes implicated EGFR signaling as a hub in C3-dependent responses. Treatment with AG1478, an EGFR inhibitor, also significantly increased the number of DBA/2J eyes with glaucoma at the same early time point. These findings suggest that C3 protects from early glaucomatous damage, a process that may involve EGFR signaling and other immune responses in the optic nerve head. Therefore, therapies that target specific components of the complement cascade, rather than global inhibition, may be more applicable for treating human glaucoma. PMID:28446616

Is knowledge translation adequate? A quality assurance study of staging investigations in early stage breast cancer patients.

PubMed

Han, Dolly; Hogeveen, Sophie; Sweet Goldstein, Miriam; George, Ralph; Brezden-Masley, Christine; Hoch, Jeffrey; Haq, Rashida; Simmons, Christine E

2012-02-01

After primary surgery, patients diagnosed with early stage breast cancer undergo radiological investigations based on pathologic stage of disease to rule out distant metastases. Published guidelines can aid clinicians in determining which tests are appropriate based on stage of disease. We wished to assess the consistency of radiological staging in an academic community oncology setting with standard guidelines and to determine the overall impact of non-adherence to these guidelines. A retrospective cohort study was conducted for new breast cancer patients seen at a single institution between January 2009 and April 2010. Patients were included if initial diagnosis and primary surgery was at this institution. Pathologic stage and radiological tests completed were recorded. A literature review was performed and the results were compared with those from this study to determine overall adherence rates. Subsequently, a cost analysis was performed to determine the financial impact at this centre. 231 patients met eligibility criteria for inclusion in this study. A large proportion of patients were over-staged with 129 patients (55%) undergoing unnecessary investigations according to guidelines. Specifically, 59% of stage I patients and 58% of stage II patients were over-investigated. Distant metastases at the time of diagnosis were found in three patients, all of whom had stage III disease (1.3%). The literature reviewed revealed similar non-adherence rates in other centres. The estimated cost of such non-adherence is in the range of $78 (CDN) per new early stage breast cancer patient seen at this centre. This oncology centre has a low adherence to practice guidelines for staging investigations in breast cancer patients, with 55% of patients undergoing unnecessary tests. Very few patients had metastases at diagnosis, and all had pathological stage III disease. Efforts may need to focus on improving knowledge translation across clinical oncology settings to increase

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

Determinants of translation ambiguity

PubMed Central

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

2016-01-01

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

Early warning systems and rapid response to the deteriorating patient in hospital: A realist evaluation.

PubMed

McGaughey, Jennifer; O'Halloran, Peter; Porter, Sam; Trinder, John; Blackwood, Bronagh

2017-12-01

To test the Rapid Response Systems programme theory against actual practice components of the Rapid Response Systems implemented to identify those contexts and mechanisms which have an impact on the successful achievement of desired outcomes in practice. Rapid Response Systems allow deteriorating patients to be recognized using Early Warning Systems, referred early via escalation protocols and managed at the bedside by competent staff. Realist evaluation. The research design was an embedded multiple case study approach of four wards in two hospitals in Northern Ireland which followed the principles of Realist Evaluation. We used various mixed methods including individual and focus group interviews, observation of nursing practice between June-November 2010 and document analysis of Early Warning Systems audit data between May-October 2010 and hospital acute care training records over 4.5 years from 2003-2008. Data were analysed using NiVivo8 and SPPS. A cross-case analysis highlighted similar patterns of factors which enabled or constrained successful recognition, referral and response to deteriorating patients in practice. Key enabling factors were the use of clinical judgement by experienced nurses and the empowerment of nurses as a result of organizational change associated with implementation of Early Warning System protocols. Key constraining factors were low staffing and inappropriate skill mix levels, rigid implementation of protocols and culturally embedded suboptimal communication processes. Successful implementation of Rapid Response Systems was dependent on adopting organizational and cultural changes that facilitated staff empowerment, flexible implementation of protocols and ongoing experiential learning. © 2017 John Wiley & Sons Ltd.

Quantitative Proteomic Profiling of Early and Late Responses to Salicylic Acid in Cucumber Leaves

PubMed Central

Li, Liang; Shang, Qing-Mao

2016-01-01

Salicylic acid (SA) is an important phytohormone that plays vital regulatory roles in plant growth, development, and stress responses. However, studies on the molecular mechanism of SA, especially during the early SA responses, are lagging behind. In this study, we initiated a comprehensive isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis to explore the early and late SA-responsive proteins in leaves of cucumber (Cucumis sativus L.) seedlings. Upon SA application through the roots, endogenous SA accumulated in cucumber leaves. By assaying the changes in marker gene expression and photosynthetic rate, we collected samples at 12 h and 72 h post treatment (hpt) to profile the early and late SA responsiveness, respectively. The iTRAQ assay followed by tandem mass spectrometry revealed 135 differentially expressed proteins (DEPs) at 12 hpt and 301 DEPs at 72 hpt. The functional categories for these SA-responsive proteins included in a variety of biochemical processes, including photosynthesis, redox homeostasis, carbohydrate and energy metabolism, lipid metabolism, transport, protein folding and modification, proteolysis, cell wall organization, and the secondary phenylpropanoid pathway. Conclusively, based on the abundant changes of these DEPs, together with their putative functions, we proposed a possible SA-responsive protein network. It appears that SA could elicit reactive oxygen species (ROS) production via enhancing the photosynthetic electron transferring, and then confer some growth-promoting and stress-priming effects on cells during the late phase, including enhanced photosynthesis and ROS scavenging, altered carbon metabolic flux for the biosynthesis of amino acids and nucleotides, and cell wall reorganization. Overall, the present iTRAQ assay provides higher proteome coverage and deepened our understanding of the molecular basis of SA-responses. PMID:27551830

A Response from the Field: Perspectives on Translating Neuroscience to Clinical Practice

ERIC Educational Resources Information Center

Sprang, Ginny; Kaak, H. Otto; Staton-Tindall, Michele; Clark, James J.; Hubbard, Kay; Whitt-Woosley, Adrienne; Mau, Aimee; Combs, Angela; Risk, Heather

2009-01-01

The scientific meeting "From Neuroscience to Social Practice: Translational Research on Violence Against Children" sparked a dialogue between clinicians, researchers, and policy makers about the applicability and relevance of neuroscientific discoveries regarding the impact of violence towards children on contemporary behavioral health…

Augmentation of sensory-evoked hemodynamic response in an early Alzheimer's disease mouse model.

PubMed

Kim, Jinho; Jeong, Yong

2013-01-01

Based on enlarged blood oxygen level-dependent (BOLD) responses in cognitively normal subjects at risk for Alzheimer's disease (AD), compensatory neuronal hyperactivation has been proposed as an early marker for diagnosis of AD. The BOLD response results from neurovascular coupling, i.e., hemodynamic response induced by neuronal activity. However, there has been no evidence of task-induced increases in hemodynamic response in animal models of AD. Here, we observed an augmented hemodynamic response pattern in a transgenic AβPP(SWE)/PS1ΔE9 mouse model of AD using three in vivo imaging methods: intrinsic optical signal imaging, multi-photon laser scanning microscopy, and laser Doppler flowmetry. Sensory stimulation resulted in augmented and prolonged hemodynamic responses in transgenic mice evidenced by changes in total, oxygenated, and deoxygenated hemoglobin concentration. This difference between transgenic and wild-type mice was significant at 7 months of age when amyloid plaques and cerebral amyloid angiopathy had developed but not at younger or older ages. Correspondingly, sensory stimulation-induced pial arteriole diameter was also augmented and prolonged in transgenic mice at 7 months of age. Cerebral blood flow response in transgenic mice was augmented but not prolonged. These results are consistent with the existence of BOLD signal hyperactivation in non-demented AD-risk human subjects, supporting its potential use as an early diagnostic marker of AD.

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

PubMed

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

2016-01-01

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

Translation Quality Assessment in Health Research: A Functionalist Alternative to Back-Translation.

PubMed

Colina, Sonia; Marrone, Nicole; Ingram, Maia; Sánchez, Daisey

2017-09-01

As international research studies become more commonplace, the importance of developing multilingual research instruments continues to increase and with it that of translated materials. It is therefore not unexpected that assessing the quality of translated materials (e.g., research instruments, questionnaires, etc.) has become essential to cross-cultural research, given that the reliability and validity of the research findings crucially depend on the translated instruments. In some fields (e.g., public health and medicine), the quality of translated instruments can also impact the effectiveness and success of interventions and public campaigns. Back-translation (BT) is a commonly used quality assessment tool in cross-cultural research. This quality assurance technique consists of (a) translation (target text [TT 1 ]) of the source text (ST), (b) translation (TT 2 ) of TT 1 back into the source language, and (c) comparison of TT 2 with ST to make sure there are no discrepancies. The accuracy of the BT with respect to the source is supposed to reflect equivalence/accuracy of the TT. This article shows how the use of BT as a translation quality assessment method can have a detrimental effect on a research study and proposes alternatives to BT. One alternative is illustrated on the basis of the translation and quality assessment methods used in a research study on hearing loss carried out in a border community in the southwest of the United States.

[French translation and validation of a short version of the Suicide Intervention Response Inventory-2 (SIRI-2-VF)].

PubMed

Kopp-Bigault, C; Audouard-Marzin, Y; Scouarnec, P; Beauchamp, G; Séguin, M; Walter, M

2017-10-30

Training health professionals about suicidal crisis is one major line of suicide prevention worldwide. France has one of the highest suicide rates in Europe, and although crisis intervention training has been set up since 2001, there presently is no training assessment tool in the French language for health professionals trained in suicide prevention. In the four levels of Kirpatrick's education pyramid, training that takes place in France today solely assesses level one status, that is to say relative to the level of satisfaction of participants (self-report). This study proposes a validated short French version of the Suicide Intervention Response Inventory-2 (SIRI-2) of Neimeyer & Mc Innes. The SIRI-2 questionnaire assesses the ability of first line intervention in dealing with suicidal individuals. The translation methodology was inspired from Vallerand's model of cross-cultural back translation. This method is regularly used for translating from the English language to a French version. In order to translate the English version, we used an extensive 7-step methodology implicating several bilingual translators, expert reviewers (psychologists and psychiatrists) and a scientific committee. Participants were 107 students from different French universities and study programs: psychology, medicine and nursing (17 were men; average age was 26.6). Fifteen of these participants answered the SIRI-2-VF on two occasions (separated by a 15-day interval) in order to estimate the temporal stability of the instrument. The scores of the students were compared to six French experts in suicide prevention and with the original expert group who worked on the development of SIRI-2 (n=7). We used Student t Test for construct validity, Cronbach's Alpha for internal consistency and Pearson's correlation coefficient for temporal stability. Following a fidelity comparison of the results of the French experts with those of the American experts, ten items presenting the least good

Population Response Profiles in Early Visual Cortex Are Biased in Favor of More Valuable Stimuli

PubMed Central

Saproo, Sameer

2010-01-01

Voluntary and stimulus-driven shifts of attention can modulate the representation of behaviorally relevant stimuli in early areas of visual cortex. In turn, attended items are processed faster and more accurately, facilitating the selection of appropriate behavioral responses. Information processing is also strongly influenced by past experience and recent studies indicate that the learned value of a stimulus can influence relatively late stages of decision making such as the process of selecting a motor response. However, the learned value of a stimulus can also influence the magnitude of cortical responses in early sensory areas such as V1 and S1. These early effects of stimulus value are presumed to improve the quality of sensory representations; however, the nature of these modulations is not clear. They could reflect nonspecific changes in response amplitude associated with changes in general arousal or they could reflect a bias in population responses so that high-value features are represented more robustly. To examine this issue, subjects performed a two-alternative forced choice paradigm with a variable-interval payoff schedule to dynamically manipulate the relative value of two stimuli defined by their orientation (one was rotated clockwise from vertical, the other counterclockwise). Activation levels in visual cortex were monitored using functional MRI and feature-selective voxel tuning functions while subjects performed the behavioral task. The results suggest that value not only modulates the relative amplitude of responses in early areas of human visual cortex, but also sharpens the response profile across the populations of feature-selective neurons that encode the critical stimulus feature (orientation). Moreover, changes in space- or feature-based attention cannot easily explain the results because representations of both the selected and the unselected stimuli underwent a similar feature-selective modulation. This sharpening in the population

Early versus later response to treatment in patients with community-acquired pneumonia: analysis of the REACH study.

PubMed

Blasi, Francesco; Ostermann, Helmut; Racketa, Jill; Medina, Jesús; McBride, Kyle; Garau, Javier

2014-01-22

Key goals in the treatment of CAP include early response to treatment and achievement of clinical stability. The US FDA recommends early response endpoints (72 hours after initiation of treatment) in clinical trials for the treatment of community-acquired bacterial pneumonia. REACH (REtrospective Study to Assess the Clinical Management of Patients With Moderate-to-Severe Complicated Skin and Soft Tissue Infections [cSSTI] or CAP in the Hospital Setting) was a retrospective observational study, providing current data on the clinical management and resource burden of CAP in real-life settings in European hospitals. This analysis reviews the characteristics and outcomes of patients showing early positive response to treatment (time to clinical stability [TCS] ≤4 days, as assessed by Halm's criteria) compared with patients with later positive response (TCS >4 days). Patients were adults, hospitalized with CAP (2010-2011) and requiring in-hospital treatment with intravenous antibiotics. Of the 2039 patients included in REACH, 585 (28.7%) had TCS assessed by Halm's criteria: 332 (56.8%) showed early response (median 3.0 days), and 253 (43.2%) showed later response to treatment (median 7.0 days). Use of Halm's criteria varied across participating countries, ranging from 0% (Belgium) to 49.1% (UK). Patient characteristics and relevant medical history were similar between the two groups. There were no notable differences in initial antibiotic therapy between groups, except that more early responders had been treated with amoxicillin-clavulanate and amoxicillin monotherapy (22.6%; 7.5%, respectively) than later responders (5.9%; 1.2%, respectively). Initial treatment modification and re-infection or recurrences were less frequent in early responders compared with later responders (14.2% and 3.3% vs. 34.8% and 5.9%, respectively). Early responders had a shorter duration of hospitalization (mean 9.4 ± SD 7.0; median 8.0 days vs. mean 15.6 ± SD 10.5; median 12

Machine Translation Project

NASA Technical Reports Server (NTRS)

Bajis, Katie

1993-01-01

The characteristics and capabilities of existing machine translation systems were examined and procurement recommendations were developed. Four systems, SYSTRAN, GLOBALINK, PC TRANSLATOR, and STYLUS, were determined to meet the NASA requirements for a machine translation system. Initially, four language pairs were selected for implementation. These are Russian-English, French-English, German-English, and Japanese-English.

Barriers and strategies for the clinical translation of advanced orthopaedic tissue engineering protocols.

