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At least 73 records · Page 4

Archaeal translation initiation revisited: the initiation factor 2 and eukaryotic initiation factor 2B alpha-beta-delta subunit families

As the amount of available sequence data increases, it becomes apparent that our understanding of translation initiation is far from comprehensive and that prior conclusions concerning the origin of the process are wrong. Contrary to earlier conclusions, key elements of translation initiation originated at the Universal Ancestor stage, for homologous counterparts exist in all three primary taxa. Herein, we explore the evolutionary relationships among the components of bacterial initiation factor 2 (IF-2) and eukaryotic IF-2 (eIF-2)/eIF-2B, i.e., the initiation factors involved in introducing the initiator tRNA into the translation mechanism and performing the first step in the peptide chain elongation cycle. All Archaea appear to posses a fully functional eIF-2 molecule, but they lack the associated GTP recycling function, eIF-2B (a five-subunit molecule). Yet, the Archaea do posses members of the gene family defined by the (related) eIF-2B subunits alpha, beta, and delta, although these are not specifically related to any of the three eukaryotic subunits. Additional members of this family also occur in some (but by no means all) Bacteria and even in some eukaryotes. The functional significance of the other members of this family is unclear and requires experimental resolution. Similarly, the occurrence of bacterial IF-2-like molecules in all Archaea and in some eukaryotes further complicates the picture of translation initiation. Overall, these data lend further support to the suggestion that the rudiments of translation initiation were present at the Universal Ancestor stage.

NASA Discipline Exobiology↗

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

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.

Non-NASA Center↗

Universal Reconfigurable Translator Module (URTM) Final Report

This report describes the Universal Reconfigurable Translation Module, or URTM. The URTM was developed by Sigma Space Corporation for NASA in order to translate specific serial protocols, both logically and physically. At present, the prototype configuration has targeted MIL-STD-1553B (RT and BC), IEEE 1394b (Firewire), and ECSS-E-50-12A (SpaceWire). The objectives of this program were to study the feasibility of a configurable URTM to translate serial link data as might be used in a space-flight mission and to design, develop, document, and deliver an engineering prototype model of the URTM with a path to spaceflight. By simply connecting two of the three Physical Interface Modules (PIM) on either end of the RPTM (Reconfigurable Protocol Translator Module), the URTM then self configures via a library of interface translation functions, thereby allowing the two data links to communicate seamlessly.

Leventhal, Edward↗

Translational Cellular Research on the International Space Station

The emerging field of Translational Research aims to coalesce interdisciplinary findings from basic science for biomedical applications. To complement spaceflight research using human subjects, translational studies can be designed to address aspects of space-related human health risks and help develop countermeasures to prevent or mitigate them, with therapeutical benefits for analogous conditions experienced on Earth. Translational research with cells and model organisms is being conducted onboard the International Space Station (ISS) in connection with various human systems impacted by spaceflight, such as the cardiovascular, musculoskeletal, and immune systems. Examples of recent cell-based translational investigations on the ISS include the following. The JAXA investigation Cell Mechanosensing seeks to identify gravity sensors in skeletal muscle cells to develop muscle atrophy countermeasures by analyzing tension fluctuations in the plasma membrane, which changes the expression of key proteins and genes. Earth applications of this study include therapeutic approaches for some forms of muscular dystrophy, which appear to parallel aspects of muscle wasting in space. Spheroids is an ESA investigation examining the system of endothelial cells lining the inner surface of all blood vessels in terms of vessel formation, cellular proliferation, and programmed cell death, because injury to the endothelium has been implicated as underpinning various cardiovascular and musculoskeletal problems arising during spaceflight. Since endothelial cells are involved in the functional integrity of the vascular wall, this research has applications to Earth diseases such as atherosclerosis, diabetes, and hypertension. The goal of the T-Cell Activation in Aging NASA investigation is to understand human immune system depression in microgravity by identifying gene expression patterns of candidate molecular regulators, which will provide further insight into factors that may play a critical role in immune function loss during aging. In addition, Omics investigations with cells have synergistic applications ranging from the evaluation of pharmacological countermeasures to drug discovery. Thus, cell-based translational research onboard the ISS is bidirectionally bridging cutting-edge cellular and molecular approaches with space bioastronautics and human health methodologies on Earth.

