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At least 865 records · Page 48

Draft genome sequence of marine alphaproteobacterial strain HIMB11, the first cultivated representative of a unique lineage within the Roseobacter clade possessing an unusually small genome

Strain HIMB11 is a planktonic marine bacterium isolated from coastal seawater in Kaneohe Bay, Oahu, Hawaii belonging to the ubiquitous and versatile Roseobacter clade of the alphaproteobacterial family Rhodobacteraceae. Here we describe the preliminary characteristics of strain HIMB11, including annotation of the draft genome sequence and comparative genomic analysis with other members of the Roseobacter lineage. The 3,098,747 bp draft genome is arranged in 34 contigs and contains 3,183 protein-coding genes and 54 RNA genes. Phylogenomic and 16S rRNA gene analyses indicate that HIMB11 represents a unique sublineage within the Roseobacter clade. Comparison with other publicly available genome sequences from members of the Roseobacter lineage reveals that strain HIMB11 has the genomic potential to utilize a wide variety of energy sources (e.g. organic matter, reduced inorganic sulfur, light, carbon monoxide), while possessing a reduced number of substrate transporters.

59 BASIC BIOLOGICAL SCIENCES↗

Draft Genome Sequence of Serratia sp. Strain ATCC 39006, a Model Bacterium for Analysis of the Biosynthesis and Regulation of Prodigiosin, a Carbapenem, and Gas Vesicles

Serratia sp. strain ATCC 39006 is a Gram-negative bacterium and a member of the Enterobacteriaceae that produces various bioactive secondary metabolites, including the tripyrrole red pigment prodigiosin and the β-lactam antibiotic 1-carbapenen-2-em- 3-carboxylic acid (a carbapenem). This strain is the only member of the Enterobacteriaceae known to naturally produce gas vesicles, as flotation organelles. Here we present the genome sequence of this strain, which has served as a model for analysis of the biosynthesis and regulation of antibiotic production.

59 BASIC BIOLOGICAL SCIENCES↗

Enhanced Resistance Pines for Improved Renewable Biofuel and Chemical Production (Technical Report)

We completed phenotyping constitutive and inducible oleoresin flow across two seasons, constitutive resin canal number and density and wood terpene content in our ADEPT2 and CCLONES populations. We completed genetic association between 19 oleoresin phenotypes and a total of 523,192 SNP markers from ADEPT2 and 13,883 SNP markers in CCLONES using four mixed linear models. A total of 293 significant SNPs (FDR = 0.20) were identified. We used the MENTOR tool to mine mechanistic connections from a multiplex network constructed from poplar multi-omic data to construct a conceptual model for a subset of these significant SNPs. Our model contains 6 transcriptional regulators in addition to 3 monoterpene synthases. To generate more lines of evidence for these significant SNPs, we completed a time course RNAseq experiment after inducing vascular zone cells to differentiate into new resin canals with a methyl jasmonate treatment, a single nuclei RNAseq that identified differentiating resin canal epithelial cells and are completing analysis for a QTL study in a hybrid pine population. The time course identified 4634 significantly down and 1890 significantly up regulated transcripts after treatment with methyl jasmonate, an inducer of new resin canal formation in the vascular cambial meristem. To analyze this large set of differentially regulated genes, we created a predictive expression network and analyzed it with random walk restart using 6 seed genes coding for transcription factors regulating xylem differentiation in poplar. Of the top ranked 200 transcripts, 119 transcripts were significant differentially expressed supporting these transcripts as potential candidates regulating resin canal formation. Analysis of single nuclei sequencing of shoot tips that contain differentiating resin canals, identified 10 clusters. One cluster was highly enriched in transcripts coding for 9 of the enzymes in the MEP pathway 3 prenyl synthetases, and 3 monoterpene synthases strongly suggesting that this cluster represents resin canal epithelial cells. We are mining the additional transcripts to create a trajectory analysis. In summary, we have identified > 10 novel genes that are strongly supported candidates for further analysis in breeding lines and for genetic engineering over- and under- expressing lines to increase wood terpene content to improve resistance to insect and fungal pathogens while simultaneously increasing terpene supplies for renewable chemicals and biofuels.