PubMed

Madry, H; Alini, M; Stoddart, M J; Evans, C; Miclau, T; Steiner, S

2014-05-06

Research in orthopaedic tissue engineering has intensified over the last decade and new protocols continue to emerge. The clinical translation of these new applications, however, remains associated with a number of obstacles. This report highlights the major issues that impede the clinical translation of advanced tissue engineering concepts, discusses strategies to overcome these barriers, and examines the need to increase incentives for translational strategies. The statements are based on presentations and discussions held at the AO Foundation-sponsored symposium "Where Science meets Clinics 2013" held at the Congress Center in Davos, Switzerland, in September, 2013. The event organisers convened a diverse group of over one hundred stakeholders involved in clinical translation of orthopaedic tissue engineering, including scientists, clinicians, healthcare industry professionals and regulatory agency representatives. A major point that emerged from the discussions was that there continues to be a critical need for early trans-disciplinary communication and collaboration in the development and execution of research approaches. Equally importantly was the need to address the shortage of sustained funding programs for multidisciplinary teams conducting translational research. Such detailed discussions between experts contribute towards the development of a roadmap to more successfully advance the clinical translation of novel tissue engineering concepts and ultimately improve patient care in orthopaedic and trauma surgery.

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

ERIC Educational Resources Information Center

Rojo, Ana

2015-01-01

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

Early-life risperidone enhances locomotor responses to amphetamine during adulthood.

PubMed

Lee Stubbeman, Bobbie; Brown, Clifford J; Yates, Justin R; Bardgett, Mark E

2017-10-05

Antipsychotic drug prescriptions for pediatric populations have increased over the past 20 years, particularly the use of atypical antipsychotic drugs such as risperidone. Most antipsychotic drugs target forebrain dopamine systems, and early-life antipsychotic drug exposure could conceivably reset forebrain neurotransmitter function in a permanent manner that persists into adulthood. This study determined whether chronic risperidone administration during development modified locomotor responses to the dopamine/norepinephrine agonist, D-amphetamine, in adult rats. Thirty-five male Long-Evans rats received an injection of one of four doses of risperidone (vehicle, .3, 1.0, 3.0mg/kg) each day from postnatal day 14 through 42. Locomotor activity was measured for 1h on postnatal days 46 and 47, and then for 24h once a week over the next two weeks. Beginning on postnatal day 75, rats received one of four doses of amphetamine (saline, .3, 1.0, 3.0mg/kg) once a week for four weeks. Locomotor activity was measured for 27h after amphetamine injection. Rats administered risperidone early in life demonstrated increased activity during the 1 and 24h test sessions conducted prior to postnatal day 75. Taking into account baseline group differences, these same rats exhibited significantly more locomotor activity in response to the moderate dose of amphetamine relative to controls. These results suggest that early-life treatment with atypical antipsychotic drugs, like risperidone, permanently alters forebrain catecholamine function and increases sensitivity to drugs that target such function. Copyright © 2017 Elsevier B.V. All rights reserved.

Impaired early visual response modulations to spatial information in chronic schizophrenia

PubMed Central

Knebel, Jean-François; Javitt, Daniel C.; Murray, Micah M.

2011-01-01

Early visual processing stages have been demonstrated to be impaired in schizophrenia patients and their first-degree relatives. The amplitude and topography of the P1 component of the visual evoked potential (VEP) are both affected; the latter of which indicates alterations in active brain networks between populations. At least two issues remain unresolved. First, the specificity of this deficit (and suitability as an endophenotype) has yet to be established, with evidence for impaired P1 responses in other clinical populations. Second, it remains unknown whether schizophrenia patients exhibit intact functional modulation of the P1 VEP component; an aspect that may assist in distinguishing effects specific to schizophrenia. We applied electrical neuroimaging analyses to VEPs from chronic schizophrenia patients and healthy controls in response to variation in the parafoveal spatial extent of stimuli. Healthy controls demonstrated robust modulation of the VEP strength and topography as a function of the spatial extent of stimuli during the P1 component. By contrast, no such modulations were evident at early latencies in the responses from patients with schizophrenia. Source estimations localized these deficits to the left precuneus and medial inferior parietal cortex. These findings provide insights on potential underlying low-level impairments in schizophrenia. PMID:21764264

Building a knowledge translation platform in Malawi to support evidence-informed health policy.

PubMed

Berman, Joshua; Mitambo, Collins; Matanje-Mwagomba, Beatrice; Khan, Shiraz; Kachimanga, Chiyembekezo; Wroe, Emily; Mwape, Lonia; van Oosterhout, Joep J; Chindebvu, Getrude; van Schoor, Vanessa; Puchalski Ritchie, Lisa M; Panisset, Ulysses; Kathyola, Damson

2015-12-08

With the support of the World Health Organization's Evidence-Informed Policy Network, knowledge translation platforms have been developed throughout Africa, the Americas, Eastern Europe, and Asia to further evidence-informed national health policy. In this commentary, we discuss the approaches, activities and early lessons learned from the development of a Knowledge Translation Platform in Malawi (KTPMalawi). Through ongoing leadership, as well as financial and administrative support, the Malawi Ministry of Health has strongly signalled its intention to utilize a knowledge translation platform methodology to support evidence-informed national health policy. A unique partnership between Dignitas International, a medical and research non-governmental organization, and the Malawi Ministry of Health, has established KTPMalawi to engage national-level policymakers, researchers and implementers in a coordinated approach to the generation and utilization of health-sector research. Utilizing a methodology developed and tested by knowledge translation platforms across Africa, a stakeholder mapping exercise and initial capacity building workshops were undertaken and a multidisciplinary Steering Committee was formed. This Steering Committee prioritized the development of two initial Communities of Practice to (1) improve data utilization in the pharmaceutical supply chain and (2) improve the screening and treatment of hypertension within HIV-infected populations. Each Community of Practice's mandate is to gather and synthesize the best available global and local evidence and produce evidence briefs for policy that have been used as the primary input into structured deliberative dialogues. While a lack of sustained initial funding slowed its early development, KTPMalawi has greatly benefited from extensive technical support and mentorship by an existing network of global knowledge translation platforms. With the continued support of the Malawi Ministry of Health and the

Response of rotation-translation blocked proteins using Langevin dynamics on a locally harmonic landscape.

PubMed

Manson, Anthony C; Coalson, Rob D

2012-10-11

Langevin dynamics is used to compute the time evolution of the nonequilibrium motion of the atomic coordinates of a protein in response to ligand dissociation. The protein potential energy surface (PES) is approximated by a harmonic basin about the minimum of the unliganded state. Upon ligand dissociation, the protein undergoes relaxation from the bound to the unbound state. A coarse graining scheme based on rotation translation blocks (RTB) is applied to the relaxation of the two domain iron transport protein, ferric binding protein. This scheme provides a natural and efficient way to freeze out the small amplitude, high frequency motions within each rigid fragment, thereby allowing for the number of dynamical degrees of freedom to be reduced. The results obtained from all flexible atom (constraint free) dynamics are compared to those obtained using RTB-Langevin dynamics. To assess the impact of the assumed rigid fragment clustering on the temporal relaxation dynamics of the protein molecule, three distinct rigid block decompositions were generated and their responses compared. Each of the decompositions was a variant of the one-block-per-residue grouping, with their force and friction matrices being derived from their fully flexible counterpart. Monitoring the time evolution of the distance separating a selected pair of amino acids, the response curves of the blocked decompositions were similar in shape to each other and to the control system in which all atomic degrees of freedom are fully independent. The similar shape of the blocked responses showed that the variations in grouping had only a minor impact on the kinematics. Compared with the all atom responses, however, the blocked responses were faster as a result of the instantaneous transmission of force throughout each rigid block. This occurred because rigid blocking does not permit any intrablock deformation that could store or divert energy. It was found, however, that this accelerated response could be

Multidecadal response of naturally regenerated southern pine to early competition control and commercial thinning

Treesearch

Andrew S. Nelson; Don C. Bragg

2016-01-01

Multidecadal responses to early competition control are poorly documented in naturally regenerated southern pine stands. This study examined the effects of the following early herbicide treatments in thinned southern pine stands through age 31: (1) no control (CK), (2) herbaceous vegetation control only (HC), (3) woody vegetation control only (WC), and (4) total (woody...

Controlling the Messenger: Regulated Translation of Maternal mRNAs in Xenopus laevis Development

PubMed Central

Fox, Catherine A.; Dowdle, Megan E.; Blaser, Susanne Imboden; Chung, Andy; Park, Sookhee

2017-01-01

The selective translation of maternal mRNAs encoding cell-fate determinants drives the earliest decisions of embryogenesis that establish the vertebrate body plan. This chapter will discuss studies in Xenopus laevis that provide insights into mechanisms underlying this translational control. Xenopus has been a powerful model organism for many discoveries relevant to the translational control of maternal mRNAs because of the large size of its oocytes and eggs that allow for microinjection of molecules and the relative ease of manipulating the oocyte to egg transition (maturation) and fertilization in culture. Consequently, many key studies have focused on the expression of maternal mRNAs during the oocyte to egg transition (the meiotic cell cycle) and the rapid cell divisions immediately following fertilization. This research has made seminal contributions to our understanding of translational regulatory mechanisms, but while some of the mRNAs under consideration at these stages encode cell-fate determinants, many encode cell cycle regulatory proteins that drive these early cell cycles. In contrast, while maternal mRNAs encoding key developmental (i.e., cell-fate) regulators that function after the first cleavage stages may exploit aspects of these foundational mechanisms, studies reveal that these mRNAs must also rely on distinct and, as of yet, incompletely understood mechanisms. These findings are logical because the functions of such developmental regulatory proteins have requirements distinct from cell cycle regulators, including becoming relevant only after fertilization and then only in specific cells of the embryo. Indeed, key maternal cell-fate determinants must be made available in exquisitely precise amounts (usually low), only at specific times and in specific cells during embryogenesis. To provide an appreciation for the regulation of maternal cell-fate determinant expression, an overview of the maternal phase of Xenopus embryogenesis will be presented

When Translation Makes the Difference: Sentence Processing in Reading and Translation

ERIC Educational Resources Information Center

Macizo, Pedro; Bajo, M. Teresa

2004-01-01

In two experiments we compared normal reading and reading for translation of object relative sentences presented word-by-word. In Experiment 1, professional translators were asked either to read and repeat Spanish sentences, or to read and translate them into English. In addition, we manipulated the availability of pragmatic information given in…

Translational Approaches Targeting Reconsolidation

PubMed Central

Kroes, Marijn C.W.; LeDoux, Joseph E.; Phelps, Elizabeth A.

2017-01-01

Maladaptive learned responses and memories contribute to psychiatric disorders that constitute a significant socio-economic burden. Primary treatment methods teach patients to inhibit maladaptive responses, but do not get rid of the memory itself, which explains why many patients experience a return of symptoms even after initially successful treatment. This highlights the need to discover more persistent and robust techniques to diminish maladaptive learned behaviours. One potentially promising approach is to alter the original memory, as opposed to inhibiting it, by targeting memory reconsolidation. Recent research shows that reactivating an old memory results in a period of memory flexibility and requires restorage, or reconsolidation, for the memory to persist. This reconsolidation period allows a window for modification of a specific old memory. Renewal of memory flexibility following reactivation holds great clinical potential as it enables targeting reconsolidation and changing of specific learned responses and memories that contribute to maladaptive mental states and behaviours. Here, we will review translational research on non-human animals, healthy human subjects, and clinical populations aimed at altering memories by targeting reconsolidation using biological treatments (electrical stimulation, noradrenergic antagonists) or behavioural interference (reactivation–extinction paradigm). Both approaches have been used successfully to modify aversive and appetitive memories, yet effectiveness in treating clinical populations has been limited. We will discuss that memory flexibility depends on the type of memory tested and the brain regions that underlie specific types of memory. Further, when and how we can most effectively reactivate a memory and induce flexibility is largely unclear. Finally, the development of drugs that can target reconsolidation and are safe for use in humans would optimize cross-species translations. Increasing the understanding of

Livestock models in translational medicine.

PubMed

Roth, James A; Tuggle, Christopher K

2015-01-01

This issue of the ILAR Journal focuses on livestock models in translational medicine. Livestock models of selected human diseases present important advantages as compared with rodent models for translating fundamental breakthroughs in biology to useful preventatives and therapeutics for humans. Livestock reflect the complexity of applying medical advances in an outbred species. In many cases, the pathogenesis of infectious, metabolic, genetic, and neoplastic diseases in livestock species more closely resembles that in humans than does the pathogenesis of rodent models. Livestock models also provide the advantage of similar organ size and function and the ability to serially sample an animal throughout the study period. Research using livestock models for human disease often benefits not only human health but animal health and food production as well. This issue of the ILAR Journal presents information on translational research using livestock models in two broad areas: microbiology and infectious disease (transmissible spongiform encephalopathies, mycobacterial infections, influenza A virus infection, vaccine development and testing, the human microbiota) and metabolic, neoplastic, and genetic disorders (stem cell therapy, male germ line cell biology, pulmonary adenocarcinoma, muscular dystrophy, wound healing). In addition, there is a manuscript devoted to Institutional Animal Care and Use Committees' responsibilities for reviewing research using livestock models. Conducting translational research using livestock models requires special facilities and researchers with expertise in livestock. There are many institutions in the world with experienced researchers and facilities designed for livestock research; primarily associated with colleges of agriculture and veterinary medicine or government laboratories. © The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions

Translation of 5′ leaders is pervasive in genes resistant to eIF2 repression

PubMed Central

Fahey, Ciara; Kenny, Elaine M; Terenin, Ilya M; Dmitriev, Sergey E; Cormican, Paul; Morris, Derek W; Shatsky, Ivan N; Baranov, Pavel V

2015-01-01

Eukaryotic cells rapidly reduce protein synthesis in response to various stress conditions. This can be achieved by the phosphorylation-mediated inactivation of a key translation initiation factor, eukaryotic initiation factor 2 (eIF2). However, the persistent translation of certain mRNAs is required for deployment of an adequate stress response. We carried out ribosome profiling of cultured human cells under conditions of severe stress induced with sodium arsenite. Although this led to a 5.4-fold general translational repression, the protein coding open reading frames (ORFs) of certain individual mRNAs exhibited resistance to the inhibition. Nearly all resistant transcripts possess at least one efficiently translated upstream open reading frame (uORF) that represses translation of the main coding ORF under normal conditions. Site-specific mutagenesis of two identified stress resistant mRNAs (PPP1R15B and IFRD1) demonstrated that a single uORF is sufficient for eIF2-mediated translation control in both cases. Phylogenetic analysis suggests that at least two regulatory uORFs (namely, in SLC35A4 and MIEF1) encode functional protein products. DOI: http://dx.doi.org/10.7554/eLife.03971.001 PMID:25621764

Translational research in genomics of Alzheimer's disease: a review of current practice and future perspectives.

