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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 361 records · Page 20
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Functional activity and functional gene diversity of a Cu-contaminated soil remediated by aided phytostabilization using compost, dolomitic limestone and a mixed tree stand

Trace elements (TEs) availability, biochemical activity and functional gene diversity was studied in a Cu-contaminated soil, revegetated for six years with a mixed stand of willow, black poplar, and false indigo-bush, and amended or not with compost plus dolomitic limestone (OMDL). The OMDL amendment significantly reduced Cu and As availability and soil toxicity, and increased the biochemical activity and microbial functional diversity assessed with the GEOCHIP technique, as compared to the unamended soil (Unt). The OMDL soil showed significantly higher abundance of 25 functional genes involved in decomposition organic compounds, and 11, 3 and 11 functional genes involved in the N, P and S biogeochemical cycles. Functional gene abundance was positively correlated with nutrient contents but negatively correlated with Cu availability and soil toxicity. The abundance of microbial functional genes encoding for resistance to various TEs also increased, possibly due to the microbial proliferation and lower Cu exposure in the presence of high total soil Cu concentration. Genes encoding for antibiotic resistance due to the co-occurrence of TEs and antibiotic resistant genes on genetic mobile elements. Finally, overall, phytomanagement confirmed its potential to restore the biological fertility and diversity of a severely Cu-contaminated soil, but the increase of TEs and antibiotic resistant gene abundances deserve attention in future studies.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2013

Phycocyanobilin promotes PC12 cell survival and modulates immune and inflammatory genes and oxidative stress markers in acute cerebral hypoperfusion in rats

Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of hypoperfused rat brain. After the permanent bilateral common carotid arteries occlusion (BCCAo), the animals were treated with saline or PCB, taking samples 24 h post-surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.1 from Affymetrix; the expression of particular genes was assessed by the Fast SYBR Green RT-PCR Master Mix and Bioplex methods; and redox markers (MDA, PP, CAT, SOD) were evaluated spectrophotometrically. The PCB treatment prevented the H{sub 2}O{sub 2} and glutamate induced PC12 cell injury assessed by the MTT assay, and modulated 190 genes (93 up- and 97 down-regulated) associated to several immunological and inflammatory processes in BCCAo rats. Furthermore, PCB positively modulated 19 genes mostly related to a detrimental pro-inflammatory environment and counteracted the oxidative imbalance in the treated BCCAo animals. Our results support the view of an effective influence of PCB on major inflammatory mediators in acute cerebral hypoperfusion. These results suggest that PCB has a potential to be a treatment for ischemic stroke for which further studies are needed. - Highlights: • Phycocyanobilin (PCB) prevents H{sub 2}O{sub 2} and glutamate induced PC12 cell viability loss. • Anterior cortex and striatum are highly vulnerable to cerebral hypoperfusion (CH). • PCB modulates 190 genes associated to inflammation in acute CH. • PCB regulates 19 genes mostly related to a detrimental pro-inflammatory environment. • PCB restores redox and immune balances showing promise as potential stroke therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

o-p′-DDT-mediated uterotrophy and gene expression in immature C57BL/6 mice and Sprague–Dawley rats

1,1,1-Trichloro-2,2-bis(2-chlorophenyl-4-chlorophenyl)ethane (o,p′-DDT) is an organochlorine pesticide and endocrine disruptor known to activate the estrogen receptor. Comprehensive ligand- and species-comparative dose- and time-dependent studies were conducted to systematically assess the uterine physiological, morphological and gene expression responses elicited by o,p′-DDT and ethynyl estradiol (EE) in immature ovariectomized C57BL/6 mice and Sprague–Dawley rats. Custom cDNA microarrays were used to identify conserved and divergent differential gene expression responses. A total of 1256 genes were differentially expressed by both ligands in both species, 559 of which exhibited similar temporal expression profiles suggesting that o,p′-DDT elicits estrogenic effects at high doses when compared to EE. However, 51 genes exhibited species-specific uterine expression elicited by o,p′-DDT. For example, carbonic anhydrase 2 exhibited species- and ligand-divergent expression as confirmed by quantitative real-time PCR. The identification of comparable temporal phenotypic responses linked to gene expression demonstrates that systematic comparative gene expression assessments are valuable for elucidating conserved and divergent estrogen signaling mechanisms in rodent uterotrophy. - Highlights: • o,p′-DDT and enthynyl estradiol (EE) both elicit uterotrophy in mice and rats. • o,p′-DDT and EE have different kinetics in uterine wet weight induction. • o,p′-DDT elicited stromal hypertrophy in rats but myometrial hypertrophy in mice. • 1256 genes were differentially expressed by both ligands in both species. • Only 51 genes had species-specific uterine expression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Analysis of changes in hepatic gene expression in a murine model of tolerance to acetaminophen hepatotoxicity (autoprotection)

