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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 433 records · Page 24
All sourcesNASA NTRSDOE OSTI
DOE OSTI2014

Down-regulation of kelch domain-containing F-box protein in Arabidopsis enhances the production of (poly)phenols and tolerance to ultraviolet radiation

Phenylpropanoid biosynthesis in plants engenders myriad phenolics with diverse biological functions. Phenylalanine ammonia-lyase (PAL) is the first committed enzyme in the pathway, directing primary metabolic flux into a phenylpropanoid branch. Previously, we demonstrated that the Arabidopsis Kelch-domain containing F-box proteins, AtKFB01, -20, and -50, function as the negative regulators controlling phenylpropanoid biosynthesis via mediating PAL’s ubiquitination and subsequent degradation. Here, we reveal that Arabidopsis KFB39, a close homolog of AtKFB50, also interacts physically with PAL isozymes and modulates PALs' stability and activity. Disturbing the expression of KFB39 reciprocally affects the accumulation/deposition of a set of phenylpropanoid end products, suggesting that KFB39 is an additional post-translational regulator responsible for the turnover of PAL and negatively controlling phenylpropanoid biosynthesis. Furthermore, we discover that exposure of Arabidopsis to UV-B radiation suppresses the expression of all four KFB genes while inducing the transcription of PAL isogenes; these data suggest that Arabidopsis consolidates both transcriptional and post-translational regulation mechanisms to maximize its responses to UV stress. Simultaneous down-regulation of all four identified KFBs significantly enhances the production of (poly)phenols and the plant’s tolerance to UV irradiation. This study offers a biotechnological approach for engineering the production of useful phenolic chemicals and for increasing a plant’s resistance to environmental stress.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

petal: Co-expression network modelling in R

Background: Networks provide effective models to study complex biological systems, such as gene and protein interaction networks. With the advent of new sequencing technologies, many life scientists are grasping for user-friendly methods and tools to examine biological components at the whole-systems level. Gene co-expression network analysis approaches are frequently used to successfully associate genes with biological processes and demonstrate great potential to gain further insights into the functionality of genes, thus becoming a standard approach in Systems Biology. Here the objective is to construct biologically meaningful and statistically strong co-expression networks, the identification of research dependent subnetworks, and the presentation of self-contained results. Results: We introduce petal, a novel approach to generate gene co-expression network models based on experimental gene expression measures. petal focuses on statistical, mathematical, and biological characteristics of both, input data and output network models. Often over-looked issues of current co-expression analysis tools include the assumption of data normality, which is seldom the case for hight-throughput expression data obtained from RNA-seq technologies. petal does not assume data normality, making it a statistically appropriate method for RNA-seq data. Also, network models are rarely tested for their known typical architecture: scale-free and small-world. petal explicitly constructs networks based on both these characteristics, thereby generating biologically meaningful models. Furthermore, many network analysis tools require a number of user-defined input variables, these often require tuning and/or an understanding of the underlying algorithm; petal requires no user input other than experimental data. This allows for reproducible results, and simplifies the use of petal. Lastly, this approach is specifically designed for very large high-throughput datasets; this way, petal’s network models represent as much of the entire system as possible to provide a whole-system approach. Conclusion: petal is a novel tool for generating co-expression network models of whole-genomics experiments. It is implemented in R and available as a library. Its application to several whole-genome experiments has generated novel meaningful results and has lead the way to new testing hypothesizes for further biological investigation.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1998

Chimeric calcium/calmodulin-dependent protein kinase in tobacco: differential regulation by calmodulin isoforms

cDNA clones of chimeric Ca2+/calmodulin-dependent protein kinase (CCaMK) from tobacco (TCCaMK-1 and TCCaMK-2) were isolated and characterized. The polypeptides encoded by TCCaMK-1 and TCCaMK-2 have 15 different amino acid substitutions, yet they both contain a total of 517 amino acids. Northern analysis revealed that CCaMK is expressed in a stage-specific manner during anther development. Messenger RNA was detected when tobacco bud sizes were between 0.5 cm and 1.0 cm. The appearance of mRNA coincided with meiosis and became undetectable at later stages of anther development. The reverse polymerase chain reaction (RT-PCR) amplification assay using isoform-specific primers showed that both of the CCaMK mRNAs were expressed in anther with similar expression patterns. The CCaMK protein expressed in Escherichia coli showed Ca2+-dependent autophosphorylation and Ca2+/calmodulin-dependent substrate phosphorylation. Calmodulin isoforms (PCM1 and PCM6) had differential effects on the regulation of autophosphorylation and substrate phosphorylation of tobacco CCaMK, but not lily CCaMK. The evolutionary tree of plant serine/threonine protein kinases revealed that calmodulin-dependent kinases form one subgroup that is distinctly different from Ca2+-dependent protein kinases (CDPKs) and other serine/threonine kinases in plants.

