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All sourcesNASA NTRSDOE OSTI
NASA NTRS2001

Searching for Organics, Fossils, and Biology on Mars

One of the goals of Astrobiology is to understand life on a fundamental level. All life on Earth is constructed from the same basic biochemical building blocks consisting of 20 amino acids with left handed symmetry, five nucleotides, a few sugars of right handed symmetry and some lipids. Using the metaphor of computers this is equivalent to saying that all life shares the same hardware. Beyond hardware similarity, it is now known that all life has fundamentally the same software. The genetic code of life is common to all organisms. Some have argued that the "hammer of evolution is heavy" and life anywhere is likely to be composed of identical biochemical and genetic patterns. However, in a system as complex as biochemistry it is likely that there are numerous local optima and the details of the optimum found by evolutionary selection on another world would likely depend on the initial conditions and random developments in the early biological history on that world. To address these fundamental questions in Astrobiology we need a second example of life: a second genesis.

McKay, Christopher P.↗
NASA NTRS2002

Biomolecular Effects of Cold Plasma Exposure

The effects of cold plasma exposure on Deinococcus radiodurans, plasmid DNA and model proteins were assessed using microbiological, spectrometric and biochemical techniques. Exposure of D. radiodurans, an extremely radiation resistant microbe, to O2 plasma (less than or equal to 25 W, approx. 45 mTorr, 90 min) yielded a approx. 99.999 % sterilization and the sterilization rate was increased approx. 10-fold at 100 W and 500 mTorr. AFM images shows that the exposed cells are significantly deformed and possess 50-70 nm concavities. IR analysis indicates the chemical degradation of lipids, proteins and carotenoids of the cell wall and membrane. Intracellular damage was indicated by major absorbance loss at 1245, 1651 and 1538/cm corresponding to degradation of DNA and proteins, respectively. Biochemical experiments demonstrate that plasmas induce strand scissions and crosslinking of plasmid DNA, and reduction of enzyme activity; the degradation is power dependent with total sample loss occurring in 60 s at 200 W and 500 mTorr. Emission spectroscopy shows that D. radiodurans is volatilized into CO2, CO, N2 and H2O confirming the removal of biological matter from contaminated surfaces. The O2 plasma impacts several cellular components predominantly through chemical degradation by atomic oxygen. A CO2, plasma, however, was not effective at degrading D. radiodurans, revealing the importance of plasma composition, which has implications for planetary protection and the contamination of Mars.

Mogul, Rakesh↗
NASA NTRS2003

Fucus as a Model System to Study the Role of Auxin Transport and the Actin Cytoskeleton in Gravity Response

The overarching goal of this proposal was to examine the mechanisms for the cellular asymmetry in auxin transport proteins. As auxin transport polarity changes in response to reorientation of algal and plant cells relative to the gravity vector, it was critical to ask how auxin transport polarity is established and how this transport polarity may change in response to gravity stimulation. The experiments conducted with this NASA grant fell into two categories. The first area of experimentation was to explore the biochemical interactions between an auxin transport protein and the actin cytoskeleton. These experiments used biochemical techniques, including actin affinity chromatography, to demonstrate that one auxin transport protein interacts with the actin cytoskeleton. The second line of experiments examined whether in the initially symmetrical single celled embryos of Fucus distichus, whether auxin regulates development and whether gravity is a cue to control the morphogenesis of these embryos and whether gravi-morphogenesis is auxin dependent. Results in these two areas are summarized separately below. As a result of this funding, in combination with results from other investigators, we have strong evidence for an important role for the actin cytoskeleton in both establishing and change auxin transport polarity. It is also clear that Fucus distichus embryos are auxin responsive and gravity controls their morphogenesis.