Pretreatment of mice with a low hepatotoxic dose of acetaminophen (APAP) results in resistance to a subsequent, higher dose of APAP. This mouse model, termed APAP autoprotection was used here to identify differentially expressed genes and cellular pathways that could contribute to this development of resistance to hepatotoxicity. Male C57BL/6J mice were pretreated with APAP (400 mg/kg) and then challenged 48 h later with 600 mg APAP/kg. Livers were obtained 4 or 24 h later and total hepatic RNA was isolated and hybridized to Affymetrix Mouse Genome MU430{sub 2} GeneChip. Statistically significant genes were determined and gene expression changes were also interrogated using the Causal Reasoning Engine (CRE). Extensive literature review narrowed our focus to methionine adenosyl transferase-1 alpha (MAT1A), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), flavin-containing monooxygenase 3 (Fmo3) and galectin-3 (Lgals3). Down-regulation of MAT1A could lead to decreases in S-adenosylmethionine (SAMe), which is known to protect against APAP toxicity. Nrf2 activation is expected to play a role in protective adaptation. Up-regulation of Lgals3, one of the genes supporting the Nrf2 hypothesis, can lead to suppression of apoptosis and reduced mitochondrial dysfunction. Fmo3 induction suggests the involvement of an enzyme not known to metabolize APAP in the development of tolerance to APAP toxicity. Subsequent quantitative RT-PCR and immunochemical analysis confirmed the differential expression of some of these genes in the APAP autoprotection model. In conclusion, our genomics strategy identified cellular pathways that might further explain the molecular basis for APAP autoprotection. - Highlights: • Differential expression of genes in mice resistant to acetaminophen hepatotoxicity. • Increased gene expression of Flavin-containing monooxygenase 3 and Galectin-3. • Decrease in MAT1A expression and compensatory hepatocellular regeneration. • Two distinct gene expression patterns support contrasting Nrf2 responses. • Genomics identification of pathways relevant to resistance to APAP hepatotoxicity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Differential DNA methylation profile of key genes in malignant prostate epithelial cells transformed by inorganic arsenic or cadmium

Previous work shows altered methylation patterns in inorganic arsenic (iAs)- or cadmium (Cd)-transformed epithelial cells. Here, the methylation status near the transcriptional start site was assessed in the normal human prostate epithelial cell line (RWPE-1) that was malignantly transformed by 10 μM Cd for 11 weeks (CTPE) or 5 μM iAs for 29 weeks (CAsE-PE), at which time cells showed multiple markers of acquired cancer phenotype. Next generation sequencing of the transcriptome of CAsE-PE cells identified multiple dysregulated genes. Of the most highly dysregulated genes, five genes that can be relevant to the carcinogenic process (S100P, HYAL1, NTM, NES, ALDH1A1) were chosen for an in-depth analysis of the DNA methylation profile. DNA was isolated, bisulfite converted, and combined bisulfite restriction analysis was used to identify differentially methylated CpG sites, which was confirmed with bisulfite sequencing. Four of the five genes showed differential methylation in transformants relative to control cells that was inversely related to altered gene expression. Increased expression of HYAL1 (> 25-fold) and S100P (> 40-fold) in transformants was correlated with hypomethylation near the transcriptional start site. Decreased expression of NES (> 15-fold) and NTM (> 1000-fold) in transformants was correlated with hypermethylation near the transcriptional start site. ALDH1A1 expression was differentially expressed in transformed cells but was not differentially methylated relative to control. In conclusion, altered gene expression observed in Cd and iAs transformed cells may result from altered DNA methylation status. - Highlights: • Cd and iAs are known human carcinogens, yet neither appears directly mutagenic. • Prior data suggest epigenetic modification plays a role in Cd or iAs induced cancer. • Altered methylation of four misregulated genes was found in Cd or iAs transformants. • The resulting altered gene expression may be relevant to cellular transformation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Global gene expression and morphological alterations in the mammary gland after gestational exposure to bisphenol A, genistein and indole-3-carbinol in female Sprague-Dawley offspring

