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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records

Human γ-glutamyl transpeptidase 1: Structures of the free enzyme, inhibitor-bound tetrahedral transition states, and glutamate-bound enzyme reveal novel movement within the active site during catalysis [Human gamma-glutamyl transpeptidase: Inhibitor binding and movement within the active site]

γ-Glutamyl transpeptidase 1 (GGT1) is a cell surface, N-terminal nucleophile hydrolase that cleaves glutathione and other γ-glutamyl compounds. GGT1 expression is essential in cysteine homeostasis, and its induction has been implicated in the pathology of asthma, reperfusion injury, and cancer. In this study, we report four new crystal structures of human GGT1 (hGGT1) that show conformational changes within the active site as the enzyme progresses from the free enzyme to inhibitor-bound tetrahedral transition states and finally to the glutamate-bound structure prior to the release of this final product of the reaction. The structure of the apoenzyme shows flexibility within the active site. The serine-borate-bound hGGT1 crystal structure demonstrates that serine-borate occupies the active site of the enzyme, resulting in an enzyme-inhibitor complex that replicates the enzyme's tetrahedral intermediate/transition state. The structure of GGsTop-bound hGGT1 reveals its interactions with the enzyme and why neutral phosphonate diesters are more potent inhibitors than monoanionic phosphonates. These structures are the first structures for any eukaryotic GGT that include a molecule in the active site covalently bound to the catalytic Thr-381. The glutamate-bound structure shows the conformation of the enzyme prior to release of the final product and reveals novel information regarding the displacement of the main chain atoms that form the oxyanion hole and movement of the lid loop region when the active site is occupied. Lastly,tThese data provide new insights into the mechanism of hGGT1-catalyzed reactions and will be invaluable in the development of new classes of hGGT1 inhibitors for therapeutic use.

36 MATERIALS SCIENCE↗

Firing behavior of vestibular neurons during active and passive head movements: vestibulo-spinal and other non-eye-movement related neurons

The firing behavior of 51 non-eye movement related central vestibular neurons that were sensitive to passive head rotation in the plane of the horizontal semicircular canal was studied in three squirrel monkeys whose heads were free to move in the horizontal plane. Unit sensitivity to active head movements during spontaneous gaze saccades was compared with sensitivity to passive head rotation. Most units (29/35 tested) were activated at monosynaptic latencies following electrical stimulation of the ipsilateral vestibular nerve. Nine were vestibulo-spinal units that were antidromically activated following electrical stimulation of the ventromedial funiculi of the spinal cord at C1. All of the units were less sensitive to active head movements than to passive whole body rotation. In the majority of cells (37/51, 73%), including all nine identified vestibulo-spinal units, the vestibular signals related to active head movements were canceled. The remaining units (n = 14, 27%) were sensitive to active head movements, but their responses were attenuated by 20-75%. Most units were nearly as sensitive to passive head-on-trunk rotation as they were to whole body rotation; this suggests that vestibular signals related to active head movements were cancelled primarily by subtraction of a head movement efference copy signal. The sensitivity of most units to passive whole body rotation was unchanged during gaze saccades. A fundamental feature of sensory processing is the ability to distinguish between self-generated and externally induced sensory events. Our observations suggest that the distinction is made at an early stage of processing in the vestibular system.

Non-NASA Center↗

Nanoscale movements of cellulose microfibrils in primary cell walls

The growing plant cell wall is commonly considered to be a fibre-reinforced structure whose strength, extensibility and anisotropy depend on the orientation of crystalline cellulose microfibrils, their bonding to the polysaccharide matrix and matrix viscoelasticity. Structural reinforcement of the wall by stiff cellulose microfibrils is central to contemporary models of plant growth, mechanics and meristem dynamics. Although passive microfibril reorientation during wall extension has been inferred from theory and from bulk measurements, nanometre-scale movements of individual microfibrils have not been directly observed. For this, we combined nanometre-scale imaging of wet cell walls by atomic force microscopy (AFM) with a stretching device and endoglucanase treatment that induces wall stress relaxation and creep, mimicking wall behaviours during cell growth. Microfibril movements during forced mechanical extensions differ from those during creep of the enzymatically loosened wall. In addition to passive angular reorientation, we observed a diverse repertoire of microfibril movements that reveal the spatial scale of molecular connections between microfibrils. Our results show that wall loosening alters microfibril connectivity, enabling microfibril dynamics not seen during mechanical stretch. These insights into microfibril movements and connectivities need to be incorporated into refined models of plant cell wall structure, growth and morphogenesis.

