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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 883 records · Page 49
All sourcesNASA NTRSDOE OSTI
DOE OSTI2013

A Meier-Gorlin syndrome mutation in a conserved C-terminal helix of Orc6 impedes origin recognition complex formation

In eukaryotes, DNA replication requires the origin recognition complex (ORC), a six-subunit assembly that promotes replisome formation on chromosomal origins. Despite extant homology between certain subunits, the degree of structural and organizational overlap between budding yeast and metazoan ORC has been unclear. Using 3D electron microscopy, we determined the subunit organization of metazoan ORC, revealing that it adopts a global architecture very similar to the budding yeast complex. Bioinformatic analysis extends this conservation to Orc6, a subunit of somewhat enigmatic function. Unexpectedly, a mutation in the Orc6 C-terminus linked to Meier-Gorlin syndrome, a dwarfism disorder, impedes proper recruitment of Orc6 into ORC; biochemical studies reveal that this region of Orc6 associates with a previously uncharacterized domain of Orc3 and is required for ORC function and MCM2–7 loading in vivo. Together, our results suggest that Meier-Gorlin syndrome mutations in Orc6 impair the formation of ORC hexamers, interfering with appropriate ORC functions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

Prediction and characterization of enzymatic activities guided by sequence similarity and genome neighborhood networks

Metabolic pathways in eubacteria and archaea often are encoded by operons and/or gene clusters (genome neighborhoods) that provide important clues for assignment of both enzyme functions and metabolic pathways. We describe a bioinformatic approach (genome neighborhood network; GNN) that enables large scale prediction of the in vitro enzymatic activities and in vivo physiological functions (metabolic pathways) of uncharacterized enzymes in protein families. We demonstrate the utility of the GNN approach by predicting in vitro activities and in vivo functions in the proline racemase superfamily (PRS; InterPro IPR008794). The predictions were verified by measuring in vitro activities for 51 proteins in 12 families in the PRS that represent ~85% of the sequences; in vitro activities of pathway enzymes, carbon/nitrogen source phenotypes, and/or transcriptomic studies confirmed the predicted pathways. The synergistic use of sequence similarity networks3 and GNNs will facilitate the discovery of the components of novel, uncharacterized metabolic pathways in sequenced genomes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Discovery and characterization of a novel family of prokaryotic nanocompartments involved in sulfur metabolism

Prokaryotic nanocompartments, also known as encapsulins, are a recently discovered proteinaceous organelle-like compartment in prokaryotes that compartmentalize cargo enzymes. While initial studies have begun to elucidate the structure and physiological roles of encapsulins, bioinformatic evidence suggests that a great diversity of encapsulin nanocompartments remains unexplored. Here, we describe a novel encapsulin in the freshwater cyanobacterium Synechococcus elongatus PCC 7942. This nanocompartment is upregulated upon sulfate starvation and encapsulates a cysteine desulfurase enzyme via an N-terminal targeting sequence. Using cryo-electron microscopy, we have determined the structure of the nanocompartment complex to 2.2 Å resolution. Lastly, biochemical characterization of the complex demonstrated that the activity of the cysteine desulfurase is enhanced upon encapsulation. Taken together, our discovery, structural analysis, and enzymatic characterization of this prokaryotic nanocompartment provide a foundation for future studies seeking to understand the physiological role of this encapsulin in various bacteria.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Novel sterol binding domains in bacteria