Gloria K Muday↗
NASA NTRS2003

The evolution of transcriptional regulation in eukaryotes

Gene expression is central to the genotype-phenotype relationship in all organisms, and it is an important component of the genetic basis for evolutionary change in diverse aspects of phenotype. However, the evolution of transcriptional regulation remains understudied and poorly understood. Here we review the evolutionary dynamics of promoter, or cis-regulatory, sequences and the evolutionary mechanisms that shape them. Existing evidence indicates that populations harbor extensive genetic variation in promoter sequences, that a substantial fraction of this variation has consequences for both biochemical and organismal phenotype, and that some of this functional variation is sorted by selection. As with protein-coding sequences, rates and patterns of promoter sequence evolution differ considerably among loci and among clades for reasons that are not well understood. Studying the evolution of transcriptional regulation poses empirical and conceptual challenges beyond those typically encountered in analyses of coding sequence evolution: promoter organization is much less regular than that of coding sequences, and sequences required for the transcription of each locus reside at multiple other loci in the genome. Because of the strong context-dependence of transcriptional regulation, sequence inspection alone provides limited information about promoter function. Understanding the functional consequences of sequence differences among promoters generally requires biochemical and in vivo functional assays. Despite these challenges, important insights have already been gained into the evolution of transcriptional regulation, and the pace of discovery is accelerating.

Review, Academic↗
NASA NTRS2001

Effect of spaceflight on isoflavonoid accumulation in etiolated soybean seedlings

In order to explore the potential impact of microgravity on flavonoid biosynthesis, we examined isoflavonoid levels in soybean (Glycine max) tissues generated under both spaceflight and clinorotation conditions. A 6-day Space Shuttle-based microgravity exposure resulted in enhanced accumulation of isoflavone glycosides (daidzin, 6"-O-malonyl-7-O-glucosyl daidzein, genistin, 6"-O-malonyl-7-O-glucosyl genistein) in hypocotyl and root tissues, but reduced levels in cotyledons (relative to 1g controls on Earth). Soybean seedlings grown on a horizontally rotating clinostat for 3, 4 and 5 days exhibited (relative to a vertical clinorotation control) an isoflavonoid accumulation pattern similar to the space-grown tissues. Elevated isoflavonoid levels attributable to the clinorotation treatment were transient, with the greatest increase observed in the three-day-treated tissues and smaller increases in the four- and five-day-treated tissues. Differences between stresses presented by spaceflight and clinorotation and the resulting biochemical adaptations are discussed, as is whether the increase in isoflavonoid concentrations were due to differential rates of development under the "gravity" treatments employed. Results suggest that spaceflight exposure does not impair isoflavonoid accumulation in developing soybean tissues and that isoflavonoids respond positively to microgravity as a biochemical strategy of adaptation.

Flight Experiment↗
NASA NTRS2002

Relative biological effectiveness of light ions in human tumoural cell lines: role of protein p53

Protons and alpha particles of high linear energy transfer (LET) have shown an increased relative biological effectiveness (RBE) with respect to X/gamma rays for several cellular and molecular endpoints in different in vitro cell systems. To contribute to understanding the biochemical mechanisms involved in the increased effectiveness of high LET radiation, an extensive study has been designed. The present work reports the preliminary result of this study on two human tumoural cell lines, DLD1 and HCT116, (with different p53 status), which indicate that for these cell lines, p53 does not appear to take a part in the response to radiation induced DNA damage, suggesting an alternative p53-independent pathway and a cell biochemical mechanism dependent on the cell type.

NASA Center JSC↗
NASA NTRS2002

Retinoid quantification by HPLC/MS(n)

Retinoic acid (RA) mediates most of the biological effects of vitamin A that are essential for vertebrate survival. It acts through binding to receptors that belong to the nuclear receptor transcription factor superfamily (Mangelsdorf et al. 1994). It is also a highly potent vertebrate teratogen. To determine the function and effects of endogenous and exogenous RA, it is important to have a highly specific, sensitive, accurate, and precise analytical procedure. Current analyses of RA and other retinoids are labor intensive, of poor sensitivity, have limited specificity, or require compatibility with RA reporter cell lines (Chen et al. 1995. BIOCHEM: Pharmacol. 50: 1257-1264; Creech Kraft et al. 1994. BIOCHEM: J. 301: 111-119; Lanvers et al. 1996. J. Chromatogr. B Biomed. Appl. 685: 233-240; Maden et al. 1998. DEVELOPMENT: 125: 4133-4144; Wagner et al. 1992. DEVELOPMENT: 116: 55-66). This paper describes an HPLC/mass spectrometry/mass spectrometry product ion scan (HPLC/MS(n)) procedure for the analysis of retinoids that employs atmospheric pressure chemical ionization MS. The retinoids are separated by normal-phase column chromatography with a linear hexane-isopropanol-dioxane gradient. Each retinoid is detected by a unique series of MS(n) functions set at optimal collision-induced dissociation energy (30% to 32%) for all MS(n) steps. The scan events are divided into three segments, based on HPLC elution order, to maximize the mass spectrometer duty cycle. The all-trans, 9-cis, and 13-cis RA isomers are separated, if desired, by an isocratic hexane-dioxane-isopropanol mobile phase. This paper describes an HPLC/MS(n) procedure possessing high sensitivity and specificity for retinoids.