PubMed

Mihaescu, Raluca; Detmar, Symone B; Cornel, Martina C; van der Flier, Wiesje M; Heutink, Peter; Hol, Elly M; Rikkert, Marcel G M Olde; van Duijn, Cornelia M; Janssens, A Cecile J W

2010-01-01

Alzheimer's disease (AD) is the most prevalent form of dementia and the number of cases is expected to increase exponentially worldwide. Three highly penetrant genes (AbetaPP, PSEN1, and PSEN2) explain only a small number of AD cases with a Mendelian transmission pattern. Many genes have been analyzed for association with non-Mendelian AD, but the only consistently replicated finding is APOE. At present, possibilities for prevention, early detection, and treatment of the disease are limited. Predictive and diagnostic genetic testing is available only in Mendelian forms of AD. Currently, APOE genotyping is not considered clinically useful for screening, presymptomatic testing, or clinical diagnosis of non-Mendelian AD. However, clinical management of the disease is expected to benefit from the rapid pace of discoveries in the genomics of AD. Following a recently developed framework for the continuum of translation research that is needed to move genetic discoveries to health applications, this paper reviews recent genetic discoveries as well as translational research on genomic applications in the prevention, early detection, and treatment of AD. The four phases of translation research include: 1) translation of basic genomics research into a potential health care application; 2) evaluation of the application for the development of evidence-based guidelines; 3) evaluation of the implementation and use of the application in health care practice; and 4) evaluation of the achieved population health impact. Most research on genome-based applications in AD is still in the first phase of the translational research framework, which means that further research is still needed before their implementation can be considered.

Tectonics of formation, translation, and dispersal of the Coast Range ophiolite of California

USGS Publications Warehouse

McLaughlin, R.J.; Blake, M.C.; Griscom, A.; Blome, C.D.; Murchey, B.

1988-01-01

Data from the Coast Range ophiolite and its tectonic outliers in the northern California Coast Ranges suggest that the lower part of the ophiolite formed 169 to 163 Ma in a forearc or back arc setting at equatorial latitudes. Beginning about 156 Ma and continuing until 145 Ma, arc magmatism was superimposed on the ophiolite, and concurrently, a transform developed along the arc axis or in the back arc area. Rapid northward translation of this rifted active magmatic arc to middle latitudes culminated in its accretion to the California margin of North America at about 145 Ma. This Late Jurassic episode of translation, arc magmatism, and accretion coincided with the Nevadan orogeny and a proposed major plate reorganization in the eastern Pacific basin. Displacement occurred between about 60 and 52 Ma. Ophiolitic rocks in the Decatur terrane of western Washington that have recently been correlated with the Coast Range ophiolite and the Great Valley sequence of California were apparently displaced at least 950 to 1200 km from the west side of the Great Valley between early Tertiary and Early Cretaceous time. Derived rates of northward translation for the ophiolite outliers in California are in the range of 1 to 4 cm/yr. -from Authors

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

ERIC Educational Resources Information Center

Mahasneh, Anjad

2013-01-01

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

Pancreatic cancer: Translational research aspects and clinical implications

PubMed Central

Ansari, Daniel; Chen, Bi-Cheng; Dong, Lei; Zhou, Meng-Tao; Andersson, Roland

2012-01-01

Despite improvements in surgical techniques and adjuvant chemotherapy, the overall mortality rates in pancreatic cancer have generally remained relatively unchanged and the 5-year survival rate is actually below 2%. This paper will address the importance of achieving an early diagnosis and identifying markers for prognosis and response to therapy such as genes, proteins, microRNAs or epigenetic modifications. However, there are still major hurdles when translating investigational biomarkers into routine clinical practice. Furthermore, novel ways of secondary screening in high-risk individuals, such as artificial neural networks and modern imaging, will be discussed. Drug resistance is ubiquitous in pancreatic cancer. Several mechanisms of drug resistance have already been revealed, including human equilibrative nucleoside transporter-1 status, multidrug resistance proteins, aberrant signaling pathways, microRNAs, stromal influence, epithelial-mesenchymal transition-type cells and recently the presence of cancer stem cells/cancer-initiating cells. These factors must be considered when developing more customized types of intervention (“personalized medicine”). In the future, multifunctional nanoparticles that combine a specific targeting agent, an imaging probe, a cell-penetrating agent, a biocompatible polymer and an anti-cancer drug may become valuable for the management of patients with pancreatic cancer. PMID:22509073

Population Sciences, Translational Research and the Opportunities and Challenges for Genomics to Reduce the Burden of Cancer in the 21st Century

PubMed Central

Khoury, Muin J.; Clauser, Steven B.; Freedman, Andrew N.; Gillanders, Elizabeth M.; Glasgow, Russ E.; Klein, William M. P.; Schully, Sheri D.

2011-01-01

Advances in genomics and related fields are promising tools for risk assessment, early detection, and targeted therapies across the entire cancer care continuum. In this commentary, we submit that this promise cannot be fulfilled without an enhanced translational genomics research agenda firmly rooted in the population sciences. Population sciences include multiple disciplines that are needed throughout the translational research continuum. For example, epidemiologic studies are needed not only to accelerate genomic discoveries and new biological insights into cancer etiology and pathogenesis, but to characterize and critically evaluate these discoveries in well defined populations for their potential for cancer prediction, prevention and response to treatments. Behavioral, social and communication sciences are needed to explore genomic-modulated responses to old and new behavioral interventions, adherence to therapies, decision-making across the continuum, and effective use in health care. Implementation science, health services, outcomes research, comparative effectiveness research and regulatory science are needed for moving validated genomic applications into practice and for measuring their effectiveness, cost effectiveness and unintended consequences. Knowledge synthesis, evidence reviews and economic modeling of the effects of promising genomic applications will facilitate policy decisions, and evidence-based recommendations. Several independent and multidisciplinary panels have recently made specific recommendations for enhanced research and policy infrastructure to inform clinical and population research for moving genomic innovations into the cancer care continuum. An enhanced translational genomics and population sciences agenda is urgently needed to fulfill the promise of genomics in reducing the burden of cancer. PMID:21795499

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

ERIC Educational Resources Information Center

Sun, Sanjun

2012-01-01

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

Early detection and rapid response

USGS Publications Warehouse

Westbrooks, Randy G.; Eplee, Robert E.; Simberloff, Daniel; Rejmánek, Marcel

2011-01-01

Prevention is the first line of defense against introduced invasive species - it is always preferable to prevent the introduction of new invaders into a region or country. However, it is not always possible to detect all alien hitchhikers imported in cargo, or to predict with any degree of certainty which introduced species will become invasive over time. Fortunately, the majority of introduced plants and animals don't become invasive. But, according to scientists at Cornell University, costs and losses due to species that do become invasive are now estimated to be over $137 billion/year in the United States. Early detection and rapid response (EDRR) is the second line of defense against introduced invasive species - EDRR is the preferred management strategy for preventing the establishment and spread of invasive species. Over the past 50 years, there has been a gradual shift away from large and medium scale federal/state single-agency-led weed eradication programs in the United States, to smaller interagency-led projects involving impacted and potential stakeholders. The importance of volunteer weed spotters in detecting and reporting suspected new invasive species has also been recognized in recent years.

In the Beginning was a Mutualism - On the Origin of Translation

NASA Astrophysics Data System (ADS)

Vitas, Marko; Dobovišek, Andrej

2018-04-01

The origin of translation is critical for understanding the evolution of life, including the origins of life. The canonical genetic code is one of the most dominant aspects of life on this planet, while the origin of heredity is one of the key evolutionary transitions in living world. Why the translation apparatus evolved is one of the enduring mysteries of molecular biology. Assuming the hypothesis, that during the emergence of life evolution had to first involve autocatalytic systems which only subsequently acquired the capacity of genetic heredity, we propose and discuss possible mechanisms, basic aspects of the emergence and subsequent molecular evolution of translation and ribosomes, as well as enzymes as we know them today. It is possible, in this sense, to view the ribosome as a digital-to-analogue information converter. The proposed mechanism is based on the abilities and tendencies of short RNA and polypeptides to fold and to catalyse biochemical reactions. The proposed mechanism is in concordance with the hypothesis of a possible chemical co-evolution of RNA and proteins in the origin of the genetic code or even more generally at the early evolution of life on Earth. The possible abundance and availability of monomers at prebiotic conditions are considered in the mechanism. The hypothesis that early polypeptides were folding on the RNA scaffold is also considered and mutualism in molecular evolutionary development of RNA and peptides is favoured.

Sexually Dimorphic Responses to Early Adversity: Implications for Affective Problems and Autism Spectrum Disorder

PubMed Central

Davis, Elysia Poggi; Pfaff, Donald

2014-01-01

During gestation, development proceeds at a pace that is unmatched by any other stage of the lifecycle. For these reason the human fetus is particularly susceptible not only to organizing influences, but also to pathogenic disorganizing influences. Growing evidence suggests that exposure to prenatal adversity leads to neurological changes that underlie lifetime risks for mental illness. Beginning early in gestation, males and females show differential developmental trajectories and responses to stress. It is likely that sex-dependent organization of neural circuits during the fetal period influences differential vulnerability to mental health problems. We consider in this review evidence that sexually dimorphic responses to early life stress are linked to two developmental disorders: affective problems (greater female prevalence) and autism spectrum disorder (greater male prevalence). Recent prospective studies illustrating the neurodevelopmental consequences of fetal exposure to stress and stress hormones for males and females are considered here. Plausible biological mechanisms including the role of the sexually differentiated placenta are discussed. We consider in this review evidence that sexually dimorphic responses to early life stress are linked to two sets of developmental disorders: affective problems (greater female prevalence) and autism spectrum disorders (greater male prevalence). PMID:25038479

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…

Translation attenuation via 3′ terminal codon usage in bovine csn1s2 is responsible for the difference in αs2- and β-casein profile in milk

PubMed Central

Kim, Julie J; Yu, Jaeju; Bag, Jnanankur; Bakovic, Marica; Cant, John P

2015-01-01

The rate of secretion of αs2-casein into bovine milk is approximately 25% of that of β-casein, yet mammary expression of their respective mRNA transcripts (csn1s2 and csn2) is not different. Our objective was to identify molecular mechanisms that explain the difference in translation efficiency between csn1s2 and csn2. Cell-free translational efficiency of csn2 was 5 times that of csn1s2. Transcripts of csn1s2 distributed into heavier polysomes than csn2 transcripts, indicating an attenuation of elongation and/or termination. Stimulatory and inhibitory effects of the 5′ and 3′ UTRs on translational efficiency were different with luciferase and casein sequences in the coding regions. Substituting the 5′ and 3′ UTRs from csn2 into csn1s2 did not improve csn1s2 translation, implicating the coding region itself in the translation difference. Deletion of a 28-codon fragment from the 3′ terminus of the csn1s2 coding region, which displays codons with low correlations to cell fitness, increased translation to a par with csn2. We conclude that the usage of the last 28 codons of csn1s2 is the main regulatory element that attenuates its expression and is responsible for the differential translational expression of csn1s2 and csn2. PMID:25826667

Evasion of Early Antiviral Responses by Herpes Simplex Viruses

PubMed Central

Suazo, Paula A.; Ibañez, Francisco J.; Retamal-Díaz, Angello R.; Paz-Fiblas, Marysol V.; Bueno, Susan M.; Kalergis, Alexis M.; González, Pablo A.

2015-01-01

Besides overcoming physical constraints, such as extreme temperatures, reduced humidity, elevated pressure, and natural predators, human pathogens further need to overcome an arsenal of antimicrobial components evolved by the host to limit infection, replication and optimally, reinfection. Herpes simplex virus-1 (HSV-1) and herpes simplex virus-2 (HSV-2) infect humans at a high frequency and persist within the host for life by establishing latency in neurons. To gain access to these cells, herpes simplex viruses (HSVs) must replicate and block immediate host antiviral responses elicited by epithelial cells and innate immune components early after infection. During these processes, infected and noninfected neighboring cells, as well as tissue-resident and patrolling immune cells, will sense viral components and cell-associated danger signals and secrete soluble mediators. While type-I interferons aim at limiting virus spread, cytokines and chemokines will modulate resident and incoming immune cells. In this paper, we discuss recent findings relative to the early steps taking place during HSV infection and replication. Further, we discuss how HSVs evade detection by host cells and the molecular mechanisms evolved by these viruses to circumvent early antiviral mechanisms, ultimately leading to neuron infection and the establishment of latency. PMID:25918478

[Impulse control in addiction: a translational perspective].

PubMed

Schmaal, L; Broos, N; Joos, L; Pattij, T; Goudriaan, A E

2013-01-01

Impulsivity is a hallmark of addiction and predicts treatment response and relapse. Impulsivity is, however, a complex construct. Translational cross-species research is needed to give us greater insight into the neurobiology and the role of impulsivity in addiction and to help with the development of new treatment strategies for improving patients' impulse control. To review recent evidence concerning the concept of impulsivity and the role of impulsivity in addiction. The concept and neurobiology of impulsivity are reviewed from a translational perspective. The role of impulsivity in addiction and implications for treatment are discussed. Our recent translational cross-species study indicates that impulsivity is made up of several, separate independent features with partly distinct underlying neurobiological substrates. There are also indications that these features make a unique and independent contribution to separate stages of the addiction cycle. In addition, the improvement of impulse control is a promising new target area for treatments that could lead to better results. However, those involved in developing new treatment strategies will have to take into account the complexity and multidimensional character of impulsivity.

Translational safety biomarkers of colonic barrier integrity in the rat.

PubMed

Erkens, Tim; Bueters, Ruud; van Heerden, Marjolein; Cuyckens, Filip; Vreeken, Rob; Goeminne, Nick; Lammens, Lieve

2018-05-20

The intestinal barrier controls intestinal permeability, and its disruption has been associated with multiple diseases. Therefore, preclinical safety biomarkers monitoring barrier integrity are essential during the development of drugs targeting the intestines, particularly if starting treatment early after onset of disease. Classical toxicology endpoints are not sensitive enough and therefore our objective was to identify non-invasive markers enabling early in vivo detection of colonic barrier perturbation. Male Sprague-Dawley rats were dosed intracolonically via the rectum, using sodium caprate or ibuprofen as tool compounds to alter barrier integrity. Several potentially translational biomarkers and probe molecules related to permeability, inflammation or tissue damage were evaluated, using various analytical platforms, including immunoassays, targeted metabolomics and highly sensitive ultra-performance liquid chromatography-tandem mass spectrometry. Several markers were identified that allow early in vivo detection of colonic barrier integrity changes, before histopathological evidence of tissue damage. The most promising permeability markers identified were plasma fluorescein isothiocyanate-dextran 4000 and a lactulose/mannitol/sucralose mixture in urine. These markers showed maximum increases over 100-fold or approximately 10-50-fold, respectively. Intracolonic administration of the above probe molecules outperformed oral administration and inflammatory or other biomarkers, such as α 2 -macroglobulin, calprotectin, cytokines, prostaglandins and a panel of metabolic molecules to identify early and subtle changes in barrier integrity. However, optimal timing of probe administration and sample collection is important for all markers evaluated. Inclusion of these probe molecules in preclinical toxicity studies might aid in risk assessment and the design of a clinical biomarker plan, as several of these markers have translational potential. Copyright © 2018 John

Early Development and the Brain: Teaching Resources for Educators

ERIC Educational Resources Information Center

Gilkerson, Linda, Ed.; Klein, Rebecca, Ed.