NASA Discipline Plant Biology↗
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 OSTI2018

Nephron segment-specific gene expression using AAV vectors

AAV9 vector provides efficient gene transfer in all segments of the renal nephron, with minimum expression in non-renal cells, when administered retrogradely via the ureter. It is important to restrict the transgene expression to the desired cell type within the kidney, so that the physiological endpoints represent the function of the transgene expressed in that specific cell type within kidney. We hypothesized that segment-specific gene expression within the kidney can be accomplished using the highly efficient AAV9 vectors carrying the promoters of genes that are expressed exclusively in the desired segment of the nephron in combination with administration by retrograde infusion into the kidney via the ureter. We constructed AAV vectors carrying eGFP under the control of: kidney-specific cadherin (KSPC) gene promoter for expression in the entire nephron; Na{sup +}/glucose co-transporter (SGLT2) gene promoter for expression in the S1 and S2 segments of the proximal tubule; sodium, potassium, 2 chloride co-transporter (NKCC2) gene promoter for expression in the thick ascending limb of Henle's loop (TALH); E-cadherin (ECAD) gene promoter for expression in the collecting duct (CD); and cytomegalovirus (CMV) early promoter that provides expression in most of the mammalian cells, as control. We tested the specificity of the promoter constructs in vitro for cell type-specific expression in mouse kidney cells in primary culture, followed by retrograde infusion of the AAV vectors via the ureter in the mouse. Our data show that AAV9 vector, in combination with the segment-specific promoters administered by retrograde infusion via the ureter, provides renal nephron segment-specific gene expression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Effect of lipo-chitooligosaccharide on early growth of C 4 grass seedlings

Although lipo-chitooligosaccharides (LCOs) are important signal molecules for plant-symbiont interactions, a number of reports suggest that LCOs can directly impact plant growth and development, separate from any role in plant symbioses. In order to investigate this more closely, maize and Setaria seedlings were treated with LCO and their growth was evaluated. The data indicate that LCO treatment significantly enhanced root growth. RNA-seq transcriptomic analysis of LCO-treated maize roots identified a number of genes whose expression was significantly affected by the treatment. Among these genes, some LCO-up-regulated genes are likely involved in root growth promotion. Interestingly, some stress-related genes were down-regulated after LCO treatment, which might indicate reallocation of resources from defense responses to plant growth. The promoter activity of several LCO-up-regulated genes using a β-glucuronidase reporter system was further analysed. The results showed that the promoters were activated by LCO treatment. Lastly, the data indicate that LCO can directly impact maize root growth and gene expression.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2005

Multiple melanocortin receptors are expressed in bone cells

Melanocortin receptors belong to the seven transmembrane domain, G-protein coupled family of receptors. There are five members of this receptor family labeled MC1R-MC5R. These receptors are activated by fragments derived from a larger molecule, proopiomelanocortin (POMC) and include ACTH, alpha beta and gamma-MSH and beta-endorphin. Because of in vitro and in vivo data suggesting direct effects of these POMC molecules on bone and bone turnover, we examined bone and bone derived cells for the presence of the various members of the melanocortin receptor family. We report that the five known melanocortin receptors are expressed to varying degrees in osteoblast-like and osteoclastic cells. POMC fragments increased proliferation and expression of a variety of genes in osteoblastic cells. Furthermore, POMC mRNA was detected in osteoclastic cells. These data demonstrate that POMC-derived peptide hormones acting through high affinity melanocortin receptors have specific effects on bone cells. Thus, in addition to the indirect effects of POMC-derived hormones on bone turnover through their modulation of steroid hormone secretion, POMC fragments may have direct and specific effects on bone cell subpopulations.