Sterol lipids are widely present in eukaryotes and play essential roles in signaling and modulating membrane fluidity. Although rare, some bacteria also produce sterols, but their function in bacteria is not known. Moreover, many more species, including pathogens and commensal microbes, acquire or modify sterols from eukaryotic hosts through poorly understood molecular mechanisms. The aerobic methanotroph Methylococcus capsulatus was the first bacterium shown to synthesize sterols, producing a mixture of C-4 methylated sterols that are distinct from those observed in eukaryotes. C-4 methylated sterols are synthesized in the cytosol and localized to the outer membrane, suggesting that a bacterial sterol transport machinery exists. Until now, the identity of such machinery remained a mystery. In this study, we identified three novel proteins that may be the first examples of transporters for bacterial sterol lipids. The proteins, which all belong to well-studied families of bacterial metabolite transporters, are predicted to reside in the inner membrane, periplasm, and outer membrane of M. capsulatus, and may work as a conduit to move modified sterols to the outer membrane. Quantitative analysis of ligand binding revealed their remarkable specificity for 4-methylsterols, and crystallographic structures coupled with docking and molecular dynamics simulations revealed the structural bases for substrate binding by two of the putative transporters. Their striking structural divergence from eukaryotic sterol transporters signals that they form a distinct sterol transport system within the bacterial domain. Finally, bioinformatics revealed the widespread presence of similar transporters in bacterial genomes, including in some pathogens that use host sterol lipids to construct their cell envelopes. The unique folds of these bacterial sterol binding proteins should now guide the discovery of other proteins that handle this essential metabolite.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1999

Hypergravity Facilities: Extending Knowledge Over the Continuum of Gravity

Historical perspectives, reasons for gravitational research, key questions regarding centrifuges, particular centrifuge discussions, vestibular research facilities, the hypergravity facility for cell culture, the human research facility, as well as the center for bioinformatics are all topics discussed in viewgraph form.

Souza, Kenneth A.↗
NASA NTRS2001

Combining Flux Balance and Energy Balance Analysis for Large-Scale Metabolic Network: Biochemical Circuit Theory for Analysis of Large-Scale Metabolic Networks

Predicting behavior of large-scale biochemical metabolic networks represents one of the greatest challenges of bioinformatics and computational biology. Approaches, such as flux balance analysis (FBA), that account for the known stoichiometry of the reaction network while avoiding implementation of detailed reaction kinetics are perhaps the most promising tools for the analysis of large complex networks. As a step towards building a complete theory of biochemical circuit analysis, we introduce energy balance analysis (EBA), which compliments the FBA approach by introducing fundamental constraints based on the first and second laws of thermodynamics. Fluxes obtained with EBA are thermodynamically feasible and provide valuable insight into the activation and suppression of biochemical pathways.

Beard, Daniel A.↗
NASA NTRS2003

Two Strategies for Microbial Production of an Industrial Enzyme-Alpha-Amylase

Extremophiles are microorganisms that thrive in, from an anthropocentric view, extreme environments including hot springs, soda lakes and arctic water. This ability of survival at extreme conditions has rendered extremophiles to be of interest in astrobiology, evolutionary biology as well as in industrial applications. Of particular interest to the biotechnology industry are the biological catalysts of the extremophiles, the extremozymes, whose unique stabilities at extreme conditions make them potential sources of novel enzymes in industrial applications. There are two major approaches to microbial enzyme production. This entails enzyme isolation directly from the natural host or creating a recombinant expression system whereby the targeted enzyme can be overexpressed in a mesophilic host. We are employing both methods in the effort to produce alpha-amylases from a hyperthermophilic archaeon (Thermococcus) isolated from a hydrothermal vent in the Atlantic Ocean, as well as from alkaliphilic bacteria (Bacillus) isolated from a soda lake in Tanzania. Alpha-amylases catalyze the hydrolysis of internal alpha-1,4-glycosidic linkages in starch to produce smaller sugars. Thermostable alpha-amylases are used in the liquefaction of starch for production of fructose and glucose syrups, whereas alpha-amylases stable at high pH have potential as detergent additives. The alpha-amylase encoding gene from Thermococcus was PCR amplified using carefully designed primers and analyzed using bioinformatics tools such as BLAST and Multiple Sequence Alignment for cloning and expression in E.coli. Four strains of Bacillus were grown in alkaline starch-enriched medium of which the culture supernatant was used as enzyme source. Amylolytic activity was detected using the starch-iodine method.

