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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 253 records · Page 14
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Evaluation in Swine of a Recombinant African Swine Fever Virus Lacking the MGF-360-1L Gene

The African swine fever (ASF) pandemic is currently affecting pigs throughout Eurasia, resulting in significant swine production losses. The causative agent, ASF virus (ASFV), is a large, structurally complex virus with a genome encoding more than 160 genes. The function of most of those genes remains unknown. Here, we presented the previously uncharacterized ASFV gene MGF360-1L, the first gene in the genome. The kinetic studies of virus RNA transcription demonstrated that the MGF360-1L gene was transcribed as a late virus protein. The essentiality of MGF360-1L to virus replication was evaluated by developing a recombinant ASFV lacking the gene (ASFV-G-ΔMGF360-1L). In primary swine macrophage cell cultures, ASFV-G-ΔMGF360-1L showed similar replication kinetics as the parental highly virulent field isolate Georgia2007 (ASFV-G). Domestic pigs experimentally infected with ASFV-G-ΔMGF360-1L presented with a clinical disease indistinguishable from that caused by ASFV-G, demonstrating that MGF360-1L was not involved in virulence in swine, the natural host of ASFV.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

scRNA seq of an F1 cross of Marek’s disease resistant and susceptible chickens identifies allele specific expression signatures enriched in transcription modulators

Abstract Marek’s disease (MD), a T cell lymphoma disease in chickens, is caused by the Marek’s disease virus (MDV) found ubiquitously in the poultry industry. Genetically resistant Line 6 3 (L6) and susceptible Line 7 2 (L7) chickens have been instrumental to research on avian immune system response to MDV infection. In this study we characterized molecular signatures unique to splenic immune cell types across different genetic backgrounds 6 days after infection. Using three populations, L6, L7, and an F1 cross between L6xL7, we evaluated the immune cell transcriptome of responding cell types using single cell RNA sequencing. Several MDV genes were found expressed mainly in cytotoxic T cells while ICP4 and MEQ MDV genes were expressed across infected cell types. Using the F1 we quantified allele specific expression (ASE) of biallelic SNPs and found biased expression of parental alleles specific to immune cell subtypes. We identified 22 SNPs with ASE in response to MDV infection mapped to gene rich regions surrounding 59 genes of critical importance for chromatin remodeling and transcriptional regulation. Histone deacetylase genes (HDAC1 and HDAC8) had increased expression of L6 alleles, while small nuclear RNA genes (SNORA68 and SNORA72) expressed higher levels of L7 alleles with infection in T cell subsets. SNPs with ASE also mapped genes important for an adequate immune response including GNLY (cytotoxic activity) and PDIA3 (component of MHC class I peptide loading complex), and genes known to promote viral replication (MCM5 and EIF3M). These results show that functional variants associated with susceptibility to MD may have a bigger impact in subsets of immune cell types, and by characterizing the transcriptomes of these subtypes we can unravel molecular signatures specific to MD genomic resistance.

Science & Technology - Other Topics↗
DOE OSTI2023

Inhibition of FAM46/TENT5 activity by BCCIPα adopting a unique fold

The FAM46 (also known as TENT5) proteins are noncanonical poly(A) polymerases (PAPs) implicated in regulating RNA stability. The regulatory mechanisms of FAM46 are poorly understood. Here, we report that the nuclear protein BCCIPα, but not the alternatively spliced isoform BCCIPβ, binds FAM46 and inhibits their PAP activity. Unexpectedly, our structures of the FAM46A/BCCIPα and FAM46C/BCCIPα complexes show that, despite sharing most of the sequence and differing only at the C-terminal portion, BCCIPα adopts a unique structure completely different from BCCIPβ. The distinct C-terminal segment of BCCIPα supports the adoption of the unique fold but does not directly interact with FAM46. The β sheets in BCCIPα and FAM46 pack side by side to form an extended β sheet. A helix-loop-helix segment in BCCIPα inserts into the active site cleft of FAM46, thereby inhibiting the PAP activity. Our results together show that the unique fold of BCCIPα underlies its interaction with and functional regulation of FAM46.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Structural coordination between active sites of a CRISPR reverse transcriptase-integrase complex