47 OTHER INSTRUMENTATION↗

A novel approach for estimating densities of secretive species from road-survey and spatial-movement data

Accurate estimates of population density are a critical component of effective wildlife conservation and management. However, many snake species are so secretive that their density cannot be determined using traditional methods such as capture–mark–recapture. Thus, the status of most terrestrial snake populations remains completely unknown. We developed a novel simulation-based technique for estimating density of secretive snakes that combined behavioural observations of snake road-crossing behaviour (crossing speed), effort-corrected road-survey data, and simulations of spatial movement patterns derived from radio-telemetry, without relying on mark–recapture. Here, we used radio-telemetry data to parameterise individual-based movement models that estimate the frequency with which individual snakes cross roads and used information on survey vehicle speed and snake crossing speed to determine the probability of detecting a snake, given that it crosses the road transect during a survey. Snake encounter frequencies during systematic road surveys were then interpreted in light of detection probabilities and simulation model results to estimate snake densities and to assess various factors likely to affect abundance estimates. We demonstrated the broad applicability of this approach through a case study of the imperiled southern hognose snake (Heterodon simus) in the North Carolina (USA) Sandhills. We estimated that H. simus occurs at average densities of 0.17 ha –1 in the North Carolina Sandhills and explored the sensitivity of this estimate to assumptions and variation in model parameters. Our novel method allowed us to generate the first abundance estimates for H. simus. We found that H. simus exists at low densities relative to congeners and other mid-sized snake species, raising concern that this species may not only have declined in geographic range, but may also occur at low densities or be declining in their strongholds, such as the North Carolina Sandhills. We present a framework for estimating density of species that have traditionally been considered too secretive to study at the population level. This method will greatly enhance our ability to study and manage a wide variety of snake species and could be applied to other secretive wildlife species that are most frequently encountered during road surveys.

59 BASIC BIOLOGICAL SCIENCES↗

Destabilizing effects of visual environment motions simulating eye movements or head movements

In the present paper, we explore effects on the human of exposure to a visual virtual environment which has been enslaved to simulate the human user's head movements or eye movements. Specifically, we have studied the capacity of our experimental subjects to maintain stable spatial orientation in the context of moving their entire visible surroundings by using the parameters of the subjects' natural movements. Our index of the subjects' spatial orientation was the extent of involuntary sways of the body while attempting to stand still, as measured by translations and rotations of the head. We also observed, informally, their symptoms of motion sickness.

White, Keith D.↗

Context-dependent adaptation of visually-guided arm movements and vestibular eye movements: role of the cerebellum

Accurate motor control requires adaptive processes that correct for gradual and rapid perturbations in the properties of the controlled object. The ability to quickly switch between different movement synergies using sensory cues, referred to as context-dependent adaptation, is a subject of considerable interest at present. The potential function of the cerebellum in context-dependent adaptation remains uncertain, but the data reviewed below suggest that it may play a fundamental role in this process.

