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At least 145 records · Page 8

The rhodopsins: structure and function. Introduction

Nature makes use of the propensity of retinal for light-dependent double-bond isomerization in a number of systems and in a variety of ways. The common theme for light receptors based on this kind of chemistry is that (1) the retinal is bound in most cases to a small membrane protein via a protonated lysine-retinal Schiff base, (2) the absorption maximum in the visible is tuned to a suitable wavelength largely by electrostatic interaction with polar protein residues, and (3) the light-induced bond rotations and strains in the retinal set off reaction chains during which at least part of the excess free energy acquired is transferred to the protein and causes pK shifts of acidic residues and/or backbone conformational changes. The physiological consequence of the process initiated by absorption of light is either the activation of an information transfer chain (sensory and visual rhodopsins) or energy transduction which drives the electrogenic movement of ions across the membrane (ion-motive rhodopsins). Rhodopsins with these functions occur in bacteria and in higher organisms; from an evolutionary standpoint they are not related to one another. Nevertheless, all of these proteins are remarkably similar and form a distinct family.

NASA Discipline Number 52-30↗

Structural and functional analyses of human cerebral cortex using a surface-based atlas

We have analyzed the geometry, geography, and functional organization of human cerebral cortex using surface reconstructions and cortical flat maps of the left and right hemispheres generated from a digital atlas (the Visible Man). The total surface area of the reconstructed Visible Man neocortex is 1570 cm2 (both hemispheres), approximately 70% of which is buried in sulci. By linking the Visible Man cerebrum to the Talairach stereotaxic coordinate space, the locations of activation foci reported in neuroimaging studies can be readily visualized in relation to the cortical surface. The associated spatial uncertainty was empirically shown to have a radius in three dimensions of approximately 10 mm. Application of this approach to studies of visual cortex reveals the overall patterns of activation associated with different aspects of visual function and the relationship of these patterns to topographically organized visual areas. Our analysis supports a distinction between an anterior region in ventral occipito-temporal cortex that is selectively involved in form processing and a more posterior region (in or near areas VP and V4v) involved in both form and color processing. Foci associated with motion processing are mainly concentrated in a region along the occipito-temporal junction, the ventral portion of which overlaps with foci also implicated in form processing. Comparisons between flat maps of human and macaque monkey cerebral cortex indicate significant differences as well as many similarities in the relative sizes and positions of cortical regions known or suspected to be homologous in the two species.

NASA Discipline Neuroscience↗

Plasma sheet turbulence observed by Cluster II

Cluster fluxgate magnetometer (FGM) and ion spectrometer (CIS) data are employed to analyze magnetic field fluctuations within the plasma sheet during passages through the magnetotail region in the summers of 2001 and 2002 and, in particular, to look for characteristics of magnetohydrodynamic (MHD) turbulence. Power spectral indices determined from power spectral density functions are on average larger than Kolmogorov's theoretical value for fluid turbulence as well as Kraichnan's theoretical value for MHD plasma turbulence. Probability distribution functions of the magnetic fluctuations show a scaling law over a large range of temporal scales with non-Gaussian distributions at small dissipative scales and inertial scales and more Gaussian distribution at large driving scales. Furthermore, a multifractal analysis of the magnetic field components shows scaling behavior in the inertial range of the fluctuations from about 20 s to 13 min for moments through the fifth order. Both the scaling behavior of the probability distribution functions and the multifractal structure function suggest that intermittent turbulence is present within the plasma sheet. The unique multispacecraft aspect and fortuitous spacecraft spacing allow us to examine the turbulent eddy scale sizes. Dynamic autocorrelation and cross correlation analysis of the magnetic field components allow us to determine that eddy scale sizes fit within the plasma sheet. These results suggest that magnetic field turbulence is occurring within the plasma sheet resulting in turbulent energy dissipation.