This study aimed to evaluate the modifying effects of dietary genistein (GEN) and indole-3-carbinol (I3C) on early mammary gland development in female Sprague-Dawley offspring born to mothers exposed to BPA during gestation. Pregnant rats were treated with BPA25 or 250 μg/kg bw/day from gestational days 10 to 21 with or without dietary intake of GEN (250 mg/kg chow) or I3C (2000 mg/kg chow). At post-natal day (PND) 21, female offspring from different litters were euthanized for mammary gland development and gene expression analyses. Our results indicated that prenatal exposure to BPA25 and 250 did not modify the ductal elongation of the mammary gland tree or the estrogen receptor alpha (ER-α) expression in terminal end buds (TEBs). However, BPA25-exposed offspring had a higher number of terminal structures (TEBs + TDs) and an increased mammary branching and cell proliferation index in TEBs. Besides that, BPA25 and 250 modulated the expression of several genes in the immature mammary gland that were not changed in a dose dependent manner and involved different clusters of up- and down-regulated genes. Furthermore, BPA25 and BPA250 + I3C-treated groups also had a higher number of enriched functional gene categories. In addition, maternal dietary GEN and I3C in association with BPA exposure produced specific gene expression alterations in the mammary gland and overcome the adverse effect of BPA25, decreasing the branching of the mammary gland. In conclusion, prenatal BPA exposure induced both morphological and gene expression modifications on the mammary gland that dietary intake of GEN and I3C reverted on BPA25-exposed animals. - Highlights: • Gestational BPA and its association with GEN and I3C modify gene expression on the early mammary gland development. • GEN and I3C induced a different gene expression signature than lower BPA dose. • Dietary GEN and I3C countered the adverse effect of lower BPA dose on the cell proliferation and mammary gland development.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Altered epigenetic regulation of homeobox genes in human oral squamous cell carcinoma cells

To gain insight into oral squamous cell carcinogenesis, we performed deep sequencing (RNAseq) of non-tumorigenic human OKF6-TERT1R and tumorigenic SCC-9 cells. Numerous homeobox genes are differentially expressed between OKF6-TERT1R and SCC-9 cells. Data from Oncomine, a cancer microarray database, also show that homeobox (HOX) genes are dysregulated in oral SCC patients. The activity of Polycomb repressive complexes (PRC), which causes epigenetic modifications, and retinoic acid (RA) signaling can control HOX gene transcription. HOXB7, HOXC10, HOXC13, and HOXD8 transcripts are higher in SCC-9 than in OKF6-TERT1R cells; using ChIP (chromatin immunoprecipitation) we detected PRC2 protein SUZ12 and the epigenetic H3K27me3 mark on histone H3 at these genes in OKF6-TERT1R, but not in SCC-9 cells. In contrast, IRX1, IRX4, SIX2 and TSHZ3 transcripts are lower in SCC-9 than in OKF6-TERT1R cells. We detected SUZ12 and the H3K27me3 mark at these genes in SCC-9, but not in OKF6-TERT1R cells. SUZ12 depletion increased HOXB7, HOXC10, HOXC13, and HOXD8 transcript levels and decreased the proliferation of OKF6-TERT1R cells. Transcriptional responses to RA are attenuated in SCC-9 versus OKF6-TERT1R cells. SUZ12 and H3K27me3 levels were not altered by RA at these HOX genes in SCC-9 and OKF6-TERT1R cells. We conclude that altered activity of PRC2 is associated with dysregulation of homeobox gene expression in human SCC cells, and that this dysregulation potentially plays a role in the neoplastic transformation of oral keratinocytes. - Highlights: • RNAseq elucidates differences between non-tumorigenic and tumorigenic oral keratinocytes. • Changes in HOX mRNA in SCC-9 vs. OKF6-TERT1R cells are a result of altered epigenetic regulation. • RNAseq shows that retinoic acid (RA) influences gene expression in both OKF6-TERT1R and SCC-9 cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Matrix mineralization controls gene expression in osteoblastic cells

