Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “Genetic interaction”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9

Symbiont acquisition as neoseme: origin of species and higher taxa

We examine the hypothesis that, in the origin of species and higher taxa of eukaryotes, symbiont acquisition followed by partner integration has been equivalent to neoseme appearance leading to speciation. The formation of stable symbiotic associations involves partner-surface recognition, behavioral and metabolic interaction, and, in some cases, gene product (RNA, protein) and genic (RNA, DNA) integration. This analysis is applied here to examples of neosemes that define specific taxa and to neosemes in plants, fungi, and animals that involve the appearance of new types of tissue. If this hypothesis is correct--if the origin of major genetic variation leading to speciation and even higher taxa may occur through symbiont acquisition and integration--then the analysis of "origins of species and higher taxa" becomes analogous to the study of microbial community ecology.

NASA Discipline Exobiology↗

Protein machines and self assembly in muscle organization

The remarkable order of striated muscle is the result of a complex series of protein interactions at different levels of organization. Within muscle, the thick filament and its major protein myosin are classical examples of functioning protein machines. Our understanding of the structure and assembly of thick filaments and their organization into the regular arrays of the A-band has recently been enhanced by the application of biochemical, genetic, and structural approaches. Detailed studies of the thick filament backbone have shown that the myosins are organized into a tubular structure. Additional protein machines and specific myosin rod sequences have been identified that play significant roles in thick filament structure, assembly, and organization. These include intrinsic filament components, cross-linking molecules of the M-band and constituents of the membrane-cytoskeleton system. Muscle organization is directed by the multistep actions of protein machines that take advantage of well-established self-assembly relationships. Copyright 1999 John Wiley & Sons, Inc.

NASA Discipline Musculoskeletal↗

Expanding Fungal Diets Through Synthetic Algal-Fungal Mutualism

Fungi can synthesize numerous molecules with important properties, and could be valuable production platforms for space exploration and colonization. However, as heterotrophs, fungi require reduced carbon. This limits their efficiency in locations such as Mars, where reduced carbon is scarce. We propose a system to induce mutualistic symbiosis between the green algae Chlamydomonas reinhardtii and the filamentous fungi Neurospora crassa. This arrangement would mimic natural algal-fungal relationships found in lichens, but have added advantages including increased growth rate and genetic tractability. N. crassa would metabolize citrate (C6H5O7 (sup -3)) and release carbon dioxide (CO2) that C. reinhardtii would assimilate into organic sugars during photosynthesis. C. reinhardtii would metabolize nitrate (NO3−) and release ammonia (NH3) as a nitrogen source for N. crassa. A N. crassa mutant incapable of reducing nitrate will be used to force this interaction. This system eliminates the need to directly supply its participants with carbon dioxide and ammonia. Furthermore, the release of oxygen by C. reinhardtii via photosynthesis would enable N. crassa to respire. We hope to eventually create a system closer to lichen, in which the algae transfers not only nitrogen but reduced carbon, as organic sugars, to the fungus for growth and production of valuable compounds.

Fungi↗

Characterization of Aircraft Structural Damage Using Guided Wave Based Finite Element Analysis for In-Flight Structural Health Management

The development of multidisciplinary Integrated Vehicle Health Management (IVHM) tools will enable accurate detection, diagnosis and prognosis of damage under normal and adverse conditions during flight. The adverse conditions include loss of control caused by environmental factors, actuator and sensor faults or failures, and structural damage conditions. A major concern is the growth of undetected damage/cracks due to fatigue and low velocity foreign object impact that can reach a critical size during flight, resulting in loss of control of the aircraft. To avoid unstable catastrophic propagation of damage during a flight, load levels must be maintained that are below the load-carrying capacity for damaged aircraft structures. Hence, a capability is needed for accurate real-time predictions of safe load carrying capacity for aircraft structures with complex damage configurations. In the present work, a procedure is developed that uses guided wave responses to interrogate damage. As the guided wave interacts with damage, the signal attenuates in some directions and reflects in others. This results in a difference in signal magnitude as well as phase shifts between signal responses for damaged and undamaged structures. Accurate estimation of damage size and location is made by evaluating the cumulative signal responses at various pre-selected sensor locations using a genetic algorithm (GA) based optimization procedure. The damage size and location is obtained by minimizing the difference between the reference responses and the responses obtained by wave propagation finite element analysis of different representative cracks, geometries and sizes.

