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At least 127 records · Page 7

ISS External Microorganisms: A Payload to Close Planetary Protection Knowledge Gaps for Crewed Missions

Before NASA or COSPAR is able to set planetary protection requirements for crewed missions to locations like Mars there are a number of critical knowledge gaps that must be addressed (1). One of the most important knowledge gaps is an understanding of microbial leakage from crewed habitats and space suits. Current ECLSS (Environmental Control and Life Support System) and PLSS (Portable Life Support System) requirements do not include any provisions to control microbes that may escape along with vented or leaked gasses. The current generation of NASA space suits can leak at rates as high as 100 cm2 /min. during nominal operation (2). ISS (International Space Station) intentionally vents atmospheric gases like CO2 to maintain habitable conditions for the crew. Furthermore, every time an airlock is used for EVA (extravehicular activity)there is an accompanying release of internal atmosphere. Since it is not possible to sterilize a crewed mission, it is important that we understand what if any microbes are entrained in these vented and leaked products. It is also important to understand if these microbes can survive on exterior surfaces. Recent sampling of the Russian segments of ISS suggest that bacteria and fungi from inside ISS may be capable of surviving on external surfaces(3). NASA is developing an aseptic sampling tool for use during EVA and plans to collect samples from vents on ISS to build on these results. The results of this work will be used to develop planetary protection requirements for vented and leaked gasses from crewed volumes. NASA has developed and tested a tool kit for collecting microbiological samples during EVA(4). This tool kit contains eight commercially available, 23 mm. diameter, foam swabs that can be used to aseptically collect samples while at vacuum. The swabs are individually housed in aluminum canisters that are equipped with 0.2 μm Teflon filters. These filters allow the canisters to equilibrate to pressure changes while preventing microbiological contamination. The canisters will be cleaned and sterilized before flight. Results from ground-based testing indicate that this tool kit is capable of aseptically collecting microbes while at vacuum without becoming contaminated during pressure changes(5). Based on the results of this ground testing we have modified the tool kit to meet NASA safety requirements and improve the ergonomics. We added additional mounting points to the tool kit to give astronauts more options for securing it during use. We also changed the opening mechanism to improve the precision with which swabs can be extracted from the tool kit. We plan to use this kit on an upcoming EVA to collect samples from non-propulsive vents and areas near the U.S. airlock on ISS. These samples will be frozen at -80 ̊C and stored on station until they can be returned to Earth. We will analyze these returned samples using next generation DNA sequencing to determine the community composition and function of external ISS environments. The results of this study will close planetary protection knowledge gaps for crewed missions and will help NASA determine appropriate planetary protection requirements for life support systems. The tool kit will also be useful for collecting aseptic samples on upcoming crewed or robotic missions and could easily be modified to collect samples with organic contamination control requirements as well.

A B Regberg↗

The BioMole Facility: Advancement of In Situ Microbiome Analysis for the International Space Station

Characterization of the International Space Station (ISS) microbiome has been enabled by sample return and Earth-based analysis. As human exploration pushes beyond low-Earth orbit, microbial-related crew health, planetary protection, and space research requires in situ capabilities. Steps toward reducing Earth-dependence for complex sample analysis began in 2016 with the amplification of DNA within the miniPCR thermal cycler and DNA sequencing with the MinION sequencer onboard the ISS; for both, samples were prepared on Earth. In 2017, these platforms synergistically enabled the in-situ identification of unknown bacteria collected and cultured from ISS surfaces, thereby shifting the paradigm that microbial cultures had to be returned to Earth. The following year, a culture-independent, swab-to-sequencer method further advanced spaceflight microbiology, demonstrating that culturing could be excluded and provided enhanced insight into the bacterial profile of ISS surfaces. Based on the success of these payloads in confirming the ability to meet crew health identification requirements and the benefits accompanying a culture-independent method, the BioMole Facility was established by the medical operations Crew Health Care Systems team. BioMole is the set of hardware, consumables, and procedures required to support sample preparation and nanopore sequencing onboard the ISS. BioMole goals include expanding sample sources, comparing data to previous methods, demonstrating onboard data analytics, and validating new hardware. To date, comparative surface analysis, molecular- and culture-based, has been completed. Additionally, the demonstration of a sample-to-answer process was achieved when BioMole data was processed onboard using the IBM Open Data and AI Edge software platform installed on the ISS-residing Spaceborne Computer-2. The taxonomic profiles generated from the edge analysis were as expected and paralleled that of the downlinked processed data. Future BioMole efforts involve microbial profiling of the ISS water system, ISS validation of the MinION Mk1C, and an expansion to a research facility available to investigators.