2008-01-01

This nine-unit curriculum translates current scientific research on early brain development into practical suggestions to help early childhood professionals understand the reciprocal link between caregiving and brain development. The curriculum was created and extensively field-tested by the Erikson Institute Faculty Development Project on the…

YB-1 regulates tiRNA-induced Stress Granule formation but not translational repression

PubMed Central

Lyons, Shawn M.; Achorn, Chris; Kedersha, Nancy L.; Anderson, Paul J.; Ivanov, Pavel

2016-01-01

Stress-induced angiogenin (ANG)-mediated tRNA cleavage promotes a cascade of cellular events that starts with production of tRNA-derived stress-induced RNAs (tiRNAs) and culminates with enhanced cell survival. This stress response program relies on a subset tiRNAs that inhibit translation initiation and induce the assembly of stress granules (SGs), cytoplasmic ribonucleoprotein complexes with cytoprotective and pro-survival properties. SG-promoting tiRNAs bear oligoguanine motifs at their 5′-ends, assemble G-quadruplex-like structures and interact with the translational silencer YB-1. We used CRISPR/Cas9-based genetic manipulations and biochemical approaches to examine the role of YB-1 in tiRNA-mediated translational repression and SG assembly. We found that YB-1 directly binds to tiRNAs via its cold shock domain. This interaction is required for packaging of tiRNA-repressed mRNAs into SGs but is dispensable for tiRNA-mediated translational repression. Our studies reveal the functional role of YB-1 in the ANG-mediated stress response program. PMID:27174937

Translation and Foreign Language Teaching.

ERIC Educational Resources Information Center

Tinsley, Royal L., Jr.

Translators and teachers of foreign languages need each other: translators need formal academic training and recognition and teachers of foreign languages need students. Unfortunately, translators know only too well that most FL teachers are not competent translators, and FL Departments generally consider translation as an activity beneath the…

Integrated Knowledge Translation: illustrated with outcome research in mental health.

PubMed

Preyde, Michele; Carter, Jeff; Penney, Randy; Lazure, Kelly; Vanderkooy, John; Chevalier, Pat

2015-01-01

Through this article the authors present a case summary of the early phases of research conducted with an Integrated Knowledge Translation (iKT) approach utilizing four factors: research question, research approach, feasibility, and outcome. iKT refers to an approach for conducting research in which community partners, referred to as knowledge users, are engaged in the entire research process. In this collaborative approach, knowledge users and researchers jointly devise the entire research agenda beginning with the development of the research question(s), determination of a feasible research design and feasible methods, interpretation of the results, dissemination of the findings, and the translation of knowledge into practice or policy decisions. Engaging clinical or community partners in the research enterprise can enhance the utility of the research results and facilitate its uptake. This collaboration can be a complex arrangement and flexibility may be required to accommodate the various configurations that the collaboration can take. For example, the research question can be jointly determined and refined; however, one person must take the responsibility for orchestrating the project, including preparing the proposal and application to the Research Ethics Board. This collaborative effort also requires the simultaneous navigation of barriers and facilitators to the research enterprise. Navigating these elements becomes part of the conduct of research with the potential for rewarding results, including an enriched work experience for clinical partners and investigators. One practice implication is that iKT may be considered of great utility to service providers due to its field friendly nature.

[Health threats and health system crises. An approach to early warning and response. 2008 SESPAS Report].

PubMed

Simón Soria, Fernando; Guillén Enríquez, Francisco Javier

2008-04-01

The world is changing more and faster than ever before. New diseases are coming to light each year, controlled diseases are reemerging as potential threats, and natural or man-made disasters are increasingly affecting human health. The "International Health Regulations (2005)" reflect the changes in the response of public health to this new situation. Surveillance of specific diseases and predefined control measures have been replaced by surveillance of public health events of international concern and control measures adapted to each situation. The public health events of international interest are characterized by their seriousness, predictability, the risk of international spread and potential for travel or trade restrictions. The development of the European Early Warning and Response System in 1998 and the creation of the European Center for Disease Prevention and Control in 2005 demonstrate political commitment in Europe, with early detection of and response to public health threats. However, timely risk evaluation and response at a national level requires improved data digitalization and accessibility, automatic notification processes, data analysis and dissemination of information, the combination of information from multiple sources and adaptation of public health services. The autonomous regions in Spain are initiating this adaptation process, but interoperability between systems and the development of guidelines for a coordinated response should be steered by the National Interregional Health Council and coordinated by the Ministry of Health. Efficient early warning systems of health threats that allow for a timely response and reduce uncertainty about information would help to minimize the risk of public health crises. The profile of public health threats is nonspecific. Early detection of threats requires access to information from multiple sources and efficient risk assessment. Key factors for improving the response to public health threats are the

Tinkering with Translation: Protein Synthesis in Virus-Infected Cells

PubMed Central

Walsh, Derek; Mathews, Michael B.; Mohr, Ian

2013-01-01

Viruses are obligate intracellular parasites, and their replication requires host cell functions. Although the size, composition, complexity, and functions encoded by their genomes are remarkably diverse, all viruses rely absolutely on the protein synthesis machinery of their host cells. Lacking their own translational apparatus, they must recruit cellular ribosomes in order to translate viral mRNAs and produce the protein products required for their replication. In addition, there are other constraints on viral protein production. Crucially, host innate defenses and stress responses capable of inactivating the translation machinery must be effectively neutralized. Furthermore, the limited coding capacity of the viral genome needs to be used optimally. These demands have resulted in complex interactions between virus and host that exploit ostensibly virus-specific mechanisms and, at the same time, illuminate the functioning of the cellular protein synthesis apparatus. PMID:23209131

uAUG-mediated translational initiations are responsible for human mu opioid receptor gene expression

PubMed Central

Song, Kyu Young; Kim, Chun Sung; Hwang, Cheol Kyu; Choi, Hack Sun; Law, Ping-Yee; Wei, Li-Na; Loh, Horace H

2010-01-01

Abstract Mu opioid receptor (MOR) is the main site of interaction for major clinical analgesics, particularly morphine. MOR expression is regulated at the transcriptional and post-transcriptional levels. However, the protein expression of the MOR gene is relatively low and the translational control of MOR gene has not been well studied. The 5′-untranslated region (UTR) of the human MOR (OPRM1) mRNA contains four upstream AUG codons (uAUG) preceding the main translation initiation site. We mutated the four uAUGs individually and in combination. Mutations of the third uAUG, containing the same open reading frame, had the strongest inhibitory effect. The inhibitory effect caused by the third in-frame uAUG was confirmed by in vitro translation and receptor-binding assays. Toeprinting results showed that OPRM1 ribosomes initiated efficiently at the first uAUG, and subsequently re-initiated at the in-frame #3 uAUG and the physiological AUG site. This re-initiation resulted in negative expression of OPRM1 under normal conditions. These results indicate that re-initiation in MOR gene expression could play an important role in OPRM1 regulation. PMID:19438807

Ketamine Suppresses the Ventral Striatal Response to Reward Anticipation: A Cross-Species Translational Neuroimaging Study

PubMed Central

Francois, Jennifer; Grimm, Oliver; Schwarz, Adam J; Schweiger, Janina; Haller, Leila; Risterucci, Celine; Böhringer, Andreas; Zang, Zhenxiang; Tost, Heike; Gilmour, Gary; Meyer-Lindenberg, Andreas

2016-01-01

Convergent evidence implicates regional neural responses to reward anticipation in the pathogenesis of several psychiatric disorders, such as schizophrenia, where blunted ventral striatal responses to positive reward are observed in patients and at-risk populations. In vivo oxygen amperometry measurements in the ventral striatum in awake, behaving rats reveal reward-related tissue oxygen changes that closely parallel blood oxygen level dependent (BOLD) signal changes observed in human functional magnetic resonance imaging (fMRI), suggesting that a cross-species approach targeting this mechanism might be feasible in psychopharmacology. The present study explored modulatory effects of acute, subanaesthetic doses of ketamine—a pharmacological model widely used in psychopharmacological research, both preclinically and clinically—on ventral striatum activity during performance of a reward anticipation task in both species, using fMRI in humans and in vivo oxygen amperometry in rats. In a region-of-interest analysis conducted following a cross-over placebo and ketamine study in human subjects, an attenuated ventral striatal response during reward anticipation was observed following ketamine relative to placebo during performance of a monetary incentive delay task. In rats, a comparable attenuation of ventral striatal signal was found after ketamine challenge, relative to vehicle, in response to a conditioned stimulus that predicted delivery of reward. This study provides the first data in both species demonstrating an attenuating effect of acute ketamine on reward-related ventral striatal (O2) and fMRI signals. These findings may help elucidate a deeper mechanistic understanding of the potential role of ketamine as a model for psychosis, show that cross-species pharmacological experiments targeting reward signaling are feasible, and suggest this phenotype as a promising translational biomarker for the development of novel compounds, assessment of disease status, and

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

Theory of Test Translation Error

ERIC Educational Resources Information Center

Solano-Flores, Guillermo; Backhoff, Eduardo; Contreras-Nino, Luis Angel

2009-01-01

In this article, we present a theory of test translation whose intent is to provide the conceptual foundation for effective, systematic work in the process of test translation and test translation review. According to the theory, translation error is multidimensional; it is not simply the consequence of defective translation but an inevitable fact…

JavaScript DNA translator: DNA-aligned protein translations.

PubMed

Perry, William L

2002-12-01

There are many instances in molecular biology when it is necessary to identify ORFs in a DNA sequence. While programs exist for displaying protein translations in multiple ORFs in alignment with a DNA sequence, they are often expensive, exist as add-ons to software that must be purchased, or are only compatible with a particular operating system. JavaScript DNA Translator is a shareware application written in JavaScript, a scripting language interpreted by the Netscape Communicator and Internet Explorer Web browsers, which makes it compatible with several different operating systems. While the program uses a familiar Web page interface, it requires no connection to the Internet since calculations are performed on the user's own computer. The program analyzes one or multiple DNA sequences and generates translations in up to six reading frames aligned to a DNA sequence, in addition to displaying translations as separate sequences in FASTA format. ORFs within a reading frame can also be displayed as separate sequences. Flexible formatting options are provided, including the ability to hide ORFs below a minimum size specified by the user. The program is available free of charge at the BioTechniques Software Library (www.Biotechniques.com).

Real-Time Imaging Reveals Properties of Glutamate-Induced Arc/Arg 3.1 Translation in Neuronal Dendrites.

PubMed

Na, Youn; Park, Sungjin; Lee, Changhee; Kim, Dong-Kyu; Park, Joo Min; Sockanathan, Shanthini; Huganir, Richard L; Worley, Paul F

2016-08-03

The immediate early gene Arc (also Arg3.1) produces rapid changes in synaptic properties that are linked to de novo translation. Here we develop a novel translation reporter that exploits the rapid maturation and "flash" kinetics of Gaussia luciferase (Gluc) to visualize Arc translation. Following glutamate stimulation, discrete Arc-Gluc bioluminescent flashes representing sites of de novo translation are detected within 15 s at distributed sites in dendrites, but not spines. Flashes are episodic, lasting ∼20 s, and may be unitary or repeated at ∼minute intervals at the same sites. Analysis of flash amplitudes suggests they represent the quantal product of one or more polyribosomes, while inter-flash intervals appear random, suggesting they arise from a stochastic process. Surprisingly, glutamate-induced translation is dependent on Arc open reading frame. Combined observations support a model in which stalled ribosomes are reactivated to rapidly generate Arc protein. Copyright © 2016 Elsevier Inc. All rights reserved.

Abnormal early brain responses during visual search are evident in schizophrenia but not bipolar affective disorder.

PubMed

VanMeerten, Nicolaas J; Dubke, Rachel E; Stanwyck, John J; Kang, Seung Suk; Sponheim, Scott R

2016-01-01

People with schizophrenia show deficits in processing visual stimuli but neural abnormalities underlying the deficits are unclear and it is unknown whether such functional brain abnormalities are present in other severe mental disorders or in individuals who carry genetic liability for schizophrenia. To better characterize brain responses underlying visual search deficits and test their specificity to schizophrenia we gathered behavioral and electrophysiological responses during visual search (i.e., Span of Apprehension [SOA] task) from 38 people with schizophrenia, 31 people with bipolar disorder, 58 biological relatives of people with schizophrenia, 37 biological relatives of people with bipolar disorder, and 65 non-psychiatric control participants. Through subtracting neural responses associated with purely sensory aspects of the stimuli we found that people with schizophrenia exhibited reduced early posterior task-related neural responses (i.e., Span Endogenous Negativity [SEN]) while other groups showed normative responses. People with schizophrenia exhibited longer reaction times than controls during visual search but nearly identical accuracy. Those individuals with schizophrenia who had larger SENs performed more efficiently (i.e., shorter reaction times) on the SOA task suggesting that modulation of early visual cortical responses facilitated their visual search. People with schizophrenia also exhibited a diminished P300 response compared to other groups. Unaffected first-degree relatives of people with bipolar disorder and schizophrenia showed an amplified N1 response over posterior brain regions in comparison to other groups. Diminished early posterior brain responses are associated with impaired visual search in schizophrenia and appear to be specifically associated with the neuropathology of schizophrenia. Published by Elsevier B.V.

Exposure to dim light at night during early development increases adult anxiety-like responses.