Seshadri, Banavara R.↗

Stereomolecular interactions and microsystems in experimental protobiogenesis

A theory on the origin of the first reproducing (in the sense of Fox, 1973) cells on earth is presented. A degree of self-ordering has been observed in the selective thermal reactions of certain ones of the amino acids which have been found in samples of meteorites, lunar samples, and terrestrial lava, and which have been synthesized from formaldehyde and ammonia under conditions modeling those assumed to have been present in the primitive earth. The genetic code is supposed to have arisen from a nonrandom matrix of preproteins. The ordering of preproteins specified limitations in the identity of the pre-enzymes and primordial microsystems which gave rise to contemporary living systems. The evolution of progresively more complex system was largely determined by stereochemical forces involving the shapes of the molecules themselves and the regulatory effects of the confines of the microsystems.

Fox, S. W.↗

Structural Health Management of Damaged Aircraft Structures Using the Digital Twin Concept

The development of multidisciplinary integrated Structural Health Management (SHM) tools will enable accurate detection, and prognosis of damaged aircraft under normal and adverse conditions during flight. As part of the digital twin concept, methodologies are developed by using integrated multiphysics models, sensor information and input data from an in-service vehicle to mirror and predict the life of its corresponding physical twin. SHM tools are necessary for both damage diagnostics and prognostics for continued safe operation of damaged aircraft structures. The adverse conditions include loss of control caused by environmental factors, actuator and sensor faults or failures, and structural damage conditions. A major concern in these structures is the growth of undetected damage/cracks due to fatigue and low velocity foreign object impact that can reach a critical size during flight, resulting in loss of control of the aircraft. To avoid unstable, catastrophic propagation of damage during a flight, load levels must be maintained that are below a reduced load-carrying capacity for continued safe operation of an aircraft. Hence, a capability is needed for accurate real-time predictions of damage size and safe load carrying capacity for structures with complex damage configurations. In the present work, a procedure is developed that uses guided wave responses to interrogate damage. As the guided wave interacts with damage, the signal attenuates in some directions and reflects in others. This results in a difference in signal magnitude as well as phase shifts between signal responses for damaged and undamaged structures. Accurate estimation of damage size, location, and orientation is made by evaluating the cumulative signal responses at various pre-selected sensor locations using a genetic algorithm (GA) based optimization procedure. The damage size, location, and orientation is obtained by minimizing the difference between the reference responses and the responses obtained by wave propagation finite element analysis of different representative cracks, geometries, and sizes.

Seshadri, Banavara R.↗

Contact-dependent growth inhibition (CDI) systems deploy a large family of polymorphic ionophoric toxins for inter-bacterial competition

Contact-dependent growth inhibition (CDI) is a widespread form of inter-bacterial competition mediated by CdiA effector proteins. CdiA is presented on the inhibitor cell surface and delivers its toxic C-terminal region (CdiA-CT) into neighboring bacteria upon contact. Inhibitor cells also produce CdiI immunity proteins, which neutralize CdiA-CT toxins to prevent auto-inhibition. Here, we describe a diverse group of CDI ionophore toxins that dissipate the transmembrane potential in target bacteria. These CdiA-CT toxins are composed of two distinct domains based on AlphaFold2 modeling. The C-terminal ionophore domains are all predicted to form five-helix bundles capable of spanning the cell membrane. The N-terminal "entry" domains are variable in structure and appear to hijack different integral membrane proteins to promote toxin assembly into the lipid bilayer. The CDI ionophores deployed by E. coli isolates partition into six major groups based on their entry domain structures. Comparative sequence analyses led to the identification of receptor proteins for ionophore toxins from groups 1 & 3 (AcrB), group 2 (SecY) and groups 4 (YciB). Using forward genetic approaches, we identify novel receptors for the group 5 and 6 ionophores. Group 5 exploits homologous putrescine import proteins encoded by puuP and plaP, and group 6 toxins recognize di/tripeptide transporters encoded by paralogous dtpA and dtpB genes. Finally, we find that the ionophore domains exhibit significant intra-group sequence variation, particularly at positions that are predicted to interact with CdiI. Accordingly, the corresponding immunity proteins are also highly polymorphic, typically sharing only ~30% sequence identity with members of the same group. Competition experiments confirm that the immunity proteins are specific for their cognate ionophores and provide no protection against other toxins from the same group. The specificity of this protein interaction network provides a mechanism for self/nonself discrimination between E. coli isolates.