Love, John↗

Testing and Maturing a Mass Translating Mechanism for a Deep Space CubeSat

Near Earth Asteroid (NEA) Scout is a deep space satellite set to launch aboard NASA’s Exploration Mission 1. The spacecraft fits within a CubeSat standard 6U (about 300 x 200 x 100 mm) and is designed to travel 1 AU over a 2.5 year mission to observe NEA VG 1991. The spacecraft will use an 86 square meter solar sail to maneuver from lunar orbit to the NEA. One of the critical mechanisms aboard NEA Scout, the Active Mass Translator (AMT), has gone through rigorous design and test cycles since its conception in July of 2015. The AMT is a two-axis translation table required to balance the spacecraft’s center of mass (CM) and solar sail center of pressure (CP) while also trimming disturbance torque created by off-nominal sail conditions. The AMT has very limited mass and volume requirements, but is still required to deliver a large translation range—about 160 x 68 mm—at sub mm accuracy and precision. The system must accommodate and protect a shielded wire harness and coax cables during translation. Lastly, the system has been constrained to operate in complete exposure to space with limited power and data budgets for mechanical and thermal needs. The NEA Scout team has developed and carried out a rigorous test suite for the prototype and engineering development unit (EDU). These tests uncovered numerous design failures and led to many failure investigations and iteration cycles. This paper will site each discovery and discuss at length the most surprising and difficult failures to date as the NEA Scout AMT moved through functional, random vibration, thermal vacuum, harnessing, and design life verification testing. A paper was previously presented at the 43rd Aerospace Mechanisms Symposia entitled, “Development of a High Performance, Low Profile Translation Table with Wire Feedthrough for a Deep Space CubeSat”. This paper will make note of specific lessons learned from the test activities: testing ideologies for high-risk missions, thermal mitigation design for small mechanisms, non-flight qualified stepper motor accommodation, harnessing volume allocation/design, and ground testing of mechanisms developed for zero-g environments.

Few, Alex↗

Neuronal RNA granules: a link between RNA localization and stimulation-dependent translation

RNA granules are a macromolecular structure observed in neurons, where they serve as motile units that translocate mRNAs. Isolated RNA granules are highly enriched in Staufen protein and ultrastructurally contain densely packed clusters of ribosomes. With depolarization, many mRNAs, including those involved in plasticity, rapidly shift from the RNA granule fraction to polysomes. Depolarization reorganizes granules and induces a less compact organization of their ribosomes. RNA granules are not translationally competent, as indicated by the failure to incorporate radioactive amino acids and the absence of eIF4E, 4G, and tRNAs. We concluded that RNA granules are a local storage compartment for mRNAs under translational arrest but are poised for release to actively translated pools. Local release of mRNAs and ribosomes from granules may serve as a macromolecular mechanism linking RNA localization to translation and synaptic plasticity.

NASA Discipline Neuroscience↗

Gene activity during germination of spores of the fern, Onoclea sensibilis. Cell-free translation analysis of mRNA of spores and the effect of alpha-amanitin on spore germination

Poly(A)-RNA fractions of dormant, dark-imbibed (non-germinating) and photoinduced (germinating) spores of Onoclea sensibilis were poor templates in the rabbit reticulocyte lysate protein synthesizing system, but the translational efficiency of poly(A)+RNA was considerably higher than that of unfractionated RNA. Poly(A)+RNA isolated from photoinduced spores had a consistently higher translational efficiency than poly(A)+RNA from dark-imbibed spores. Analysis of the translation products by one-dimensional polyacrylamide gel electrophoresis showed no qualitative differences in the mRNA populations of dormant, dark-imbibed, and photoinduced spores. However, poly(A)+RNA from dark-imbibed spores appeared to encode in vitro fewer detectable polypeptides at a reduced intensity than photoinduced spores. A DNA clone encoding the large subunit of maize ribulose bisphosphate carboxylase hybridized at strong to moderate intensity to RNA isolated from dark-imbibed spores, indicating the absence of mRNA degradation. Although alpha-amanitin did not inhibit the germination of spores, the drug prevented the elongation of the rhizoid and protonemal initial with a concomitant effect on the synthesis of poly(A)+RNA. These results are consistent with the view that some form of translational control involving stored mRNA operates during dark-imbibition and photoinduced germination of spores.