NASA Discipline Musculoskeletal↗
DOE OSTI2017

Proteomic analysis of hair shafts from monozygotic twins: Expression profiles and genetically variant peptides

Forensic association of hair shaft evidence with individuals is currently assessed by comparing mitochondrial DNA haplotypes of reference and casework samples, primarily for exclusionary purposes. Present work tests and validates more recent proteomic approaches to extract quantitative transcriptional and genetic information from hair samples of monozygotic twin pairs, which would be predicted to partition away from unrelated individuals if the datasets contain identifying information. Protein expression profiles and polymorphic, genetically variant hair peptides were generated from ten pairs of monozygotic twins. Profiling using the protein tryptic digests revealed that samples from identical twins had typically an order of magnitude fewer protein expression differences than unrelated individuals. The data did not indicate that the degree of difference within twin pairs increased with age. In parallel, data from the digests were used to detect genetically variant peptides that result from common nonsynonymous single nucleotide polymorphisms in genes expressed in the hair follicle. Compilation of the variants permitted sorting of the samples by hierarchical clustering, permitting accurate matching of twin pairs. The results demonstrate that genetic differences are detectable by proteomic methods and provide a framework for developing quantitative statistical estimates of personal identification that increase the value of hair shaft evidence.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

PRRT2 inhibits the proliferation of glioma cells by modulating unfolded protein response pathway

Accumulating studies reported mutations in the gene encoding the proline-rich transmembrane protein 2 (PRRT2) to be causative for several paroxysmal neurological disorders, including paroxysmal kinesigenic dyskinesia (PKD), PKD combined with infantile seizures (ICCA), and benign familial infantile seizures (BFIS). However, the impact of PRRT2 in tumorigenesis is not known. Based on a large-scale data analysis, we found that PRRT2 was down-regulated in glioma tumor tissues compared with normal brain tissue. Dysregulation of PRRT2 was not induced by mutation, copy number variation and epigenetic modification, but modulated by microRNA-30a-5p. Overexpression of PRRT2 strongly impaired the cell viability and promoted cell apoptosis and these anti-tumor effects could be largely reversed by microRNA-30a-5p. Mechanistically, PRRT2 expression was closely correlated genes involved in unfolded protein response (UPR) pathway and introduction of PRRT2 inhibited gene expression in the three branches of UPR, including PERK axis, IRE1 axis and ATF6 axis. Taken together, our findings identify PRRT2 as a tumor suppressor in glioma and provide a promising target for potential therapeutic intervention. - Highlights: • PRRT2 is decreased in glioma and is targeted by miR-30a-5p. • PRRT2 exhibits tumor-suppressive effects on glioma cells. • PRRT2 correlates genes involved in unfolded protein response. • Over-expressed PRRT2 induces unfolded protein response in glioma in vitro.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2003

WVD2 and WDL1 modulate helical organ growth and anisotropic cell expansion in Arabidopsis

Wild-type Arabidopsis roots develop a wavy pattern of growth on tilted agar surfaces. For many Arabidopsis ecotypes, roots also grow askew on such surfaces, typically slanting to the right of the gravity vector. We identified a mutant, wvd2-1, that displays suppressed root waving and leftward root slanting under these conditions. These phenotypes arise from transcriptional activation of the novel WAVE-DAMPENED2 (WVD2) gene by the cauliflower mosaic virus 35S promoter in mutant plants. Seedlings overexpressing WVD2 exhibit constitutive right-handed helical growth in both roots and etiolated hypocotyls, whereas the petioles of WVD2-overexpressing rosette leaves exhibit left-handed twisting. Moreover, the anisotropic expansion of cells is impaired, resulting in the formation of shorter and stockier organs. In roots, the phenotype is accompanied by a change in the arrangement of cortical microtubules within peripheral cap cells and cells at the basal end of the elongation zone. WVD2 transcripts are detectable by reverse transcriptase-polymerase chain reaction in multiple organs of wild-type plants. Its predicted gene product contains a conserved region named "KLEEK," which is found only in plant proteins. The Arabidopsis genome possesses seven other genes predicted to encode KLEEK-containing products. Overexpression of one of these genes, WVD2-LIKE 1, which encodes a protein with regions of similarity to WVD2 extending beyond the KLEEK domain, results in phenotypes that are highly similar to wvd2-1. Silencing of WVD2 and its paralogs results in enhanced root skewing in the wild-type direction. Our observations suggest that at least two members of this gene family may modulate both rotational polarity and anisotropic cell expansion during organ growth.