Sarah L. Castro-Wallace↗

ISS External Microorganisms: Tools and Techniques for Collecting Planetary Protection Samples During Extravehicular Activity

We have designed, built, and tested a sampling kit (Fig. 1) to aseptically collect microbiological samples from exterior surfaces on the ISS (International Space Station). The kit was flown to ISS as part of the NG-19 commercial cargo mission in August of 2023. Astronauts will use the kit to collect samples from six exterior surfaces on ISS. These samples will be frozen at -80°C after collection and returned to the ground for next generation DNA sequencing. The results of this experiment will help inform planetary protection requirements for crewed missions. We hypothesize that there are detectable microbial communities outside ISS and that these communities originate from inside ISS. Current life support systems do not include any components for reducing microbial leakage. Gases are vented from inside ISS without filtration and there are currently no protocols in place to minimize bioburden on space suit exteriors prior to use. It is important to quantify the bioburden on current vehicles so that achievable limits can be set for crewed missions to astrobiologically relevant locations like Mars.

Planetary Protection↗

Fractal landscape analysis of DNA walks

By mapping nucleotide sequences onto a "DNA walk", we uncovered remarkably long-range power law correlations [Nature 356 (1992) 168] that imply a new scale invariant property of DNA. We found such long-range correlations in intron-containing genes and in non-transcribed regulatory DNA sequences, but not in cDNA sequences or intron-less genes. In this paper, we present more explicit evidences to support our findings.

NASA Program Space Physiology and Countermeasures↗

Fractal landscapes in biological systems: long-range correlations in DNA and interbeat heart intervals

Here we discuss recent advances in applying ideas of fractals and disordered systems to two topics of biological interest, both topics having common the appearance of scale-free phenomena, i.e., correlations that have no characteristic length scale, typically exhibited by physical systems near a critical point and dynamical systems far from equilibrium. (i) DNA nucleotide sequences have traditionally been analyzed using models which incorporate the possibility of short-range nucleotide correlations. We found, instead, a remarkably long-range power law correlation. We found such long-range correlations in intron-containing genes and in non-transcribed regulatory DNA sequences as well as intragenomic DNA, but not in cDNA sequences or intron-less genes. We also found that the myosin heavy chain family gene evolution increases the fractal complexity of the DNA landscapes, consistent with the intron-late hypothesis of gene evolution. (ii) The healthy heartbeat is traditionally thought to be regulated according to the classical principle of homeostasis, whereby physiologic systems operate to reduce variability and achieve an equilibrium-like state. We found, however, that under normal conditions, beat-to-beat fluctuations in heart rate display long-range power law correlations.

Non-NASA Center↗

Identification of a dual-specificity protein phosphatase that inactivates a MAP kinase from Arabidopsis

Mitogen-activated protein kinases (MAPKs) play a key role in plant responses to stress and pathogens. Activation and inactivation of MAPKs involve phosphorylation and dephosphorylation on both threonine and tyrosine residues in the kinase domain. Here we report the identification of an Arabidopsis gene encoding a dual-specificity protein phosphatase capable of hydrolysing both phosphoserine/threonine and phosphotyrosine in protein substrates. This enzyme, designated AtDsPTP1 (Arabidopsis thaliana dual-specificity protein tyrosine phosphatase), dephosphorylated and inactivated AtMPK4, a MAPK member from the same plant. Replacement of a highly conserved cysteine by serine abolished phosphatase activity of AtDsPTP1, indicating a conserved catalytic mechanism of dual-specificity protein phosphatases from all eukaryotes.

Non-NASA Center↗

Crystal structure of four-stranded Oxytricha telomeric DNA

The sequence d(GGGGTTTTGGGG) from the 3' overhang of the Oxytricha telomere has been crystallized and its three-dimensional structure solved to 2.5 A resolution. The oligonucleotide forms hairpins, two of which join to make a four-stranded helical structure with the loops containing four thymine residues at either end. The guanine residues are held together by cyclic hydrogen bonding and an ion is located in the centre. The four guanine residues in each segment have a glycosyl conformation that alternates between anti and syn. There are two four-stranded molecules in the asymmetric unit showing that the structure has some intrinsic flexibility.