CRISPR-Cas systems provide adaptive immunity in bacteria and archaea, beginning with integration of foreign sequences into the host CRISPR genomic locus and followed by transcription and maturation of CRISPR RNAs (crRNAs). In some CRISPR systems, a reverse transcriptase (RT) fusion to the Cas1 integrase and Cas6 maturase creates a single protein that enables concerted sequence integration and crRNA production. To elucidate how the RT-integrase organizes distinct enzymatic activities, we present the cryo-EM structure of a Cas6-RT-Cas1—Cas2 CRISPR integrase complex. The structure reveals a heterohexamer in which the RT directly contacts the integrase and maturase domains, suggesting functional coordination between all three active sites. Together with biochemical experiments, our data support a model of sequential enzymatic activities that enable CRISPR sequence acquisition from RNA and DNA substrates. These findings highlight an expanded capacity of some CRISPR systems to acquire diverse sequences that direct CRISPR-mediated interference.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Structural basis of DNA binding by the WhiB-like transcription factor WhiB3 in Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) WhiB3 is an iron–sulfur cluster-containing transcription factor belonging to a subclass of the WhiB-Like (Wbl) family that is widely distributed in the phylum Actinobacteria. WhiB3 plays a crucial role in the survival and pathogenesis of Mtb. It binds to the conserved region 4 of the principal sigma factor (σ A 4 ) in the RNA polymerase holoenzyme to regulate gene expression like other known Wbl proteins in Mtb. However, the structural basis of how WhiB3 coordinates with σ A 4 to bind DNA and regulate transcription is unclear. Here we determined crystal structures of the WhiB3:σ A 4 complex without and with DNA at 1.5 Å and 2.45 Å, respectively, to elucidate how WhiB3 interacts with DNA to regulate gene expression. These structures reveal that the WhiB3:σ A 4 complex shares a molecular interface similar to other structurally characterized Wbl proteins and also possesses a subclass-specific Arg-rich DNA-binding motif. We demonstrate that this newly defined Arg-rich motif is required for WhiB3 binding to DNA in vitro and transcriptional regulation in Mycobacterium smegmatis. Together, our study provides empirical evidence of how WhiB3 regulates gene expression in Mtb by partnering with σ A 4 and engaging with DNA via the subclass-specific structural motif, distinct from the modes of DNA interaction by WhiB1 and WhiB7.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

A FAIR-compliant parts catalogue for genome engineering and expression control in Saccharomyces cerevisiae

The synthetic biology toolkit for baker's yeast, Saccharomyces cerevisiae, includes extensive genome engineering toolkits and parts repositories. However, with the increasing complexity of engineering tasks and versatile applications of this model eukaryote, there is a continued interest to expand and diversify the rational engineering capabilities in this chassis by FAIR (findable, accessible, interoperable, and reproducible) compliance. In this study, we designed and characterised 41 synthetic guide RNA sequences to expand the CRISPR-based genome engineering capabilities for easy and efficient replacement of genomically encoded elements. Moreover, we characterize in high temporal resolution 20 native promoters and 18 terminators using fluorescein and LUDOX CL-X as references for GFP expression and OD600 measurements, respectively. Additionally, all data and reported analysis is provided in a publicly accessible jupyter notebook providing a tool for researchers with low-coding skills to further explore the generated data as well as a template for researchers to write their own scripts. We expect the data, parts, and databases associated with this study to support a FAIR-compliant resource for further advancing the engineering of yeasts.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Caveat mutator: alanine substitutions for conserved amino acids in RNA ligase elicit unexpected rearrangements of the active site for lysine adenylylation