PubMed

Borniger, Jeremy C; McHenry, Zachary D; Abi Salloum, Bachir A; Nelson, Randy J

2014-06-22

Early experiences produce effects that may persist throughout life. Therefore, to understand adult phenotype, it is important to investigate the role of early environmental stimuli in adult behavior and health. Artificial light at night (LAN) is an increasingly common phenomenon throughout the world. However, animals, including humans, evolved under dark night conditions. Many studies have revealed affective, immune, and metabolic alterations provoked by aberrant light exposure and subsequent circadian disruption. Pups are receptive to entraining cues from the mother and then light early during development, raising the possibility that the early life light environment may influence subsequent behavior. Thus, to investigate potential influences of early life exposure to LAN on adult phenotype, we exposed mice to dim (~5 lux; full spectrum white light) or dark (~0 lux) nights pre- and/or postnatally. After weaning at 3 weeks of age, all mice were maintained in dark nights until adulthood (9 weeks of age) when behavior was assessed. Mice exposed to dim light in early life increased anxiety-like behavior and fearful responses on the elevated plus maze and passive avoidance tests. These mice also displayed reduced growth rates, which ultimately normalized during adolescence. mRNA expression of brain derived neurotrophic factor (BDNF), a neurotrophin previously linked to early life environment and adult phenotype, was not altered in the prefrontal cortex or hippocampus by early life LAN exposure. Serum corticosterone concentrations were similar between groups at weaning, suggesting that early life LAN does not elicit a long-term physiologic stress response. Dim light exposure did not influence behavior on the open field, novel object, sucrose anhedonia, or forced swim tests. Our data highlight the potential deleterious consequences of low levels of light during early life to development and subsequent behavior. Whether these changes are due to altered maternal behavior

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

Introduction of translation stop codons into the viral glycoprotein gene in a fish DNA vaccine eliminates induction of protective immunity

USGS Publications Warehouse

Garver, K.A.; Conway, C.M.; Kurath, G.

2006-01-01

A highly efficacious DNA vaccine against a fish rhabdovirus, infectious hematopoietic necrosis virus (IHNV), was mutated to introduce two stop codons to prevent glycoprotein translation while maintaining the plasmid DNA integrity and RNA transcription ability. The mutated plasmid vaccine, denoted pIHNw-G2stop, when injected intramuscularly into fish at high doses, lacked detectable glycoprotein expression in the injection site muscle, and did not provide protection against lethal virus challenge 7 days post-vaccination. These results suggest that the G-protein itself is required to stimulate the early protective antiviral response observed after vaccination with the nonmutated parental DNA vaccine. ?? Springer Science+Business Media, Inc. 2006.

Integrating Bioethics into Clinical and Translational Science Research: A Roadmap

PubMed Central

Shapiro, Robyn S.; Layde, Peter M.

2008-01-01

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

Cambio : a file format translation and analysis application for the nuclear response emergency community.

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

Lasche, George P.

2009-10-01

Cambio is an application intended to automatically read and display any spectrum file of any format in the world that the nuclear emergency response community might encounter. Cambio also provides an analysis capability suitable for HPGe spectra when detector response and scattering environment are not well known. Why is Cambio needed: (1) Cambio solves the following problem - With over 50 types of formats from instruments used in the field and new format variations appearing frequently, it is impractical for every responder to have current versions of the manufacturer's software from every instrument used in the field; (2) Cambio convertsmore » field spectra to any one of several common formats that are used for analysis, saving valuable time in an emergency situation; (3) Cambio provides basic tools for comparing spectra, calibrating spectra, and isotope identification with analysis suited especially for HPGe spectra; and (4) Cambio has a batch processing capability to automatically translate a large number of archival spectral files of any format to one of several common formats, such as the IAEA SPE or the DHS N42. Currently over 540 analysts and members of the nuclear emergency response community worldwide are on the distribution list for updates to Cambio. Cambio users come from all levels of government, university, and commercial partners around the world that support efforts to counter terrorist nuclear activities. Cambio is Unclassified Unlimited Release (UUR) and distributed by internet downloads with email notifications whenever a new build of Cambio provides for new formats, bug fixes, or new or improved capabilities. Cambio is also provided as a DLL to the Karlsruhe Institute for Transuranium Elements so that Cambio's automatic file-reading capability can be included at the Nucleonica web site.« less

Early developmental gene regulation in Strongylocentrotus purpuratus embryos in response to elevated CO₂ seawater conditions.

PubMed

Hammond, LaTisha M; Hofmann, Gretchen E

2012-07-15

Ocean acidification, or the increased uptake of CO(2) by the ocean due to elevated atmospheric CO(2) concentrations, may variably impact marine early life history stages, as they may be especially susceptible to changes in ocean chemistry. Investigating the regulatory mechanisms of early development in an environmental context, or ecological development, will contribute to increased understanding of potential organismal responses to such rapid, large-scale environmental changes. We examined transcript-level responses to elevated seawater CO(2) during gastrulation and the initiation of spiculogenesis, two crucial developmental processes in the purple sea urchin, Strongylocentrotus purpuratus. Embryos were reared at the current, accepted oceanic CO(2) concentration of 380 microatmospheres (μatm), and at the elevated levels of 1000 and 1350 μatm, simulating predictions for oceans and upwelling regions, respectively. The seven genes of interest comprised a subset of pathways in the primary mesenchyme cell gene regulatory network (PMC GRN) shown to be necessary for the regulation and execution of gastrulation and spiculogenesis. Of the seven genes, qPCR analysis indicated that elevated CO(2) concentrations only had a significant but subtle effect on two genes, one important for early embryo patterning, Wnt8, and the other an integral component in spiculogenesis and biomineralization, SM30b. Protein levels of another spicule matrix component, SM50, demonstrated significant variable responses to elevated CO(2). These data link the regulation of crucial early developmental processes with the environment that these embryos would be developing within, situating the study of organismal responses to ocean acidification in a developmental context.

On Literal Translation of English Idioms

ERIC Educational Resources Information Center

Chen, Linli

2009-01-01

There are six translation tactics in translating English idioms into Chinese: literal translation, compensatory translation, free translation, explanational translation, borrowing, integrated approach. Each tactic should be reasonably employed in the process of translating, so as to keep the flavor of the original English idioms as well as to…

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

Evaluating cardiac risk: exposure response analysis in early clinical drug development.

PubMed

Grenier, Julie; Paglialunga, Sabina; Morimoto, Bruce H; Lester, Robert M

2018-01-01

The assessment of a drug's cardiac liability has undergone considerable metamorphosis by regulators since International Council for Harmonization of Technical Requirement for Pharmaceuticals for Human Use E14 guideline was introduced in 2005. Drug developers now have a choice in how proarrhythmia risk can be evaluated; the options include a dedicated thorough QT (TQT) study or exposure response (ER) modeling of intensive electrocardiogram (ECG) captured in early clinical development. The alternative approach of ER modeling was incorporated into a guidance document in 2015 as a primary analysis tool which could be utilized in early phase dose escalation studies as an option to perform a dedicated TQT trial. This review will describe the current state of ER modeling of intensive ECG data collected during early clinical drug development; the requirements with regard to the use of a positive control; and address the challenges and opportunities of this alternative approach to assessing QT liability.

Properties of cerebellar fastigial neurons during translation, rotation, and eye movements

NASA Technical Reports Server (NTRS)

Shaikh, Aasef G.; Ghasia, Fatema F.; Dickman, J. David; Angelaki, Dora E.

2005-01-01

The most medial of the deep cerebellar nuclei, the fastigial nucleus (FN), receives sensory vestibular information and direct inhibition from the cerebellar vermis. We investigated the signal processing in the primate FN by recording single-unit activities during translational motion, rotational motion, and eye movements. Firing rate modulation during horizontal plane translation in the absence of eye movements was observed in all non-eye-movement-sensitive cells and 26% of the pursuit eye-movement-sensitive neurons in the caudal FN. Many non-eye-movement-sensitive cells recorded in the rostral FN of three fascicularis monkeys exhibited convergence of signals from both the otolith organs and the semicircular canals. At low frequencies of translation, the majority of these rostral FN cells changed their firing rates in phase with head velocity rather than linear acceleration. As frequency increased, FN vestibular neurons exhibited a wide range of response dynamics with most cells being characterized by increasing phase leads as a function of frequency. Unlike cells in the vestibular nuclei, none of the rostral FN cells responded to rotational motion alone, without simultaneously exhibiting sensitivity to translational motion. Modulation during earth-horizontal axis rotation was observed in more than half (77%) of the neurons, although with smaller gains than during translation. In contrast, only 47% of the cells changed their firing rates during earth-vertical axis rotations in the absence of a dynamic linear acceleration stimulus. These response properties suggest that the rostral FN represents a main processing center of otolith-driven information for inertial motion detection and spatial orientation.

Comparative transcriptional and translational analysis of leptospiral outer membrane protein expression in response to temperature.

PubMed

Lo, Miranda; Cordwell, Stuart J; Bulach, Dieter M; Adler, Ben

2009-12-08

Leptospirosis is a global zoonosis affecting millions of people annually. Transcriptional changes in response to temperature were previously investigated using microarrays to identify genes potentially expressed upon host entry. Past studies found that various leptospiral outer membrane proteins are differentially expressed at different temperatures. However, our microarray studies highlighted a divergence between protein abundance and transcript levels for some proteins. Given the abundance of post-transcriptional expression control mechanisms, this finding highlighted the importance of global protein analysis systems. To complement our previous transcription study, we evaluated differences in the proteins of the leptospiral outer membrane fraction in response to temperature upshift. Outer membrane protein-enriched fractions from Leptospira interrogans grown at 30 degrees C or overnight upshift to 37 degrees C were isolated and the relative abundance of each protein was determined by iTRAQ analysis coupled with two-dimensional liquid chromatography and tandem mass spectrometry (2-DLC/MS-MS). We identified 1026 proteins with 99% confidence; 27 and 66 were present at elevated and reduced abundance respectively. Protein abundance changes were compared with transcriptional differences determined from the microarray studies. While there was some correlation between the microarray and iTRAQ data, a subset of genes that showed no differential expression by microarray was found to encode temperature-regulated proteins. This set of genes is of particular interest as it is likely that regulation of their expression occurs post-transcriptionally, providing an opportunity to develop hypotheses about the molecular dynamics of the outer membrane of Leptospira in response to changing environments. This is the first study to compare transcriptional and translational responses to temperature shift in L. interrogans. The results thus provide an insight into the mechanisms used by L

Rapid RNase L-driven arrest of protein synthesis in the dsRNA response without degradation of translation machinery.

PubMed

Donovan, Jesse; Rath, Sneha; Kolet-Mandrikov, David; Korennykh, Alexei

2017-11-01

Mammalian cells respond to double-stranded RNA (dsRNA) by activating a translation-inhibiting endoribonuclease, RNase L. Consensus in the field indicates that RNase L arrests protein synthesis by degrading ribosomal RNAs (rRNAs) and messenger RNAs (mRNAs). However, here we provide evidence for a different and far more efficient mechanism. By sequencing abundant RNA fragments generated by RNase L in human cells, we identify site-specific cleavage of two groups of noncoding RNAs: Y-RNAs, whose function is poorly understood, and cytosolic tRNAs, which are essential for translation. Quantitative analysis of human RNA cleavage versus nascent protein synthesis in lung carcinoma cells shows that RNase L stops global translation when tRNAs, as well as rRNAs and mRNAs, are still intact. Therefore, RNase L does not have to degrade the translation machinery to stop protein synthesis. Our data point to a rapid mechanism that transforms a subtle RNA cleavage into a cell-wide translation arrest. © 2017 Donovan et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

The Impact of Translators' Epistemological Beliefs and Gender on Their Translation Quality

ERIC Educational Resources Information Center

Araghizade, Elmira; Jadidi, Esmaeil

2016-01-01

This study aimed to determine the relationship between translators' epistemological beliefs and gender on their Persian-to-English translation quality. To do so, a group of 53 MA translation students both male and female were selected, through convenient sampling to participate in this study. For data collection two instruments were employed: 1…

The Translational Science Training Program at NIH: Introducing Early Career Researchers to the Science and Operation of Translation of Basic Research to Medical Interventions

ERIC Educational Resources Information Center

Gilliland, C. Taylor; Sittampalam, G. Sitta; Wang, Philip Y.; Ryan, Philip E.

2017-01-01

Translational science is an emerging field that holds great promise to accelerate the development of novel medical interventions. As the field grows, so does the demand for highly trained biomedical scientists to fill the positions that are being created. Many graduate and postdoctorate training programs do not provide their trainees with…

Exposure to Violence Predicting Cortisol Response During Adolescence and Early Adulthood: Understanding Moderating Factors

PubMed Central

Heinze, Justin E.; Miller, Alison L.; Stoddard, Sarah A.; Zimmerman, Marc A.

2014-01-01

Previous research on the association between violence and biological stress regulation has been largely cross-sectional, and has also focused on childhood. Using longitudinal data from a low-income, high-risk, predominantly African-American sample (n = 266; 57 % female), we tested hypotheses about the influence of cumulative exposure to violence during adolescence and early adulthood on cortisol responses in early adulthood. We found that cumulative exposure to violence predicted an attenuated cortisol response. Further, we tested whether sex, mothers’ support, or fathers’ support moderated the effect of exposure to violence on cortisol responses. We found that the effect of cumulative exposure to violence on cortisol was modified by sex; specifically, males exposed to violence exhibited a more attenuated response pattern. In addition, the effect of cumulative exposure to violence on cortisol was moderated by the presence of fathers’ support during adolescence. The findings contribute to a better understanding of how cumulative exposure to violence influences biological outcomes, emphasizing the need to understand sex and parental support as moderators of risk. PMID:24458765

Early vs. asymptotic growth responses of herbaceous plants to elevated CO[sub 2

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

Thomas, S.C.; Jasienski, M.; Bazzaz, F.A.

1999-07-01

Although many studies have examined the effects of elevated carbon dioxide on plant growth,'' the dynamics of growth involve at least two parameters, namely, an early rate of exponential size increase and an asymptotic size reached late in plant ontogeny. The common practice of quantifying CO[sub 2] responses as a single response ratio thus obscures two qualitatively distinct kinds of effects. The present experiment examines effects of elevated CO[sub 2] on both early and asymptotic growth parameters in eight C[sub 3] herbaceous plant species (Abutilon theophrasti, Cassia obtusifolia, Plantago major, Rumex crispus, Taraxacum officinale, Dactylis glomerata, Lolium multiflorum, and Panicummore » dichotomoflorum). Plants were grown for 118--172 d in a factorial design of CO[sub 2] (350 and 700 [micro]L/L) and plant density (individually grown vs. high-density monocultures) under edaphic conditions approximating those of coastal areas in Massachusetts. For Abutilon theophrasti, intraspecific patterns of plant response were also assessed using eight genotypes randomly sampled from a natural population and propagated as inbred lines.« less

A Practical Guide for Translators (Third Revised Edition). Topics in Translation 13.

ERIC Educational Resources Information Center

Samuelsson-Brown, Geoffrey

This third edition of a guide for translators contains more information than the second edition and looks at translation as a business as well as an occupation, focusing on marketing and quality control. It is designed for people with little or no practical experience with translation in a commercial environment. The 16 chapters examine these…

Coordinated Pulses of mRNA and of Protein Translation or Degradation Produce EGF-Induced Protein Bursts.