NASA Discipline Exobiology↗

Method Development for In-situ Detection of Latent Herpesvirus DNA from Saliva using Nanopore Sequencing

Research toward latent herpesvirus reactivation has been intensively addressed through Space Shuttle and International Space Station (ISS) investigations. This work has provided the understanding that persistent reactivation of herpesviruses from asymptomatic crew can be detected through viral shedding in saliva, urine, and blood. Occasionally, viral reactivation from the latency stage can pose a threat to crew health (clinical manifestation) before, during, and after flight missions. Furthermore, previous work detailing correlations with immunity indicate that monitoring viral reactivation could be implemented to assess potential immune dysfunction. While in-flight monitoring is desirable, there is no well-established procedure or method for real-time evaluations, and research to date has relied on postflight, ground-based analysis. The development of portable molecular technologies like the miniPCR™ (miniPCR Bio) thermal cycler and the MinION™ sequencer (Oxford Nanopore Technologies) have confirmed that real-time monitoring is possible in extreme and low resource environments. These devices, combined with simple sample preparation methods, have been used to demonstrate bacterial identification onboard the ISS, as well as rapid viral detection in remote locations on Earth. The work here builds upon previous molecular advancements onboard the ISS toward the development and validation of a spaceflight-compatible method for viral detection from crew samples. Several herpesviruses can be detected in saliva, which provides a non-invasive means to collect samples for monitoring. While the basis for this method lies in previous spaceflight investigations, key points for method optimization include DNA extraction from saliva, viral primer selection, and bioinformatic processes for data analysis. To increase viral yield, numerous DNA extraction methods have been evaluated and will be discussed in detail. For initial development and testing, varicella-zoster virus (VZV) is being targeted though open reading frame 51 and 63 (ORF51, ORF63), as the replication origin-binding protein is highly expressed during latency. Optimization of the thermal cycling parameters has resulted in the ability to test the entire process. The full method has been tested with both viral VZV DNA standards and saliva spiked with varying concentrations of VZV. Viral sequence data were mapped to the reference sequence using minimap2. Prior to mapping, DNA sequencing reads were filtered for length and quality, barcodes were removed, and alignment identity calculated. Following further assessments, statistics were compared across multiple sequencing experiments and are being used to determine the success of the protocols. Forward work will include the incorporation of herpes simplex virus 1 (HSV-1) and Epstein-Barr virus (EBV) primers as well as the validation of results to the terrestrial qPCR standard assay. Upon full validation of the developed method, saliva will be collected from 20 healthy subjects and spiked with viral DNA. These samples will be split and assayed with the MinION and standard qPCR assay.

Hang N Nguyen↗

Phylogenetic and physiological diversity of microorganisms isolated from a deep greenland glacier ice core

We studied a sample from the GISP 2 (Greenland Ice Sheet Project) ice core to determine the diversity and survival of microorganisms trapped in the ice at least 120,000 years ago. Previously, we examined the phylogenetic relationships among 16S ribosomal DNA (rDNA) sequences in a clone library obtained by PCR amplification from genomic DNA extracted from anaerobic enrichments. Here we report the isolation of nearly 800 aerobic organisms that were grouped by morphology and amplified rDNA restriction analysis patterns to select isolates for further study. The phylogenetic analyses of 56 representative rDNA sequences showed that the isolates belonged to four major phylogenetic groups: the high-G+C gram-positives, low-G+C gram-positives, Proteobacteria, and the Cytophaga-Flavobacterium-Bacteroides group. The most abundant and diverse isolates were within the high-G+C gram-positive cluster that had not been represented in the clone library. The Jukes-Cantor evolutionary distance matrix results suggested that at least 7 isolates represent new species within characterized genera and that 49 are different strains of known species. The isolates were further categorized based on the isolation conditions, temperature range for growth, enzyme activity, antibiotic resistance, presence of plasmids, and strain-specific genomic variations. A significant observation with implications for the development of novel and more effective cultivation methods was that preliminary incubation in anaerobic and aerobic liquid prior to plating on agar media greatly increased the recovery of CFU from the ice core sample.