59 BASIC BIOLOGICAL SCIENCES↗

The Effects of Herbarium Specimen Characteristics on Short-Read NGS Sequencing Success in Nearly 8000 Specimens: Old, Degraded Samples Have Lower DNA Yields but Consistent Sequencing Success

Phylogenetic datasets are now commonly generated using short-read sequencing technologies unhampered by degraded DNA, such as that often extracted from herbarium specimens. The compatibility of these methods with herbarium specimens has precipitated an increase in broad sampling of herbarium specimens for inclusion in phylogenetic studies. Understanding which sample characteristics are predictive of sequencing success can guide researchers in the selection of tissues and specimens most likely to yield good results. Multiple recent studies have considered the relationship between sample characteristics and DNA yield and sequence capture success. Here we report an analysis of the relationship between sample characteristics and sequencing success for nearly 8,000 herbarium specimens. This study, the largest of its kind, is also the first to include a measure of specimen quality (“greenness”) as a predictor of DNA sequencing success. We found that taxonomic group and source herbarium are strong predictors of both DNA yield and sequencing success and that the most important specimen characteristics for predicting success differ for DNA yield and sequencing: greenness was the strongest predictor of DNA yield, and age was the strongest predictor of proportion-on-target reads recovered. Surprisingly, the relationship between age and proportion-on-target reads is the inverse of expectations; older specimens performed slightly better in our capture-based protocols. We also found that DNA yield itself is not a strong predictor of sequencing success. Most literature on DNA sequencing from herbarium specimens considers specimen selection for optimal DNA extraction success, which we find to be an inappropriate metric for predicting success using next-generation sequencing technologies.

54 ENVIRONMENTAL SCIENCES↗

Phylogeonomics and Ecogenomics of the Mycorrhizal Symbiosis

Mycorrhizal fungi play critical roles in host plant health, soil community structure and chemistry, and carbon and nutrient cycling, all areas of intense interest to the US Dept. of Energy (DOE) Joint Genome Institute (JGI). To this end we are building on our earlier sequencing of the Laccaria bicolor genome by partnering with INRA-Nancy and the mycorrhizal research community in the MGI to sequence and analyze 2 dozen mycorrhizal genomes of numerous known mycorrhizal orders and several ecological types (ectomycorrhizal [ECM], ericoid, orchid, and arbuscular). JGI has developed and deployed high-throughput pipelines for genomic, transcriptomic, and re-sequencing, and platforms for assembly, annotation, and analysis. In the last 2 years we have sequenced 21 genomes of mycorrhizal fungi, and resequenced 6 additional strains of L. bicolor. Most of this data is publicly available on JGI MycoCosm?s Mycorrhizal Fungi Portal (http://jgi.doe.gov/Mycorrhizal_fungi/), which provides access to both the genome data and tools with which to analyze the data. These data allow us to address long-standing issues in mycorrhizal evolution and ecology. For example, a major observation of mycorrhizal evolution is that each of the major ecological types appears to have evolved independently in multiple fungal clades. Using an ecogenomic approach we provide preliminary evidence that 2 clades (Cantharellales and Sebacinales) of a single symbiotic ecotype (orchid) utilize some common regulatory (protein tyrosine kinase) and metabolic (lipase) paths, the latter of which may be the product of HGT. Using a phylogenomic approach we provide preliminary evidence that a particular ecotype (ericoid) may have evolved more than once within a major clade (Leotiomycetes).

