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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 307 records · Page 17
All sourcesNASA NTRSDOE OSTI
DOE OSTI2012

Molecular basis for the Kallmann syndrome-linked fibroblast growth factor receptor mutation

Highlights: Black-Right-Pointing-Pointer The structural basis of the Kallmann syndrome is elucidated. Black-Right-Pointing-Pointer Kallmann syndrome mutation (A168S) induces a subtle conformational change(s). Black-Right-Pointing-Pointer Structural interactions mediated by beta-sheet G are most perturbed. Black-Right-Pointing-Pointer Ligand (FGF)-receptor interaction(s) is completely abolished by Kallmann mutation. Black-Right-Pointing-Pointer Kallmann mutation directly affects the FGF signaling process. -- Abstract: Kallmann syndrome (KS) is a developmental disease that expresses in patients as hypogonadotropic hypogonadism and anosmia. KS is commonly associated with mutations in the extracellular D2 domain of the fibroblast growth factor receptor (FGFR). In this study, for the first time, the molecular basis for the FGFR associated KS mutation (A168S) is elucidated using a variety of biophysical experiments, including multidimensional NMR spectroscopy. Secondary and tertiary structural analysis using far UV circular dichroism, fluorescence and limited trypsin digestion assays suggest that the KS mutation induces subtle tertiary structure change in the D2 domain of FGFR. Results of isothermal titration calorimetry experiments show the KS mutation causes a 10-fold decrease in heparin binding affinity and also a complete loss in ligand (FGF-1) binding. {sup 1}H-{sup 15}N chemical perturbation data suggest that complete loss in the ligand (FGF) binding affinity is triggered by a subtle conformational change that disrupts crucial structural interactions in both the heparin and the FGF binding sites in the D2 domain of FGFR. The novel findings reported in this study are expected to provide valuable clues toward a complete understanding of the other genetic diseases linked to mutations in the FGFR.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Tension-dependent free energies of nucleosome unwrapping

Here, nucleosomes form the basic unit of compaction within eukaryotic genomes, and their locations represent an important, yet poorly understood, mechanism of genetic regulation. Quantifying the strength of interactions within the nucleosome is a central problem in biophysics and is critical to understanding how nucleosome positions influence gene expression. By comparing to single-molecule experiments, we demonstrate that a coarse-grained molecular model of the nucleosome can reproduce key aspects of nucleosome unwrapping. Using detailed simulations of DNA and histone proteins, we calculate the tension-dependent free energy surface corresponding to the unwrapping process. The model reproduces quantitatively the forces required to unwrap the nucleosome and reveals the role played by electrostatic interactions during this process. We then demonstrate that histone modifications and DNA sequence can have significant effects on the energies of nucleosome formation. Most notably, we show that histone tails contribute asymmetrically to the stability of the outer and inner turn of nucleosomal DNA and that depending on which histone tails are modified, the tension-dependent response is modulated differently.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
NASA NTRS2004

Quantifying Grassland-to-Woodland Transitions and the Implications for Carbon and Nitrogen Dynamics in the Southwest United States

Replacement of grasslands and savannas by shrublands and woodlands has been widely reported in tropical, temperate and high-latitude rangelands worldwide (Archer 1994). These changes in vegetation structure may reflect historical shifts in climate and land use; and are likely to influence biodiversity, productivity, above- and below ground carbon and nitrogen sequestration and biophysical aspects of land surface-atmosphere interactions. The goal of our proposed research is to investigate how changes in the relative abundance of herbaceous and woody vegetation affect carbon and nitrogen dynamics across heterogeneous savannas and shrub/woodlands. By linking actual land-cover composition (derived through spectral mixture analysis of AVIRIS, TM, and AVHRR imagery) with a process-based ecosystem model, we will generate explicit predictions of the C and N storage in plants and soils resulting from changes in vegetation structure. Our specific objectives will be to (1) continue development and test applications of spectral mixture analysis across grassland-to-woodland transitions; (2) quantify temporal changes in plant and soil C and N storage and turnover for remote sensing and process model parameterization and verification; and (3) couple landscape fraction maps to an ecosystem simulation model to observe biogeochemical dynamics under changing landscape structure and climatological forcings.