NASA Discipline Plant Biology↗
NASA NTRS2003

Conservation of Endo16 expression in sea urchins despite evolutionary divergence in both cis and trans-acting components of transcriptional regulation

Evolutionary changes in transcriptional regulation undoubtedly play an important role in creating morphological diversity. However, there is little information about the evolutionary dynamics of cis-regulatory sequences. This study examines the functional consequence of evolutionary changes in the Endo16 promoter of sea urchins. The Endo16 gene encodes a large extracellular protein that is expressed in the endoderm and may play a role in cell adhesion. Its promoter has been characterized in exceptional detail in the purple sea urchin, Strongylocentrotus purpuratus. We have characterized the structure and function of the Endo16 promoter from a second sea urchin species, Lytechinus variegatus. The Endo16 promoter sequences have evolved in a strongly mosaic manner since these species diverged approximately 35 million years ago: the most proximal region (module A) is conserved, but the remaining modules (B-G) are unalignable. Despite extensive divergence in promoter sequences, the pattern of Endo16 transcription is largely conserved during embryonic and larval development. Transient expression assays demonstrate that 2.2 kb of upstream sequence in either species is sufficient to drive GFP reporter expression that correctly mimics this pattern of Endo16 transcription. Reciprocal cross-species transient expression assays imply that changes have also evolved in the set of transcription factors that interact with the Endo16 promoter. Taken together, these results suggest that stabilizing selection on the transcriptional output may have operated to maintain a similar pattern of Endo16 expression in S. purpuratus and L. variegatus, despite dramatic divergence in promoter sequence and mechanisms of transcriptional regulation.

NASA Discipline Evolutionary Biology↗
NASA NTRSDate not supplied

Murine Host-gut Microbiota Interactions are Modulated During Spaceflight

The rodent habitat on the International Space Station has provided critical insight into the impact of spaceflight on mammalian physiology. These effects include dysfunction of carbohydrate, steroid and lipid metabolism, and immune response, as well as induction of symptoms characteristic of liver disease, insulin resistance, osteopenia and myopathy, which are anticipated to intensify over long-duration spaceflight. Although these physiological responses can involve the microbiome, the host-microorganism interactions during spaceflight are still largely unknown. NASA GeneLab curates a wide range of space research data and the current work harnesses GeneLab multi’omic data from recent Rodent Research studies to explore changes to gut microbiota during spaceflight and their associations with host physiology when compared to ground controls. Using a hybrid analysis of DNA barcoding and whole genome shotgun data, an array of bacteria, fungi and nematodes could be identified at species level, and significant differences in relative abundances associated with spaceflight. Functional prediction based on differential abundance of species and metagenome gene inventories as well as metatranscriptomic gene expression at the host-gut microbiome interface implicate microbiota interactions could contribute to spaceflight pathology. Harnessing carefully curated publicly available data, such as from Genelab, to generate multi‘omic space science discoveries can help decipher the complex host-microbiome interactions that influence both health on Earth and the feasibility of long-duration spaceflight.

Microbiome↗
DOE OSTI2023

Generating Co-expression Networks for Three Cyanobacteria: Synechococcus sp. PCC 7942, Synechococcus sp. PCC 7002, Synechocystis sp. PCC 6803

Cyanobacteria are photosynthetic organisms capable of high growth rate and represent a promising bioplatform for harnessing the sun’s energy to make biofuel. Additionally, the process of photosynthesis absorbs CO2 from the environment. Understanding the metabolic processes involved in photosynthesis could lead to solutions to the recent rise of CO2 concentration in Earth’s atmosphere and the associated climate change. More research on the transcriptional regulation of these cells is needed to learn how to harness the untapped potential of cyanobacteria for these applications. Transcriptional analysis via RNA-seq provides an understanding of how gene expression changes at the mRNA level under diverse growing conditions. I systematically collected and analyzed RNA-Seq data obtained under a variety of conditions and available on the NCBI database for three cyanobacteria model organisms: Synechococcus elongatus sp. PCC 7942, Synechococcus sp. PCC 7002, and Synechocystis sp. PCC 6803. For each organism, the data was mapped to a reference genome to characterize the RNA expression profile. Samples were checked for quality based on the number of reads and the correlation of the expression profile between labeled replicates. All samples were transformed into transcripts per million reads, followed by a log transformation to account for the wide range of sample sizes. Gene co-expression networks were generated and analyzed for each species using Cytoscape. These networks provide a base level of gene expression for each species. The network topology and high-betweeness nodes of these networks need to be analyzed further to provide insight on potential ways to harness cyanobacteria genetics. Additionally, these datasets can be used together to form a core genome network analysis- one that includes only the genes that are homologous between the three species. This project has prepared the way for a more in-depth study on photosynthetic microbes on a genetic level.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