Bernhardsdotter, Eva C. M. J.↗
NASA NTRS2003

Macromolecular Expression and Function: A New Paradigm for NASA Risk Assessment

Predicting risks in humans of either acute effects such as bone loss or muscle wasting, or late effects such as cancer, is challenging. To an approximation, this is because uncertainties of exposure to stress factors or toxic agents and the uniformity of processing subsequent damage at the cellular level within a complex set of biological variables degrade the confidence of predicting pathologic outcome. A cellular biodosimeter that simultaneously reports 1) the type of damage due to that exposure, 2) the quantity of damage incurred by that exposure, and 3) the dataset used to assess risk of developing pathologic outcome caused by that exposure would therefore be useful for predicting ultimate risks faced by an individual, such as an astronaut. It is suggested that such a biodosimeter can be based upon analyses of gene-expression and protein expression whereby large datasets of cellular response to damage are obtained and analyzed for expression-profiles correlated with established end points and molecular markers predictive for risks being assessed. The usefulness of multiparametric cellular biodosimeters could be realized by quantitatively profiling these datasets using techniques of bioinformatics. Such an approach contributes to the foundation of molecular epidemiology as a new scientific discipline, and represents a new paradigm of risk assessment.

Richmond, Robert↗
NASA NTRS2004

Workshop on Molecular Evolution

Molecular evolution has become the nexus of many areas of biological research. It both brings together and enriches such areas as biochemistry, molecular biology, microbiology, population genetics, systematics, developmental biology, genomics, bioinformatics, in vitro evolution, and molecular ecology. The Workshop provides an important contribution to these fields in that it promotes interdisciplinary research and interaction, and thus provides a glue that sticks together disparate fields. Due to the wide range of fields addressed by the study of molecular evolution, it is difficult to offer a comprehensive course in a university setting. It is rare for a single institution to maintain expertise in all necessary areas. In contrast, the Workshop is uniquely able to provide necessary breadth and depth by utilizing a large number of faculty with appropriate expertise. Furthermore, the flexible nature of the Workshop allows for rapid adaptation to changes in the dynamic field of molecular evolution. For example, the 2003 Workshop included recently emergent research areas of molecular evolution of development and genomics.

Cummings, Michael P.↗
NASA NTRS2003

Ionizing radiation induces heritable disruption of epithelial cell interactions

Ionizing radiation (IR) is a known human breast carcinogen. Although the mutagenic capacity of IR is widely acknowledged as the basis for its action as a carcinogen, we and others have shown that IR can also induce growth factors and extracellular matrix remodeling. As a consequence, we have proposed that an additional factor contributing to IR carcinogenesis is the potential disruption of critical constraints that are imposed by normal cell interactions. To test this hypothesis, we asked whether IR affected the ability of nonmalignant human mammary epithelial cells (HMEC) to undergo tissue-specific morphogenesis in culture by using confocal microscopy and imaging bioinformatics. We found that irradiated single HMEC gave rise to colonies exhibiting decreased localization of E-cadherin, beta-catenin, and connexin-43, proteins necessary for the establishment of polarity and communication. Severely compromised acinar organization was manifested by the majority of irradiated HMEC progeny as quantified by image analysis. Disrupted cell-cell communication, aberrant cell-extracellular matrix interactions, and loss of tissue-specific architecture observed in the daughters of irradiated HMEC are characteristic of neoplastic progression. These data point to a heritable, nonmutational mechanism whereby IR compromises cell polarity and multicellular organization.