Weygand, James M.↗

DNA Recombinase Proteins, their Function and Structure in the Active Form, a Computational Study

Homologous recombination is a crucial sequence of reactions in all cells for the repair of double strand DNA (dsDNA) breaks. While it was traditionally considered as a means for generating genetic diversity, it is now known to be essential for restart of collapsed replication forks that have met a lesion on the DNA template (Cox et al., 2000). The central stage of this process requires the presence of the DNA recombinase protein, RecA in bacteria, RadA in archaea, or Rad51 in eukaryotes, which leads to an ATP-mediated DNA strand-exchange process. Despite many years of intense study, some aspects of the biochemical mechanism, and structure of the active form of recombinase proteins are not well understood. Our theoretical study is an attempt to shed light on the main structural and mechanistic issues encountered on the RecA of the e-coli, the RecA of the extremely radio resistant Deinococcus Radiodurans (promoting an inverse DNA strand-exchange repair), and the homolog human Rad51. The conformational changes are analyzed for the naked enzymes, and when they are linked to ATP and ADP. The average structures are determined over 2ns time scale of Langevian dynamics using a collision frequency of 1.0 ps(sup -1). The systems are inserted in an octahedron periodic box with a 10 Angstrom buffer of water molecules explicitly described by the TIP3P model. The corresponding binding free energies are calculated in an implicit solvent using the Poisson-Boltzmann solvent accessible surface area, MM-PBSA model. The role of the ATP is not only in stabilizing the interaction RecA-DNA, but its hydrolysis is required to allow the DNA strand-exchange to proceed. Furthermore, we extended our study, using the hybrid QM/MM method, on the mechanism of this chemical process. All the calculations were performed using the commercial code Amber 9.

Carra, Claudio↗

Structure and Function of the Snail Statocyst System after a 16-Day Flight on Foton-M-2

In terrestrial gastropod snail Helix lucorum L. we studied the changes after a 16-day exposure to microgravity in: behavior, neural responses to adequate motion stimulation, intersensory interactions between the photosensory pathways and the statocyst receptors, and in expression of the HPeP gene in the statocyst receptors. In behavioral experiments it was found that the latency of body position change to sudden orientation change (flip from horizontal to downwards position) was significantly reduced in the postflight snails. Extracellularly recorded neural responses of the statocyst nerve to adequate motion stimulation in the postflight snails were independent of the motion direction while in the control animals an orientation selectivity was observed. Significant differences in the HPeP gene mRNA expression pattern in the statocyst receptor neurons were observed in postflight (30h) and control snails. Obtained results confirm the possibility to elucidate the influence of microgravity exposure on mechanisms and function of gravireceptors using this simple model animal.

Balaban, P. M.↗

Multi-functional layered structure having structural and radiation shielding attributes

A cosmic and solar radiation shielding structure that also has structural attributes is comprised of three layers. The first layer is 30-42 percent by volume of ultra-high molecular weight (UHMW) polyethylene fibers, 18-30 percent by volume of graphite fibers, and a remaining percent by volume of an epoxy resin matrix. The second layer is approximately 68 percent by volume of UHMW polyethylene fibers and a remaining percent by volume of a polyethylene matrix. The third layer is a ceramic material.

Kaul, Raj K.↗

A simulator for evaluating methods for the detection of lesion-deficit associations

Although much has been learned about the functional organization of the human brain through lesion-deficit analysis, the variety of statistical and image-processing methods developed for this purpose precludes a closed-form analysis of the statistical power of these systems. Therefore, we developed a lesion-deficit simulator (LDS), which generates artificial subjects, each of which consists of a set of functional deficits, and a brain image with lesions; the deficits and lesions conform to predefined distributions. We used probability distributions to model the number, sizes, and spatial distribution of lesions, to model the structure-function associations, and to model registration error. We used the LDS to evaluate, as examples, the effects of the complexities and strengths of lesion-deficit associations, and of registration error, on the power of lesion-deficit analysis. We measured the numbers of recovered associations from these simulated data, as a function of the number of subjects analyzed, the strengths and number of associations in the statistical model, the number of structures associated with a particular function, and the prior probabilities of structures being abnormal. The number of subjects required to recover the simulated lesion-deficit associations was found to have an inverse relationship to the strength of associations, and to the smallest probability in the structure-function model. The number of structures associated with a particular function (i.e., the complexity of associations) had a much greater effect on the performance of the analysis method than did the total number of associations. We also found that registration error of 5 mm or less reduces the number of associations discovered by approximately 13% compared to perfect registration. The LDS provides a flexible framework for evaluating many aspects of lesion-deficit analysis.