NASA Discipline Developmental Biology↗
NASA NTRS2002

The cytoskeleton and gravitropism in higher plants

The cellular and molecular mechanisms underlying the gravitropic response of plants have continued to elude plant biologists despite more than a century of research. Lately there has been increased attention on the role of the cytoskeleton in plant gravitropism, but several controversies and major gaps in our understanding of cytoskeletal involvement in gravitropism remain. A major question in the study of plant gravitropism is how the cytoskeleton mediates early sensing and signal transduction events in plants. Much has been made of the actin cytoskeleton as the cellular structure that sedimenting amyloplasts impinge upon to trigger the downstream signaling events leading to the bending response. There is also strong molecular and biochemical evidence that the transport of auxin, an important player in gravitropism, is regulated by actin. Organizational changes in microtubules during the growth response phase of gravitropism have also been well documented, but the significance of such reorientations in controlling differential cellular growth is unclear. Studies employing pharmacological approaches to dissect cytoskeletal involvement in gravitropism have led to conflicting results and therefore need to be interpreted with caution. Despite the current controversies, the revolutionary advances in molecular, biochemical, and cell biological techniques have opened up several possibilities for further research into this difficult area. The myriad proteins associated with the plant cytoskeleton that are being rapidly characterized provide a rich assortment of candidate regulators that could be targets of the gravity signal transduction chain. Cytoskeletal and ion imaging in real time combined with mutant analysis promises to provide a fresh start into this controversial area of research.

Review↗
NASA NTRS2001

Plants, plant pathogens, and microgravity--a deadly trio

Plants grown in spaceflight conditions are more susceptible to colonization by plant pathogens. The underlying causes for this enhanced susceptibility are not known. Possibly the formation of structural barriers and the activation of plant defense response components are impaired in spaceflight conditions. Either condition would result from altered gene expression of the plant. Because of the tools available, past studies focused on a few physiological responses or biochemical pathways. With recent advances in genomics research, new tools, including microarray technologies, are available to examine the global impact of growth in the spacecraft on the plant's gene expression profile. In ground-based studies, we have developed cDNA subtraction libraries of rice that are enriched for genes induced during pathogen infection and the defense response. Arrays of these genes are being used to dissect plant defense response pathways in a model system involving wild-type rice plants and lesion mimic mutants. The lesion mimic mutants are ideal experimental tools because they erratically develop defense response-like lesions in the absence of pathogens. The gene expression profiles from these ground-based studies will provide the molecular basis for understanding the biochemical and physiological impacts of spaceflight on plant growth, development and disease defense responses. This, in turn, will allow the development of strategies to manage plant disease for life in the space environment.

NASA Discipline Plant Biology↗
NASA NTRS1993

Calcium and signal transduction in plants

Environmental and hormonal signals control diverse physiological processes in plants. The mechanisms by which plant cells perceive and transduce these signals are poorly understood. Understanding biochemical and molecular events involved in signal transduction pathways has become one of the most active areas of plant research. Research during the last 15 years has established that Ca2+ acts as a messenger in transducing external signals. The evidence in support of Ca2+ as a messenger is unequivocal and fulfills all the requirements of a messenger. The role of Ca2+ becomes even more important because it is the only messenger known so far in plants. Since our last review on the Ca2+ messenger system in 1987, there has been tremendous progress in elucidating various aspects of Ca(2+) -signaling pathways in plants. These include demonstration of signal-induced changes in cytosolic Ca2+, calmodulin and calmodulin-like proteins, identification of different Ca2+ channels, characterization of Ca(2+) -dependent protein kinases (CDPKs) both at the biochemical and molecular levels, evidence for the presence of calmodulin-dependent protein kinases, and increased evidence in support of the role of inositol phospholipids in the Ca(2+) -signaling system. Despite the progress in Ca2+ research in plants, it is still in its infancy and much more needs to be done to understand the precise mechanisms by which Ca2+ regulates a wide variety of physiological processes. The purpose of this review is to summarize some of these recent developments in Ca2+ research as it relates to signal transduction in plants.