PubMed

Golan-Lavi, Roni; Giacomelli, Chiara; Fuks, Garold; Zeisel, Amit; Sonntag, Johanna; Sinha, Sanchari; Köstler, Wolfgang; Wiemann, Stefan; Korf, Ulrike; Yarden, Yosef; Domany, Eytan

2017-03-28

Protein responses to extracellular cues are governed by gene transcription, mRNA degradation and translation, and protein degradation. In order to understand how these time-dependent processes cooperate to generate dynamic responses, we analyzed the response of human mammary cells to the epidermal growth factor (EGF). Integrating time-dependent transcript and protein data into a mathematical model, we inferred for several proteins their pre-and post-stimulus translation and degradation coefficients and found that they exhibit complex, time-dependent variation. Specifically, we identified strategies of protein production and degradation acting in concert to generate rapid, transient protein bursts in response to EGF. Remarkably, for some proteins, for which the response necessitates rapidly decreased abundance, cells exhibit a transient increase in the corresponding degradation coefficient. Our model and analysis allow inference of the kinetics of mRNA translation and protein degradation, without perturbing cells, and open a way to understanding the fundamental processes governing time-dependent protein abundance profiles. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

A Temporal Locality-Aware Page-Mapped Flash Translation Layer

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

Kim, Youngjae; Gupta, Aayush; Urgaonkar, Bhuvan

2013-01-01

The poor performance of random writes has been a cause of major concern which needs to be addressed to better utilize the potential of flash in enterprise-scale environments. We examine one of the important causes of this poor performance: the design of the flash translation layer (FTL) which performs the virtual-to-physical address translations and hides the erase-before-write characteristics of flash. We propose a complete paradigm shift in the design of the core FTL engine from the existing techniques with our Demand-Based Flash Translation Layer (DFTL) which selectively caches page- level address mappings. Our experimental evaluation using FlashSim with realistic enterprise-scalemore » workloads endorses the utility of DFTL in enterprise-scale storage systems by demonstrating: 1) improved performance, 2) reduced garbage collection overhead and 3) better overload behavior compared with hybrid FTL schemes which are the most popular implementation methods. For example, a predominantly random-write dominant I/O trace from an OLTP application running at a large financial institution shows a 78% improvement in average response time (due to a 3-fold reduction in operations of the garbage collector), compared with the hybrid FTL scheme. Even for the well-known read-dominant TPC-H benchmark, for which DFTL introduces additional overheads, we improve system response time by 56%. Moreover, interestingly, when write-back cache on DFTL-based SSD is enabled, DFTL even outperforms the page-based FTL scheme, improving their response time by 72% in Financial trace.« less

Early changes in emotional processing as a marker of clinical response to SSRI treatment in depression.

PubMed

Godlewska, B R; Browning, M; Norbury, R; Cowen, P J; Harmer, C J

2016-11-22

Antidepressant treatment reduces behavioural and neural markers of negative emotional bias early in treatment and has been proposed as a mechanism of antidepressant drug action. Here, we provide a critical test of this hypothesis by assessing whether neural markers of early emotional processing changes predict later clinical response in depression. Thirty-five unmedicated patients with major depression took the selective serotonin re-uptake inhibitor (SSRI), escitalopram (10 mg), over 6 weeks, and were classified as responders (22 patients) versus non-responders (13 patients), based on at least a 50% reduction in symptoms by the end of treatment. The neural response to fearful and happy emotional facial expressions was assessed before and after 7 days of treatment using functional magnetic resonance imaging. Changes in the neural response to these facial cues after 7 days of escitalopram were compared in patients as a function of later clinical response. A sample of healthy controls was also assessed. At baseline, depressed patients showed greater activation to fear versus happy faces than controls in the insula and dorsal anterior cingulate. Depressed patients who went on to respond to the SSRI had a greater reduction in neural activity to fearful versus happy facial expressions after just 7 days of escitalopram across a network of regions including the anterior cingulate, insula, amygdala and thalamus. Mediation analysis confirmed that the direct effect of neural change on symptom response was not mediated by initial changes in depressive symptoms. These results support the hypothesis that early changes in emotional processing with antidepressant treatment are the basis of later clinical improvement. As such, early correction of negative bias may be a key mechanism of antidepressant drug action and a potentially useful predictor of therapeutic response.

Dutch translation of the ICMART-WHO revised glossary on ART terminology.

PubMed

De Neubourg, D; van Duijnhoven, N T L; Nelen, W L D M; D'Hooghe, T M

2012-01-01

A standardized set of definitions was needed in the field of medically assisted reproduction (MAR) to standardize and harmonize international data acquisition and to monitor the availability, efficacy, and safety of assisted reproductive technology (ART) worldwide. In order to provide accurate national data, the use of a terminology list which was composed and negotiated by the International Committee for Monitoring Assisted Reproductive Technology (ICMART) is essential, and a translation into Dutch was crucial for its implementation in Belgium and the Netherlands. The authors of the Dutch article translated the English publication that appeared simultaneously in Human Reproduction and Fertility and Sterility in 2009. A consensus text was obtained after evaluation by experts in the field of MAR both in the Netherlands and in Belgium and then by the board of the respective organizations of obstetrics and gynecology. It was then sent to the World Health Organization (WHO) for approval of publication. A translation into Dutch of the ICMART terminology of 2009 was obtained after consensus was reached on clinical and laboratory procedures, outcome variables, and birth. The availability and use of standardized terminology and its translation into Dutch will add to a more standardized communication between professionals responsible for the practice of ART and for those responsible for national, regional, and international registries. Copyright © 2012 S. Karger AG, Basel.

Ethanol, saccharin, and quinine: early ontogeny of taste responsiveness and intake.

PubMed

Kozlov, Andrey P; Varlinskaya, Elena I; Spear, Norman E

2008-02-01

Rat pups demonstrate high levels of immediate acceptance of ethanol during the first 2 weeks of postnatal life. Given that the taste of ethanol is most likely perceived by infant rats as a combination of sweet and bitter, high intake of ethanol early in ontogeny may be associated with age-related enhanced responsiveness to the sweet component of ethanol taste, as well as with ontogenetic decreases in sensitivity to its bitter component. Therefore, the present study compared responsiveness to ethanol and solutions with bitter (quinine) and sweet (saccharin) taste in terms of intake and palatability across the first 2 weeks of postnatal life. Characteristic patterns of responsiveness to 10% (v/v) ethanol, 0.1% saccharin, 0.2% quinine, and water in terms of taste reactivity and fluid intake were assessed in rat pups tested on postnatal day (P) 4, 9, or 12 using a new technique of on-line monitoring of fluid flow through a two-channel intraoral cannula. Taste reactivity included analysis of ingestive and aversive responses following six intraoral infusions of the test fluids. This taste reactivity probe was followed by the intake test, in which animals were allowed to voluntarily ingest fluids from an intraoral cannula. Pups of all ages showed more appetitive responses to saccharin and ethanol than to water or quinine. No age-related differences were apparent in taste responsiveness to saccharin and ethanol. However, the age-related pattern of ethanol intake drastically differed from that of saccharin. Intake of saccharin increased from P4 to P9 and decreased substantially by P12, whereas intake of ethanol gradually increased from P4 to P12. Intake of ethanol was significantly lower than intake of saccharin on P9, whereas P12 pups took in more ethanol than saccharin. The findings of the present study indicate ontogenetic dissociations between taste reactivity to ethanol and saccharin and intake of these solutions, and suggest that high acceptance of ethanol early in

[Historical Study of the Etymological Form and Translational Process of Gout (Tongfeng,)].

PubMed

Cho, Jae-Heung; Jung, Jae Young

2015-08-01

This study aims to address questions regarding the translation of 'gout' into 'tongfeng ()' in East Asia. To this end, the formation process of the origins, 'gout' from Western medicine and 'tongfeng' from Oriental medicine, and the translational process were investigated through the relevant records and literature dating from the 16th century on. Symptoms associated with gout were originally mentioned in ancient Egypt and various terminologies were used to refer to gout, such as podagra, cheiragra and gonogra. The word 'gout', which is derived from Latin, was used for the first time in the 13th century. The reason for this linguistic alteration is thought to be the need for a comprehensive term to cover the various terms for gout in symptomatic body parts, since it can occur concurrently in many joints. However, it took hundreds of years before gout was independently established as a medical term. In oriental medicine, terms describing diseases with features similar to gout include bibing (), lijiefeng (), baihufeng () and tongfeng (). Among them, the concept of 'tongfeng' has been established since the Jin and Yuan dynasties. The cause, prevention and various treatments for tongfeng were proposed throughout the Ming and Qing dynasties. The early translation of gout and tongfeng in East Asia, respectively, is estimated to have occurred in the 18th century. The first literature translating gout in China was 'An English and Chinese Vocabulary in the Court Dialect (yinghua yunfu lijie, )'. From the publication of this book until the late 19th century, gout was translated into an unfamiliar Chinese character 'Jiu feng jiao ()', likely because the translation was done mostly by foreign missionaries at the time, and they created a new word on the basis of Western medicine instead of researching and translating similar diseases in oriental medicine. In Japan, the first book translating gout was 'A Pocket Dictionary of the English and Japanese Language (Eiwa taiyaku

Subrenal capsule grafting technology in human cancer modeling and translational cancer research.

PubMed

Wang, Yuzhuo; Wang, Joy X; Xue, Hui; Lin, Dong; Dong, Xin; Gout, Peter W; Gao, Xin; Pang, Jun

2016-01-01

Patient-derived xenograft (PDX) cancer models with high fidelity are in great demand. While the majority of PDXs are grafted under the skin of immunodeficient mice, the Living Tumor Laboratory (LTL), using unique subrenal capsule grafting techniques, has successfully established more than 200 transplantable PDX models of various low to high grade human cancers. The LTL PDX models retain key biological properties of the original malignancies, including histopathological and molecular characteristics, tumor heterogeneity, metastatic ability, and response to treatment. The PDXs are stored frozen at early transplant generations in a resurrectable form, which eliminates continuous passaging in mice, thus ensuring maintenance of the high biologic and molecular fidelity and reproducibility of the models. The PDX models have been demonstrated to be powerful tools for (i) studies of cancer progression, metastasis and drug resistance, (ii) evidenced-based precision cancer therapy, (iii) preclinical drug efficacy testing and discovery of new anti-cancer drug candidates. To better provide resources for the research community, an LTL website (www.livingtumorlab.com) has been designed as a publicly accessible database which allows researchers to identify PDX models suitable for translational/preclinical cancer research. In summary, subrenal capsule grafting technology maximizes both tumor engraftment rate and retention of human cancer heterogeneity. Moreover, the method makes possible the recovery of PDXs from frozen stocks for further applications, thus providing a powerful platform for translational cancer research. Copyright © 2015 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Expression of glucocorticoid receptor and early growth response gene 1 during postnatal development of two inbred strains of mice exposed to early life stress.

PubMed

Navailles, Sylvia; Zimnisky, Ross; Schmauss, Claudia

2010-07-01

Early life stress can elicit profound changes in adult gene expression and behavior. One consequence of early life stress is a decreased expression of glucocorticoid receptors (GRs) in the frontal cortex and hippocampus. However, neither the time of onset nor the mechanism(s) leading to decreased GR expression during postnatal development are known. The present study used two inbred strains of mice that differ in their behavioral responsiveness to stress (Balb/c and C57Bl/6), exposed them to an established paradigm of early life stress (infant maternal separation), and measured their expression of frontal cortical and hippocampal GRs and the putative transcriptional activator of the GR gene, early growth response gene (egr)-1, at defined stages of postnatal development. In both strains, real-time RT-PCR experiments revealed that decreased expression of GR in adolescence and adulthood is, in fact, preceded by increased GR expression during early life stress exposure. Thus, the early life stress-induced disruption of the normal stress-hyporesponsive period during infancy is accompanied by increased GR expression. Moreover, chronic treatment with the antidepressant drug fluoxetine during adolescence or adulthood reversed the effect of early life stress on adult GR mRNA expression. In contrast to the strain-independent effect of early life stress on GR expression, however, changes in egr-1 expression occurred only in Balb/c mice, and unlike the biphasic developmental changes in GR mRNA expression, egr-1 mRNA was decreased throughout postnatal development. Moreover, there was no consistent overlap of anatomic regions affected by decreased GR and egr-1 protein expression. Thus, in Balb/c mice, changes in GR and egr-1 expression can independently contribute to the phenotypes resulting from early life stress exposure. These findings illustrate that the impact of early life stress on gene expression changes is modulated by the genetic background and that the persistent

Regenerative Endodontics: Barriers and Strategies for Clinical Translation

PubMed Central

Kim, Sahng G.; Zhou, Jian; Ye, Ling; Cho, Shoko; Suzuki, Takahiro; Fu, Susan Y.; Yang, Rujing; Zhou, Xuedong; Mao, Jeremy J.

2014-01-01

SYNOPSIS Despite a great deal of enthusiasm and effort, regenerative endodontics has encountered substantial challenges towards clinical translation. Recent adoption by the American Dental Association (ADA) of evoked pulp bleeding in immature permanent teeth is an important step for regenerative endodontics. However, there is no regenerative therapy for the majority of endodontic diseases. Simple recapitulation of cell therapy and tissue engineering strategies that are under development for other organ systems has not led to clinical translation in regeneration endodontics. Dental pulp stem cells may appear to be a priori choice for dental pulp regeneration. However, dental pulp stem cells may not be available in a patient who is in need of pulp regeneration. Even if dental pulp stem cells are available autologously or perhaps allogeneically, one must address a multitude of scientific, regulatory and commercialization barriers, and unless these issues are resolved, transplantation of dental pulp stem cells will remain a scientific exercise, rather than a clinical reality. Recent work using novel biomaterial scaffolds and growth factors that orchestrate the homing of host endogenous cells represents a departure from traditional cell transplantation approaches and may accelerate clinical translation. Given the functions and scale of dental pulp and dentin, regenerative endodontics is poised to become one of the early biological solutions in regenerative dental medicine. PMID:22835543

[About the accomplishment of translator in standardized English translation of TCM].

PubMed

He, Yang

2007-07-01

The accomplishment of translator in standardized English translation of TCM should be paid more attention, since it cannot but influence the foreign academic inter-communion and quality of transmission of TCM.

Designing a Measurement Framework for Response to Intervention in Early Childhood Programs

ERIC Educational Resources Information Center

McConnell, Scott R.; Wackerle-Hollman, Alisha K.; Roloff, Tracy A.; Rodriguez, Michael

2014-01-01

The overall architecture and major components of a measurement system designed and evaluated to support Response to Intervention (RTI) in the areas of language and literacy in early childhood programs are described. Efficient and reliable measurement is essential for implementing any viable RTI system, and implementing such a system in early…

The Modelling of Axially Translating Flexible Beams

NASA Astrophysics Data System (ADS)

Theodore, R. J.; Arakeri, J. H.; Ghosal, A.