NASA Program Biomedical Research and Countermeasur↗

The Effects of Spaceflight and a Spaceflight Analog on Neurocognitive Perfonnance: Extent, Longevity, and Neural Bases

We are conducting ongoing experiments in which we are performing structural and functional magnetic resonance brain imaging to identify the relationships between changes in neurocognitive function and neural structural alterations following a six month International Space Station mission and following 70 days exposure to a spaceflight analog, head down tilt bedrest. Our central hypothesis is that measures of brain structure, function, and network integrity will change from pre to post intervention (spaceflight, bedrest). Moreover, we predict that these changes will correlate with indices of cognitive, sensory, and motor function in a neuroanatomically selective fashion. Our interdisciplinary approach utilizes cutting edge neuroimaging techniques and a broad ranging battery of sensory, motor, and cognitive assessments that will be conducted pre flight, during flight, and post flight to investigate potential neuroplastic and maladaptive brain changes in crewmembers following long-duration spaceflight. Success in this endeavor would 1) result in identification of the underlying neural mechanisms and operational risks of spaceflight-induced changes in behavior, and 2) identify whether a return to normative behavioral function following re-adaptation to Earth's gravitational environment is associated with a restitution of brain structure and function or instead is supported by substitution with compensatory brain processes. With the bedrest study, we will be able to determine the neural and neurocognitive effects of extended duration unloading, reduced sensory inputs, and increased cephalic fluid distribution. This will enable us to parse out the multiple mechanisms contributing to any spaceflight-induced neural structural and behavioral changes that we observe in the flight study. In this presentation I will discuss preliminary results from six participants who have undergone the bed rest protocol. These individuals show decrements in balance and functional mobility, and alterations in brain structure and function, in association with extended bed rest.

Seidler, R. D.↗

The Effects of Spaceflight and Head Down Tilt Bed Rest on Neurocognitive Performance: Extent, Longevity, and Neural Bases

Spaceflight effects on gait, balance, & manual motor control have been well studied; some evidence for cognitive deficits. Rodent cortical motor & sensory systems show neural structural alterations with spaceflight. specific Aims: Aim 1-Identify changes in brain structure, function, and network integrity as a function of head down tilt bed rest and spaceflight, and characterize their time course. Aim 2-Specify relationships between structural and functional brain changes and performance and characterize their time course.

Seidler, Rachael D.↗

Proteolytic dissection of Zab, the Z-DNA-binding domain of human ADAR1

Zalpha is a peptide motif that binds to Z-DNA with high affinity. This motif binds to alternating dC-dG sequences stabilized in the Z-conformation by means of bromination or supercoiling, but not to B-DNA. Zalpha is part of the N-terminal region of double-stranded RNA adenosine deaminase (ADAR1), a candidate enzyme for nuclear pre-mRNA editing in mammals. Zalpha is conserved in ADAR1 from many species; in each case, there is a second similar motif, Zbeta, separated from Zalpha by a more divergent linker. To investigate the structure-function relationship of Zalpha, its domain structure was studied by limited proteolysis. Proteolytic profiles indicated that Zalpha is part of a domain, Zab, of 229 amino acids (residues 133-361 in human ADAR1). This domain contains both Zalpha and Zbeta as well as a tandem repeat of a 49-amino acid linker module. Prolonged proteolysis revealed a minimal core domain of 77 amino acids (positions 133-209), containing only Zalpha, which is sufficient to bind left-handed Z-DNA; however, the substrate binding is strikingly different from that of Zab. The second motif, Zbeta, retains its structural integrity only in the context of Zab and does not bind Z-DNA as a separate entity. These results suggest that Zalpha and Zbeta act as a single bipartite domain. In the presence of substrate DNA, Zab becomes more resistant to proteases, suggesting that it adopts a more rigid structure when bound to its substrate, possibly with conformational changes in parts of the protein.