Non-NASA Center↗
NASA NTRS2000

Horizontal transfer of archaeal genes into the deinococcaceae: detection by molecular and computer-based approaches

Members of the Deinococcaceae (e.g., Thermus, Meiothermus, Deinococcus) contain A/V-ATPases typically found in Archaea or Eukaryotes which were probably acquired by horizontal gene transfer. Two methods were used to quantify the extent to which archaeal or eukaryotic genes have been acquired by this lineage. Screening of a Meiothermus ruber library with probes made against Thermoplasma acidophilum DNA yielded a number of clones which hybridized more strongly than background. One of these contained the prolyl tRNA synthetase (RS) gene. Phylogenetic analysis shows the M. ruber and D. radiodurans prolyl RS to be more closely related to archaeal and eukaryal forms of this gene than to the typical bacterial type. Using a bioinformatics approach, putative open reading frames (ORFs) from the prerelease version of the D. radiodurans genome were screened for genes more closely related to archaeal or eukaryotic genes. Putative ORFs were searched against representative genomes from each of the three domains using automated BLAST. ORFs showing the highest matches against archaeal and eukaryotic genes were collected and ranked. Among the top-ranked hits were the A/V-ATPase catalytic and noncatalytic subunits and the prolyl RS genes. Using phylogenetic methods, ORFs were analyzed and trees assessed for evidence of horizontal gene transfer. Of the 45 genes examined, 20 showed topologies in which D. radiodurans homologues clearly group with eukaryotic or archaeal homologues, and 17 additional trees were found to show probable evidence of horizontal gene transfer. Compared to the total number of ORFs in the genome, those that can be identified as having been acquired from Archaea or Eukaryotes are relatively few (approximately 1%), suggesting that interdomain transfer is rare.

Non-NASA Center↗
NASA NTRS2005

The Future of Bio-technology

Hosts of technologies, most notably in electronics, have been on the path of miniaturization for decades and in 2005 they have crossed the threshold of the nano-scale. Crossing the nano-scale threshold is a milestone in miniaturization, setting impressive new standards for component-packing densities. It also brings technology to a scale at which quantum effects and fault tolerance play significant roles and approaches the feasible physical limit form many conventional "top-down" manufacturing methods. I will suggest that the most formidable manufacturing problems in nanotechnology will be overcome and major breakthroughs will occur in a host of technologies, when nanotechnology converges with bio-technology; i.e. I will argue that the future of bio-technology is in nanotechnology. In 2005, methods in molecular biology, microscopy, bioinformatics, biochemistry, and genetic engineering have focused considerable attention on the nano-scale. On this scale, biology is a kind of recursive chemistry in which molecular recognition, self-assembly, self-organization and self-referencing context-control lead to the emergence of the complexity of structures and processes that are fundamental to all life forms. While we are still far from understanding this complexity, we are on the threshold of being able to use at least some of these biological properties for .technology. I will discuss the use of biomolecules, such as DNA, RNA, and proteins as "tools" for the bio-technologist of the future. More specifically, I will present in some detail an example of how we are using a genetically engineered 60-kDa protein (HSP60) from an organism living in near boiling sulfuric acid to build nano-scale templates for arranging metallic nanoparticles. These "extremophile" HSP60s self-assemble into robust double-ring structures called "chaperonins," which further assemble into filaments and arrays with nanometer accuracy. I will discuss our efforts to use chaperonins to organize quantum dots, electronic and magnetic nano-particles for electronic and photonic applications.

Trent, Jonathan↗
NASA NTRS2006

The 'Biologically-Inspired Computing' Column

The field of Biology changed dramatically in 1953, with the determination by Francis Crick and James Dewey Watson of the double helix structure of DNA. This discovery changed Biology for ever, allowing the sequencing of the human genome, and the emergence of a "new Biology" focused on DNA, genes, proteins, data, and search. Computational Biology and Bioinformatics heavily rely on computing to facilitate research into life and development. Simultaneously, an understanding of the biology of living organisms indicates a parallel with computing systems: molecules in living cells interact, grow, and transform according to the "program" dictated by DNA. Moreover, paradigms of Computing are emerging based on modelling and developing computer-based systems exploiting ideas that are observed in nature. This includes building into computer systems self-management and self-governance mechanisms that are inspired by the human body's autonomic nervous system, modelling evolutionary systems analogous to colonies of ants or other insects, and developing highly-efficient and highly-complex distributed systems from large numbers of (often quite simple) largely homogeneous components to reflect the behaviour of flocks of birds, swarms of bees, herds of animals, or schools of fish. This new field of "Biologically-Inspired Computing", often known in other incarnations by other names, such as: Autonomic Computing, Pervasive Computing, Organic Computing, Biomimetics, and Artificial Life, amongst others, is poised at the intersection of Computer Science, Engineering, Mathematics, and the Life Sciences. Successes have been reported in the fields of drug discovery, data communications, computer animation, control and command, exploration systems for space, undersea, and harsh environments, to name but a few, and augur much promise for future progress.