Osteoblasts are adherent cells, and under physiological conditions they attach to both mineralized and non-mineralized osseous surfaces. However, how exactly osteoblasts respond to these different osseous surfaces is largely unknown. Our hypothesis was that the state of matrix mineralization provides a functional signal to osteoblasts. To assess the osteoblast response to mineralized compared to demineralized osseous surfaces, we developed and validated a novel tissue surface model. We demonstrated that with the exception of the absence of mineral, the mineralized and demineralized surfaces were similar in molecular composition as determined, for example, by collagen content and maturity. Subsequently, we used the human osteoblastic cell line MG63 in combination with genome-wide gene set enrichment analysis (GSEA) to record and compare the gene expression signatures on mineralized and demineralized surfaces. Assessment of the 5 most significant gene sets showed on mineralized surfaces an enrichment exclusively of genes sets linked to protein synthesis, while on the demineralized surfaces 3 of the 5 enriched gene sets were associated with the matrix. Focusing on these three gene sets, we observed not only the expected structural components of the bone matrix, but also gene products, such as HMCN1 or NID2, that are likely to act as temporal migration guides. Together, these findings suggest that in osteoblasts mineralized and demineralized osseous surfaces favor intracellular protein production and matrix formation, respectively. Further, they demonstrate that the mineralization state of bone independently controls gene expression in osteoblastic cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Information-incorporated gene network construction with FDR control

Abstract Motivation Large-scale gene expression studies allow gene network construction to uncover associations among genes. To study direct associations among genes, partial correlation-based networks are preferred over marginal correlations. However, FDR control for partial correlation-based network construction is not well-studied. In addition, currently available partial correlation-based methods cannot take existing biological knowledge to help network construction while controlling FDR. Results In this paper, we propose a method called Partial Correlation Graph with Information Incorporation (PCGII). PCGII estimates partial correlations between each pair of genes by regularized node-wise regression that can incorporate prior knowledge while controlling the effects of all other genes. It handles high-dimensional data where the number of genes can be much larger than the sample size and controls FDR at the same time. We compare PCGII with several existing approaches through extensive simulation studies and demonstrate that PCGII has better FDR control and higher power. We apply PCGII to a plant gene expression dataset where it recovers confirmed regulatory relationships and a hub node, as well as several direct associations that shed light on potential functional relationships in the system. We also introduce a method to supplement observed data with a pseudogene to apply PCGII when no prior information is available, which also allows checking FDR control and power for real data analysis. Availability and implementation R package is freely available for download at https://cran.r-project.org/package=PCGII.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

MO-DE-207B-05: Predicting Gene Mutations in Renal Cell Carcinoma Based On CT Imaging Features: Validation Using TCGA-TCIA Datasets

Purpose: The goal of this work is to investigate the use of contrast enhanced computed tomographic (CT) features for the prediction of mutations of BAP1, PBRM1, and VHL genes in renal cell carcinoma (RCC). Methods: For this study, we used two patient databases with renal cell carcinoma (RCC). The first one consisted of 33 patients from our institution (UT Southwestern Medical Center, UTSW). The second one consisted of 24 patients from the Cancer Imaging Archive (TCIA), where each patient is connected by a unique identi?er to the tissue samples from the Cancer Genome Atlas (TCGA). From the contrast enhanced CT image of each patient, tumor contour was first delineated by a physician. Geometry, intensity, and texture features were extracted from the delineated tumor. Based on UTSW dataset, we completed feature selection and trained a support vector machine (SVM) classifier to predict mutations of BAP1, PBRM1 and VHL genes. We then used TCIA-TCGA dataset to validate the predictive model build upon UTSW dataset. Results: The prediction accuracy of gene expression of TCIA-TCGA patients was 0.83 (20 of 24), 0.83 (20 of 24), and 0.75 (18 of 24) for BAP1, PBRM1, and VHL respectively. For BAP1 gene, texture feature was the most prominent feature type. For PBRM1 gene, intensity feature was the most prominent. For VHL gene, geometry, intensity, and texture features were all important. Conclusion: Using our feature selection strategy and models, we achieved predictive accuracy over 0.75 for all three genes under the condition of using patient data from one institution for training and data from other institutions for testing. These results suggest that radiogenomics can be used to aid in prognosis and used as convenient surrogates for expensive and time consuming gene assay procedures.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