NASA Program Space Biology↗
NASA NTRS2004

Halotolerant and Resistant to High pH Hydrogenase from Haloalkaliphilic Sulfate-Reducing Bacterium Desulfonatronum thiodismutans

Hydrogenase is the key enzyme of energetic metabolism in cells, it catalyzing the converse reaction of hydrogen oxidation and responsible for consumption and excretion of hydrogen in bacteria. Hydrogenases are proteins containing either Nickel and Iron, or the only Iron in theirs active center. Hydrogenases have been found in many microorganisms, such as Methanogenic, acetogenic, nitrogen-fixing, photosynthetic and sulfate-reducing bacteria that could utilize the hydrogen as energy source or use it as electron sink. Hydrogenases are subject for wide physiological, biochemical, physicochemical and genetic studies due to theirs abilities produce the molecular hydrogen as alternative source of pure energy. Notwithstanding on enough large quantity of works that deal with intracellular and extrasellular enzymes of halophilic bacteria, the data about hydrogenases and theirs functions of salts practically are absent. The study of hydrogenase in cell-free extracts of extremely halophilic eubacterium Acetohalobium mabaticum showed dramatic increasing activity of the enzyme at high concentrations of NaCl and KCI (close to saturated solution). Here we present the data of free-cells extracted hydrogenase from new haloalkaliphilic sulfate-reducing bacterium Desulfonatronum thiodismutans, which grow on highly miniralized carbonate-bicarbonate medium in salinity range 1 to 7 % and at pH 7.8 - 10.5. Studied enzyme was active in Concentration range from 0 to 4.3 M NaCl with optimum at 1.0 M NaCl. At 1.0 M NaCl the enzyme activity was increased on 20 %, but with changing concentration from 2.1 M to 3.4 M the activity decreased and was kept on constant level. NaHCO3 inhibited hydrogenase activity on more then 30 %. The maximum of enzyme activity was observed at pH 9.5 with limits 7.5 and 11.5 that practically equal to pH optimum of bacterial growth. Therefore the hydrogenase of Desulfanatronum thiodismutans is tolerant to high concentrations of sodium salts and it also resistant to high pH that make it the unique subject for different biochemical research and detects the possibility for biotechnological application.

Detkova, Ekaterina N.↗
NASA NTRS2001

Molecular motors and their functions in plants

Molecular motors that hydrolyze ATP and use the derived energy to generate force are involved in a variety of diverse cellular functions. Genetic, biochemical, and cellular localization data have implicated motors in a variety of functions such as vesicle and organelle transport, cytoskeleton dynamics, morphogenesis, polarized growth, cell movements, spindle formation, chromosome movement, nuclear fusion, and signal transduction. In non-plant systems three families of molecular motors (kinesins, dyneins, and myosins) have been well characterized. These motors use microtubules (in the case of kinesines and dyneins) or actin filaments (in the case of myosins) as tracks to transport cargo materials intracellularly. During the last decade tremendous progress has been made in understanding the structure and function of various motors in animals. These studies are yielding interesting insights into the functions of molecular motors and the origin of different families of motors. Furthermore, the paradigm that motors bind cargo and move along cytoskeletal tracks does not explain the functions of some of the motors. Relatively little is known about the molecular motors and their roles in plants. In recent years, by using biochemical, cell biological, molecular, and genetic approaches a few molecular motors have been isolated and characterized from plants. These studies indicate that some of the motors in plants have novel features and regulatory mechanisms. The role of molecular motors in plant cell division, cell expansion, cytoplasmic streaming, cell-to-cell communication, membrane trafficking, and morphogenesis is beginning to be understood. Analyses of the Arabidopsis genome sequence database (51% of genome) with conserved motor domains of kinesin and myosin families indicates the presence of a large number (about 40) of molecular motors and the functions of many of these motors remain to be discovered. It is likely that many more motors with novel regulatory mechanisms that perform plant-specific functions are yet to be discovered. Although the identification of motors in plants, especially in Arabidopsis, is progressing at a rapid pace because of the ongoing plant genome sequencing projects, only a few plant motors have been characterized in any detail. Elucidation of function and regulation of this multitude of motors in a given species is going to be a challenging and exciting area of research in plant cell biology. Structural features of some plant motors suggest calcium, through calmodulin, is likely to play a key role in regulating the function of both microtubule- and actin-based motors in plants.