NASA Discipline Neuroscience↗

Coriolis-force-induced trajectory and endpoint deviations in the reaching movements of labyrinthine-defective subjects

When reaching movements are made during passive constant velocity body rotation, inertial Coriolis accelerations are generated that displace both movement paths and endpoints in their direction. These findings directly contradict equilibrium point theories of movement control. However, it has been argued that these movement errors relate to subjects sensing their body rotation through continuing vestibular activity and making corrective movements. In the present study, we evaluated the reaching movements of five labyrinthine-defective subjects (lacking both semicircular canal and otolith function) who cannot sense passive body rotation in the dark and five age-matched, normal control subjects. Each pointed 40 times in complete darkness to the location of a just extinguished visual target before, during, and after constant velocity rotation at 10 rpm in the center of a fully enclosed slow rotation room. All subjects, including the normal controls, always felt completely stationary when making their movements. During rotation, both groups initially showed large deviations of their movement paths and endpoints in the direction of the transient Coriolis forces generated by their movements. With additional per-rotation movements, both groups showed complete adaptation of movement curvature (restoration of straight-line reaches) during rotation. The labyrinthine-defective subjects, however, failed to regain fully accurate movement endpoints after 40 reaches, unlike the control subjects who did so within 11 reaches. Postrotation, both groups' movements initially had mirror image curvatures to their initial per-rotation reaches; the endpoint aftereffects were significantly different from prerotation baseline for the control subjects but not for the labyrinthine-defective subjects reflecting the smaller amount of endpoint adaptation they achieved during rotation. The labyrinthine-defective subjects' movements had significantly lower peak velocity, higher peak elevation, lower terminal velocity, and a more vertical touchdown than those of the control subjects. Thus the way their reaches terminated denied them the somatosensory contact cues necessary for full endpoint adaptation. These findings fully contradict equilibrium point theories of movement control. They emphasize the importance of contact cues in adaptive movement control and indicate that movement errors generated by Coriolis perturbations of limb movements reveal characteristics of motor planning and adaptation in both healthy and clinical populations.

NASA Discipline Neuroscience↗

Coordinated turn-and-reach movements. II. Planning in an external frame of reference

The preceding study demonstrated that normal subjects compensate for the additional interaction torques generated when a reaching movement is made during voluntary trunk rotation. The present paper assesses the influence of trunk rotation on finger trajectories and on interjoint coordination and determines whether simultaneous turn-and-reach movements are most simply described relative to a trunk-based or an external reference frame. Subjects reached to targets requiring different extents of arm joint and trunk rotation at a natural pace and quickly in normal lighting and in total darkness. We first examined whether the larger interaction torques generated during rapid turn-and-reach movements perturb finger trajectories and interjoint coordination and whether visual feedback plays a role in compensating for these torques. These issues were addressed using generalized Procrustes analysis (GPA), which attempts to overlap a group of configurations (e.g., joint trajectories) through translations and rotations in multi-dimensional space. We first used GPA to identify the mean intrinsic patterns of finger and joint trajectories (i.e., their average shape irrespective of location and orientation variability in the external and joint workspaces) from turn-and-reach movements performed in each experimental condition and then calculated their curvatures. We then quantified the discrepancy between each finger or joint trajectory and the intrinsic pattern both after GPA was applied individually to trajectories from a pair of experimental conditions and after GPA was applied to the same trajectories pooled together. For several subjects, joint trajectories but not finger trajectories were more curved in fast than slow movements. The curvature of both joint and finger trajectories of turn-and-reach movements was relatively unaffected by the vision conditions. Pooling across speed conditions significantly increased the discrepancy between joint but not finger trajectories for most subjects, indicating that subjects used different patterns of interjoint coordination in slow and fast movements while nevertheless preserving the shape of their finger trajectory. Higher movement speeds did not disrupt the arm joint rotations despite the larger interaction torques generated. Rather, subjects used the redundant degrees of freedom of the arm/trunk system to achieve similar finger trajectories with differing joint configurations. We examined finger movement patterns and velocity profiles to determine the frame of reference in which turn-and-reach movements could be most simply described. Finger trajectories of turn-and-reach movements had much larger curvatures and their velocity profiles were less smooth and less bell-like in trunk-based coordinates than in external coordinates. Taken together, these results support the conclusion that turn-and-reach movements are controlled in an external frame of reference.

NASA Discipline Neuroscience↗