59 BASIC BIOLOGICAL SCIENCES↗

Streptococcus pneumoniae HtrA is a dynamic and monomeric virulence factor capable of forming larger oligomeric complexes

Abstract High‐temperature requirement A (HtrA) proteases are a conserved family of serine proteases central to protein quality control and bacterial virulence. While Gram‐negative and human HtrAs are structurally well studied, Gram‐positive homologs remain essentially uncharacterized. Here, we present the first integrated structural and mechanistic analysis of a Gram‐positive HtrA, from Streptococcus pneumoniae , a virulence factor essential for adhesion and infection in vivo. Proteomic profiling of an htrA knockout and cleavage assays demonstrate that S. pneumoniae HtrA is required for protein quality control, with the PDZ domain mediating substrate recognition. Biochemically, S. pneumoniae HtrA exists exclusively as a monomer in solution, a striking divergence from canonical trimeric HtrAs that we show is shared with other Gram‐positive homologs. NMR analyses reveal that the monomer dynamically samples open and closed conformations, while cryo‐EM of a catalytic mutant identifies a hexamer stabilized by a unique LoopA–PDZ interaction. Together, these findings define S. pneumoniae HtrA as a dynamic monomer with interdomain coupling between its protease and PDZ domains, establishing Gram‐positive HtrAs as a mechanistically divergent subgroup within the HtrA family.

Lee, Eunjeong [Department of Biochemistry and Mole↗

Knocking out the carboxyltransferase interactor 1 (CTI1) in Chlamydomonas boosted oil content by fivefold without affecting cell growth

Summary The first step in chloroplast de novo fatty acid synthesis is catalysed by acetyl‐CoA carboxylase (ACCase). As the rate‐limiting step for this pathway, ACCase is subject to both positive and negative regulation. In this study, we identify a Chlamydomonas homologue of the plant carboxyltransferase interactor 1 (CrCTI1) and show that this protein interacts with the Chlamydomonas α‐carboxyltransferase (Crα‐CT) subunit of the ACCase by yeast two‐hybrid protein–protein interaction assay. Three independent CRISPR‐Cas9 mediated knockout mutants for CrCTI1 each produced an ‘enhanced oil’ phenotype, accumulating 25% more total fatty acids and storing up to fivefold more triacylglycerols (TAGs) in lipid droplets. The TAG phenotype of the crcti1 mutants was not influenced by light but was affected by trophic growth conditions. By growing cells under heterotrophic conditions, we observed a crucial function of CrCTI1 in balancing lipid accumulation and cell growth. Mutating a previously mapped in vivo phosphorylation site (CrCTI1 Ser108 to either Ala or to Asp), did not affect the interaction with Crα‐CT. However, mutating all six predicted phosphorylation sites within Crα‐CT to create a phosphomimetic mutant reduced this pairwise interaction significantly. Comparative proteomic analyses of the crcti1 mutants and WT suggested a role for CrCTI1 in regulating carbon flux by coordinating carbon metabolism, antioxidant and fatty acid β‐oxidation pathways, to enable cells to adapt to carbon availability. Taken together, this study identifies CrCTI1 as a negative regulator of fatty acid synthesis in algae and provides a new molecular brick for the genetic engineering of microalgae for biotechnology purposes.

Li, Zhongze [Aix‐Marseille Université, CEA, CNRS, ↗

Physical interaction of the activator protein-1 factors c-Fos and c-Jun with Cbfa1 for collagenase-3 promoter activation

Previously, we determined that the activator protein-1 (AP-1)-binding site and the runt domain (RD)-binding site and their binding proteins, c-Fos.c-Jun and Cbfa, regulate the collagenase-3 promoter in parathyroid hormone-treated and differentiating osteoblasts. Here we show that Cbfa1 and c-Fos.c-Jun appear to cooperatively bind the RD- and AP-1-binding sites and form ternary structures in vitro. Both in vitro and in vivo co-immunoprecipitation and yeast two-hybrid studies further demonstrate interaction between Cbfa1 with c-Fos and c-Jun in the absence of phosphorylation and without binding to DNA. Additionally, only the runt domain of Cbfa1 was required for interaction with c-Jun and c-Fos. In mammalian cells, overexpression of Cbfa1 enhanced c-Jun activation of AP-1-binding site promoter activity, demonstrating functional interaction. Finally, insertion of base pairs that disrupted the helical phasing between the AP-1- and RD-binding sites also inhibited collagenase-3 promoter activation. Thus, we provide direct evidence that Cbfa1 and c-Fos.c-Jun physically interact and cooperatively bind the AP-1- and RD-binding sites in the collagenase-3 promoter. Moreover, the AP-1- and RD-binding sites appear to be organized in a specific required helical arrangement that facilitates transcription factor interaction and enables promoter activation.