Non-NASA Center↗
NASA NTRS2000

Kinetics of DSB rejoining and formation of simple chromosome exchange aberrations

PURPOSE: To investigate the role of kinetics in the processing of DNA double strand breaks (DSB), and the formation of simple chromosome exchange aberrations following X-ray exposures to mammalian cells based on an enzymatic approach. METHODS: Using computer simulations based on a biochemical approach, rate-equations that describe the processing of DSB through the formation of a DNA-enzyme complex were formulated. A second model that allows for competition between two processing pathways was also formulated. The formation of simple exchange aberrations was modelled as misrepair during the recombination of single DSB with undamaged DNA. Non-linear coupled differential equations corresponding to biochemical pathways were solved numerically by fitting to experimental data. RESULTS: When mediated by a DSB repair enzyme complex, the processing of single DSB showed a complex behaviour that gives the appearance of fast and slow components of rejoining. This is due to the time-delay caused by the action time of enzymes in biomolecular reactions. It is shown that the kinetic- and dose-responses of simple chromosome exchange aberrations are well described by a recombination model of DSB interacting with undamaged DNA when aberration formation increases with linear dose-dependence. Competition between two or more recombination processes is shown to lead to the formation of simple exchange aberrations with a dose-dependence similar to that of a linear quadratic model. CONCLUSIONS: Using a minimal number of assumptions, the kinetics and dose response observed experimentally for DSB rejoining and the formation of simple chromosome exchange aberrations are shown to be consistent with kinetic models based on enzymatic reaction approaches. A non-linear dose response for simple exchange aberrations is possible in a model of recombination of DNA containing a DSB with undamaged DNA when two or more pathways compete for DSB repair.

DNA Damage↗
NASA NTRS1999

In vitro activities of four xyloglucan endotransglycosylases from Arabidopsis

Xyloglucan endotransglycosylases (XETs) are encoded by a gene family in Arabidopsis thaliana. These enzymes modify a major structural component of the plant cell wall, xyloglucan, and therefore may influence plant growth and development. We have produced four Arabidopsis XETs (TCH4, Meri-5, EXGT and XTR9) using the baculovirus/insect cell system and compared their biochemical activities. TCH4, as previously demonstrated, and the other three proteins are capable of carrying out transglycosylation of xyloglucans. The K(m) for XLLGol acceptor oligosaccharide is in the range of 20-40 microM for all the XETs except XTR9, which has a Km of 5 microM and is significantly inhibited by high levels of XLLGol. All four enzymes are most active between pH 6.0 and 6.5. TCH4 and XTR9 have temperature optima of 18 degrees C, whereas Meri-5 and EXGT are most active at 28 and 37 degrees C, respectively. Although the activity levels of three of the XETs are not influenced by the presence of fucose on the xyloglucan polymer, XTR9 has a clear preference for non-fucosylated xyloglucan polymer. The four XETs show a marked preference for XLLGol over either XXFGol or XXXGol as acceptor oligosaccharide. All four XETs are glycosylated; however, only the activities of TCH4 and Meri-5 are affected by the removal of the N-glycan with PNGase F. These four enzymes most likely function solely as transglycosylases because xyloglucan endoglucanase activity was not apparent. Subtle differences in biochemical activities may influence the physiological functions of the distinct XETs in vivo.

Non-NASA Center↗
NASA NTRS1998

Biomarkers as tracers for life on early earth and Mars

Biomarkers in geological samples are products derived from biochemical (natural product) precursors by reductive and oxidative processes (e.g., cholestanes from cholesterol). Generally, lipids, pigments and biomembranes are preserved best over longer geological times and labile compounds such as amino acids, sugars, etc. are useful biomarkers for recent times. Thus, the detailed characterization of biomarker compositions permits the assessment of the major contributing species of extinct and/or extant life. In the case of the early Earth, work has progressed to elucidate molecular structure and carbon isotropic signals preserved in ancient sedimentary rocks. In addition, the combination of bacterial biochemistry with the organic geochemistry of contemporary and ancient hydrothermal ecosystems permits the modeling of the nature, behavior and preservation potential of primitive microbial communities. This approach uses combined molecular and isotopic analyses to characterize lipids produced by cultured bacteria (representative of ancient strains) and to test a variety of culture conditions which affect their biosynthesis. On considering Mars, the biomarkers from lipids and biopolymers would be expected to be preserved best if life flourished there during its early history (3.5-4 x 10(9) yr ago). Both oxidized and reduced products would be expected. This is based on the inferred occurrence of hydrothermal activity during that time with the concomitant preservation of biochemically-derived organic matter. Both known biomarkers (i.e., as elucidated for early terrestrial samples and for primitive terrestrial microbiota) and novel, potentially unknown compounds should be characterized.

