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At least 163 records · Page 9

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DOE OSTI2025

Empirical evidence that glucan-interacting amino acid side chains within the transmembrane channel collectively facilitate cellulose synthase function

The fundamental mechanism of cellulose synthesis is widely conserved across Kingdoms and depends on cellulose synthases, which are processive, dual-function, family 2 glycosyltransferases (GT-2). These enzymes polymerize glucose on the cytoplasmic side of the plasma membrane and export the glucan chain to the cell surface through an integral transmembrane (TM) channel. Structural studies of active plant cellulose synthases (CESAs) have revealed interactions between the nascent glucan chain and the side chains of polar, charged, and aromatic amino acid residues that line the TM channel. However, the functional consequences of modifying these side chains have not been tested in vivo in CESAs or other processive GT-2s. To test this, we used an established in vivo assay based on genetic complementation of CESA5 in the moss, Physcomitrium patens. For accurate prediction of glucan-interacting amino acid residues, we generated a complete homotrimeric molecular model of PpCESA5 using a combination of homology and de novo modeling. All-atom molecular dynamics-based analyses of contact metrics and interaction energy identified 23 amino acid residues with high propensity to interact with the nascent glucan chain within the TM channel or on the apoplastic surface of PpCESA5. Mutating any one of 18 of these amino acid residues to alanine, thereby removing their side chains, abolished or impaired CESA function, with the strongest effects observed upon the loss of charged amino acid side chains. This provides direct evidence to support the hypothesis that multiple amino acid residues collectively maintain a smooth energy landscape within the TM channel to facilitate glucan translocation.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2024

Extreme elevational migration spurred cryptic speciation in giant hummingbirds

The ecoevolutionary drivers of species niche expansion or contraction are critical for biodiversity but challenging to infer. Niche expansion may be promoted by local adaptation or constrained by physiological performance trade-offs. For birds, evolutionary shifts in migratory behavior permit the broadening of the climatic niche by expansion into varied, seasonal environments. Broader niches can be short-lived if diversifying selection and geography promote speciation and niche subdivision across climatic gradients. To illuminate niche breadth dynamics, we can ask how “outlier” species defy constraints. Of the 363 hummingbird species, the giant hummingbird (Patagona gigas) has the broadest climatic niche by a large margin. To test the roles of migratory behavior, performance trade-offs, and genetic structure in maintaining its exceptional niche breadth, we studied its movements, respiratory traits, and population genomics. Satellite and light-level geolocator tracks revealed an >8,300-km loop migration over the Central Andean Plateau. This migration included a 3-wk, ~4,100-m ascent punctuated by upward bursts and pauses, resembling the acclimatization routines of human mountain climbers, and accompanied by surging blood-hemoglobin concentrations. Extreme migration was accompanied by deep genomic divergence from high-elevation resident populations, with decisive postzygotic barriers to gene flow. The two forms occur side-by-side but differ almost imperceptibly in size, plumage, and respiratory traits. The high-elevation resident taxon is the world’s largest hummingbird, a previously undiscovered species that we describe and name here. The giant hummingbirds demonstrate evolutionary limits on niche breadth: when the ancestral niche expanded due to evolution (or loss) of an extreme migratory behavior, speciation followed.

Science & Technology - Other Topics↗

NASA NTRS1974

Experimental-clinical validation of the use of amitetravit, ATP and autologous bone marrow in radiation injuries caused by prolonged radiation

Experimental clinical studies show that early pathogenetic treatment against the effects of prolonged radiation includes amitetravit as a means of increasing natural radio resistance, ATP as protective therapeutic agent, and automyelotransplantation for early pathogenetic treatment. The high effectiveness of the combined use of ATP and amitetravit in tests on dogs indicates an ability to prevent primary damages to genetic structures and accelerated processes of reparation in the first stages of radiopathological processes.