Bacteria/classification/genetics/isolation & purif↗

ISS External Microorganisms: A Planetary Protection Experiment to Inform Requirements for Crewed Missions to Mars

We have developed, tested, and flown a caddy capable of collecting aseptic samples from external surfaces of the ISS (International Space Station). The sampling caddy is certified for use during US EVA (extra vehicular activity) and was launched to ISS in the summer of 2023. We are scheduled to collect samples from 6 locations outside ISS during an EVA in May of 2024. We will freeze these samples at -80°C on orbit and return them to Earth. We will then extract and sequence any DNA collected during the EVA using next generation sequencing technologies to characterize the community composition and function of each sample. Measuring the type and quantity of microbes present on the exterior of ISS will allow us to address knowledge gap 2B, “Acceptable levels of microbial/organic releases from humans and support systems” described in a 2019 COSPAR report. Collecting data about microbial release from current crewed vehicles will inform requirements for acceptable leak rates for future crewed missions to Mars. The sampling kit consists of eight commercially available, sterile, DNA free, macrofoam swabs ( 23 mm. diameter ) installed in custom aluminum end effectors. Each end effector is housed in and individual aluminum canister. Each canister contains a 0.2 μm Teflon filter to allow the interior volume to accommodate pressure changes without permitting microbial contaminants to enter the sterile interior volume. A handle repurposed from the space shuttle tile repair kit is used to remove the end effector from the sample canister, collect a sample by swabbing a surface and then replace the end effector in its canister. The canisters and end effectors were cleaned and assembled on Earth. Prior to installing the sterile swab the canisters and end effectors were sterilized in an autoclave at 134°C, 215 kPA, for 7 min.. The final assembly occurred in a sterilized class II biosafety cabinet. We will collect six samples from the 1) airlock vestibule, 2) airlock thermal cover, 3) a gap in the micrometeorite shielding near the airlock, 4) a handrail near the airlock, 5) the CDRA (Carbon Dioxide Removal Assembly) vent, and 6) the VES (Vacuum Exhaust System) vent. The remaining two swabs will be reserved as controls. One swab will be exposed during the EVA without touching any surfaces to act as a blank. The final swab will remain sealed until the entire sampling kit is returned to earth. Based on previously published results from the Russian segment, we hypothesize that there will be detectable microbes at some or all of these locations. Ground-based testing of this sampling caddy confirms that the swabs remain sterile as the canisters transition in and out of vacuum. We were able to retrieve, viable bacterial and fungal cells as well as DNA from samples collected from US space suits during vacuum chamber tests lasting as long as seven hours. Based on these results and feedback from the test subjects the sampling caddy was modified to improve ergonomics and meet US EVA safety requirements. Bayonet probes were added to the sides of the sample kit as alternate mounting points. Additional locking features were added to the end effector and the filter stack to prevent inadvertent release during use. The opening mechanism was changed from one where the end effector was rocked laterally to defeat a ball detent to a twist-to-open threaded closure for similar reasons. Demonstrating, this sampling caddy’s effectiveness during a US EVA will allow us to address knowledge gaps identified in COSPAR reports and begin to define planetary protection requirements for life support systems on crewed missions to mars. This kit could also be used to collect contamination control samples during Artemis missions to verify requirements and could be easily modified for robotic sample collection.

Planetary Protection↗

ISS External Microorganisms: Collecting Planetary Protection Samples During Extravehicular Activity

We have developed, tested, and flown a caddy capable of collecting aseptic samples from external surfaces of the ISS (International Space Station). The sampling caddy is certified for use during US EVA (extra vehicular activity) and was launched to ISS in the summer of 2023. We are scheduled to collect samples from 6 locations outside ISS during an EVA in May of 2024. We will freeze these samples at -80°C on orbit and return them to Earth. We will then extract and sequence any DNA collected during the EVA using next generation sequencing technologies to characterize the community composition and function of each sample. Measuring the type and quantity of microbes present on the exterior of ISS will allow us to address knowledge gap 2B, “Acceptable levels of microbial/organic releases from humans and support systems” described in a 2019 COSPAR report. Collecting data about microbial release from current crewed vehicles will inform requirements for acceptable leak rates for future crewed missions to Mars. The sampling kit consists of eight commercially available, sterile, DNA free, macrofoam swabs ( 23 mm. diameter ) installed in custom aluminum end effectors. Each end effector is housed in and individual aluminum canister. Each canister contains a 0.2 μm Teflon filter to allow the interior volume to accommodate pressure changes without permitting microbial contaminants to enter the sterile interior volume. A handle repurposed from the space shuttle tile repair kit is used to remove the end effector from the sample canister, collect a sample by swabbing a surface and then replace the end effector in its canister. The canisters and end effectors were cleaned and assembled on Earth. Prior to installing the sterile swab the canisters and end effectors were sterilized in an autoclave at 134°C, 215 kPA, for 7 min.. The final assembly occurred in a sterilized class II biosafety cabinet. We will collect six samples from the 1) airlock vestibule, 2) airlock thermal cover, 3) a gap in the micrometeorite shielding near the airlock, 4) a handrail near the airlock, 5) the CDRA (Carbon Dioxide Removal Assembly) vent, and 6) the VES (Vacuum Exhaust System) vent. The remaining two swabs will be reserved as controls. One swab will be exposed during the EVA without touching any surfaces to act as a blank. The final swab will remain sealed until the entire sampling kit is returned to earth. Based on previously published results from the Russian segment, we hypothesize that there will be detectable microbes at some or all of these locations. Ground-based testing of this sampling caddy confirms that the swabs remain sterile as the canisters transition in and out of vacuum. We were able to retrieve, viable bacterial and fungal cells as well as DNA from samples collected from US space suits during vacuum chamber tests lasting as long as seven hours. Based on these results and feedback from the test subjects the sampling caddy was modified to improve ergonomics and meet US EVA safety requirements. Bayonet probes were added to the sides of the sample kit as alternate mounting points. Additional locking features were added to the end effector and the filter stack to prevent inadvertent release during use. The opening mechanism was changed from one where the end effector was rocked laterally to defeat a ball detent to a twist-to-open threaded closure for similar reasons. Demonstrating, this sampling caddy’s effectiveness during a US EVA will allow us to address knowledge gaps identified in COSPAR reports and begin to define planetary protection requirements for life support systems on crewed missions to mars. This kit could also be used to collect contamination control samples during Artemis missions to verify requirements and could be easily modified for robotic sample collection.