Wessman, Carol A.↗
DOE OSTI2015

Membrane Protein Structure, Function, and Dynamics: a Perspective from Experiments and Theory

It is fundamental for the flourishing biological cells that membrane proteins mediate the process. Membrane-embedded transporters move ions and larger solutes across membranes; receptors mediate communication between the cell and its environment and membrane-embedded enzymes catalyze chemical reactions. Understanding these mechanisms of action requires knowledge of how the proteins couple to their fluid, hydrated lipid membrane environment. Here, we present here current studies in computational and experimental membrane protein biophysics, and show how they address outstanding challenges in understanding the complex environmental effects on the structure, function, and dynamics of membrane proteins.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Aβ1-40 mediated aggregation of proteins and metabolites unveils the relevance of amyloid cross-seeding in amyloidogenesis

The multicomponent nature of neuronal plaques in Alzheimer's disease signifies the possible recruitment of non-Aβ candidates during the amyloid growth of Aβ peptides. Here, we show that amyloid fibrils of Aβ{sub 1-40} peptide can effectively initiate amyloid formation in different globular proteins and metabolites, converting native structures into β-sheet rich assemblies. Structural and biophysical properties of the resultant protein fibrils display amyloid like characteristic features. Viable contacts between Aβ peptide's cross-β architecture and the native structure of proteins, mediated through H-bonds and hydrophobic interactions seem crucial for the onset of amyloid cross-seeding. Results reveal the inherent cross-seeding potential of Aβ amyloids to initiate amyloid formation process in proteins and metabolites and revelation of such a property may further our mechanistic understanding of amyloid pathologies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Hypericin-mediated selective photomodification of connective tissues

Controllable modification of biological molecules and supramolecular components of connective tissue are important for biophysical and biomedical applications. Through the use of second harmonic generation imaging, two-photon fluorescence microscopy, and spectrofluorimetry, we found that hypericin, a natural pigment, induces photosensitized destruction of collagen fibers but does not affect elastic fibers and lipids in chicken tendon, skin, and blood vessels. We demonstrated the dynamics and efficiency of collagen photomodification and investigated mechanisms of this processes. Our results suggest that hypericin–mediated photoprocesses in biological tissues may be useful in biomedical applications that require selective modification of connective tissues.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Ewald: an extended wide-angle Laue diffractometer for the second target station of the Spallation Neutron Source

Visualizing hydrogen atoms in biological materials is one of the biggest remaining challenges in biophysical analysis. While X-ray techniques have unrivaled capacity for high-throughput structure determination, neutron diffraction is uniquely sensitive to hydrogen atom positions in crystals of biological materials and can provide a more complete picture of the atomic and electronic structures of biological macromolecules. This information can be essential in providing predictive understanding and engineering control of key biological processes, for example, in catalysis, ligand binding and light harvesting, and to guide bioengineering of enzymes and drug design. One very common and large capability gap for all neutron atomic resolution single-crystal diffractometers is the weak flux of available neutron beams, which results in limited signal-to-noise ratios giving a requirement for sample volumes of at least 0.1 mm 3 . The ability to operate on crystals an order of magnitude smaller (0.01 mm 3 ) will open up new and more complex systems to studies with neutrons which will help in our understanding of enzyme mechanisms and enable us to improve drugs against multi resistant bacteria. With this is mind, an extended wide-angle Laue diffractometer, `Ewald', has been designed, which can collect data using crystal volumes below 0.01 mm 3 .

36 MATERIALS SCIENCE↗
DOE OSTI2019

18. Combining experiment and simulation to study complex biomimetic membranes

The three-dimensional architecture of biological membranes has functional consequences for the living cell. In the outer leaflet of the plasma membrane, lipids are thought to self-organize into domains enriched in high-melting lipids and cholesterol. Currently, there is much evidence implicating these lipid domains in a variety of membrane processes, including protein sorting, cell signaling, and the maintenance of membrane physical properties. Cells also actively maintain an asymmetric distribution of different lipid types between their plasma membrane inner and outer leaflets, resulting in monolayers with different fluidities and charge densities. Moreover, it is an open question how these and other bilayer properties are coupled, if at all. A variety of biophysical techniques are being employed to interrogate both lateral and transverse bilayer structures with sub-nanometer resolution. Molecular dynamic simulations are also used to probe the membrane’s finer details, providing a glimpse of membrane organization with atomic resolution. In this chapter, we present a discussion of these two approaches to investigate the organization of complex biomimetic membranes and present recent examples of how they have been used to complement each other.