Atamanova, O. M.↗

NASA NTRS1991

Experiences with the use of axisymmetric elements in cosmic NASTRAN for static analysis

Discussed here are some recent finite element modeling experiences using the axisymmetric elements CONEAX, TRAPAX, and TRIAAX, from the COSMIC NASTRAN element library. These experiences were gained in the practical application of these elements to the static analysis of helicopter rotor force measuring systems for two design projects for the NASA Ames Research Center. These design projects were the Rotor Test Apparatus and the Large Rotor Test Apparatus, which are dedicated to basic helicopter research. Here, a genetic axisymmetric model is generated for illustrative purposes. Modeling considerations are discussed, and the advantages and disadvantages of using axisymmetric elements are presented. Asymmetric mechanical and thermal loads are applied to the structure, and single and multi-point constraints are addressed. An example that couples the axisymmetric model to a non-axisymmtric model is demonstrated, complete with DMAP alters. Recommendations for improving the elements and making them easier to use are offered.

Cooper, Michael J.↗

NASA NTRS2013

Dual-Polarization, Multi-Frequency Antenna Array for use with Hurricane Imaging Radiometer

Advancements in common aperture antenna technology were employed to utilize its proprietary genetic algorithmbased modeling tools in an effort to develop, build, and test a dual-polarization array for Hurricane Imaging Radiometer (HIRAD) applications. Final program results demonstrate the ability to achieve a lightweight, thin, higher-gain aperture that covers the desired spectral band. NASA employs various passive microwave and millimeter-wave instruments, such as spectral radiometers, for a range of remote sensing applications, from measurements of the Earth's surface and atmosphere, to cosmic background emission. These instruments such as the HIRAD, SFMR (Stepped Frequency Microwave Radiometer), and LRR (Lightweight Rainfall Radiometer), provide unique data accumulation capabilities for observing sea surface wind, temperature, and rainfall, and significantly enhance the understanding and predictability of hurricane intensity. These microwave instruments require extremely efficient wideband or multiband antennas in order to conserve space on the airborne platform. In addition, the thickness and weight of the antenna arrays is of paramount importance in reducing platform drag, permitting greater time on station. Current sensors are often heavy, single- polarization, or limited in frequency coverage. The ideal wideband antenna will have reduced size, weight, and profile (a conformal construct) without sacrificing optimum performance. The technology applied to this new HIRAD array will allow NASA, NOAA, and other users to gather information related to hurricanes and other tropical storms more cost effectively without sacrificing sensor performance or the aircraft time on station. The results of the initial analysis and numerical design indicated strong potential for an antenna array that would satisfy all of the design requirements for a replacement HIRAD array. Multiple common aperture antenna methodologies were employed to achieve exceptional gain over the entire spectral frequency band while exhibiting superb VSWR (voltage standing wave ratio) values. Element size and spacing requirements were addressed for a direct replacement of the thicker, lower-performance, stack ed patch antenna array currently employed for the HIRAD application. Several variants to the multiband arrays were developed that exhibited four, equally spaced, high efficiency, "sweet spot" frequency bands, as well as the option for a high-performance wideband array. The 0.25-in. (≈6.4- mm) thickness of the antenna stack-up itself was achieved through the application of specialized antenna techniques and meta-materials to accomplish all design objectives.

Little, John↗

NASA NTRS2005

Retrieval of Dry Snow Parameters from Radiometric Data Using a Dense Medium Model and Genetic Algorithms

In this paper, GA-based techniques are used to invert the equations of an electromagnetic model based on Dense Medium Radiative Transfer Theory (DMRT) under the Quasi Crystalline Approximation with Coherent Potential to retrieve snow depth, mean grain size and fractional volume from microwave brightness temperatures. The technique is initially tested on both noisy and not-noisy simulated data. During this phase, different configurations of genetic algorithm parameters are considered to quantify how their change can affect the algorithm performance. A configuration of GA parameters is then selected and the algorithm is applied to experimental data acquired during the NASA Cold Land Process Experiment. Snow parameters retrieved with the GA-DMRT technique are then compared with snow parameters measured on field.