59 BASIC BIOLOGICAL SCIENCES↗

The Role of Viral Population Diversity in Adaptation of Bovine Coronavirus to New Host Environments

The high mutation rate of RNA viruses enables a diverse genetic population of viral genotypes to exist within a single infected host. In-host genetic diversity could better position the virus population to respond and adapt to a diverse array of selective pressures such as host-switching events. Multiple new coronaviruses, including SARS, have been identified in human samples just within the last ten years, demonstrating the potential of coronaviruses as emergent human pathogens. Deep sequencing was used to characterize genomic changes in coronavirus quasispecies during simulated host-switching. Three bovine nasal samples infected with bovine coronavirus were used to infect human and bovine macrophage and lung cell lines. The virus reproduced relatively well in macrophages, but the lung cell lines were not infected efficiently enough to allow passage of non lab-adapted samples. Approximately 12 kb of the genome was amplified before and after passage and sequenced at average coverages of nearly 9506(454 sequencing) and 38,0006(Illumina). The consensus sequence of many of the passaged samples had a 12 nucleotide insert in the consensus sequence of the spike gene, and multiple point mutations were associated with the presence of the insert. Deep sequencing revealed that the insert was present but very rare in the unpassaged samples and could quickly shift to dominate the population when placed in a different environment. The insert coded for three arginine residues, occurred in a region associated with fusion entry into host cells, and may allow infection of new cell types via heparin sulfate binding. Analysis of the deep sequencing data indicated that two distinct genotypes circulated at different frequency levels in each sample, and support the hypothesis that the mutations present in passaged strains were ‘‘selected’’ from a pre-existing pool rather than through de novo mutation and subsequent population fixation.

59 BASIC BIOLOGICAL SCIENCES↗

Identification, Expression, and Interaction Analysis of Ovate Family Proteins in Populus trichocarpa Reveals a Role of PtOFP1 Regulating Drought Stress Response

Ovate family proteins (OFPs) are a family of plant growth regulators that play diverse roles in many aspects of physiological processes. OFPs have been characterized in various plant species including tomato, Arabidopsis , and rice. However, little is known about OFPs in woody species. Here, a total of 30 PtOFP genes were identified from the genome of Populus trichocarpa and were further grouped into four subfamilies based on their sequence similarities. Gene expression analysis indicated that some members of the PtOFP gene family displayed tissue/organ-specific patterns. Analysis of cis -acting elements in the promoter as well as gene expression by hormone treatment revealed putative involvement of PtOFPs in hormonal response. Furthermore, PtOFP1 (Potri.006G107700) was further experimentally demonstrated to act as a transcriptional repressor. Yeast two-hybrid assay showed physical interactions of PtOFP1 with other proteins, which suggests that they might function in various cellular processes by forming protein complexes. In addition, overexpression of PtOFP1 in Arabidopsis conferred enhanced tolerance to PEG-induced drought stress at seedling stage, as well as a higher survival rate than the wild type at mature stage. These results provide a systematic analysis of the Populus OFP gene family and lay a foundation for functional characterization of this gene family.

59 BASIC BIOLOGICAL SCIENCES↗

Data requirements for improving the Quantitative Risk Assessment of liquid hydrogen storage systems

Quantitative Risk Assessment (QRA) supports the development of risk-informed safety codes and standards which are employed to enable the safe deployment of hydrogen technologies essential to decarbonize the transportation sector. System reliability data is a necessary input for rigorous QRA. Here, the lack of reliability data for bulk liquid hydrogen (LH 2 ) storage systems located on site at fueling stations limits the use of QRAs. In turn, this hinders the ability to develop the necessary safety codes and standards that enable worldwide deployment of these stations. Through a QRA-based analysis of a LH 2 storage system, this work focuses on identifying relevant scenario and probability data currently available and ascertaining future data collection requirements regarding risks specific to liquid hydrogen releases. The work developed consists of the analysis of a general bulk LH 2 storage system design located at a hydrogen fueling station. Failure Mode and Effect Analysis (FMEA) and traditional QRA modeling tools such as Event Sequence Diagrams (ESD) and Fault Tree Analysis (FTA) are employed to identify, rank, and model risk scenarios related to the release of LH 2 . Based on this analysis, scenario and reliability data needs to add LH 2 -related components to QRA are identified with the purpose of improving the future safety and risk assessment of these systems.