1996-04-01

The axially translating flexible beam with a prismatic joint can be modelled by using the Euler-Bernoulli beam equation together with the convective terms. In general, the method of separation of variables cannot be applied to solve this partial differential equation. In this paper, a non-dimensional form of the Euler Bernoulli beam equation is presented, obtained by using the concept of group velocity, and also the conditions under which separation of variables and assumed modes method can be used. The use of clamped-mass boundary conditions leads to a time-dependent frequency equation for the translating flexible beam. A novel method is presented for solving this time dependent frequency equation by using a differential form of the frequency equation. The assume mode/Lagrangian formulation of dynamics is employed to derive closed form equations of motion. It is shown by using Lyapunov's first method that the dynamic responses of flexural modal variables become unstable during retraction of the flexible beam, which the dynamic response during extension of the beam is stable. Numerical simulation results are presented for the uniform axial motion induced transverse vibration for a typical flexible beam.

The herpes simplex virus 1 virion host shutoff protein enhances translation of viral late mRNAs by preventing mRNA overload.

PubMed

Dauber, Bianca; Saffran, Holly A; Smiley, James R

2014-09-01

We recently demonstrated that the virion host shutoff (vhs) protein, an mRNA-specific endonuclease, is required for efficient herpes simplex virus 1 (HSV-1) replication and translation of viral true-late mRNAs, but not other viral and cellular mRNAs, in many cell types (B. Dauber, J. Pelletier, and J. R. Smiley, J. Virol. 85:5363-5373, 2011, http://dx.doi.org/10.1128/JVI.00115-11). Here, we evaluated whether the structure of true-late mRNAs or the timing of their transcription is responsible for the poor translation efficiency in the absence of vhs. To test whether the highly structured 5' untranslated region (5'UTR) of the true-late gC mRNA is the primary obstacle for translation initiation, we replaced it with the less structured 5'UTR of the γ-actin mRNA. However, this mutation did not restore translation in the context of a vhs-deficient virus. We then examined whether the timing of transcription affects translation efficiency at late times. To this end, we engineered a vhs-deficient virus mutant that transcribes the true-late gene US11 with immediate-early kinetics (IEUS11-ΔSma). Interestingly, IEUS11-ΔSma showed increased translational activity on the US11 transcript at late times postinfection, and US11 protein levels were restored to wild-type levels. These results suggest that mRNAs can maintain translational activity throughout the late stage of infection if they are present before translation factors and/or ribosomes become limiting. Taken together, these results provide evidence that in the absence of the mRNA-destabilizing function of vhs, accumulation of viral mRNAs overwhelms the capacity of the host translational machinery, leading to functional exclusion of the last mRNAs that are made during infection. The process of mRNA translation accounts for a significant portion of a cell's energy consumption. To ensure efficient use of cellular resources, transcription, translation, and mRNA decay are tightly linked and highly regulated. However, during

Rapid and early α-fetoprotein and des-γ-carboxy prothrombin responses to initial arterial infusion chemotherapy predict treatment outcomes of advanced hepatocellular carcinoma

PubMed Central

OYAMA, KENJI; KODA, MASAHIKO; SUGIHARA, TAKAAKI; KISHINA, MANABU; MIYOSHI, KENICHI; OKAMOTO, TOSHIAKI; HODOTSUKA, MASANORI; FUJISE, YUKI; MATONO, TOMOMITSU; TOKUNAGA, SHIHO; OKAMOTO, KINYA; HOSHO, KEIKO; OKANO, JUNICHI; MURAWAKI, YOSHIKAZU

2015-01-01

The aim of the present study was to predict the effects of transarterial infusion (TAI) chemotherapy based on early changes in α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) in patients with advanced hepatocellular carcinoma (HCC). Seventy-four patients who underwent TAI with cisplatin, 5-fluorouracil, mitomycin C and epirubicin for advanced HCC were enrolled. Antitumor responses were evaluated 6 months after TAI. Rapid and early responses were defined as the ratio of AFP or DCP after 1 week and 1 month compared to baseline. A total of 5, 10, 17 and 42 patients had complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD), respectively. Early AFP response was significantly lower in the CR+PR compared to the SD+PD groups (P<0.01). The early DCP response was significantly lower in the CR+PR compared to the SD+PD. The sensitivity and specificity of rapid and early AFP responses in the CR+PR were 0.78 and 0.72, and 0.80 and 0.73, respectively, and those of rapid and early DCP responses were 0.67 and 0.65, and 0.77 and 0.71, respectively. The combination of AFP and DCP responses had higher specificity compared to AFP or DCP alone responses. Patients were divided into responder and non-responder groups to evaluate the prediction of survival outcome. Early responders of AFP, DCP and AFP+DCP, who were divided based on the cut-off values of CR+PR survived significantly longer than the non-responders (P<0.05). In conclusion, rapid or early responses of AFP and/or DCP levels 1 and 4 weeks after TAI chemotherapy helped to predict the treatment effects. PMID:26137283

Successfully accelerating translational research at an academic medical center: the University of Michigan-Coulter translational research partnership program.

PubMed

Pienta, Kenneth J

2010-12-01

Translational research encompasses the effective movement of new knowledge and discoveries into new approaches for prevention, diagnosis, and treatment of disease. There are many roadblocks to successful bench to bedside research, but few have received as much recent attention as the "valley of death". The valley of death refers to the lack of funding and support for research that moves basic science discoveries into diagnostics, devices, and treatments in humans, and is ascribed to be the result of companies unwilling to fund research development that may not result in a drug or device that will be utilized in the clinic and conversely, the fact that researchers have no access to the funding needed to carry out preclinical and early clinical development to demonstrate potential efficacy in humans. The valley of death also exists because bridging the translational gap is dependent on successfully managing an additional four risks: scientific, intellectual property, market, and regulatory. The University of Michigan (UM) has partnered with the Wallace H. Coulter Foundation (CF) to create a model providing an infrastructure to overcome these risks. This model is easily adoptable to other academic medical centers (AMCs). © 2010 Wiley Periodicals, Inc.

Girls' challenging social experiences in early adolescence predict neural response to rewards and depressive symptoms.

PubMed

Casement, Melynda D; Guyer, Amanda E; Hipwell, Alison E; McAloon, Rose L; Hoffmann, Amy M; Keenan, Kathryn E; Forbes, Erika E

2014-04-01

Developmental models of psychopathology posit that exposure to social stressors may confer risk for depression in adolescent girls by disrupting neural reward circuitry. The current study tested this hypothesis by examining the relationship between early adolescent social stressors and later neural reward processing and depressive symptoms. Participants were 120 girls from an ongoing longitudinal study of precursors to depression across adolescent development. Low parental warmth, peer victimization, and depressive symptoms were assessed when the girls were 11 and 12 years old, and participants completed a monetary reward guessing fMRI task and assessment of depressive symptoms at age 16. Results indicate that low parental warmth was associated with increased response to potential rewards in the medial prefrontal cortex (mPFC), striatum, and amygdala, whereas peer victimization was associated with decreased response to potential rewards in the mPFC. Furthermore, concurrent depressive symptoms were associated with increased reward anticipation response in mPFC and striatal regions that were also associated with early adolescent psychosocial stressors, with mPFC and striatal response mediating the association between social stressors and depressive symptoms. These findings are consistent with developmental models that emphasize the adverse impact of early psychosocial stressors on neural reward processing and risk for depression in adolescence. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

How Do English Translation Majors Use Translation Strategies? A Survey of the Iranian EFL Context

ERIC Educational Resources Information Center

Asgarian, Amir; Vefali, Gülsen Musayeva

2015-01-01

Translation language learning strategies, especially in relation to translation students, have not received adequate attention in the research to date. Therefore, the present study attempted to explore Iranian translation students' use of translation strategies, related beliefs, and academic achievement. It was a survey study involving…

The Practical Value of Translation Theory.

ERIC Educational Resources Information Center

Komissarov, Vilen

1985-01-01

Discusses why translation theory has had an inadequate impact on translation practice and gives specific examples of ways in which translation theory can provide the translator with general principles and methods of translating idioms. (SED)

How to create innovation by building the translation bridge from basic research into medicinal drugs: an industrial perspective

PubMed Central

2013-01-01

The global healthcare industry is undergoing substantial changes and adaptations to the constant decline of approved new medical entities. This decrease in internal research productivity is resulting in a major decline of patent-protected sales (patent cliff) of most of the pharmaceutical companies. Three major global adaptive trends as driving forces to cope with these challenges are evident: cut backs of internal research and development jobs in the western hemisphere (Europe and USA), following the market growth potential of Asia by building up internal or external research and development capabilities there and finally, ‘early innovation hunting’ with an increased focus on identifying and investing in very early innovation sources within academia and small start-up companies. Early innovation hunting can be done by different approaches: increased corporate funding, establishment of translational institutions to bridge innovation, increasing sponsored collaborations and formation of technology hunting groups for capturing very early scientific ideas and concepts. This emerging trend towards early innovation hunting demands special adaptations from both the pharmaceutical industry and basic researchers in academia to bridge the translation into new medicines which deliver innovative medicines that matters to the patient. This opinion article describes the different modalities of cross-fertilisation between basic university or publicly funded institutional research and the applied research and development activities within the pharmaceutical industry. Two key factors in this important translational bridge can be identified: preparation of both partnering organisations to open up for new and sometime disruptive ideas and creation of truly trust-based relationships between the different groups allowing long-term scientific collaborations while acknowledging that value-creating differences are an essential factor for successful collaboration building. PMID

How to create innovation by building the translation bridge from basic research into medicinal drugs: an industrial perspective.

PubMed

Germann, Paul G; Schuhmacher, Alexander; Harrison, Juan; Law, Ronald; Haug, Kevin; Wong, Gordon

2013-03-05

The global healthcare industry is undergoing substantial changes and adaptations to the constant decline of approved new medical entities. This decrease in internal research productivity is resulting in a major decline of patent-protected sales (patent cliff) of most of the pharmaceutical companies. Three major global adaptive trends as driving forces to cope with these challenges are evident: cut backs of internal research and development jobs in the western hemisphere (Europe and USA), following the market growth potential of Asia by building up internal or external research and development capabilities there and finally, 'early innovation hunting' with an increased focus on identifying and investing in very early innovation sources within academia and small start-up companies. Early innovation hunting can be done by different approaches: increased corporate funding, establishment of translational institutions to bridge innovation, increasing sponsored collaborations and formation of technology hunting groups for capturing very early scientific ideas and concepts. This emerging trend towards early innovation hunting demands special adaptations from both the pharmaceutical industry and basic researchers in academia to bridge the translation into new medicines which deliver innovative medicines that matters to the patient. This opinion article describes the different modalities of cross-fertilisation between basic university or publicly funded institutional research and the applied research and development activities within the pharmaceutical industry. Two key factors in this important translational bridge can be identified: preparation of both partnering organisations to open up for new and sometime disruptive ideas and creation of truly trust-based relationships between the different groups allowing long-term scientific collaborations while acknowledging that value-creating differences are an essential factor for successful collaboration building.

Translation: Aids, Robots, and Automation.

ERIC Educational Resources Information Center

Andreyewsky, Alexander

1981-01-01

Examines electronic aids to translation both as ways to automate it and as an approach to solve problems resulting from shortage of qualified translators. Describes the limitations of robotic MT (Machine Translation) systems, viewing MAT (Machine-Aided Translation) as the only practical solution and the best vehicle for further automation. (MES)

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

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

Negative electric susceptibility and magnetism from translational invariance and rotational invariance

NASA Astrophysics Data System (ADS)

Koo, Je Huan

2015-02-01

In this work we investigate magnetic effects in terms of the translational and rotational invariances of magnetisation. Whilst Landau-type diamagnetism originates from translational invariance, a new diamagnetism could result from rotational invariance. Translational invariance results in only conventional Landau-type diamagnetism, whereas rotational invariance can induce a paramagnetic susceptibility for localised electrons and also a new kind of diamagnetism that is specific to conducting electrons. In solids, the moving electron shows a paramagnetic susceptibility but the surrounding screening of electrons may produce a new diamagnetic response by Lenz's law, resulting in a total susceptibility that tends to zero. For electricity, similar behaviours are obtained. We also derive the DC-type negative electric susceptibility via two methods in analogy with Landau diamagnetism.

CO2 exposure as translational cross-species experimental model for panic.

PubMed

Leibold, N K; van den Hove, D L A; Viechtbauer, W; Buchanan, G F; Goossens, L; Lange, I; Knuts, I; Lesch, K P; Steinbusch, H W M; Schruers, K R J

2016-09-06

The current diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders are being challenged by the heterogeneity and the symptom overlap of psychiatric disorders. Therefore, a framework toward a more etiology-based classification has been initiated by the US National Institute of Mental Health, the research domain criteria project. The basic neurobiology of human psychiatric disorders is often studied in rodent models. However, the differences in outcome measurements hamper the translation of knowledge. Here, we aimed to present a translational panic model by using the same stimulus and by quantitatively comparing the same outcome measurements in rodents, healthy human subjects and panic disorder patients within one large project. We measured the behavioral-emotional and bodily response to CO2 exposure in all three samples, allowing for a reliable cross-species comparison. We show that CO2 exposure causes a robust fear response in terms of behavior in mice and panic symptom ratings in healthy volunteers and panic disorder patients. To improve comparability, we next assessed the respiratory and cardiovascular response to CO2, demonstrating corresponding respiratory and cardiovascular effects across both species. This project bridges the gap between basic and human research to improve the translation of knowledge between these disciplines. This will allow significant progress in unraveling the etiological basis of panic disorder and will be highly beneficial for refining the diagnostic categories as well as treatment strategies.

Outward bound: women translators and scientific travel writing, 1780-1800.

PubMed

Martin, Alison E

2016-04-01

As the Enlightenment drew to a close, translation had gradually acquired an increasingly important role in the international circulation and transmission of scientific knowledge. Yet comparatively little attention has been paid to the translators responsible for making such accounts accessible in other languages, some of whom were women. In this article I explore how European women cast themselves as intellectually enquiring, knowledgeable and authoritative figures in their translations. Focusing specifically on the genre of scientific travel writing, I investigate the narrative strategies deployed by women translators to mark their involvement in the process of scientific knowledge-making. These strategies ranged from rhetorical near-invisibility, driven by women's modest marginalization of their own public engagement in science, to the active advertisement of themselves as intellectually curious consumers of scientific knowledge. A detailed study of Elizabeth Helme's translation of the French ornithologist François le Vaillant's Voyage dans l'intérieur de l'Afrique [Voyage into the Interior of Africa] (1790) allows me to explore how her reworking of the original text for an Anglophone reading public enabled her to engage cautiously - or sometimes more openly - with questions regarding how scientific knowledge was constructed, for whom and with which aims in mind.

Sleep Moderates the Association Between Response Inhibition and Self-Regulation in Early Childhood

PubMed Central

Schumacher, Allyson M.; Miller, Alison L.; Watamura, Sarah E.; Kurth, Salome; Lassonde, Jonathan M.; LeBourgeois, Monique K.