Development of a Low Input and sustainable Switchgrass Feedstock Production System Utilizing Beneficial Bacterial Endophytes

Switchgrass represents a promising feedstock crop for US energy sustainability. However, its broad utilization for bioenergy requires improvements of biomass yields and stress tolerance. In this DOE funded project, we have been working on harnessing beneficial bacterial endophytes to enhance switchgrass performance and to develop a low input feedstock production system for marginal lands that do not compete with the production of food crops. We have demonstrated that one of most promising plant growth-promoting bacterial endophytes, Burkholderia phytofirmans strain PsJN, is able to colonize roots and significantly promote growth of switchgrass cv. Alamo under in vitro, growth chamber, greenhouse, as well as field conditions. Furthermore, PsJN bacterization improved growth and development of switchgrass seedlings, significantly stimulated plant root and shoot growth, and tiller number in the field, and enhanced biomass accumulation on both poor (p<0.001) and rich (p<0.05) soils, with more effective stimulation of plant growth in low fertility soil. Plant physiology measurements showed that PsJN inoculated Alamo had consistently lower transpiration, lower stomatal conductance, and higher water use efficiency in greenhouse conditions. These physiological changes may significantly contribute to the recorded growth enhancement. PsJN inoculation rapidly results in an increase in photosynthetic rates which contributes to the advanced growth and development. Some evidence suggests that this initial growth advantage decreases with time when resources are not limited such as in greenhouse studies. Additionally, better drought resistance and drought hardening were observed in PsJN inoculated switchgrass. Using the DOE-funded switchgrass EST microarray, in a collaboration with the Genomics Core Facility at the Noble Foundation, we have determined gene expression profile changes in both responsive switchgrass cv. Alamo and non-responsive cv. Cave-in-Rock (CR) following PsJN bacterization. With the MapMan software to analyze microarray data, the number of up- and down-regulated probes was calculated. The number of up-regulated probes in Alamo was 26, 14, 14, and 12% at 0.5, 2, 4 and 8 days after inoculation (DAI) with PsJN, respectively while the corresponding number in CR was 24, 22, 21, and 19%, respectively. In both cultivars, the largest number of up-regulated probes occurred at 0.5 DAI. Noticeable differences throughout the timeframe between Alamo and CR were that the number was dramatically decreased to half (12%) in Alamo but remained high in CR (approximately 20%). The number of down regulated genes demonstrated different trends in Alamo and CR. Alamo had an increasing trend from 9% at 0.5 DAI to 11, 17, and 28% at 2, 4, and 8 DAI, respectively. However, CR had 13% at 0.5 and 2 DAI, and declined to 10% at 4 and 8 DAI. With the aid of MapMan and PageMan, we mapped the response of the ID probes to the observed major gene regulatory network and major biosynthetic pathway changes associated with the beneficial bacterial endophyte infection, colonization, and early growth promotion process. We found significant differences in gene expression patterns between responsive and non-responsive cultivars in many pathways, including redox state regulation, signaling, proteolysis, transcription factors, as well as hormone (SA and JA in particular)-associated pathways. Form microarray data, a total of 50 key genes have been verified using qPCR. Ten of these genes were chosen for further functional study via either overexpression and/or RNAi knockout technologies. These genes were calmodulin-related calcium sensor protein (CAM), glutathione S-transferase (GST), histidine-containing phosphotransfer protein (H-221), 3 different zinc finger proteins (ZF-371, ZF131 and ZF242), EF hand transcription factor (EF-622), peroxidase, cellulose synthase catalytic submit A2 (CESA2), and Aux/IAA family. A total of 8 overexpression and 5 RNAi transgenic plants have been regenerated, and their gene expression levels determined using qPCR. Consequently high, medium and low expression lines were propagated in vitro for gene function study. When adequate numbers of individual transgenic lines were obtained, they were challenged with PsJN to see if PsJN promotes or inhibits growth of transgenic plants. Our results demonstrated that EF-622 overexpression, ZF-371, GST, H-221 and CAM RNAi transgenic lines lost responses to PsJN, i.e. PsJN had no growth promotive effects on these transgenic plants. Further study needs to be done to characterize this loss of responsiveness to PsJN. During this funding period, we have done more work related to this funded project and established collaborations with other institutions and obtained some interesting results, building a foundation for further research projects. For example, we isolated a naturally-occurring bacterium from surface-sterilized switchgrass seeds, identified as a unique Panteoa agglomerans species, and named strain PaKM. PaKM has been proved to be an efficient growth promoter of switchgrass over a broad spectrum of genotypes and has potential in applications with low input and sustainable production systems on marginal lands. In collaboration with Dr. Shuijin Hu (North Carolina State University), we conducted experiments on how endophyte-inoculated switchgrass affects soil N and P availability and the number of AMF in roots. Our preliminary results showed that PsJN increased AMF infection of switchgrass roots, and enhanced soil N availability and soil N mineralization on a low nutrient field. Further study of this phenomenon on different soils, over longer time periods, is needed to assess its potential impact on the productivity and longevity of switchgrass stands.