08 HYDROGEN↗

Structure of the AvrBs3–DNA complex provides new insights into the initial thymine-recognition mechanism

The crystal structure of the AvrBs3–DNA complex is reported. Transcription activator-like effectors contain a DNA-binding domain organized in tandem repeats. The repeats include two adjacent residues known as the repeat variable di-residue, which recognize a single base pair, establishing a direct code between the dipeptides and the target DNA. This feature suggests this scaffold as an excellent candidate to generate new protein–DNA specificities for biotechnological applications. Here, the crystal structure of AvrBs3 (residues 152–895, molecular mass 82 kDa) in complex with its target DNA sequence is presented, revealing a new mode of interaction with the initial thymine of the target sequence, together with an analysis of both the binding specificity and the thermodynamic properties of AvrBs3. This study quantifies the affinity and the specificity between AvrBs3 and its target DNA. Moreover, in vitro and in vivo analyses reveal that AvrBs3 does not show a strict nucleotide-binding preference for the nucleotide at the zero position of the DNA, widening the number of possible sequences that could be targeted by this scaffold.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Low Cost Mission Operations Workshop

The presentations given at the Low Cost (Space) Mission Operations (LCMO) Workshop are outlined. The LCMO concepts are covered in four introductory sections: Definition of Mission Operations (OPS); Mission Operations (MOS) Elements; The Operations Concept; and Mission Operations for Two Classes of Missions (operationally simple and complex). Individual presentations cover the following topics: Science Data Processing and Analysis; Mis sion Design, Planning, and Sequencing; Data Transport and Delivery, and Mission Coordination and Engineering Analysis. A list of panelists who participated in the conference is included along with a listing of the contact persons for obtaining more information concerning LCMO at JPL. The presentation of this document is in outline and graphic form.

Source record↗

GRC MILab Software: Quick Start Guide

This document provides detailed installation and operating instructions for the GRC MILab Excel Add-In software developed at the NASA Glenn Research Center. The software described has been implemented to facilitate the process of importing into Microsoft Excel and analyzing materials test data from a wide range of materials tests. All resulting data is then ready for automated upload to the relevant table of the GRC Materials Intelligence (MI) database. This new software represents an update to the original MILab software developed by Granta Design Ltd.—a company specializing in materials software, data, and databases—for members of the Materials Data Management Consortium (MDMC), a collaboration between Granta, ASM International, NASA Glenn, and several other materials-oriented corporations and government agencies in the aerospace and defense industries. The updated software consists of the addition of two test type modules, the Generic and Generic Cyclic modules, with both representing a generalization of the original software. The Generic module supports the import and analysis of multiaxial data from any sequence of tensile, compression, relaxation, and/or creep test stages; and the Generic Cyclic module expands the functionality to include repeated sequences during cyclic testing. During processing, all imported data and analysis results are formatted by the software so as to be ready for immediate automated upload to the MI database, ensuring minimal overhead on the part of the user and access to persistent and reliable data for all relevant personnel.

Quick Start Guide↗

Rare key functional domain missense substitutions in MRE11A, RAD50 , and NBN contribute to breast cancer susceptibility: results from a Breast Cancer Family Registry case-control mutation-screening study