Tedesco, Marco↗

DOE OSTI2024

Type 1 Diabetes Genetic Risk in 109,954 Veterans With Adult-Onset Diabetes: The Million Veteran Program (MVP)

OBJECTIVE To characterize high type 1 diabetes (T1D) genetic risk in a population where type 2 diabetes (T2D) predominates. RESEARCH DESIGN AND METHODS Characteristics typically associated with T1D were assessed in 109,594 Million Veteran Program participants with adult-onset diabetes, 2011–2021, who had T1D genetic risk scores (GRS) defined as low (0 to <45%), medium (45 to <90%), high (90 to <95%), or highest (≥95%). RESULTS T1D characteristics increased progressively with higher genetic risk (P < 0.001 for trend). A GRS ≥90% was more common with diabetes diagnoses before age 40 years, but 95% of those participants were diagnosed at age ≥40 years, and their characteristics resembled those of individuals with T2D in mean age (64.3 years) and BMI (32.3 kg/m2). Compared with the low-risk group, the highest-risk group was more likely to have diabetic ketoacidosis (low GRS 0.9% vs. highest GRS 3.7%), hypoglycemia prompting emergency visits (3.7% vs. 5.8%), outpatient plasma glucose <50 mg/dL (7.5% vs. 13.4%), a shorter median time to start insulin (3.5 vs. 1.4 years), use of a T1D diagnostic code (16.3% vs. 28.1%), low C-peptide levels if tested (1.8% vs. 32.4%), and glutamic acid decarboxylase antibodies (6.9% vs. 45.2%), all P < 0.001. CONCLUSIONS Characteristics associated with T1D were increased with higher genetic risk, and especially with the top 10% of risk. However, the age and BMI of those participants resemble those of people with T2D, and a substantial proportion did not have diagnostic testing or use of T1D diagnostic codes. T1D genetic screening could be used to aid identification of adult-onset T1D in settings in which T2D predominates.

Yang, Peter K. (ORCID:0000000193796981)↗

DOE OSTI2021

Increasing temperature weakens the positive effect of genetic diversity on population growth

Abstract Genetic diversity and temperature increases associated with global climate change are known to independently influence population growth and extinction risk. Whether increasing temperature may influence the effect of genetic diversity on population growth, however, is not known. We address this issue in the model protist system Tetrahymena thermophila . We test the hypothesis that at temperatures closer to the species’ thermal optimum (i.e., the temperature at which population growth is maximal, or T opt ), genetic diversity should have a weaker effect on population growth compared to temperatures away from the thermal optimum. To do so, we grew populations of T . thermophila with varying levels of genetic diversity at increasingly warmer temperatures and quantified their intrinsic population growth rate, r . We found that genetic diversity increases population growth at cooler temperatures, but that as temperature increases, this effect weakens. We also show that a combination of changes in the amount of expressed genetic diversity (G) in r , plastic changes in population growth across temperatures (E), and strong G × E interactions underlie this temperature effect. Our results uncover important but largely overlooked temperature effects that have implications for the management of small populations with depauperate genetic stocks in an increasingly warming world.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS1999

Transduction-like gene transfer in the methanogen Methanococcus voltae

Strain PS of Methanococcus voltae (a methanogenic, anaerobic archaebacterium) was shown to generate spontaneously 4.4-kbp chromosomal DNA fragments that are fully protected from DNase and that, upon contact with a cell, transform it genetically. This activity, here called VTA (voltae transfer agent), affects all markers tested: three different auxotrophies (histidine, purine, and cobalamin) and resistance to BES (2-bromoethanesulfonate, an inhibitor of methanogenesis). VTA was most effectively prepared by culture filtration. This process disrupted a fraction of the M. voltae cells (which have only an S-layer covering their cytoplasmic membrane). VTA was rapidly inactivated upon storage. VTA particles were present in cultures at concentrations of approximately two per cell. Gene transfer activity varied from a minimum of 2 x 10(-5) (BES resistance) to a maximum of 10(-3) (histidine independence) per donor cell. Very little VTA was found free in culture supernatants. The phenomenon is functionally similar to generalized transduction, but there is no evidence, for the time being, of intrinsically viral (i.e., containing a complete viral genome) particles. Consideration of VTA DNA size makes the existence of such viral particles unlikely. If they exist, they must be relatively few in number;perhaps they differ from VTA particles in size and other properties and thus escaped detection. Digestion of VTA DNA with the AluI restriction enzyme suggests that it is a random sample of the bacterial DNA, except for a 0.9-kbp sequence which is amplified relative to the rest of the bacterial chromosome. A VTA-sized DNA fraction was demonstrated in a few other isolates of M. voltae.