Non-NASA Center↗
NASA NTRS1999

Regulatory Physiology

As noted elsewhere in this report, a central goal of the Extended Duration Orbiter Medical Project (EDOMP) was to ensure that cardiovascular and muscle function were adequate to perform an emergency egress after 16 days of spaceflight. The goals of the Regulatory Physiology component of the EDOMP were to identify and subsequently ameliorate those biochemical and nutritional factors that deplete physiological reserves or increase risk for disease, and to facilitate the development of effective muscle, exercise, and cardiovascular countermeasures. The component investigations designed to meet these goals focused on biochemical and physiological aspects of nutrition and metabolism, the risk of renal (kidney) stone formation, gastrointestinal function, and sleep in space. Investigations involved both ground-based protocols to validate proposed methods and flight studies to test those methods. Two hardware tests were also completed.

Lane, Helen W.↗
NASA NTRS1992

Identification of a nuclear localization sequence in the polyomavirus capsid protein VP2

A nuclear localization signal (NLS) has been identified in the C-terminal (Glu307-Glu-Asp-Gly-Pro-Gln-Lys-Lys-Lys-Arg-Arg-Leu318) amino acid sequence of the polyomavirus minor capsid protein VP2. The importance of this amino acid sequence for nuclear transport of newly synthesized VP2 was demonstrated by a genetic "subtractive" study using the constructs pSG5VP2 (expressing full-length VP2) and pSG5 delta 3VP2 (expressing truncated VP2, lacking amino acids Glu307-Leu318). These constructs were transfected into COS-7 cells, and the intracellular localization of the VP2 protein was determined by indirect immunofluorescence. These studies revealed that the full-length VP2 was localized in the nucleus, while the truncated VP2 protein was localized in the cytoplasm and not transported to the nucleus. A biochemical "additive" approach was also used to determine whether this sequence could target nonnuclear proteins to the nucleus. A synthetic peptide identical to VP2 amino acids Glu307-Leu318 was cross-linked to the nonnuclear proteins bovine serum albumin (BSA) or immunoglobulin G (IgG). The conjugates were then labeled with fluorescein isothiocyanate and microinjected into the cytoplasm of NIH 3T6 cells. Both conjugates localized in the nucleus of the microinjected cells, whereas unconjugated BSA and IgG remained in the cytoplasm. Taken together, these genetic subtractive and biochemical additive approaches have identified the C-terminal sequence of polyoma-virus VP2 (containing amino acids Glu307-Leu318) as the NLS of this protein.

Non-NASA Center↗
NASA NTRS2005

Heritability of markers of bone metabolism

Several classic twin studies show genetic effects on markers of bone health, including bone mineral density and parathyroid hormone (PTH). This study was performed to assess the relative contribution of genetics to biochemical markers of bone metabolism. Fifteen sets of identical twins (8 male, 7 female) were housed in a clinical research center where diet was controlled (15% protein, 55% carbohydrate, 30% fat) for 3 consecutive days. Each day, 24-h urine pools were collected and N-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and serum PTH were measured. The broad-sense heritability factor (H2) is an estimation of the portion of the total variance of a given phenotype that is attributable to genetic variance. H2 was estimated from the correlation coefficient of the phenotype data. H2 for NTX was 94% for males and 80% for females, DPD was 88% for males and 97% for females, urinary calcium excretion was 97% for males and 90% for females, and PTH was 92% for males and 79% for females. Since environmental variability was minimized for the 3 days of data collection, these heritability factors are likely overestimated. Nonetheless, the data support the concept that PTH is a predominantly heritable trait, and suggest that NTX, DPD, and calcium excretion are as well. These biochemical data support the previously documented heritability of bone health.

Smith, Scott M.↗