Hinchey, Mike↗
NASA NTRS2009

NASA Tech Briefs, August 2009

Topics covered include: Aligning a Receiving Antenna Array to Reduce Interference; Collecting Ground Samples for Balloon-Borne Instruments; Tethered Pyrotechnic Apparatus for Acquiring a Ground Sample; Enhanced Video-Oculography System; Joint Carrier-Phase Synchronization and LDPC Decoding; Dual-Polarization, Sideband-Separating, Balanced Receiver for 1.5 THz Modular Battery Charge Controller; Efficient Multiplexer FPGA Block Structures Based on G4FETs; VLSI Microsystem for Rapid Bioinformatic Pattern Recognition; Low-Noise Amplifier for 100 to 180 GHz; Improved Fabrication of Ceramic Matrix Composite/Foam Core Integrated Structures; Inert Welding/Brazing Gas Filters and Dryers; Fabricating Copper Nanotubes by Electrodeposition; Reducing Aerodynamic Drag on Empty Open Cargo Vehicles; Rotary Percussive Auto-Gopher for Deep Drilling and Sampling; More About Reconfigurable Exploratory Robotic Vehicles; Thermostatic Valves Containing Silicone-Oil Actuators; Improving Heat Flux Performance of Flat Surface in Spray-Cooling Systems; Treating Fibrous Insulation to Reduce Thermal Conductivity; Silica-Aerogel Composites Opacified with La(sub0.7)Sr(sub0.3)MnO3; Cyclic Oxidation Behavior of CuCrAl Cold-Sprayed Coatings for Reusable Launch Vehicles; Ceramic Fiber Structures for Cryogenic Load-Bearing Applications; Elastomer Reinforced with Carbon Nanotubes; Biologically Inspired Purification and Dispersion of SWCNTs; A Technique for Adjusting Eigenfrequencies of WGM Resonators; Low-Pressure, Field-Ionizing Mass Spectrometer; Modifying Operating Cycles to Increase Stability in a LITS; Chamber for Simulating Martian and Terrestrial Environments; Algorithm for Detecting a Bright Spot in an Image; Extreme Programming: Maestro Style; Adaptive Behavior for Mobile Robots; Protocol for Communication Networking for Formation Flying; Planning Complex Sequences Using Compressed Representations; and Self-Supervised Learning of Terrain Traversability from Proprioceptive Sensors.

Source record↗
NASA NTRS2009

A Local Scalable Distributed Expectation Maximization Algorithm for Large Peer-to-Peer Networks

This paper offers a local distributed algorithm for expectation maximization in large peer-to-peer environments. The algorithm can be used for a variety of well-known data mining tasks in a distributed environment such as clustering, anomaly detection, target tracking to name a few. This technology is crucial for many emerging peer-to-peer applications for bioinformatics, astronomy, social networking, sensor networks and web mining. Centralizing all or some of the data for building global models is impractical in such peer-to-peer environments because of the large number of data sources, the asynchronous nature of the peer-to-peer networks, and dynamic nature of the data/network. The distributed algorithm we have developed in this paper is provably-correct i.e. it converges to the same result compared to a similar centralized algorithm and can automatically adapt to changes to the data and the network. We show that the communication overhead of the algorithm is very low due to its local nature. This monitoring algorithm is then used as a feedback loop to sample data from the network and rebuild the model when it is outdated. We present thorough experimental results to verify our theoretical claims.