NASA Discipline Number 29-20↗

Insights into the molecular mechanism of translation inhibition by the ribosome-targeting antibiotic thermorubin

Thermorubin (THR) is an aromatic anthracenopyranone antibiotic active against both Gram-positive and Gram-negative bacteria. It is known to bind to the 70S ribosome at the intersubunit bridge B2a and was thought to inhibit factor-dependent initiation of translation and obstruct the accommodation of tRNAs into the A site. Here, we show that thermorubin causes ribosomes to stall in vivo and in vitro at internal and termination codons, thereby allowing the ribosome to initiate protein synthesis and translate at least a few codons before stalling. Our biochemical data show that THR affects multiple steps of translation elongation with a significant impact on the binding stability of the tRNA in the A site, explaining premature cessation of translation. Our high-resolution crystal and cryo-EM structures of the 70S-THR complex show that THR can co-exist with P- and A-site tRNAs, explaining how ribosomes can elongate in the presence of the drug. Remarkable is the ability of THR to arrest ribosomes at the stop codons. Our data suggest that by causing structural re-arrangements in the decoding center, THR interferes with the accommodation of tRNAs or release factors into the ribosomal A site.

59 BASIC BIOLOGICAL SCIENCES↗

Crystal structure of a cap-independent translation enhancer RNA

In eukaryotic messenger RNAs, the 5' cap structure binds to the translation initiation factor 4E to facilitate early stages of translation. Although many plant viruses lack the 5' cap structure, some contain cap-independent translation elements (CITEs) in their 3' untranslated region. The PTE (Panicum mosaic virus translation element) class of CITEs contains a G-rich asymmetric bulge and a C-rich helical junction that were proposed to interact via formation of a pseudoknot. SHAPE analysis of PTE homologs reveals a highly reactive guanosine residue within the G-rich region proposed to mediate eukaryotic initiation factor 4E (eIF4E) recognition. Here we have obtained the crystal structure of the PTE from Pea enation mosaic virus 2 (PEMV 2 ) RNA in complex with our structural chaperone, Fab BL3–6. The structure reveals that the G-rich and C-rich regions interact through a complex network of interactions distinct from those expected for a pseudoknot. The motif, which contains a short parallel duplex, provides a structural mechanism for how the guanosine is extruded from the core stack to enable eIF4E recognition. Homologous PTE elements harbor a G-rich bulge and a three-way junction and exhibit covariation at crucial positions, suggesting that the PEMV 2 tertiary architecture is conserved among these homologs.

59 BASIC BIOLOGICAL SCIENCES↗

Biolink Model: A universal schema for knowledge graphs in clinical, biomedical, and translational science

Abstract Within clinical, biomedical, and translational science, an increasing number of projects are adopting graphs for knowledge representation. Graph‐based data models elucidate the interconnectedness among core biomedical concepts, enable data structures to be easily updated, and support intuitive queries, visualizations, and inference algorithms. However, knowledge discovery across these “knowledge graphs” (KGs) has remained difficult. Data set heterogeneity and complexity; the proliferation of ad hoc data formats; poor compliance with guidelines on findability, accessibility, interoperability, and reusability; and, in particular, the lack of a universally accepted, open‐access model for standardization across biomedical KGs has left the task of reconciling data sources to downstream consumers. Biolink Model is an open‐source data model that can be used to formalize the relationships between data structures in translational science. It incorporates object‐oriented classification and graph‐oriented features. The core of the model is a set of hierarchical, interconnected classes (or categories) and relationships between them (or predicates) representing biomedical entities such as gene, disease, chemical, anatomic structure, and phenotype. The model provides class and edge attributes and associations that guide how entities should relate to one another. Here, we highlight the need for a standardized data model for KGs, describe Biolink Model, and compare it with other models. We demonstrate the utility of Biolink Model in various initiatives, including the Biomedical Data Translator Consortium and the Monarch Initiative, and show how it has supported easier integration and interoperability of biomedical KGs, bringing together knowledge from multiple sources and helping to realize the goals of translational science.