09 BIOMASS FUELS↗
DOE OSTI2018

MiR-940 promotes the proliferation and migration of gastric cancer cells through up-regulation of programmed death ligand-1 expression

Although anti-programmed death ligand-1 (PD-L1) therapy has shown light in treatment of gastric cancer, only a limited number of patients respond to the treatment. In addition to its immunosuppressive effect, PD-L1 is involved in other functions of tumor cells. Previously study showed that PD-L1 promoted EMT in lung cancer cells. However, the other effect and role of PD-L1 in gastric cancer remains unclear. In the present study, we first demonstrated that PD-L1 promoted the proliferation and migration in gastric cancer cell lines. We found that another STAT family member, STAT5a, is involved in regulating the expression of PD-L1 in gastric cancer. Additionally, Cbl-b interacted and ubiquitated STAT5a, down-regulated the expression of STAT5a and PD-L1. Moreover, bioinformatics predictions and experimental data showed that Cbl-b is a target gene of the microRNA miR-940. We further found that miR-940 promoted the proliferation and migration of gastric cancer in vivo and in vitro. Taken together, our findings suggest that miR-940/Cbl-b/STAT5a axis regulated the expression of PD-L1, which promotes the proliferation and migration of gastric cancer cells.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2016

Integrating Large Scale Data Sets to Develop Predictive Hypotheses of Low-Dose Radiation-Induced Health Effects

Over one hundred years of radiation biology research has revealed much about the DNA damages induced by the deposition of energy from exposure to ionizing radiation and the subsequent cellular responses. However, there are still significant gaps in our understanding of how these might lead to detrimental health effects, particularly at low doses (100 mGy (milligray)). Recent advances in high throughput omics technologies enable interrogation of induced radiation effects at the genomic, proteomic and metabolomic levels. These include changes in gene expression, protein modifications, e.g., phosphorylation, acetylation, and methylation, and metabolic changes. We will discuss the integration of data obtained from multiple omics platforms to understand radiation dose, and dose rate effects in a complex human tissue model as a function of time. We will use as an example our results on the low dose responses in a 3D human skin model.

ionizing radiation↗
DOE OSTI2022

Identification of new marker genes from plant single‐cell RNA‐seq data using interpretable machine learning methods

Summary An essential step in the analysis of single‐cell RNA sequencing data is to classify cells into specific cell types using marker genes. In this study, we have developed a machine learning pipeline called single‐cell predictive marker (SPmarker) to identify novel cell‐type marker genes in the Arabidopsis root. Unlike traditional approaches, our method uses interpretable machine learning models to select marker genes. We have demonstrated that our method can: assign cell types based on cells that were labelled using published methods; project cell types identified by trajectory analysis from one data set to other data sets; and assign cell types based on internal GFP markers. Using SPmarker, we have identified hundreds of new marker genes that were not identified before. As compared to known marker genes, the new marker genes have more orthologous genes identifiable in the corresponding rice single‐cell clusters. The new root hair marker genes also include 172 genes with orthologs expressed in root hair cells in five non‐ Arabidopsis species, which expands the number of marker genes for this cell type by 35–154%. Our results represent a new approach to identifying cell‐type marker genes from scRNA‐seq data and pave the way for cross‐species mapping of scRNA‐seq data in plants.

54 ENVIRONMENTAL SCIENCES↗