Katsaras, John↗
DOE OSTI2011

The E2 Domains of APP and APLP1 Share a Conserved Mode of Dimerization

Amyloid precursor protein (APP) is genetically linked to Alzheimer's disease. APP is a type I membrane protein, and its oligomeric structure is potentially important because this property may play a role in its function or affect the processing of the precursor by the secretases to generate amyloid {beta}-peptide. Several independent studies have shown that APP can form dimers in the cell, but how it dimerizes remains controversial. At least three regions of the precursor, including a centrally located and conserved domain called E2, have been proposed to contribute to dimerization. Here we report two new crystal structures of E2, one from APP and the other from APLP1, a mammalian APP homologue. Comparison with an earlier APP structure, which was determined in a different space group, shows that the E2 domains share a conserved and antiparallel mode of dimerization. Biophysical measurements in solution show that heparin binding induces E2 dimerization. The 2.1 {angstrom} resolution electron density map also reveals phosphate ions that are bound to the protein surface. Mutational analysis shows that protein residues interacting with the phosphate ions are also involved in heparin binding. The locations of two of these residues, Arg-369 and His-433, at the dimeric interface suggest a mechanism for heparin-induced protein dimerization.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

A multi criteria analog model for assessing the vulnerability of rural catchments to road spills of hazardous substances

Road spills of hazardous substances are common in developing countries due to increasing industrialization and traffic accidents, and represent a serious threat to soils and water in catchments. There is abundant literature on equations describing the wash-off of pollutants from roads during a storm event and there are a number of watershed models incorporating those equations in storm water quality algorithms that route runoff and pollution yields through a drainage system towards the catchment outlet. However, methods describing catchment vulnerability to contamination by road spills based solely on biophysical parameters are scarce. These methods could be particularly attractive to managers because they can operate with a limited amount of easily collectable data, while still being able to provide important insights on the areas more prone to contamination within the studied watershed. The purpose of this paper was then to contribute with a new vulnerability model. To accomplish the goal, a selection of medium properties appearing in wash-off equations and routing algorithms were assembled and processed in a parametric framework based on multi criteria analysis to define the watershed vulnerability. However, parameters had to be adapted because wash-off equations and water quality models have been developed to operate primarily in the urban environment while the vulnerability model is meant to run in rural watersheds. The selected parameters were hillside slope, ground roughness (depending on land use), soil permeability (depending on soil type), distance to water courses and stream density. The vulnerability model is a spatially distributed algorithm that was prepared to run under the IDRISI Selva software, a GIS platform capable of handling spatial and alphanumeric data and execute the necessary terrain model, hydrographic and thematic analyses. For illustrative purposes, the vulnerability model was applied to the legally protected Environmental Protection Area (APA), located in the Uberaba region, state of Minas Gerais, Brazil. In this region, the risk of accidents causing chemical spills is preoccupying because large quantities of dangerous materials are transported in two important distribution highways while the APA is fundamental for the protection of water resources, the riverine ecosystems and remnants of native vegetation. In some tested scenarios, model results show 60% of vulnerable areas within the studied area. The most sensitive parameter to vulnerability is soil type. To prevent soils from contamination, specific measures were proposed involving minimization of land use conflicts that would presumably raise the soil's organic matter and in the sequel restore the soil's structural functions. Additionally, the present study proposed the preservation and reinforcement of riparian forests as one measure to protect the quality of surface water. - Highlights: • A multi criteria analog model was developed to assess rural catchment vulnerability along roads. • Model parameters were defined by analogy with urban wash-off equations and routing algorithms. • The model mixes up various biophysical and socio-economic parameters. • Model application was based on a scenario analysis. • The study is focused on the Environmental Protection Area of Uberaba River, Brazil.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2011

An approach to assessing stochastic radiogenic risk in medical imaging

Purpose: This letter suggests a formalism, the medical effective dose (MED), that is suitable for assessing stochastic radiogenic risks in diagnostic medical procedures. Methods: The MED is derived from radiobiological and probabilistic first principals, including: (1) The independence of radiation-induced biological effects in neighboring voxels at low doses; (2) the linear no-threshold assumption for stochastic radiation injury (although other dose-response relationships could be incorporated, instead); (3) the best human radiation dose-response data currently available; and (4) the built-in possibility that the carcinogenic risk to an irradiated organ may depend on its volume. The MED involves a dose-risk summation over irradiated voxels at high spatial resolution; it reduces to the traditional effective dose when every organ is irradiated uniformly and when the dependence of risk on organ volumes is ignored. Standard relative-risk tissue weighting factors can be used with the MED approach until more refined data become available. Results: The MED is intended for clinical and phantom dosimetry, and it provides an estimate of overall relative radiogenic stochastic risk for any given dose distribution. A result of the MED derivation is that the stochastic risk may increase with the volume of tissue (i.e., the number of cells) irradiated, a feature that can be activated when forthcoming radiobiological research warrants it. In this regard, the MED resembles neither the standard effective dose (E) nor the CT dose index (CTDI), but it is somewhat like the CT dose-length product (DLP). Conclusions: The MED is a novel, probabilistically and biologically based means of estimating stochastic-risk-weighted doses associated with medical imaging. Built in, ab initio, is the ability to link radiogenic risk to organ volume and other clinical factors. It is straightforward to implement when medical dose distributions are available, provided that one is content, for the time being, to accept the relative tissue weighting factors published by the International Commission of Radiological Protection (ICRP). It requires no new radiobiological data and avoids major problems encountered by the E, CTDI, and CT-E formalisms. It makes possible relative inter-patient dosimetry, and also realistic intercomparisons of stochastic risks from different protocols that yield images of comparable quality.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2025