Non-NASA Center↗

Code Migration and Optimization for Calculating Atmospheric Attenuation in RF Link Budgets Within Glenn Research Center Communication Analysis Suite

This technical report encompasses development completed on the Glenn Research Center Communication Analysis Suite (GCAS) as it relates to converting code from the original MATLAB® (The MathWorks, Inc.) GCAS code base to C++. It focuses on a majority of the functions, structures, and intermediate code developed for radiofrequency (RF) links calculations. The report serves as a comprehensive record of the current progress and outlines the technical challenges overcome during this research. Throughout this project, numerous functions and structures were migrated end to end, with validation test cases conducted in accordance with NASA’s verification and validation efforts for standard models and simulations. This report also provides high-level documentation of the completed work; detailed low-level documentation has been compiled to provide a line-by-line explanation in alignment with NASA’s goals. This development has largely been focused on atmospheric effects on calculating RF link budgets for both terrestrial and space links. Some developments outside of atmospheric functions are also covered throughout this report; these are largely related to mathematical operations and MATLAB® structure conversions.

Brady M. Phelps↗

Spaceflight Effects on Neurocognitive Performance: Extent, Longevity and Neural Bases

We are conducting ongoing experiments in which we are performing structural and functional magnetic resonance brain imaging to identify the relationships between changes in neurocognitive function and neural structural alterations following a six month International Space Station mission. Our central hypothesis is that measures of brain structure, function, and network integrity will change from pre to post spaceflight. Moreover, we predict that these changes will correlate with indices of cognitive, sensory, and motor function in a neuroanatomically selective fashion. Our interdisciplinary approach utilizes cutting edge neuroimaging techniques and a broad ranging battery of sensory, motor, and cognitive assessments that are conducted pre flight, during flight, and post flight to investigate potential neuroplastic and maladaptive brain changes in crewmembers following long-duration spaceflight. Success in this endeavor would 1) result in identification of the underlying neural mechanisms and operational risks of spaceflight-induced changes in behavior, and 2) identify whether a return to normative behavioral function following re-adaptation to Earth's gravitational environment is associated with a restitution of brain structure and function or instead is supported by substitution with compensatory brain processes. We have collected data on several crewmembers and preliminary findings will be presented. Eventual comparison to results from our parallel bed rest study will enable us to parse out the multiple mechanisms contributing to any spaceflight-induced neural structural and behavioral changes that we observe.

Seidler, R. D.↗

The Effects of Long Duration Head Down Tilt Bed Rest on Neurocognitive Performance: The Effects of Exercise Interventions

We are conducting ongoing experiments in which we are performing structural and functional magnetic resonance brain imaging to identify the relationships between changes in neurocognitive function and neural structural alterations following a six month International Space Station mission and following 70 days exposure to a spaceflight analog, head down tilt bedrest. Our central hypothesis is that measures of brain structure, function, and network integrity will change from pre to post intervention (spaceflight, bedrest). Moreover, we predict that these changes will correlate with indices of cognitive, sensory, and motor function in a neuroanatomically selective fashion. Our interdisciplinary approach utilizes cutting edge neuroimaging techniques and a broad ranging battery of sensory, motor, and cognitive assessments that will be conducted pre flight, during flight, and post flight to investigate potential neuroplastic and maladaptive brain changes in crewmembers following long-duration spaceflight. Success in this endeavor would 1) result in identification of the underlying neural mechanisms and operational risks of spaceflight-induced changes in behavior, and 2) identify whether a return to normative behavioral function following re-adaptation to Earth's gravitational environment is associated with a restitution of brain structure and function or instead is supported by substitution with compensatory brain processes. Our ongoing bed rest participants are also engaging in exercise studies directed by Dr. Lori Ploutz Snyder. In this presentation, I will briefly highlight the existing literature linking exercise and fitness to brain and behavioral functions. I will also overview the metrics from my study that could be investigated in relation to the exercise and control subgroups.

Seidler, R. D.↗