The MRE11A-RAD50-Nibrin (MRN) complex plays several critical roles related to repair of DNA double-strand breaks. Inherited mutations in the three components predispose to genetic instability disorders and the MRN genes have been implicated in breast cancer susceptibility, but the underlying data are not entirely convincing. Here, we address two related questions: (1) are some rare MRN variants intermediate-risk breast cancer susceptibility alleles, and if so (2) do the MRN genes follow a BRCA1/BRCA2 pattern wherein most susceptibility alleles are protein-truncating variants, or do they follow an ATM/CHEK2 pattern wherein half or more of the susceptibility alleles are missense substitutions? Using high-resolution melt curve analysis followed by Sanger sequencing, we mutation screened the coding exons and proximal splice junction regions of the MRN genes in 1,313 early-onset breast cancer cases and 1,123 population controls. Rare variants in the three genes were pooled using bioinformatics methods similar to those previously applied to ATM, BRCA1, BRCA2, and CHEK2, and then assessed by logistic regression. Results: Re-analysis of our ATM, BRCA1, and BRCA2 mutation screening data revealed that these genes do not harbor pathogenic alleles (other than modest-risk SNPs) with minor allele frequencies >0.1% in Caucasian Americans, African Americans, or East Asians. Limiting our MRN analyses to variants with allele frequencies of <0.1% and combining protein-truncating variants, likely spliceogenic variants, and key functional domain rare missense substitutions, we found significant evidence that the MRN genes are indeed intermediate-risk breast cancer susceptibility genes (odds ratio (OR) = 2.88, P = 0.0090). Key domain missense substitutions were more frequent than the truncating variants (24 versus 12 observations) and conferred a slightly higher OR (3.07 versus 2.61) with a lower P value (0.029 versus 0.14). These data establish that MRE11A, RAD50, and NBN are intermediate-risk breast cancer susceptibility genes. Like ATM and CHEK2, their spectrum of pathogenic variants includes a relatively high proportion of missense substitutions. However, the data neither establish whether variants in each of the three genes are best evaluated under the same analysis model nor achieve clinically actionable classification of individual variants observed in this study.

59 BASIC BIOLOGICAL SCIENCES↗

SU-E-I-62: Reduction of Susceptibility Artifacts by Increasing the Bandwidth (BW) and Echo Train Length (ETL)

Purpose: The aim of this present study is to increase bandwidth (BW) and echo train length (ETL) in Proton Density Turbo Spin Echo (PD TSE) sequences with and without fat saturation (FS) as well as in Turbo Inversion Recovery Magnitude sequences (TIRM) in order to assess whether these sequences are capable of reducing susceptibility artifacts. Methods: We compared 1) TIRM coronal (COR) with the same sequence with increased both BW and ETL 2) Conventional PD TSE sagittal (SAG) with FS with an increased BW 3) Conventional PD TSE SAG without FS with an increased BW 4) Conventional PD TSE SAG without FS with increased both BW and ETL. A quantitative analysis was performed to measure the extent of the susceptibility artifacts. Furthermore, a qualitative analysis was performed by two radiologists in order to evaluate the susceptibility artifacts, image distortion and fat suppression. The depiction of cartilage, menisci, muscles, tendons and bone marrow were also qualitatively analyzed. Results: The quantitative analysis found that the modified TIRM sequence is significantly superior to the conventional one regarding the extent of the susceptibility artifacts. In the qualitative analysis, the modified TIRM sequence was superior to the corresponding conventional one in eight characteristics out of ten that were analyzed. The modified PD TSE with FS was superior to the corresponding conventional one regarding the susceptibility artifacts, image distortion and depiction of bone marrow and cartilage while achieving effective fat saturation. The modified PD TSE sequence without FS with a high (H) BW was found to be superior corresponding to the conventional one in the case of cartilage. Conclusion: Consequently, TIRM sequence with an increased BW and ETL is proposed for producing images of high quality and modified PD TSE with H BW for smaller metals, especially when FS is used.