2017-01-01

Early childhood is a time of rapid developmental changes in sleep, cognitive control processes, and the regulation of emotion and behavior. This experimental study examined sleep-dependent effects on response inhibition and self-regulation, as well as whether acute sleep restriction moderated the association between these processes. Preschool children (N = 19; 45.6 ± 2.2 months; 11 female) followed a strict sleep schedule for at least 3 days before each of 2 morning behavior assessments: baseline (habitual nap/night sleep) and sleep restriction (missed nap/delayed bedtime). Response inhibition was evaluated via a go/no-go task. Twelve self-regulation strategies were coded from videotapes of children while attempting an unsolvable puzzle. We then created composite variables representing adaptive and maladaptive self-regulation strategies. Although we found no sleep-dependent effects on response inhibition or self-regulation measures, linear mixed-effects regression showed that acute sleep restriction moderated the relationship between these processes. At baseline, children with better response inhibition were more likely to use adaptive self-regulation strategies (e.g., self-talk, alternate strategies), and those with poorer response inhibition showed increased use of maladaptive self-regulation strategies (e.g., perseveration, fidgeting); however, response inhibition was not related to self-regulation strategies following sleep restriction. Our results showing a sleep-dependent effect on the associations between response inhibition and self-regulation strategies indicate that adequate sleep facilitates synergy between processes supporting optimal social-emotional functioning in early childhood. Although replication studies are needed, findings suggest that sleep may alter connections between maturing emotional and cognitive systems, which have important implications for understanding risk for or resilience to developmental psychopathology. PMID:27652491

Sleep Moderates the Association Between Response Inhibition and Self-Regulation in Early Childhood.

PubMed

Schumacher, Allyson M; Miller, Alison L; Watamura, Sarah E; Kurth, Salome; Lassonde, Jonathan M; LeBourgeois, Monique K

2017-01-01

Early childhood is a time of rapid developmental changes in sleep, cognitive control processes, and the regulation of emotion and behavior. This experimental study examined sleep-dependent effects on response inhibition and self-regulation, as well as whether acute sleep restriction moderated the association between these processes. Preschool children (N = 19; 45.6 ± 2.2 months; 11 female) followed a strict sleep schedule for at least 3 days before each of 2 morning behavior assessments: baseline (habitual nap/night sleep) and sleep restriction (missed nap/delayed bedtime). Response inhibition was evaluated via a go/no-go task. Twelve self-regulation strategies were coded from videotapes of children while attempting an unsolvable puzzle. We then created composite variables representing adaptive and maladaptive self-regulation strategies. Although we found no sleep-dependent effects on response inhibition or self-regulation measures, linear mixed-effects regression showed that acute sleep restriction moderated the relationship between these processes. At baseline, children with better response inhibition were more likely to use adaptive self-regulation strategies (e.g., self-talk, alternate strategies), and those with poorer response inhibition showed increased use of maladaptive self-regulation strategies (e.g., perseveration, fidgeting); however, response inhibition was not related to self-regulation strategies following sleep restriction. Our results showing a sleep-dependent effect on the associations between response inhibition and self-regulation strategies indicate that adequate sleep facilitates synergy between processes supporting optimal social-emotional functioning in early childhood. Although replication studies are needed, findings suggest that sleep may alter connections between maturing emotional and cognitive systems, which have important implications for understanding risk for or resilience to developmental psychopathology.

Implementation of an alert and response system in Haiti during the early stage of the response to the cholera epidemic.

PubMed

Santa-Olalla, Patricia; Gayer, Michelle; Magloire, Roc; Barrais, Robert; Valenciano, Marta; Aramburu, Carmen; Poncelet, Jean Luc; Gustavo Alonso, Juan Carlos; Van Alphen, Dana; Heuschen, Florence; Andraghetti, Roberta; Lee, Robert; Drury, Patrick; Aldighieri, Sylvain

2013-10-01

The start of the cholera epidemic in Haiti quickly highlighted the necessity of the implementation of an Alert and Response (A&R) System to complement the existing national surveillance system. The national system had been able to detect and confirm the outbreak etiology but required external support to monitor the spread of cholera and coordinate response, because much of the information produced was insufficiently timely for real-time monitoring and directing of a rapid, targeted response. The A&R System was designed by the Pan American Health Organization/World Health Organization in collaboration with the Haiti Ministry of Health, and it was based on a network of partners, including any institution, structure, or individual that could identify, verify, and respond to alerts. The defined objectives were to (1) save lives through early detection and treatment of cases and (2) control the spread through early intervention at the community level. The operational structure could be broken down into three principle categories: (1) alert (early warning), (2) verification and assessment of the information, and (3) efficient and timely response in coordination with partners to avoid duplication. Information generated by the A&R System was analyzed and interpreted, and the qualitative information was critical in qualifying the epidemic and defining vulnerable areas, particularly because the national surveillance system reported incomplete data for more than one department. The A&R System detected a number of alerts unrelated to cholera and facilitated rapid access to that information. The sensitivity of the system and its ability to react quickly was shown in May of 2011, when an abnormal increase in alerts coming from several communes in the Sud-Est Department in epidemiological weeks (EWs) 17 and 18 were noted and disseminated network-wide and response activities were implemented. The national cholera surveillance system did not register the increase until EWs 21 and

Implementation of an Alert and Response System in Haiti during the Early Stage of the Response to the Cholera Epidemic

PubMed Central

Santa-Olalla, Patricia; Gayer, Michelle; Magloire, Roc; Barrais, Robert; Valenciano, Marta; Aramburu, Carmen; Poncelet, Jean Luc; Gustavo Alonso, Juan Carlos; Van Alphen, Dana; Heuschen, Florence; Andraghetti, Roberta; Lee, Robert; Drury, Patrick; Aldighieri, Sylvain

2013-01-01

The start of the cholera epidemic in Haiti quickly highlighted the necessity of the implementation of an Alert and Response (A&R) System to complement the existing national surveillance system. The national system had been able to detect and confirm the outbreak etiology but required external support to monitor the spread of cholera and coordinate response, because much of the information produced was insufficiently timely for real-time monitoring and directing of a rapid, targeted response. The A&R System was designed by the Pan American Health Organization/World Health Organization in collaboration with the Haiti Ministry of Health, and it was based on a network of partners, including any institution, structure, or individual that could identify, verify, and respond to alerts. The defined objectives were to (1) save lives through early detection and treatment of cases and (2) control the spread through early intervention at the community level. The operational structure could be broken down into three principle categories: (1) alert (early warning), (2) verification and assessment of the information, and (3) efficient and timely response in coordination with partners to avoid duplication. Information generated by the A&R System was analyzed and interpreted, and the qualitative information was critical in qualifying the epidemic and defining vulnerable areas, particularly because the national surveillance system reported incomplete data for more than one department. The A&R System detected a number of alerts unrelated to cholera and facilitated rapid access to that information. The sensitivity of the system and its ability to react quickly was shown in May of 2011, when an abnormal increase in alerts coming from several communes in the Sud-Est Department in epidemiological weeks (EWs) 17 and 18 were noted and disseminated network-wide and response activities were implemented. The national cholera surveillance system did not register the increase until EWs 21 and

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

Translating Classical Literature Into Swahili.

ERIC Educational Resources Information Center

Harries, Lyndon

1970-01-01

Translations generally result from two general situations: (1) where translation is the only means of understanding what has been written in another language, and (2) where a translation is an alternative and preferable means of understanding what has been written in a foreign language. In East Africa, so far as translations from English are…

Translation: Elements of a Craft.

ERIC Educational Resources Information Center

Heiderson, Mazin A.

An overview of the skills, techniques, tools, and compensation of language translators and interpreters is offered. It begins with a definition of translation and a brief history of translation in the western world. Basic principles of translation dating back to Roman writers are also outlined. A five-step process in producing a good translation…

Expression of putative immune response genes during early ontogeny in the coral Acropora millepora.

PubMed

Puill-Stephan, Eneour; Seneca, François O; Miller, David J; van Oppen, Madeleine J H; Willis, Bette L

2012-01-01

Corals, like many other marine invertebrates, lack a mature allorecognition system in early life history stages. Indeed, in early ontogeny, when corals acquire and establish associations with various surface microbiota and dinoflagellate endosymbionts, they do not efficiently distinguish between closely and distantly related individuals from the same population. However, very little is known about the molecular components that underpin allorecognition and immunity responses or how they change through early ontogeny in corals. Patterns in the expression of four putative immune response genes (apextrin, complement C3, and two CELIII type lectin genes) were examined in juvenile colonies of Acropora millepora throughout a six-month post-settlement period using quantitative real-time PCR (qPCR). Expression of a CELIII type lectin gene peaked in the fourth month for most of the coral juveniles sampled and was significantly higher at this time than at any other sampling time during the six months following settlement. The timing of this increase in expression levels of putative immune response genes may be linked to allorecognition maturation which occurs around this time in A. millepora. Alternatively, the increase may represent a response to immune challenges, such as would be involved in the recognition of symbionts (such as Symbiodinium spp. or bacteria) during winnowing processes as symbioses are fine-tuned. Our data, although preliminary, are consistent with the hypothesis that lectins may play an important role in the maturation of allorecognition responses in corals. The co-expression of lectins with apextrin during development of coral juveniles also raises the possibility that these proteins, which are components of innate immunity in other invertebrates, may influence the innate immune systems of corals through a common pathway or system. However, further studies investigating the expression of these genes in alloimmune-challenged corals are needed to further

Prenatal and Early Postnatal Odorant Exposure Heightens Odor-Evoked Mitral Cell Responses in the Mouse Olfactory Bulb

PubMed Central

2017-01-01

Abstract Early sensory experience shapes the anatomy and function of sensory circuits. In the mouse olfactory bulb (OB), prenatal and early postnatal odorant exposure through odorized food (food/odorant pairing) not only increases the volume of activated glomeruli but also increases the number of mitral and tufted cells (M/TCs) connected to activated glomeruli. Given the importance of M/TCs in OB output and in mediating lateral inhibitory networks, increasing the number of M/TCs connected to a single glomerulus may significantly change odorant representation by increasing the total output of that glomerulus and/or by increasing the strength of lateral inhibition mediated by cells connected to the affected glomerulus. Here, we seek to understand the functional impact of this long-term odorant exposure paradigm on the population activity of mitral cells (MCs). We use viral expression of GCaMP6s to examine odor-evoked responses of MCs following prenatal and early postnatal odorant exposure to two dissimilar odorants, methyl salicylate (MS) and hexanal, which are both strong activators of glomeruli on the dorsal OB surface. Previous work suggests that odor familiarity may decrease odor-evoked MC response in rodents. However, we find that early food-based odorant exposure significantly changes MC responses in an unexpected way, resulting in broad increases in the amplitude, number, and reliability of excitatory MC responses across the dorsal OB. PMID:28955723

Maternal buffering beyond glucocorticoids: impact of early life stress on corticolimbic circuits that control infant responses to novelty

PubMed Central

Howell, Brittany R.; McMurray, Matthew S.; Guzman, Dora B.; Nair, Govind; Shi, Yundi; McCormack, Kai M.; Hu, Xiaoping; Styner, Martin A.; Sanchez, Mar M.

2017-01-01

Maternal presence has a potent buffering effect on infant fear and stress responses in primates. We previously reported that maternal presence is not effective in buffering the endocrine stress response in infant rhesus monkeys reared by maltreating mothers. We have also reported that maltreating mothers show low maternal responsiveness and permissiveness/secure-base behavior. Although still not understood, it is possible that this maternal buffering effect is mediated, at least partially, through deactivation of amygdala response circuits when mothers are present. Here we studied rhesus monkey infants that differed in the quality of early maternal care to investigate how this early experience modulated maternal buffering effects on behavioral responses to novelty during the weaning period. We also examined the relationship between these behavioral responses and structural connectivity in one of the underlying regulatory neural circuits: amygdala-prefrontal pathways. Our findings suggest that infant exploration in a novel situation is predicted by maternal responsiveness and structural integrity of amygdala-prefrontal white matter depending on maternal presence (positive relationships when mother is absent). These results provide evidence that maternal buffering of infant behavioral inhibition is dependent on the quality of maternal care and structural connectivity of neural pathways that are sensitive to early life stress. PMID:27295326

Early Response to treatment in Eating Disorders: A Systematic Review and a Diagnostic Test Accuracy Meta-Analysis.

PubMed

Nazar, Bruno Palazzo; Gregor, Louise Kathrine; Albano, Gaia; Marchica, Angelo; Coco, Gianluca Lo; Cardi, Valentina; Treasure, Janet

2017-03-01

Early response to eating disorders treatment is thought to predict a later favourable outcome. A systematic review of the literature and meta-analyses examined the robustness of this concept. The criteria used across studies to define early response were summarised following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Diagnostic Test Accuracy methodology was used to estimate the size of the effect. Findings from 24 studies were synthesized and data from 14 studies were included in the meta-analysis. In Anorexia Nervosa, the odds ratio of early response predicting remission was 4.85(95%CI: 2.94-8.01) and the summary Area Under the Curve (AUC) = .77. In Bulimia Nervosa, the odds ratio was 2.75(95%CI:1.24-6.09) and AUC = .67. For Binge Eating Disorder, the odds ratio was 5.01(95%CI: 3.38-7.42) and AUC = .71. Early behaviour change accurately predicts later symptom remission for Anorexia Nervosa and Binge Eating Disorder but there is less predictive accuracy for Bulimia Nervosa. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Future Translational Applications From the Contemporary Genomics Era

PubMed Central

Fox, Caroline S.; Hall, Jennifer L.; Arnett, Donna K.; Ashley, Euan A.; Delles, Christian; Engler, Mary B.; Freeman, Mason W.; Johnson, Julie A.; Lanfear, David E.; Liggett, Stephen B.; Lusis, Aldons J.; Loscalzo, Joseph; MacRae, Calum A.; Musunuru, Kiran; Newby, L. Kristin; O’Donnell, Christopher J.; Rich, Stephen S.; Terzic, Andre

2016-01-01

The field of genetics and genomics has advanced considerably with the achievement of recent milestones encompassing the identification of many loci for cardiovascular disease and variable drug responses. Despite this achievement, a gap exists in the understanding and advancement to meaningful translation that directly affects disease prevention and clinical care. The purpose of this scientific statement is to address the gap between genetic discoveries and their practical application to cardiovascular clinical care. In brief, this scientific statement assesses the current timeline for effective translation of basic discoveries to clinical advances, highlighting past successes. Current discoveries in the area of genetics and genomics are covered next, followed by future expectations, tools, and competencies for achieving the goal of improving clinical care. PMID:25882488

Translating Addictions Research into Evidence-based Practice: the Polaris CD Outcomes Management System