Naegleria gruberi RNA ligase (NgrRnl) exemplifies the Rnl5 family of adenosine triphosphate (ATP)-dependent polynucleotide ligases that seal 3'-OH RNA strands in the context of 3'-OH/5'-PO 4 nicked duplexes. Like all classic ligases, NgrRnl forms a covalent lysyl–AMP intermediate. A two-metal mechanism of lysine adenylylation was established via a crystal structure of the NgrRnl•ATP•(Mn 2+ ) 2 Michaelis complex. Here we conducted an alanine scan of active site constituents that engage the ATP phosphates and the metal cofactors. We then determined crystal structures of ligase-defective NgrRnl-Ala mutants in complexes with ATP/Mn 2+ . The unexpected findings were that mutations K170A, E227A, K326A and R149A (none of which impacted overall enzyme structure) triggered adverse secondary changes in the active site entailing dislocations of the ATP phosphates, altered contacts to ATP, and variations in the numbers and positions of the metal ions that perverted the active sites into off-pathway states incompatible with lysine adenylylation. Each alanine mutation elicited a distinctive off-pathway distortion of the ligase active site. Our results illuminate a surprising plasticity of the ligase active site in its interactions with ATP and metals. More broadly, they underscore a valuable caveat when interpreting mutational data in the course of enzyme structure-function studies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Biochemical and structural basis for YTH domain of human YTHDC1 binding to methylated adenine in DNA

The recently characterized mammalian writer (methyltransferase) and eraser (demethylase) of the DNA N6-methyladenine (N6mA) methyl mark act on single-stranded (ss) and transiently-unpaired DNA. As YTH domain-containing proteins bind N6mA-containing RNA in mammalian cells, we investigated whether mammalian YTH domains are also methyl mark readers of N6mA DNA. Here, we show that the YTH domain of YTHDC1 (known to localize in the nucleus) binds ssDNA containing N6mA, with a 10 nM dissociation constant. This binding is stronger by a factor of 5 than in an RNA context, tested under the same conditions. However, the YTH domains of YTHDF2 and YTHDF1 (predominantly cytoplasmic) exhibited the opposite effect with ~1.5–2× stronger binding to ssRNA containing N6mA than to the corresponding DNA. We determined two structures of the YTH domain of YTHDC1 in complex with N6mA-containing ssDNA, which illustrated that YTHDC1 binds the methylated adenine in a single-stranded region flanked by duplexed DNA. We discuss the hypothesis that the writer-reader-eraser of N6mA-containining ssDNA is associated with maintaining genome stability. Structural comparison of YTH and SRA domains (the latter a DNA 5-methylcytosine reader) revealed them to be diverse members of a larger family of DNA/RNA modification readers, apparently having originated from bacterial modification-dependent restriction enzymes.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

Single-Cell Transcriptomic Analysis of Tumor-Derived Fibroblasts and Normal Tissue-Resident Fibroblasts Reveals Fibroblast Heterogeneity in Breast Cancer

Cancer-associated fibroblasts (CAFs) are a prominent stromal cell type in solid tumors and molecules secreted by CAFs play an important role in tumor progression and metastasis. CAFs coexist as heterogeneous populations with potentially different biological functions. Although CAFs are a major component of the breast cancer stroma, molecular and phenotypic heterogeneity of CAFs in breast cancer is poorly understood. In this study, we investigated CAF heterogeneity in triple-negative breast cancer (TNBC) using a syngeneic mouse model, BALB/c-derived 4T1 mammary tumors. Using single-cell RNA sequencing (scRNA-seq), we identified six CAF subpopulations in 4T1 tumors including: 1) myofibroblastic CAFs, enriched for α-smooth muscle actin and several other contractile proteins; 2) ‘inflammatory’ CAFs with elevated expression of inflammatory cytokines; and 3) a CAF subpopulation expressing major histocompatibility complex (MHC) class II proteins that are generally expressed in antigen-presenting cells. Comparison of 4T1-derived CAFs to CAFs from pancreatic cancer revealed that these three CAF subpopulations exist in both tumor types. Interestingly, cells with inflammatory and MHC class II-expressing CAF profiles were also detected in normal breast/pancreas tissue, suggesting that these phenotypes are not tumor microenvironment-induced. This work enhances our understanding of CAF heterogeneity, and specifically targeting these CAF subpopulations could be an effective therapeutic approach for treating highly aggressive TNBCs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Multiplex RNA-guided genome engineering

Methods of multiplex genome engineering in cells using Cas9 is provided which includes a cycle of steps of introducing into the cell a first foreign nucleic acid encoding one or more RNAs complementary to the target DNA and which guide the enzyme to the target DNA, wherein the one or more RNAs and the enzyme are members of a co-localization complex for the target DNA, and introducing into the cell a second foreign nucleic acid encoding one or more donor nucleic acid sequences, and wherein the cycle is repeated a desired number of times to multiplex DNA engineering in cells.