Bhaduri, Kanishka↗
NASA NTRS2010

The Use of Behavior Models for Predicting Complex Operations

Modeling and simulation (M&S) plays an important role when complex human-system notions are being proposed, developed and tested within the system design process. National Aeronautics and Space Administration (NASA) as an agency uses many different types of M&S approaches for predicting human-system interactions, especially when it is early in the development phase of a conceptual design. NASA Ames Research Center possesses a number of M&S capabilities ranging from airflow, flight path models, aircraft models, scheduling models, human performance models (HPMs), and bioinformatics models among a host of other kinds of M&S capabilities that are used for predicting whether the proposed designs will benefit the specific mission criteria. The Man-Machine Integration Design and Analysis System (MIDAS) is a NASA ARC HPM software tool that integrates many models of human behavior with environment models, equipment models, and procedural / task models. The challenge to model comprehensibility is heightened as the number of models that are integrated and the requisite fidelity of the procedural sets are increased. Model transparency is needed for some of the more complex HPMs to maintain comprehensibility of the integrated model performance. This will be exemplified in a recent MIDAS v5 application model and plans for future model refinements will be presented.

Gore, Brian F.↗
NASA NTRS2014

Cofactors in the RNA World

RNA world theories figure prominently in many scenarios for the origin and early evolution of life. These theories posit that RNA molecules played a much larger role in ancient biology than they do now, acting both as the dominant biocatalysts and as the repository of genetic information. Many features of modern RNA biology are potential examples of molecular fossils from an RNA world, such as the pervasive involvement of nucleotides in coenzymes, the existence of natural aptamers that bind these coenzymes, the existence of natural ribozymes, a biosynthetic pathway in which deoxynucleotides are produced from ribonucleotides, and the central role of ribosomal RNA in protein synthesis in the peptidyl transferase center of the ribosome. Here, we uses both a top-down approach that evaluates RNA function in modern biology and a bottom-up approach that examines the capacities of RNA independent of modern biology. These complementary approaches exploit multiple in vitro evolution techniques coupled with high-throughput sequencing and bioinformatics analysis. Together these complementary approaches advance our understanding of the most primitive organisms, their early evolution, and their eventual transition to modern biochemistry.

RNA↗
NASA NTRS2014

NASA GeneLab Concept of Operations

NASA's GeneLab aims to greatly increase the number of scientists that are using data from space biology investigations on board ISS, emphasizing a systems biology approach to the science. When completed, GeneLab will provide the integrated software and hardware infrastructure, analytical tools and reference datasets for an assortment of model organisms. GeneLab will also provide an environment for scientists to collaborate thereby increasing the possibility for data to be reused for future experimentation. To maximize the value of data from life science experiments performed in space and to make the most advantageous use of the remaining ISS research window, GeneLab will apply an open access approach to conducting spaceflight experiments by generating, and sharing the datasets derived from these biological studies in space.Onboard the ISS, a wide variety of model organisms will be studied and returned to Earth for analysis. Laboratories on the ground will analyze these samples and provide genomic, transcriptomic, metabolomic and proteomic data. Upon receipt, NASA will conduct data quality control tasks and format raw data returned from the omics centers into standardized, annotated information sets that can be readily searched and linked to spaceflight metadata. Once prepared, the biological datasets, as well as any analysis completed, will be made public through the GeneLab Space Bioinformatics System webb as edportal. These efforts will support a collaborative research environment for spaceflight studies that will closely resemble environments created by the Department of Energy (DOE), National Center for Biotechnology Information (NCBI), and other institutions in additional areas of study, such as cancer and environmental biology. The results will allow for comparative analyses that will help scientists around the world take a major leap forward in understanding the effect of microgravity, radiation, and other aspects of the space environment on model organisms. These efforts will speed the process of scientific sharing, iteration, and discovery.

Space Life Science↗