Methanococcus/genetics/growth & development/metabo↗

DOE OSTI2024

Genetic Complexity of CC5 Staphylococcus aureus Isolates Associated with Sternal Bursitis in Chickens: Antimicrobial Resistance, Virulence, Plasmids, and Biofilm Formation

Sternal bursitis, a common inflammatory condition in poultry, poses significant challenges to both animal welfare and public health. This study aimed to investigate the prevalence, antimicrobial resistance, and genetic characteristics of Staphylococcus aureus isolates associated with sternal bursitis in chickens. Ninety-eight samples were collected from affected chickens, and 24 S. aureus isolates were identified. Antimicrobial susceptibility testing revealed resistance to multiple agents, with a notable prevalence of aminoglycoside resistance genes. Whole genome sequencing elucidated the genetic diversity and virulence profiles of the isolates, highlighting the predominance of clonal complex 5 (CC5) strains. Additionally, biofilm formation assays demonstrated moderate biofilm production capacity among the isolates. These findings underscore the importance of vigilant monitoring and targeted interventions to mitigate the impact of sternal bursitis in poultry production systems.

Silva, Vanessa (ORCID:0000000194068433)↗

DOE OSTI2022

Dynamic and single cell characterization of a CRISPR-interference toolset in Pseudomonas putida KT2440 for β-ketoadipate production from p -coumarate

We report Pseudomonas putida KT2440 is a well-studied bacterium for the conversion of lignin-derived aromatic compounds to bioproducts. The development of advanced genetic tools in P. putida has reduced the turnaround time for hypothesis testing and enabled the construction of strains capable of producing various products of interest. Here, we evaluate an inducible CRISPR-interference (CRISPRi) toolset on fluorescent, essential, and metabolic targets. Nuclease-deficient Cas9 (dCas9) expressed with the arabinose (8K)-inducible promoter was shown to be tightly regulated across various media conditions and when targeting essential genes. In addition to bulk growth data, single cell time lapse microscopy was conducted, which revealed intrinsic heterogeneity in knockdown rate within an isoclonal population. The dynamics of knockdown were studied across genomic targets in exponentially-growing cells, revealing a universal 1.75 ± 0.38 hour quiescent phase after induction where 1.5 ± 0.35 doublings occur before a phenotypic response is observed. To demonstrate application of this CRISPRi toolset, β-ketoadipate, a monomer for performance-advantaged nylon, was produced at a 4.39 ± 0.5 g/L and yield of 0.76 ± 0.10 mol/mol from p-coumarate, a hydroxycinnamic acid that can be derived from grasses. These cultivation metrics were achieved by using the higher strength IPTG (1K)-inducible promoter to knockdown the pcaIJ operon in the βKA pathway during early exponential phase. This allowed the majority of the carbon to be shunted into the desired product while eliminating the need for a supplemental carbon and energy source to support growth and maintenance.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2025

Local adaptation of both plant and pathogen: an arms‐race compromise in switchgrass rust