Planetary Protection↗

Comparison of repair of DNA double-strand breaks in identical sequences in primary human fibroblast and immortal hamster-human hybrid cells harboring a single copy of human chromosome 11

We have optimized a pulsed-field gel electrophoresis assay that measures induction and repair of double-strand breaks (DSBs) in specific regions of the genome (Lobrich et al., Proc. Natl. Acad. Sci. USA 92, 12050-12054, 1995). The increased sensitivity resulting from these improvements makes it possible to analyze the size distribution of broken DNA molecules immediately after the introduction of DSBs and after repair incubation. This analysis shows that the distribution of broken DNA pieces after exposure to sparsely ionizing radiation is consistent with the distribution expected from randomly induced DSBs. It is apparent from the distribution of rejoined DNA pieces after repair incubation that DNA ends continue to rejoin between 3 and 24 h postirradiation and that some of these rejoining events are in fact misrejoining events, since novel restriction fragments both larger and smaller than the original fragment are generated after repair. This improved assay was also used to study the kinetics of DSB rejoining and the extent of misrejoining in identical DNA sequences in human GM38 cells and human-hamster hybrid A(L) cells containing a single human chromosome 11. Despite the numerous differences between these cells, which include species and tissue of origin, levels of TP53, expression of telomerase, and the presence or absence of a homologous chromosome for the restriction fragments examined, the kinetics of rejoining of radiation-induced DSBs and the extent of misrejoining were similar in the two cell lines when studied in the G(1) phase of the cell cycle. Furthermore, DSBs were removed from the single-copy human chromosome in the hamster A(L) cells with similar kinetics and misrejoining frequency as at a locus on this hybrid's CHO chromosomes.

NASA Program Biomedical Research and Countermeasur↗

A novel calmodulin-regulated Ca2+-ATPase (ACA2) from Arabidopsis with an N-terminal autoinhibitory domain

To study transporters involved in regulating intracellular Ca2+, we isolated a full-length cDNA encoding a Ca2+-ATPase from a model plant, Arabidopsis, and named it ACA2 (Arabidopsis Ca2+-ATPase, isoform 2). ACA2p is most similar to a "plasma membrane-type" Ca2+-ATPase, but is smaller (110 kDa), contains a unique N-terminal domain, and is missing a long C-terminal calmodulin-binding regulatory domain. In addition, ACA2p is localized to an endomembrane system and not the plasma membrane, as shown by aqueous-two phase fractionation of microsomal membranes. ACA2p was expressed in yeast as both a full-length protein (ACA2-1p) and an N-terminal truncation mutant (ACA2-2p; Delta residues 2-80). Only the truncation mutant restored the growth on Ca2+-depleted medium of a yeast mutant defective in both endogenous Ca2+ pumps, PMR1 and PMC1. Although basal Ca2+-ATPase activity of the full-length protein was low, it was stimulated 5-fold by calmodulin (50% activation around 30 nM). In contrast, the truncated pump was fully active and insensitive to calmodulin. A calmodulin-binding sequence was identified within the first 36 residues of the N-terminal domain, as shown by calmodulin gel overlays on fusion proteins. Thus, ACA2 encodes a novel calmodulin-regulated Ca2+-ATPase distinguished by a unique N-terminal regulatory domain and a non-plasma membrane localization.