60 APPLIED LIFE SCIENCES↗

Genetic and antigenic variation of foot-and-mouth disease virus during persistent infection in naturally infected cattle and Asian buffalo in India

The role of foot-and-mouth disease virus (FMDV) persistently infected ruminants in initiating new outbreaks remains controversial, and the perceived threat posed by such animals hinders international trade in FMD-endemic countries. In this study we report longitudinal analyses of genetic and antigenic variations of FMDV serotype O/ME-SA/Ind2001d sublineage during naturally occurring, persistent infection in cattle and buffalo at an organised dairy farm in India. The proportion of animals from which FMDV RNA was recovered was not significantly different between convalescent (post-clinical) and sub-clinically infected animals or between cattle and buffalo across the sampling period. However, infectious virus was isolated from a higher proportion of buffalo samples and for a longer duration compared to cattle. Analysis of the P1 sequences from recovered viruses indicated fixation of mutations at the rate of 1.816 x 10 -2 substitution/site/year (s/s/y) (95% CI 1.362–2.31 x 10 -2 s/s/y). However, the majority of point mutations were transitional substitutions. Within individual animals, the mean dN/dS (ω) value for the P1 region varied from 0.076 to 0.357, suggesting the selection pressure acting on viral genomes differed substantially across individual animals. Statistical parsimony analysis indicated that all of the virus isolates from carrier animals originated from the outbreak virus. The antigenic relationship value as determined by 2D-VNT assay revealed fluctuation of antigenic variants within and between carrier animals during the carrier state which suggested that some carrier viruses had diverged substantially from the protection provided by the vaccine strain. This study contributes to understanding the extent of within-host and within-herd evolution that occurs during the carrier state of FMDV.

60 APPLIED LIFE SCIENCES↗

Robust verification analysis

We introduce a new methodology for inferring the accuracy of computational simulations through the practice of solution verification. We demonstrate this methodology on examples from computational heat transfer, fluid dynamics and radiation transport. Our methodology is suited to both well- and ill-behaved sequences of simulations. Our approach to the analysis of these sequences of simulations incorporates expert judgment into the process directly via a flexible optimization framework, and the application of robust statistics. The expert judgment is systematically applied as constraints to the analysis, and together with the robust statistics guards against over-emphasis on anomalous analysis results. We have named our methodology Robust Verification. Our methodology is based on utilizing multiple constrained optimization problems to solve the verification model in a manner that varies the analysis' underlying assumptions. Constraints applied in the analysis can include expert judgment regarding convergence rates (bounds and expectations) as well as bounding values for physical quantities (e.g., positivity of energy or density). This approach then produces a number of error models, which are then analyzed through robust statistical techniques (median instead of mean statistics). This provides self-contained, data and expert informed error estimation including uncertainties for both the solution itself and order of convergence. Our method produces high quality results for the well-behaved cases relatively consistent with existing practice. The methodology can also produce reliable results for ill-behaved circumstances predicated on appropriate expert judgment. We demonstrate the method and compare the results with standard approaches used for both code and solution verification on well-behaved and ill-behaved simulations.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Molecular Epidemiology of Foot-and-Mouth Disease Virus in the Context of Transboundary Animal Movement in the Far North Region of Cameroon

Transboundary movement of animals is an important mechanism for foot-and-mouth disease virus (FMDV) spread in endemic regions, such as Cameroon. Several transboundary animal trade routes cross the Far North Region of Cameroon, and cattle moved on foot along these routes often come in contact with native (sedentary and transhumant) herds. The purpose of this study was to investigate the role of transboundary trade cattle in the epidemiology of FMDV in the Far North Region of Cameroon. A total of 582 oropharyngeal fluid (OPF) samples were collected from asymptomatic transboundary trade cattle at official border check points and 57 vesicle epithelial tissues were collected from clinically affected native cattle in the Far North Region of Cameroon during 2010–2014. Viral protein 1 (VP1) coding sequences were obtained from 6 OPF samples from transboundary cattle (4 serotype O, 2 serotype SAT2) and 19 epithelial tissue samples from native cattle (7 serotype O, 3 serotype SAT2, 9 serotype A). FMDV serotype O viruses belonged to two topotypes (East Africa-3 and West Africa), and phylogenetic analyses suggested a pattern of continuous transmission in the region. Serotype SAT2 viruses belonged to a single topotype (VII), and phylogenetic analysis suggested a pattern of repeated introductions of different SAT2 lineages in the region. Serotype A viruses belonged to topotype AFRICA/G-IV, and the pattern of transmission was unclear. Spearman rank correlation analysis of VP1 coding sequences obtained in this study from transboundary and native cattle showed a positive correlation between genetic distance and time for serotype O ( ρ = 0.71, p = 0.003) and between genetic distance and geographic distance for serotype SAT2 ( ρ = 0.54, p = 0.1). These data suggest that transboundary trade cattle participate in the transmission of FMDV in the Far North Region of Cameroon, however the dynamics and direction of transmission could not be determined in this study. Results of this study contribute to the understanding of transboundary FMDV epidemiology in Central Africa and will help to inform control programs in Cameroon and in the region.