In coevolving species, parasites locally adapt to host populations as hosts locally adapt to resist parasites. Parasites often outpace host local adaptation since they have rapid life cycles, but host diversity, the strength of selection, and external environmental influence can result in complex outcomes. To better understand local adaptation in host–parasite systems, we examined locally adapted switchgrass (Panicum virgatum), and its leaf rust pathogen (Puccinia novopanici) across a latitudinal range in North America. We grew switchgrass genotypes in 10 replicated multiyear common gardens, measuring rust severity from natural infection in a ‘host reciprocal transplant’ framework for testing local adaptation. We conducted genome-wide association mapping to identify genetic loci associated with rust severity. Genetically differentiated rust populations were locally adapted to northern and southern switchgrass, despite host local adaptation to environmental conditions in the same regions. Rust resistance was polygenic, and distinct loci were associated with rust severity in the north and south. We narrowed a previously identified large-effect quantitative trait locus for rust severity to a candidate YELLOW STRIPE-LIKE gene and linked numerous other loci to defense-related genes. Overall, our results suggest that both hosts and parasites can be simultaneously locally adapted, especially when parasites impose less selection than other environmental factors.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS2000

Multidisciplinary Techniques and Novel Aircraft Control Systems

The Aircraft Morphing Program at NASA Langley Research Center explores opportunities to improve airframe designs with smart technologies. Two elements of this basic research program are multidisciplinary design optimization (MDO) and advanced flow control. This paper describes examples where MDO techniques such as sensitivity analysis, automatic differentiation, and genetic algorithms contribute to the design of novel control systems. In the test case, the design and use of distributed shapechange devices to provide low-rate maneuvering capability for a tailless aircraft is considered. The ability of MDO to add value to control system development is illustrated using results from several years of research funded by the Aircraft Morphing Program.

Padula, Sharon L.↗

NASA NTRS2000

Multidisciplinary Techniques and Novel Aircraft Control Systems

The Aircraft Morphing Program at NASA Langley Research Center explores opportunities to improve airframe designs with smart technologies. Two elements of this basic research program are multidisciplinary design optimization (MDO) and advanced flow control. This paper describes examples where MDO techniques such as sensitivity analysis, automatic differentiation, and genetic algorithms contribute to the design of novel control systems. In the test case, the design and use of distributed shape-change devices to provide low-rate maneuvering capability for a tailless aircraft is considered. The ability of MDO to add value to control system development is illustrated using results from several years of research funded by the Aircraft Morphing Program.

Padula, Sharon L.↗

NASA NTRS2012

Optimal Integration of Departure and Arrivals in Terminal Airspace

Coordination of operations with spatially and temporally shared resources such as route segments, fixes, and runways improves the efficiency of terminal airspace management. Problems in this category include scheduling and routing, thus they are normally difficult to solve compared with pure scheduling problems. In order to reduce the computational time, a fast time algorithm formulation using a non-dominated sorting genetic algorithm (NSGA) was introduced in this work and applied to a test case based on existing literature. The experiment showed that new method can solve the whole problem in fast time instead of solving sub-problems sequentially with a window technique. The results showed a 60% or 406 second delay reduction was achieved by sharing departure fixes (more details on the comparison with MILP results will be presented in the final paper). Furthermore, the NSGA algorithm was applied to a problem in LAX terminal airspace, where interactions between 28% of LAX arrivals and 10% of LAX departures are resolved by spatial segregation, which may introduce unnecessary delays. In this work, spatial segregation, temporal segregation, and hybrid segregation were formulated using the new algorithm. Results showed that spatial and temporal segregation approaches achieved similar delay. Hybrid segregation introduced much less delay than the other two approaches. For a total of 9 interacting departures and arrivals, delay reduction varied from 4 minutes to 6.4 minutes corresponding flight time uncertainty from 0 to 60 seconds. Considering the amount of flights that could be affected, total annual savings with hybrid segregation would be significant.