Non-NASA Center↗

B-DNA to Z-DNA structural transitions in the SV40 enhancer: stabilization of Z-DNA in negatively supercoiled DNA minicircles

During replication and transcription, the SV40 control region is subjected to significant levels of DNA unwinding. There are three, alternating purine-pyrimidine tracts within this region that can adopt the Z-DNA conformation in response to negative superhelix density: a single copy of ACACACAT and two copies of ATGCATGC. Since the control region is essential for both efficient transcription and replication, B-DNA to Z-DNA transitions in these vital sequence tracts may have significant biological consequences. We have synthesized DNA minicircles to detect B-DNA to Z-DNA transitions in the SV40 enhancer, and to determine the negative superhelix density required to stabilize the Z-DNA. A variety of DNA sequences, including the entire SV40 enhancer and the two segments of the enhancer with alternating purine-pyrimidine tracts, were incorporated into topologically relaxed minicircles. Negative supercoils were generated, and the resulting topoisomers were resolved by electrophoresis. Using an anti-Z-DNA Fab and an electrophoretic mobility shift assay, Z-DNA was detected in the enhancer-containing minicircles at a superhelix density of -0.05. Fab saturation binding experiments demonstrated that three, independent Z-DNA tracts were stabilized in the supercoiled minicircles. Two other minicircles, each with one of the two alternating purine-pyrimidine tracts, also contained single Z-DNA sites. These results confirm the identities of the Z-DNA-forming sequences within the control region. Moreover, the B-DNA to Z-DNA transitions were detected at superhelix densities observed during normal replication and transcription processes in the SV40 life cycle.

Non-NASA Center↗

Molecular cloning and characterization of a tumor-associated, growth-related, and time-keeping hydroquinone (NADH) oxidase (tNOX) of the HeLa cell surface

NOX proteins are growth-related cell surface proteins that catalyze both hydroquinone or NADH oxidation and protein disulfide interchange and exhibit prion-like properties. The two enzymatic activities alternate to generate a regular period length of about 24 min. Here we report the expression, cloning, and characterization of a tumor-associated NADH oxidase (tNOX). The cDNA sequence of 1830 bp is located on gene Xq25-26 with an open reading frame encoding 610 amino acids. The activities of the bacterially expressed tNOX oscillate with a period length of 22 min as is characteristic of tNOX activities in situ. The activities are inhibited completely by capsaicin, which represents a defining characteristic of tNOX activity. Functional motifs identified by site-directed mutagenesis within the C-terminal portion of the tNOX protein corresponding to the processed plasma membrane-associated form include quinone (capsaicin), copper and adenine nucleotide binding domains, and two cysteines essential for catalytic activity. Four of the six cysteine to alanine replacements retained enzymatic activity, but the period lengths of the oscillations were increased. A single protein with two alternating enzymatic activities indicative of a time-keeping function is unprecedented in the biochemical literature.

NASA Discipline Cell Biology↗

Negatively supercoiled simian virus 40 DNA contains Z-DNA segments within transcriptional enhancer sequences

Three 8-base pair (bp) segments of alternating purine-pyrimidine from the simian virus 40 enhancer region form Z-DNA on negative supercoiling; minichromosome DNase I-hypersensitive sites determined by others bracket these three segments. A survey of transcriptional enhancer sequences reveals a pattern of potential Z-DNA-forming regions which occur in pairs 50-80 bp apart. This may influence local chromatin structure and may be related to transcriptional activation.