How Much Do rRNA Gene Surveys Underestimate Extant Bacterial Diversity?

The most common practice in studying and cataloguing prokaryotic diversity involves the grouping of sequences into operational taxonomic units (OTUs) at the 97% 16S rRNA gene sequence identity level, often using partial gene sequences, such as PCR-generated amplicons. Due to the high sequence conservation of rRNA genes, organisms belonging to closely related yet distinct species may be grouped under the same OTU. With this being said, it remains unclear how much diversity has been underestimated by this practice. To address this question, we compared the OTUs of genomes defined at the 97% or 98.5% 16S rRNA gene identity level against OTUs of the same genomes defined at the 95% whole-genome average nucleotide identity (ANI), which is a much more accurate proxy for species. Our results show that OTUs resulting from a 98.5% 16S rRNA gene identity cutoff are more accurate than 97% compared to 95% ANI (90.5% versus 89.9% accuracy) but indistinguishable from any other threshold in the 98.29 to 98.78% range. Even with the more stringent thresholds, the 16S rRNA gene-based approach commonly underestimates the number of OTUs by ~12%, on average, compared to the ANI-based approach (~14% underestimation when using the 97% identity threshold). Moreover, the degree of underestimation can become 50% or more for certain taxa, such as the genera Pseudomonas , Burkholderia , Escherichia , Campylobacter , and Citrobacter . These results provide a quantitative view of the degree of underestimation of extant prokaryotic diversity by 16S rRNA gene-defined OTUs and suggest that genomic resolution is often necessary. IMPORTANCE: Species diversity is one of the most fundamental pieces of information for community ecology and conservational biology. Thus, employing accurate proxies for what a species or the unit of diversity is are cornerstones for a large set of microbial ecology and diversity studies. The most common proxies currently used rely on the clustering of 16S rRNA gene sequences at some threshold of nucleotide identity, typically 97% or 98.5%. Here, we explore how well this strategy reflects the more accurate whole-genome-based proxies and determine the frequency with which the high conservation of 16S rRNA sequences masks substantial species-level diversity.

16S rRNA gene↗
DOE OSTI2021

De novo transcriptome analysis of white teak (Gmelina arborea Roxb) wood reveals critical genes involved in xylem development and secondary metabolism

Gmelina arborea Roxb is a fast-growing tree species of commercial importance for tropical countries due to multiple industrial uses of its wood. Wood is primarily composed of thick secondary cell walls of xylem cells which imparts the strength to the wood. Identification of the genes involved in the secondary cell wall biosynthesis as well as their cognate regulators is crucial to understand how the production of wood occurs and serves as a starting point for developing breeding strategies to produce varieties with improved wood quality, better paper pulping or new potential uses such as biofuel production. In order to gain knowledge on the molecular mechanisms and gene regulation related with wood development in white teak, a de novo sequencing and transcriptome assembly approach was used employing secondary cell wall synthesizing cells from young white teak trees. For generation of transcriptome, RNA-seq reads were assembled into 110,992 transcripts and 49,364 genes were functionally annotated using plant databases; 5071 GO terms and 25,460 SSR markers were identified within xylem transcripts and 10,256 unigenes were assigned to KEGG database in 130 pathways. Among transcription factor families, C2H2, C3H, bLHLH and MYB were the most represented in xylem. Differential gene expression analysis using leaves as a reference was carried out and a total of 20,954 differentially expressed genes were identified including monolignol biosynthetic pathway genes. The differential expression of selected genes (4CL, COMT, CCoAOMT, CCR and NST1) was validated using qPCR. We report the very first de novo transcriptome of xylem-related genes in this tropical timber species of commercial importance and constitutes a valuable extension of the publicly available transcriptomic resource aimed at fostering both basic and breeding studies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Gene flow and introgression are pervasive forces shaping the evolution of bacterial species