Non-NASA Center↗

Three stages in the evolution of the genetic code

A diversification of the genetic code based on the number of codons available for the proteinous amino acids is established. Three groups of amino acids during evolution of the code are distinguished. On the basis of their chemical complexity those amino acids emerging later in a translation process are derived. Codon number and chemical complexity indicate that His, Phe, Tyr, Cys and either Lys or Asn were introduced in the second stage, whereas the number of codons alone gives evidence that Trp and Met were introduced in the third stage. The amino acids of stage 1 use purine-rich codons, while all the amino acids introduced in the second stage, in contrast, use pyrimidines in the third position of their codons. A low abundance of pyrimidines during early translation is derived. This assumption is supported by experiments on non-enzymatic replication and interactions of hairpin loops with a complementary strand. A back extrapolation concludes a high purine content of the first nucleic acids, which gradually decreased during their evolution. Amino acids independently available from prebiotic synthesis were thus correlated to purine-rich codons. Implications on the prebiotic replication are discussed also in the light of recent codon usage data.

Review↗

Genome resources for three modern cotton lines guide future breeding efforts

Cotton ( Gossypium hirsutum L.) is the key renewable fibre crop worldwide, yet its yield and fibre quality show high variability due to genotype-specific traits and complex interactions among cultivars, management practices and environmental factors. Modern breeding practices may limit future yield gains due to a narrow founding gene pool. Precision breeding and biotechnological approaches offer potential solutions, contingent on accurate cultivar-specific data. Here we address this need by generating high-quality reference genomes for three modern cotton cultivars (‘UGA230’, ‘UA48’ and ‘CSX8308’) and updating the ‘TM-1’ cotton genetic standard reference. Despite hypothesized genetic uniformity, considerable sequence and structural variation was observed among the four genomes, which overlap with ancient and ongoing genomic introgressions from ‘Pima’ cotton, gene regulatory mechanisms and phenotypic trait divergence. Differentially expressed genes across fibre development correlate with fibre production, potentially contributing to the distinctive fibre quality traits observed in modern cotton cultivars. These genomes and comparative analyses provide a valuable foundation for future genetic endeavours to enhance global cotton yield and sustainability.

59 BASIC BIOLOGICAL SCIENCES↗

Ames interactive molecular model building system - A 3-D computer modelling system applied to the study of the origin of life

The investigation of specific interactions among biological molecules must take into consideration the stereochemistry of the structures. Thus, models of the molecules are essential for describing the spatial organization of potentially interacting groups, and estimations of conformation are required for a description of spatial organization. Both the function of visualizing molecules, and that of estimating conformation through calculations of energy, are part of the molecular modeling system described in the present paper. The potential uses of the system in investigating some aspects of the origin of life rest on the assumption that translation of conformation from genetic elements to catalytic elements would have been required for the development of the first replicating systems subject to the process of biological evolution.

Coeckelenbergh, Y.↗

CMPLE: Correlation Modeling to Decode Photosynthesis Using the Minorize–Maximize Algorithm

In plant genomic experiments, correlations among various biological traits (phenotypes) give new insights into how genetic diversity may have tuned biological processes to enhance fitness under diverse conditions. Consequently, knowing how the correlations are affected by genetic (G) and environmental (E) factors helps develop climate-resilient plants. However, the current literature lacks any method for assessing the effect of predictors on pairwise correlations among multiple phenotypes together with easily interpretable model parameters. To address this need, we propose to model pairwise correlations directly in terms of G and E and develop a computationally efficient inference procedure. Two major novelties in our methodology are (1) the use of a composite pairwise likelihood method to avoid the positive definiteness restriction on the correlation matrix and (2) the use of a novel Minorize–Maximize (MM) algorithm for the efficient estimation of a large number of parameters. The proposed method shows excellent numerical performance on synthetic datasets. Here, the analysis of the motivating data on cowpea reveals that the rates of solar energy storage by photosynthesis (the aggregate trait) are differentially affected by different genetic loci through two distinct processes: “photoinhibition” which results from photodamage caused by excess light, and “photoprotection” which protects plants from photodamage but also results in energy loss.

Correlation modeling↗

Animal models for osteoporosis

Animal models will continue to be important tools in the quest to understand the contribution of specific genes to establishment of peak bone mass and optimal bone architecture, as well as the genetic basis for a predisposition toward accelerated bone loss in the presence of co-morbidity factors such as estrogen deficiency. Existing animal models will continue to be useful for modeling changes in bone metabolism and architecture induced by well-defined local and systemic factors. However, there is a critical unfulfilled need to develop and validate better animal models to allow fruitful investigation of the interaction of the multitude of factors which precipitate senile osteoporosis. Well characterized and validated animal models that can be recommended for investigation of the etiology, prevention and treatment of several forms of osteoporosis have been listed in Table 1. Also listed are models which are provisionally recommended. These latter models have potential but are inadequately characterized, deviate significantly from the human response, require careful choice of strain or age, or are not practical for most investigators to adopt. It cannot be stressed strongly enough that the enormous potential of laboratory animals as models for osteoporosis can only be realized if great care is taken in the choice of an appropriate species, age, experimental design, and measurements. Poor choices will results in misinterpretation of results which ultimately can bring harm to patients who suffer from osteoporosis by delaying advancement of knowledge.