Detection of non‐native species formed during fibrillization of the myocilin olfactomedin domain

Abstract Glaucoma is a group of neurodegenerative diseases that together are the leading cause of irreversible blindness worldwide. Myocilin‐associated glaucoma is an inherited form of this disease, caused by intracellular aggregation of misfolded mutant myocilin. In vitro, the myocilin C‐terminal olfactomedin domain (OLF), the relevant domain for glaucoma pathogenesis, can be driven to form amyloid‐like fibrils under mild conditions. Here we characterize a species present during in vitro fibrillization. Purified OLF was subjected to fibrillization at concentrations required for downstream electron microscopy imaging and NMR spectroscopy. Additional biophysical techniques, including analytical ultracentrifugation and X‐ray crystallography, were employed to further characterize the multicomponent mixture. Negative stain transmission electron microscopy (TEM) shows a non‐native species reminiscent of known prefibrillar oligomers from other amyloid systems, NMR indicates a minor population of partially misfolded species is present in solution, and cryo‐EM imaging shows two‐dimensional protein arrays. The predominant soluble species remaining in solution after the fibril reaction is natively folded, as evidenced by X‐ray crystallography. In summary, after incubating OLF under fibrillization‐promoting conditions, there is a heterogeneous mixture consisting of soluble folded protein, mature amyloid‐like fibrils, and partially misfolded intermediate species that at present belie additional molecular detail. The characterization of OLF fibrillar species illustrates the challenges associated with developing a comprehensive understanding of the fibrillization process for large, non‐model amyloidogenic proteins.

Scelsi, Hailee F. [School of Chemistry and Biochem↗
DOE OSTI2021

Programmable Aggregation of Artificial Cells with DNA Signals

Cell aggregation is a complex behavior, which is closely related to the viability, differentiation, and migration of cells. An effort to create synthetic analogs could lead to considerable advances in cell physiology and biophysics. Rendering and modulating such a dynamic artificial cell system require mechanisms for receiving, transducing, and transmitting intercellular signals, yet effective tools are limited at present. Here we construct synthetic cells from engineered lipids and show their programmable aggregation behaviors using DNA oligonucleotides as a signaling molecule. The artificial cells have transmembrane channels made of DNA origami that are used to recognize and process intercellular signals. We demonstrate that multiple small vesicles aggregate onto a giant vesicle after a transduction of external DNA signals by an intracellular enzyme, and that the small vesicles dissociate when receiving ‘release’ signals. Furthermore, this work provides new possibilities for building synthetic protocells capable of chemical communication and coordination.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Comprehensive analysis of the human ESCRT-III-MIT domain interactome reveals new cofactors for cytokinetic abscission

The 12 related human ESCRT-III proteins form filaments that constrict membranes and mediate fission, including during cytokinetic abscission. The C-terminal tails of polymerized ESCRT-III subunits also bind proteins that contain Microtubule-Interacting and Trafficking (MIT) domains. MIT domains can interact with ESCRT-III tails in many different ways to create a complex binding code that is used to recruit essential cofactors to sites of ESCRT activity. Here, we have comprehensively and quantitatively mapped the interactions between all known ESCRT-III tails and 19 recombinant human MIT domains. We measured 228 pairwise interactions, quantified 60 positive interactions, and discovered 18 previously unreported interactions. We also report the crystal structure of the SPASTIN MIT domain in complex with the IST1 C-terminal tail. Three MIT enzymes were studied in detail and shown to: (1) localize to cytokinetic midbody membrane bridges through interactions with their specific ESCRT-III binding partners (SPASTIN-IST1, KATNA1-CHMP3, and CAPN7-IST1), (2) function in abscission (SPASTIN, KATNA1, and CAPN7), and (3) function in the ‘NoCut’ abscission checkpoint (SPASTIN and CAPN7). Our studies define the human MIT-ESCRT-III interactome, identify new factors and activities required for cytokinetic abscission and its regulation, and provide a platform for analyzing ESCRT-III and MIT cofactor interactions in all ESCRT-mediated processes.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2002