Veterinary Sciences↗

Genomics Study of Effect of Redox-Active Metalloporphyrin on Murine Retina During Spaceflight

Astronauts returning from spaceflight have experienced eye problems, which may decrease retinal performance and lead to long-term effects on visual acuity. This study leverages the collected data from spaceflown murine retinas that were treated with redox-active metalloporphyrin (BuOE) to mitigate spaceflight-induced changes. 10-week-old adult C57BL/6 male mice (n=5 in each of BuOE treated and saline control groups) were flown on Space-X 24 to the ISS national lab, kept in low earth orbit for 35 days and returned to Earth alive. Our analysis of RNA-sequencing data generated from subsequent murine retina tissues uncovered genes, pathways, and epigenetic modifications consistent with therapeutic potential of BuOE. For spaceflown murine samples, the treatment group show differentially expressed genes relative to saline controls that reached significance (adjusted p-value < 0.05) and included genes Gpx3 and Crhbp, which are related to protection against cell oxidative damage and cellular response to organonitrogen compounds. Ranked fold-changes from the same contrast were used for gene set enrichment analysis, which showed biological processes reaching significance (adjusted p-value < 0.05) including glutathione metabolic processes and cellular response to xenobiotic stimulus. The findings from this investigation have the potential to provide valuable insights into the molecular mechanisms underlying conditions like spaceflight associated neuro-ocular syndrome and assess the effectiveness of BuOE as a countermeasure for astronauts experiencing neuro-ophthalmic abnormalities, which can lead to long-term effects on visual acuity.

Machine Learning↗

Genomics Study of Effect of Redox-Active Metalloporphyrin on Murine Retina During Spaceflight

Astronauts returning from spaceflight have experienced eye problems, which may decrease retinal performance and lead to long-term effects on visual acuity. This study leverages the collected data from spaceflown murine retinas that were treated with redox-active metalloporphyrin (BuOE) to mitigate spaceflight-induced changes. 10-week-old adult C57BL/6 male mice (n=5 in each of BuOE treated and saline control groups) were flown on Space-X 24 to the ISS national lab, kept in low earth orbit for 35 days and returned to Earth alive. Our analysis of RNA-sequencing data generated from subsequent murine retina tissues uncovered genes, pathways, and epigenetic modifications consistent with therapeutic potential of BuOE. For spaceflown murine samples, the treatment group show differentially expressed genes relative to saline controls that reached significance (adjusted p-value < 0.05) and included genes Gpx3 and Crhbp, which are related to protection against cell oxidative damage and cellular response to organonitrogen compounds. Ranked fold-changes from the same contrast were used for gene set enrichment analysis, which showed biological processes reaching significance (adjusted p-value < 0.05) including glutathione metabolic processes and cellular response to xenobiotic stimulus. The findings from this investigation have the potential to provide valuable insights into the molecular mechanisms underlying conditions like spaceflight associated neuro-ocular syndrome and assess the effectiveness of BuOE as a countermeasure for astronauts experiencing neuro-ophthalmic abnormalities, which can lead to long-term effects on visual acuity.

Machine Learning↗