Nordheim, A.↗

Transcriptional control of monolignol biosynthesis in Pinus taeda: factors affecting monolignol ratios and carbon allocation in phenylpropanoid metabolism

Transcriptional profiling of the phenylpropanoid pathway in Pinus taeda cell suspension cultures was carried out using quantitative real time PCR analyses of all known genes involved in the biosynthesis of the two monolignols, p-coumaryl and coniferyl alcohols (lignin/lignan precursors). When the cells were transferred to a medium containing 8% sucrose and 20 mm potassium iodide, the monolignol/phenylpropanoid pathway was induced, and transcript levels for phenylalanine ammonia lyase, cinnamate 4-hydroxylase, p-coumarate 3-hydroxylase, 4-coumarate:CoA ligase, caffeoyl-CoA O-methyltransferase, cinnamoyl-CoA reductase, and cinnamyl alcohol dehydrogenase were coordinately up-regulated. Provision of increasing levels of exogenously supplied Phe to saturating levels (40 mm) to the induction medium resulted in further up-regulation of their transcript levels in the P. taeda cell cultures; this in turn was accompanied by considerable increases in both p-coumaryl and coniferyl alcohol formation and excretion. By contrast, transcript levels for both cinnamate 4-hydroxylase and p-coumarate 3-hydroxylase were only slightly up-regulated. These data, when considered together with metabolic profiling results and genetic manipulation of various plant species, reveal that carbon allocation to the pathway and its differential distribution into the two monolignols is controlled by Phe supply and differential modulation of cinnamate 4-hydroxylase and p-coumarate 3-hydroxylase activities, respectively. The coordinated up-regulation of phenylalanine ammonia lyase, 4-coumarate:CoA ligase, caffeoyl-CoA O-methyltransferase, cinnamoyl-CoA reductase and cinnamyl alcohol dehydrogenase in the presence of increasing concentrations of Phe also indicates that these steps are not truly rate-limiting, because they are modulated according to metabolic demand. Finally, the transcript profile of a putative acid/ester O-methyltransferase, proposed as an alternative catalyst for O-methylation leading to coniferyl alcohol, was not up-regulated under any of the conditions employed, suggesting that it is not, in fact, involved in monolignol biosynthesis.

NASA Discipline Plant Biology↗

EVA Swab Kit: Tools and Techniques for Collecting Aseptic Samples from Crewed Space Missions