Biological-Physical Coupling in the Gulf of Maine: Satellite and Model Studies of Phytoplankton Variability

The goals of this project were to acquire, process, QC, archive and analyze SeaWiFS chlorophyll fields over the Gulf of Maine and Scotia Shelf region. The focus of the analysis effort was to calculate and quantify seasonality and interannual. variability of SeaWiFS-measured phytoplankton biomass in the study area and compare these to physical forcing and hydrography. An additional focus within this effort was on regional differences within the heterogeneous biophysical regions of the Gulf of Maine / Scotia Shelf. Overall goals were approached through the combined use of SeaWiFS and AVHRR data and the development of a coupled biology-physical numerical model.

Thomas, Andrew C.↗
NASA NTRS2016

Using the Light Microscopy Module (LMM) on the International Space Station (ISS), The Advanced Colloids Experiment (ACE) and MacroMolecular Biophysics (MMB)

The Light Microscopy Module (LMM) was launched to the International Space Station (ISS) in 2009 and began science operations in 2010. It continues to support Physical and Biological scientific research on ISS. During 2016, if all goes as planned, three experiments will be completed: [1] Advanced Colloids Experiments with Heated base-2 (ACE-H2) and [2] Advanced Colloids Experiments with Temperature control (ACE-T1). Preliminary results, along with an overview of present and future LMM capabilities will be presented; this includes details on the planned data imaging processing and storage system, along with the confocal upgrade to the core microscope. [1] a consortium of universities from the State of Kentucky working through the Experimental Program to Stimulate Competitive Research (EPSCoR): Stuart Williams, Gerold Willing, Hemali Rathnayake, et al. and [2] from Chungnam National University, Daejeon, S. Korea: Chang-Soo Lee, et al.

Microgravity Biology Research↗
DOE OSTI2016

Energy Minimization of Discrete Protein Titration State Models Using Graph Theory

There are several applications in computational biophysics which require the optimization of discrete interacting states; e.g., amino acid titration states, ligand oxidation states, or discrete rotamer angles. Such optimization can be very time-consuming as it scales exponentially in the number of sites to be optimized. In this paper, we describe a new polynomial-time algorithm for optimization of discrete states in macromolecular systems. This algorithm was adapted from image processing and uses techniques from discrete mathematics and graph theory to restate the optimization problem in terms of maximum flow-minimum cut graph analysis. The interaction energy graph, a graph in which vertices (amino acids) and edges (interactions) are weighted with their respective energies, is transformed into a flow network in which the value of the minimum cut in the network equals the minimum free energy of the protein, and the cut itself encodes the state that achieves the minimum free energy. Because of its deterministic nature and polynomial-time performance, this algorithm has the potential to allow for the ionization state of larger proteins to be discovered.

energy minimization↗
DOE OSTI2018

Methane emissions from tree stems: a new frontier in the global carbon cycle

Tree stems from wetland, floodplain and upland forests can produce and emit methane (CH 4 ). Tree CH 4 stem emissions have high spatial and temporal variability, but there is no consensus on the biophysical mechanisms that drive stem CH 4 production and emissions. Here, we summarize up to 30 opportunities and challenges for stem CH 4 emissions research, which when addressed will improve estimates of magnitudes, patterns, drivers and trace the potential origin of CH 4 emissions. We identified the need (i) for both long–term high frequency measurements of stem CH 4 emissions to understand the fine scale processes, alongside rapid large–scale measurements designed to understand variability across individuals, species and ecosystems; (ii) to identify microorganisms and biogeochemical pathways associated with CH 4 production; and (iii) to develop a mechanistic model including passive and active transport of CH 4 from the soil–tree–atmosphere continuum. Addressing these challenges would help to constrain magnitudes and patterns of CH 4 emissions, and would allow for the integration of pathways and mechanisms of CH 4 production and emissions into process–based models. As a result, these advances will facilitate upscaling of stem CH 4 emissions to the ecosystem level and quantify the role of stem CH 4 emissions for the local–to–global CH 4 budget.

54 ENVIRONMENTAL SCIENCES↗