Abstract Background Although originally thought to evolve clonally, studies have revealed that most bacteria exchange DNA. However, it remains unclear to what extent gene flow shapes the evolution of bacterial genomes and maintains the cohesion of species. Results Here, we analyze the patterns of gene flow within and between >2600 bacterial species. Our results show that fewer than 10% of bacterial species are truly clonal, indicating that purely asexual species are rare in nature. We further demonstrate that the taxonomic criterion of ~95% genome sequence identity routinely used to define bacterial species does not accurately represent a level of divergence that imposes an effective barrier to gene flow across bacterial species. Interruption of gene flow can occur at various sequence identities across lineages, generally from 90 to 98% genome identity. This likely explains why a ~95% genome sequence identity threshold has empirically been judged as a good approximation to define bacterial species. Our results support a universal mechanism where the availability of identical genomic DNA segments required to initiate homologous recombination is the primary determinant of gene flow and species boundaries in bacteria. We show that these barriers of gene flow remain porous since many distinct species maintain some level of gene flow, similar to introgression in sexual organisms. Conclusions Overall, bacterial evolution and speciation are likely shaped by similar forces driving the evolution of sexual organisms. Our findings support a model where the interruption of gene flow—although not necessarily the initial cause of speciation—leads to the establishment of permanent and irreversible species borders.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2012

A Bayesian Model for Pooling Gene Expression Studies That Incorporates Co-Regulation Information

Current Bayesian microarray models that pool multiple studies assume gene expression is independent of other genes. However, in prokaryotic organisms, genes are arranged in units that are co-regulated (called operons). Here, we introduce a new Bayesian model for pooling gene expression studies that incorporates operon information into the model. Our Bayesian model borrows information from other genes within the same operon to improve estimation of gene expression. The model produces the gene-specific posterior probability of differential expression, which is the basis for inference. We found in simulations and in biological studies that incorporating co-regulation information improves upon the independence model. We assume that each study contains two experimental conditions: a treatment and control. We note that there exist environmental conditions for which genes that are supposed to be transcribed together lose their operon structure, and that our model is best carried out for known operon structures.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Phylogenomic Analyses of Non-Dikarya Fungi Supports Horizontal Gene Transfer Driving Diversification of Secondary Metabolism in the Amphibian Gastrointestinal Symbiont, Basidiobolus

Research into secondary metabolism (SM) production by fungi has resulted in the discovery of diverse, biologically active compounds with significant medicinal applications. The fungi rich in SM production are taxonomically concentrated in the subkingdom Dikarya, which comprises the phyla Ascomycota and Basidiomycota. Here, we explore the potential for SM production in Mucoromycota and Zoopagomycota, two phyla of nonflagellated fungi that are not members of Dikarya, by predicting and identifying core genes and gene clusters involved in SM. The majority of non-Dikarya have few genes and gene clusters involved in SM production except for the amphibian gut symbionts in the genus Basidiobolus. Basidiobolus genomes exhibit an enrichment of SM genes involved in siderophore, surfactin-like, and terpene cyclase production, all these with evidence of constitutive gene expression. Gene expression and chemical assays also confirm that Basidiobolus has significant siderophore activity. Finally, the expansion of SMs in Basidiobolus are partially due to horizontal gene transfer from bacteria, likely as a consequence of its ecology as an amphibian gut endosymbiont.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

A novel gene expression-based prognostic scoring system to predict survival in gastric cancer