Church, George M.↗
DOE OSTI2024

An RNA aptamer exploits exosite-dependent allostery to achieve specific inhibition of coagulation factor IXa

Hemostasis relies on a reaction network of serine proteases and their cofactors to form a blood clot. Coagulation factor IXa (protease) plays an essential role in hemostasis as evident from the bleeding disease associated with its absence. RNA aptamers specifically targeting individual coagulation factors have potential as anticoagulants and as probes of the relationship between structure and function. Here, we report X-ray structures of human factor IXa without a ligand bound to the active site either in the apo-form or in complex with an inhibitory aptamer specific for factor IXa. The aptamer binds to an exosite in the catalytic domain and allosterically distorts the active site. Our studies reveal a conformational ensemble of IXa states, wherein large movements of Trp 215 near the active site drive functional transitions between the closed (aptamer-bound), latent (apo), and open (substrate-bound) states. The latent state of the apo-enzyme may bear on the uniquely poor catalytic activity of IXa compared to other coagulation proteases. The exosite, to which the aptamer binds, has been implicated in binding VIIIa and heparin, both of which regulate IXa function. Our findings reveal the importance of exosite-driven allosteric modulation of IXa function and new strategies to rebalance hemostasis for therapeutic gain.

Science & Technology - Other Topics↗
DOE OSTI2020

HEXIM1 controls P-TEFb processing and regulates drug sensitivity in triple-negative breast cancer

The positive transcription elongation factor b (P-TEFb), composed of CDK9 and cyclin T, stimulates transcriptional elongation by RNA polymerase (Pol) II and regulates cell growth and differentiation. Recently, we demonstrated that P-TEFb also controls the expression of EMT regulators to promote breast cancer progression. In the nucleus, more than half of P-TEFb are sequestered in the inactive-state 7SK snRNP complex. Here, we show that the assembly of the 7SK snRNP is preceded by an intermediate complex between HEXIM1 and P-TEFb that allows transfer of the kinase active P-TEFb from Hsp90 to 7SK snRNP for its suppression. Down-regulation of HEXIM1 locks P-TEFb in the Hsp90 complex, keeping it in the active state to enhance breast cancer progression, but also rendering the cells highly sensitive to Hsp90 inhibition. Because HEXIM1 is often down-regulated in human triple-negative breast cancer (TNBC), these cells are particularly sensitive to Hsp90 inhibition. Our study provides a mechanistic explanation for the increased sensitivity of TNBC to Hsp90 inhibition.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1996

Distinct transcripts are recognized by sense and antisense riboprobes for a member of the murine HSP70 gene family, HSP70.2, in various reproductive tissues

The expression of hsp70.2, an hsp70 gene family member, originally characterized by its high levels of expression in germ cells in the adult mouse testis, was detected in several other reproductive tissues, including epididymis, prostate, and seminal vesicles, as well as in extraembryonic tissues of mid-gestation fetuses. In addition, hybridization with RNA probes transcribed in the sense orientation surprisingly indicated the presence of slightly larger "antisense" transcripts in several tissues. The levels of antisense transcripts varied among the tissues, with the highest signal detected in the prostate and no signal being detectable in the testis. Consistent with these results, in situ hybridization analysis clearly localized the sense-orientation transcripts to pachytene spermatocytes, while no antisense-orientation transcripts were observed in adjacent sections of the same tubules. Our findings have thus shown that although hsp70.2 was expressed abundantly and in a highly stage-specific manner in the male germ line, it was also expressed in other murine tissues. Furthermore, we have made the surprising observation of antisense transcription of the hsp70.2 gene in several mouse tissues, revealing another level of complexity in the regulation and function of heat shock proteins.