Introduction: When we send humans to search for life on other planets, we'll need to know what we brought with us versus what may already be there. To ensure our crewed spacecraft meet planetary protection requirements—and to protect our science from human contamination—we'll need to assess and verify whether micro-organisms may be leaking/venting from our spacesuits. This requires collecting samples under Extravehicular Activity (EVA) conditions. Detailed, systematic research on forward contamination from robotic spacecraft has been steadily progressing since the Viking missions, but systematic studies of contamination from space suits has not been conducted in many years. The modern EMU (Extravehicular Mobility Unit) suit used by NASA is designed to leak at rates as high as 100 cc/min. Before humans land on Mars there is a critical need to understand the types and quantities of microbes that could be introduced via space suits. The Human Forward Contamination Assessment team at NASA’s Johnson Space Center (JSC) has developed a prototype EVA swab tool [1,2,3,4] designed for use in space to sample cleaned and uncleaned space suits to determine the present day microbial load and eventually the rate of leakage. The ability to assess microbial leakage early in advanced space suit and life support system design cycles will help avoid costly hardware redesign later. Test Objectives: The primary objective of EMU testing was to characterize the type of micro-organisms typically found on or near selected suit pressure joints under suit differential pressure conditions. Most human-borne microbes can fit through a 0.5 to 1.0 µm gap. Knowing which joints are more likely to leak will inform hardware design decisions. Knowing which types of micro-organisms may leak from EVA suits provides a basis for subsequent studies to characterize the viability of those organisms under destination conditions, as well as how far they might spread through natural or human-influenced processes. That data, in turn, will inform exploration mission operations and hardware design. The secondary objective of testing was to evaluate the interface between a fully suited test subject and the EVA swab tool at vacuum. Bulky EVA suits can restrict movement and limit visibility through the helmet visor. Fully suited testing is important for identifying tool design issues prior to flight. At exploration destinations, such as Mars, suited crew may be required to periodically sample their suits as part of an environmental monitoring protocol. Suit Microbial Sampling Results: This report details results of microbial swabs collected from current flight suit configurations worn by crew members assigned to upcoming ISS expedition missions as well as swabs collected from prototype suits intended for use on the Orion spacecraft. These tests were intended to characterize the types of contaminants found on flight suits under current, typical handling conditions. No attempt was made to change suit handling procedures, provide additional sterilization, or to limit typical potential contaminant sources. Using culture based techniques, we cultivated 235 CFU (colony forming units) comprised of 26 bacterial species and one fungal species on the outside of the suits. The fungal species and 14 of the bacterial species were unique to the suit surfaces and were not detected in any of the background samples collected within the chambers. We sequenced 755,434 ribosomal fragments on all of the suit surfaces from swab samples. 557,016 of these sequences represent DNA that survived at least 4 hours at vacuum. These sequences formed 2,464 OTU's (Operational Taxonomic Units, 97% similarity) showing low diversity in the samples. The most abundant sequences that survived vacuum belong to the genera Staphyloccocus, Ralstona, Bacillus and Rhodobacter all of which are common to the human microbiome. [5] See Danko et al., (2021) for more complete details of these first analyses. Further analysis of EVA suit materials with respect to the efficacy of various cleaning protocols and engineered containment solutions is planned to inform suit design for NASA’s Artemis Moon to Mars program crew testing. Swab Tool Function Results: The kit was demonstrated for fit and function in suited subject vacuum tests to determine how well the tool worked as an aseptic microbial sampling device as well as to identify any design elements that could be upgraded for EVA task specific improvement. It was found that sample acquisition efficacy could be enhanced by redesign of the sample canister to end-effector interface. Several modifications of the sample caddy assemblies to optimize EVA safety and functionality were also identified. Consequently, fabrication of the redesigned sample canister to end-effector assembly interfaces and and the sample caddy assemblies are required. Fabrication of sixteen flight sample canister assemblies (8 per each of two EVA Swab Kits) and two sample caddy assemblies are in process to be followed by hardware testing and certification to produce two flight-certified EVA Swab Kits for transport to ISS no earlier than summer of 2022. Sampling Strategy: The International Space Station is an ideal testbed for systematic studies of contamination from crewed vehicles since it has been continuously occupied for 20 years and exposed to non-terrestrial conditions. We will sample the exterior of the ISS during EVA using a purpose-built swab tool capable of maintaining sterility while undergoing temperature changes from -151 to +121°C under hard vacuum. Prior to each EVA, the project team will work with ISS mission managers to identify precise sampling locations, which will vary by EVA based on the translation paths and worksites scheduled for that particular EVA. Ideally, translation path handrails and areas near ECLSS (Environmental Control and Life Support System) external vent openings on a spacecraft would be assessed. There are currently more than a dozen ECLSS external vents on the ISS. Some are connected to systems that vent waste products, while others are intended to equalize cabin pressure. As EVA opportunity allows, microbial samples from any of these external vents would provide a valuable data point, though some will be more useful than others. Four criteria have been identified to help prioritize sampling sites near vents: • EVA Accessibility: To minimize cost, it is desired to piggy-back onto a planned EVA. Therefore, the sampling location must be readily accessible by an EVA crew • Type of Vented Products: Vent products that have been in direct contact with crew, such as cabin air, are more likely to contain microorganisms than vent products associated with isolated systems, such as experiment module combustion products. • Mass of Vented Products: Higher-flow vents are more likely to contain detectible levels of microbial contaminants than lower-flow vents. • Local Environment: Sample locations with relatively benign local conditions, such as warm surfaces shielded from direct ultraviolet (UV) radiation exposure, may be more likely to support microbial growth than locations with harsher local environmental conditions. Because EVA accessibility is the most important criteria, the proposal team worked with an astronaut and flight controllers using the Dynamic Onboard Ubiquitous Graphics (DOUG) tool. The DOUG virtual environment allows an operator to “fly” around the current ISS vehicle configuration to assess EVA translation paths, attach points, and keep-out zones. While analysis on station or rapid return to Earth would be preferable, samples collected from the exterior of the ISS have already been exposed to temperature variations between -157 and +121 °C as well as hard vacuum. Therefore, they should be fairly stable and robust. We hypothesize that samples collected from the ISS exterior could be stored for up to 6 months at -80°C without degradation. Sample canisters will be returned to Earth while frozen at -80°C for analysis, and sterilized canisters can be re-flown back to ISS to support additional sampling opportunities Relevance to NASA Exploration Objectives: These data will allow us to identify new or improved methods, technologies, and procedures for spacecraft sterilization and leakage mitigation to minimize the amount of contamination introduced to the environment by human explorers. This work is funded by NASA research grant: NNH18ZDA001N-PPR References: [1] Bell, M.S. et al. (2015) LPS XLVI, Abst. #1832 [2] Rucker et al. (2018) 42nd COSPAR (PPP.3) [3] Bell, M.S. et al. (2019) Mars Extant Life Conference, Abst. #5096.[4] Bell, M.S. et al., (2020) 43rd COSPAR (BO.2).[5] Danko D, et.al.,(2021)Front.Microbiol.12:608478.

Mary Suzanne Bell↗