high density terminal↗

NASA NTRS2017

Abiotic Synthesis of Nucleic Acids: Hypochromicity and Future Research

The earliest forms of life would likely have a protocellular form, with a membrane encapsulating some form of linear charged polymer. These polymers could have enzymatic as well as genetic properties. We can simulate plausible prebiotic conditions in the laboratory to test hypotheses related to this concept. In earlier work we have shown that mononucleotides organized within a multilamellar lipid matrix can produce oligomers in the anhydrous phase of dehydration- rehydration cycles (Rajamani, 2008). If mononucleotides are in solution at millimolar concentrations, then oligomers resembling RNA are synthesized and exist in a steady state with their monomers DeGuzman, 2014). We have used conventional and novel techniques to demonstrate that secondary structures stabilized by hydrogen bonds may be present in the condensation products produced in dehydration- rehydration cycles that simulate hydrothermal fields that were present on the early Earth. Gel electrophoresis data corroborates the presence of up to 200-base pair length RNA fragments in products of Hydration-Dehydration experiments. Furthermore, hypochromicity measurements demonstrate a degree of hypochromicity found in single RNA strand of known sequence, as well as results that indicate this is true also for a sample of complementary strands of RNA. Analysis of ionic current signatures of known RNA hairpin molecule as measured using a nanopore detector indicate a significant variability in pattern, different from the signatures produced by DNA hairpin molecules. This informs how we may interpret nanopore data gathered from prebiotic simulations.

Glass, K.↗

NASA NTRS2019

A Multi-Omics Approach Demonstrates that Spaceflight Leads to Lipid Accumulation in Mouse Livers

Spaceflight has several detrimental effects on the physiology of astronauts, many of which are recapitulated in rodent models. We analyzed liver transcriptomic and proteomic data from three mouse spaceflight experiments flown aboard the International Space Station (Rodent Research-1 NASA (RR-1 NASA), Rodent Research-1 CASIS (RR-1 CASIS), Rodent Research-3 (RR-3)), and one mouse experiment flown on the Space Shuttle (Commercial Biomedical Testing Module-3 (CBTM-3) aboard STS-135). Despite the differences in genetic background and time of exposure to microgravity it was shown through Oil Red staining and histology that increased lipid accumulation was occurring in the liver of all mice flown in space compared to the ground controls. This led to further pursue the existing GeneLab datasets related to liver omics data from these mice. We were able to discover key conserved pathways across all the mice independent of the flight conditions that were related to increased lipid metabolism, fatty acid metabolism, both lipid and fatty acid processing, lipid catabolic processing, and lipid localization. In addition, key upstream regulators were predicted to be commonly regulated across all conditions which include ESR1, GCG, and NR1I2 being inhibited and INS being activated. Interestingly, estrogen receptor alpha (ESR1) expression has been known to be heavily involved with lipoprotein metabolism. In addition, insulin (INS) is the primary driver for fat metabolism and increased INS has been associated with increased fatty acids in the liver. Through additional proteomic analysis we were able to identify the majority of the key proteins related to lipids for both the RR-1 and RR-3 rodents were being up-regulated in the livers when comparing flight to ground controls. This additional confirmation of the lipid associated activity also showed that the lipid related proteins are heavily involved with lipid metabolism, cholesterol binding, and cholesterol metabolism. Lastly, the analysis also revealed that the circadian clock related pathways in the liver are commonly being increased across all space flight conditions which has also been reported in the literature to potentially cause increased liver damage. The combination of the very strong lipid uptake in the liver and the transcriptomic/proteomic signatures (including the circadian clock pathways) following spaceflight are consistent with early onset of liver disease. Taken together, these data indicate that, activation of lipotoxic pathways could persist during longer duration spaceflight which might result in the development of liver disease

Lipids↗

NASA NTRSDate not supplied

Machine Learning for Dynamic Test Sensor Placement

There are multiple different algorithms to perform modal test sensor placement optimization: effective independence, residual kinetic energy, iterative Guyan reduction, genetic algorithms, or a brute-force methodology. However, any of these methods may be computationally expensive, especially for structural models with a large number of degrees of freedom. Given the high-cost and the need to optimize the solution, modal sensor placement is a great application for machine learning (ML) algorithms. In this paper, we will apply ML algorithms to determine the optimal sensor locations for simple and complex structures. We will also discuss the benefits and drawbacks of using machine learning over other sensor placement algorithms.

Kelsey Buckles↗