Non-NASA Center↗
NASA NTRS1994

Ultraviolet photochemistry of cyanoacetylene: Application to Titan

Cyanoacetylene is believed to have had a central role in the formation of the pyrimidines essential for RNA synthesis leading to the origin of life on Earth. Cyanoacetylene has also been detected on Titan, Saturn's largest moon, and the only moon in the solar system that possesses a dense atmosphere. It is generally accepted that photochemistry plays a major role in the formation of the complex organic molecules and aerosols found in Titan's atmosphere. Because of its long wavelength absorption and low dissociation threshold it is expected that cyanoacetylene is an important part of these photochemical processes. Since cyanoacetylene would also have been subject to ultraviolet light in the atmosphere of early Earth, an investigation of cyanoacetylene photochemistry on Titan might lead to a better understanding of both the photochemical reactions occurring on primitive earth and the processes of chemical evolution as they occur in planetary atmospheres. The effects of irradiation wavelength, mixing with Titan's atmospheric gases, reducing the temperature and lowering cyanoacetylene partial pressures on product formation and polymer composition have been determined with the ultimate goal of understanding the chemical transformations taking place in Titan's atmosphere.

Clarke, D. W.↗
NASA NTRS2017

Exploring Connectivity in Sequence Space of Functional RNA

Emergence of replicable genetic molecules was one of the marking points in the origin of life, evolution of which can be conceptualized as a walk through the space of all possible sequences. A theoretical concept of fitness landscape helps to understand evolutionary processes through assigning a value of fitness to each genotype. Then, evolution of a phenotype is viewed as a series of consecutive, single-point mutations. Natural selection biases evolution toward peaks of high fitness and away from valleys of low fitness. whereas neutral drift occurs in the sequence space without direction as mutations are introduced at random. Large networks of neutral or near-neutral mutations on a fitness landscape, especially for sufficiently long genomes, are possible or even inevitable. Their detection in experiments, however, has been elusive. Although a few near-neutral evolutionary pathways have been found, recent experimental evidence indicates landscapes consist of largely isolated islands. The generality of these results, however, is not clear, as the genome length or the fraction of functional molecules in the genotypic space might have been insufficient for the emergence of large, neutral networks. Thorough investigation on the structure of the fitness landscape is essential to understand the mechanisms of evolution of early genomes. RNA molecules are commonly assumed to play the pivotal role in the origin of genetic systems. They are widely believed to be early, if not the earliest, genetic and catalytic molecules, with abundant biochemical activities as aptamers and ribozymes, i.e. RNA molecules capable, respectively, to bind small molecules or catalyze chemical reactions. Here, we present results of our recent studies on the structure of the sequence space of RNA ligase ribozymes selected through in vitro evolution. Several hundred thousands of sequences active to a different degree were obtained by way of deep sequencing. Analysis of these sequences revealed several large clusters defined such that every sequence in a cluster can be reached from any other sequence in the same cluster through a series of single point mutations. Sequences in a single cluster appear to adopt more than one secondary structure. The mechanism of refolding within a single cluster was examined. To shed light on possible evolutionary paths in the space of ribozymes, the connectivity between clusters was investigated. The effect of length of RNA molecules on the structure of the fitness landscape and possible evolutionary paths was examined by way of comparing functional sequences of 20 and 80 nucleobases in length. It was found that sequences of different lengths shared secondary structure motifs that were presumed responsible for catalytic activity, with increasing complexity and global structural rearrangements emerging in longer molecules.

Wei, Chenyu↗
NASA NTRS2017

Sugar Derivatives in Residues Produced from the UV Irradiation of Astrophysical Ice Analogs