60 APPLIED LIFE SCIENCES↗

Robust T cell activation requires an eIF3-driven burst in T cell receptor translation

Activation of T cells requires a rapid surge in cellular protein synthesis. However, the role of translation initiation in the early induction of specific genes remains unclear. Here, we show human translation initiation factor eIF3 interacts with select immune system related mRNAs including those encoding the T cell receptor (TCR) subunits TCRA and TCRB. Binding of eIF3 to the TCRA and TCRB mRNA 3’-untranslated regions (3’-UTRs) depends on CD28 coreceptor signaling and regulates a burst in TCR translation required for robust T cell activation. Use of the TCRA or TCRB 3’-UTRs to control expression of an anti-CD19 chimeric antigen receptor (CAR) improves the ability of CAR-T cells to kill tumor cells in vitro. These results identify a new mechanism of eIF3-mediated translation control that can aid T cell engineering for immunotherapy applications.

59 BASIC BIOLOGICAL SCIENCES↗

GOAL-to-HAL translation study

This report deals with the feasibility, problems, solutions, and mapping of a GOAL language to HAL language translator. Ground Operations Aerospace Language, or GOAL, is a test-oriented higher order language developed by the John F. Kennedy Space Center to be used in checkout and launch of the space shuttle. HAL is a structured higher order language developed by the Johnson Space Center to be used in writing the flight software for the onboard shuttle computers. Since the onboard computers will extensively support ground checkout of the space shuttle, and since these computers and the software development facilities on the ground use the HAL language as baseline, the translation of GOAL to HAL becomes significant. The issue of feasibility was examined and it was found that a GOAL to HAL translator is feasible. Special problems are identified and solutions proposed. Finally, examples of translation are provided for each category of complete GOAL statement.

Flanders, J. H.↗

The international aerospace industry - New challenges and opportunities for translation suppliers

Attention is given to the recent trend toward internationalization in the aerospace industry and its effects on commercial and governmental translation programs. The aerospace industry, once dominated by organizations from a small number of countries, is now widely international in scope. In effect, there has been in increase in the demand for translations from German, Japanese, Chinese, French and Spanish source material while that for translation from Russian source material has remained constant. The impact of the Challenger disaster on aerospace translation programs is discussed as well as the impact of international participation in Space Station research.

Rowe, T.↗

JTEC panel report on machine translation in Japan

The goal of this report is to provide an overview of the state of the art of machine translation (MT) in Japan and to provide a comparison between Japanese and Western technology in this area. The term 'machine translation' as used here, includes both the science and technology required for automating the translation of text from one human language to another. Machine translation is viewed in Japan as an important strategic technology that is expected to play a key role in Japan's increasing participation in the world economy. MT is seen in Japan as important both for assimilating information into Japanese as well as for disseminating Japanese information throughout the world. Most of the MT systems now available in Japan are transfer-based systems. The majority of them exploit a case-frame representation of the source text as the basis of the transfer process. There is a gradual movement toward the use of deeper semantic representations, and some groups are beginning to look at interlingua-based systems.