NASA Discipline Regulatory Physiology↗

Sustainable Use of Groundwater May Dramatically Reduce Irrigated Production of Maize, Soybean, and Wheat

Groundwater extraction in the United States (US) is unsustainable, making it essential to understand the impacts of limited water use on irrigated agriculture. To improve this understanding, we integrated a gridded crop model with satellite observations, recharge estimates, and water survey data to assess the effects of sustainable groundwater withdrawals on US irrigated agricultural production. The gridded crop model agrees with satellite-based estimates of evapotranspiration (R2 = 0.68), as well as survey data from the United States Department of Agriculture (R2 = 0.82–0.94 for county-level production and 0.37–0.54 for county-level yield). Using the optimistic assumption that groundwater extraction equals effective aquifer recharge rate, we find that sustainable groundwater use decreases US irrigated production of maize, soybean, and winter wheat by 20%, 6%, and 25%, respectively. Using a more conservative assumption of groundwater availability, US irrigated production of maize, soybean, and winter wheat decreases by 45%, 37%, and 36%, respectively. The wide range of simulated losses is driven by considerable uncertainty in surface water and groundwater interactions, as well as accounting for the many aspects of sustainability. Our results demonstrate the vulnerability of US irrigated agriculture to unsustainable groundwater pumping, highlighting the difficulty of expanding or even maintaining irrigated food production in the face of climate change, population growth, and shifting dietary demands. These findings are based on reducing pumping by fallowing irrigated farmland; however, alternate pumping reduction strategies or technological advances in crop genetics and irrigation could produce different results.

sustainability↗

CrossMP: Enabling Cross-Modality Translation between Single-Cell RNA-Seq and Single-Cell ATAC-Seq through Web-Based Portal

In recent years, there has been a growing interest in profiling multiomic modalities within individual cells simultaneously. One such example is integrating combined single-cell RNA sequencing (scRNA-seq) data and single-cell transposase-accessible chromatin sequencing (scATAC-seq) data. Integrated analysis of diverse modalities has helped researchers make more accurate predictions and gain a more comprehensive understanding than with single-modality analysis. However, generating such multimodal data is technically challenging and expensive, leading to limited availability of single-cell co-assay data. Here, we propose a model for cross-modal prediction between the transcriptome and chromatin profiles in single cells. Our model is based on a deep neural network architecture that learns the latent representations from the source modality and then predicts the target modality. It demonstrates reliable performance in accurately translating between these modalities across multiple paired human scATAC-seq and scRNA-seq datasets. Additionally, we developed CrossMP, a web-based portal allowing researchers to upload their single-cell modality data through an interactive web interface and predict the other type of modality data, using high-performance computing resources plugged at the backend.

59 BASIC BIOLOGICAL SCIENCES↗

Dissection of Carbon and Nitrogen Cycling in Post-Fire Soil Environments using a Genome- Informed Experimental Community (Final Technical Report)

Wildfires are a natural part of many forest ecosystems, with globally important carbon (C) storage and nutrient cycling consequences, and they are increasing in frequency and severity in Western North America. Forest fires affect soil C stocks in complex ways; some C is released into the atmosphere through combustion, while a large percentage of the C is added to the soil in the form of pyrogenic organic matter. Worldwide, it is estimated that 16% of soil organic matter is pyrogenic, while locally, this number may be as high as 80%. Understanding how wildfires affect soil organic matter cycling requires understanding how microbes respond to pyrogenic organic matter and other post-fire soil conditions. However, our understanding of microbial interactions within post-fire soil was in its infancy at the time of our proposal. Outstanding questions included: Which microbes are capable of degrading pyrogenic organic matter? What are the relevant genes and metabolites associated with this degradation? What are the key interactions among post-fire microbes? Key highlights of outcomes supported by this grant included training eleven early-career scientists and two early-career PIs, publication of twelve peer-reviewed papers, cross-lab collaborations that empowered complex scientific approaches, the development of an open-source automated gas sampler to drive novel insights in C cycling, enhanced understanding of post-fire microbial community dynamics, and novel genetic and molecular insights into microbial responses to fire.

54 ENVIRONMENTAL SCIENCES↗