Analysis of gene expression patterns in gastric cancer (GC) can help to identify a comprehensive panel of gene biomarkers for predicting clinical outcomes and to discover potential new therapeutic targets. Here, a multi-step bioinformatics analytic approach was developed to establish a novel prognostic scoring system for GC. We first identified 276 genes that were robustly differentially expressed between normal and GC tissues, of which, 249 were found to be significantly associated with overall survival (OS) by univariate Cox regression analysis. The biological functions of 249 genes are related to cell cycle, RNA/ncRNA process, acetylation and extracellular matrix organization. A network was generated for view of the gene expression architecture of 249 genes in 265 GCs. Finally, we applied a canonical discriminant analysis approach to identify a 53-gene signature and a prognostic scoring system was established based on a canonical discriminant function of 53 genes. The prognostic scores strongly predicted patients with GC to have either a poor or good OS. Our study raises the prospect that the practicality of GC patient prognosis can be assessed by this prognostic scoring system.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Comparative Genomic Analysis of Ochratoxin A Biosynthetic Cluster in Producing Fungi: New Evidence of a Cyclase Gene Involvement

The widespread use of Next-Generation Sequencing has opened a new era in the study of biological systems by significantly increasing the catalog of fungal genomes sequences and identifying gene clusters for known secondary metabolites as well as novel cryptic ones. However, most of these clusters still need to be examined in detail to completely understand the pathway steps and the regulation of the biosynthesis of metabolites. Genome sequencing approach led to the identification of the biosynthetic genes cluster of ochratoxin A (OTA) in a number of producing fungal species. Ochratoxin A is a potent pentaketide nephrotoxin produced by Aspergillus and Penicillium species and found as widely contaminant in food, beverages and feed. The increasing availability of several new genome sequences of OTA producer species in JGI Mycocosm and/or GenBank databanks led us to analyze and update the gene cluster structure in 19 Aspergillus and 2 Penicillium OTA producing species, resulting in a well conserved organization of OTA core genes among the species. Furthermore, our comparative genome analyses evidenced the presence of an additional gene, previously undescribed, located between the polyketide and non-ribosomal synthase genes in the cluster of all the species analyzed. The presence of a SnoaL cyclase domain in the sequence of this gene supports its putative role in the polyketide cyclization reaction during the initial steps of the OTA biosynthesis pathway. The phylogenetic analysis showed a clustering of OTA SnoaL domains in accordance with the phylogeny of OTA producing species at species and section levels. The characterization of this new OTA gene, its putative role and its expression evidence in three important representative producing species, are reported here for the first time.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

A Novel G-Protein-Coupled Receptors Gene from Upland Cotton Enhances Salt Stress Tolerance in Transgenic Arabidopsis

Plants have developed a number of survival strategies which are significant for enhancing their adaptation to various biotic and abiotic stress factors. At the transcriptome level, G-protein-coupled receptors (GPCRs) are of great significance, enabling the plants to detect a wide range of endogenous and exogenous signals which are employed by the plants in regulating various responses in development and adaptation. In this research work, we carried out genome-wide analysis of target of Myb1 ( TOM1 ), a member of the GPCR gene family. The functional role of TOM1 in salt stress tolerance was studied using a transgenic Arabidopsis plants over-expressing the gene. By the use of the functional domain PF06454, we obtained 16 TOM genes members in Gossypium hirsutum , 9 in Gossypium arboreum , and 11 in Gossypium raimondii . The genes had varying physiochemical properties, and it is significant to note that all the grand average of hydropathy (GRAVY) values were less than one, indicating that all are hydrophobic in nature. In all the genes analysed here, both the exonic and intronic regions were found. The expression level of Gh_A07G0747 (GhTOM) was significantly high in the transgenic lines as compared to the wild type; a similar trend in expression was observed in all the salt-related genes tested in this study. The study in epidermal cells confirmed the localization of the protein coded by the gene TOM1 in the plasma membrane. Analysis of anti-oxidant enzymes showed higher concentrations of antioxidants in transgenic lines and relatively lower levels of oxidant substances such as H 2 O 2 . The low malondialdehyde (MDA) level in transgenic lines indicated that the transgenic lines had relatively low level of oxidative damage compared to the wild types. The results obtained indicate that Gh_A07G0747 (GhTOM) can be a putative target gene for enhancing salt stress tolerance in plants and could be exploited in the future for the development of salt stress-tolerant cotton cultivars.

G-protein-coupled receptors↗