A large variety of organic compounds of astrobiological and prebiotic interest have been detected in carbonaceous meteorites. These include amino acids, carboxylic acids, amphiphiles, functionalized nitrogen heterocycles such as nucleobases, functionalized polycylic aromatic hydrocarbons such as quinones, and sugar derivatives. The sugar derivatives identified in the Murchison and Murray meteorites are mainly sugar alcohols and sugar acids, and only the smallest sugar (dihydroxyacetone) has been detected. The presence of such a variety of organics in meteorites strongly suggests that molecules essential to life can form abiotically under astrophysical conditions. This hypothesis is further supported by laboratory studies in which astrophysical ice analogs (mixtures of H2O, CO, CO2, CH3OH, CH4, NH3, etc.) are subjected to ultraviolet (UV) irradiation at low temperature (<15 K) to simulate cold interstellar environments. These studies show that the organic residues recovered at room temperature after irradiation contain amino acids, amphiphiles, nucleobases, sugar derivatives, as well as other complex organic compounds. The finding of such compounds under plausible interstellar conditions is consistent with the presence of organic compounds in meteorites. Until very recently, no systematic search for the presence of sugar derivatives in laboratory residues had been carried out. The detection of ribose, the sugar constituent of RNA in all living systems, as well as other sugars, sugar alcohols, and sugar acids have been recently reported in one organic residue produced from the UV irradiation of an H2O:CH3OH:NH3 (10:3.5:1) ice mixture at 80 K. In this work, we present a detailed study of organic residues produced from the UV irradiation ice mixtures of several starting compositions (containing H2O, CH3OH, CO, CO2, and/or NH3) at <15 K for their sugar derivative content. Our results confirm the presence of all 3C‒5C sugar alcohols, several 3C‒5C sugars, and all 3C‒4C sugar acids (in decreasing order of abundances) in the residues. The higher abundances of sugar alcohols in these residues suggest a pathway in which sugar alcohols are formed first, while the formation of sugars and sugar acids require more steps. Finally, our results are compared with the detection of sugars derivatives in primitive meteorites.

Astrophysical Ice Analogs↗
DOE OSTI2021

A metal ion orients SARS-CoV-2 mRNA to ensure accurate 2'- O methylation of its first nucleotide

The SARS-CoV-2 nsp16/nsp10 enzyme complex modifies the 2'-OH of the first transcribed nucleotide of the viral mRNA by covalently attaching a methyl group to it. The 2'-O methylation of the first nucleotide converts the status of mRNA cap from Cap-0 to Cap-1, and thus, helps the virus evade immune surveillance in host cells. Here, we report two structures of nsp16/nsp10 representing pre- and post-release states of the RNA product (Cap-1). We observe overall widening of the enzyme upon product formation, and an inward twisting motion in the substrate binding region upon product release. These conformational changes reset the enzyme for the next round of catalysis. The structures also identify a unique binding mode and the importance of a divalent metal ion for 2'-O methylation. We also describe underlying structural basis for the perturbed enzymatic activity of a clinical variant of SARS-CoV-2, and a previous SARS-CoV outbreak strain.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2017

NASA Ames Institutional Scientific Collection (ISC)

NASA's current human space flight research is directed towards enabling human space exploration beyond Low Earth Orbit (LEO). The Space Flight Payload Projects; Rodent Research, Cell Science, and Microbial Labs, flown on the International Space Station (ISS), benefit both the global life sciences and commercial space communities. Verified data sets, science results, peer-reviewed publications, and returned biospecimens, collected and analyzed for flight and ground investigations, are all part of the knowledge base within NASA’s Human Exploration and Operations Mission Directorate’s Space Life and Physical Sciences Research and Applications (SLPSRA) Division, specifically the Human Research and Space Biology Programs. These data and biospecimens are made available through the public LSDA website. The Ames Institutional Scientific Collection (ISC), or ARC Biobank, stores flight and ground biospecimens from Space Shuttle and ISS programs. These specimens are curated and managed by the Ames Life Sciences Data Archive (ALSDA), an internal node of NASA's Life Sciences Data Archive (LSDA). The ARC Biolbank stores over 15,000 specimens from experiments dating from 1984 to present. Currently available specimens include tissues from the circulatory, digestive, endocrine, excretory, integumentary, muscular, neurosensory, reproductive, respiratory and skeletal systems. The most recent contributions include RNA, DNA and protein extracts from Rodent Research 1 and tissues from Rodent Research 4. NASA's biospecimen collection represents a unique and limited resource. The use of these biospecimens maximizes utilization and scientific return from these unique spaceflight payload and ground control research subjects. These biospecimens are harvested following complex, costly NASA research activities to meet primary scientific objectives. Once the primary scientific objectives have been met, the remaining specimens are made available to provide secondary opportunities for complementary studies or new investigations to broaden research without large expenditures of time or resources. Innovative ways of sharing this information ultimately advances the frontiers of human space exploration as well as scientific understanding of the effects of gravity on life on earth.

French, Alison J.↗