Carbonell, Jaime↗

A Low Mass Translation Mechanism for Planetary FTIR Spectrometry using an Ultrasonic Piezo Linear Motor

One of the key components of a Fourier Transform Infrared Spectrometer (FTIR) is the linear translation stage used to vary the optical path length between the two arms of the interferometer. This translation mechanism must produce extremely constant velocity motion across its entire range of travel to allow the instrument to attain high signal-to-noise ratio and spectral resolving power. A new spectrometer is being developed at the Jet Propulsion Laboratory under NASA s Planetary Instrument Definition and Development Program (PIDDP). The goal of this project is to build upon existing spaceborne FTIR spectrometer technology to produce a new instrument prototype that has drastically superior spectral resolution and substantially lower mass, making it feasible for planetary exploration. In order to achieve these goals, Alliance Spacesystems, Inc. (ASI) has developed a linear translation mechanism using a novel ultrasonic piezo linear motor in conjunction with a fully kinematic, fault tolerant linear rail system. The piezo motor provides extremely smooth motion, is inherently redundant, and is capable of producing unlimited travel. The kinematic rail uses spherical Vespel(R). rollers and bushings, which eliminates the need for wet lubrication, while providing a fault tolerant platform for smooth linear motion that will not bind under misalignment or structural deformation. This system can produce velocities from 10 - 100 mm/s with less than 1% velocity error over the entire 100-mm length of travel for a total mechanism mass of less than 850 grams. This system has performed over half a million strokes under vacuum without excessive wear or degradation in performance. This paper covers the design, development, and testing of this linear translation mechanism as part of the Planetary Atmosphere Occultation Spectrometer (PAOS) instrument prototype development program.

Heverly, Matthew↗

Rapid motor learning in the translational vestibulo-ocular reflex

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

Non-NASA Center↗

MEMS Micro-Translation Device with Improved Linear Travel Capability

A microscopic translation device for a microelectromechanical system includes a pair of linear stator assemblies disposed in spaced relation to define an elongate channel. Each assembly is formed by a plurality of stators arranged in a row along the channel. A shuttle member is disposed between the stator assemblies for translating movement along the channel. The shuttle member includes a plurality of rotors extending outwardly from opposite sides. The shuttle is grounded through the stator assemblies and includes a mounting area for an object to be translated. Electrical lines are individually connected to alternate stators of a plurality of groups of the stators. A current supply sequentially supplies current through the electrical lines to the alternate stators so as to effect charging of the stators in a predetermined sequence. This produces a tangential capacitive force that causes translation of the shuttle.

Abushagur, Mustafa A. G.↗

Spatial Cognitive Performance During Adaptation to Conflicting Tilt-Translation Stimuli as a Sensorimotor Spaceflight Analog

The need to resolve new patterns of sensory feedback in altered gravitoinertial environments requires cognitive processes to develop appropriate reference frames for spatial orientation awareness. The purpose of this study was to examine deficits in spatial cognitive performance during adaptation to conflicting tilt-translation stimuli. Fourteen subjects were tilted within a lighted enclosure that simultaneously translated at one of 3 frequencies. Tilt and translation motion was synchronized to maintain the resultant gravitoinertial force aligned with the longitudinal body axis, resulting in a mismatch analogous to spaceflight in which the canals and vision signal tilt while the otoliths do not. Changes in performance on different spatial cognitive tasks were compared 1) without motion, 2) with tilt motion alone (pitch at 0.15, 0.3 and 0.6 Hz or roll at 0.3 Hz), and 3) with conflicting tilt-translation motion. The adaptation paradigm was continued for up to 30 min or until the onset of nausea. The order of the adaptation conditions were counter-balanced across 4 different test sessions. There was a significant effect of stimulus frequency on both motion sickness and spatial cognitive performance. Only 3 of 14 were able to complete the full 30 min protocol at 0.15 Hz, while 7 of 14 completed 0.3 Hz and 13 of 14 completed 0.6 Hz. There were no changes in simple visual-spatial cognitive tests, e.g., mental rotation or match-to-sample. There were significant deficits during 0.15 Hz adaptation in both accuracy and reaction time during a spatial reference task in which subjects are asked to identify a match of a 3D reoriented cube assemblage. Our results are consistent with antidotal reports of cognitive impairment that are common during sensorimotor adaptation with G-transitions. We conclude that these cognitive deficits stem from the ambiguity of spatial reference frames for central processing of inertial motion cues.

Kayanickupuram, A. J.↗