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At least 343 records · Page 19
All sourcesNASA NTRSDOE OSTI
NASA NTRS2003

Developmental gene regulatory network architecture across 500 million years of echinoderm evolution

Evolutionary change in morphological features must depend on architectural reorganization of developmental gene regulatory networks (GRNs), just as true conservation of morphological features must imply retention of ancestral developmental GRN features. Key elements of the provisional GRN for embryonic endomesoderm development in the sea urchin are here compared with those operating in embryos of a distantly related echinoderm, a starfish. These animals diverged from their common ancestor 520-480 million years ago. Their endomesodermal fate maps are similar, except that sea urchins generate a skeletogenic cell lineage that produces a prominent skeleton lacking entirely in starfish larvae. A relevant set of regulatory genes was isolated from the starfish Asterina miniata, their expression patterns determined, and effects on the other genes of perturbing the expression of each were demonstrated. A three-gene feedback loop that is a fundamental feature of the sea urchin GRN for endoderm specification is found in almost identical form in the starfish: a detailed element of GRN architecture has been retained since the Cambrian Period in both echinoderm lineages. The significance of this retention is highlighted by the observation of numerous specific differences in the GRN connections as well. A regulatory gene used to drive skeletogenesis in the sea urchin is used entirely differently in the starfish, where it responds to endomesodermal inputs that do not affect it in the sea urchin embryo. Evolutionary changes in the GRNs since divergence are limited sharply to certain cis-regulatory elements, whereas others have persisted unaltered.

NASA Program Fundamental Space Biology↗
NASA NTRS2003

The complexities of skeletal biology

For a long time, the skeleton was seen as an amorphous tissue of little biological interest. But such a view ignored the large number of genetic and degenerative diseases affecting this organ. Over the past 15 years, molecular and genetic studies have modified our understanding of skeletal biology. By so doing this progress has affected our understanding of diseases and suggested in many instances new therapeutic opportunities.

Review↗
NASA NTRS2003

Disuse exaggerates the detrimental effects of alcohol on cortical bone

BACKGROUND: Alcohol abuse is associated with an increased risk for osteoporosis. However, comorbidity factors may play an important role in the pathogenesis of alcohol-related bone fractures. Suboptimal mechanical loading of the skeleton, an established risk factor for bone loss, may occur in some alcohol abusers due to reduced physical activity, muscle atrophy, or both. The effect of alcohol consumption and reduced physical activity on bone metabolism has not been well studied. The purpose of this study was to determine whether mechanical disuse alters bone metabolism in a rat model for chronic alcohol abuse. METHODS: Alcohol was administered in the diet (35% caloric intake) of 6-month-old male rats for 4 weeks. Rats were hindlimb-unloaded the final 2 weeks of the experiment to prevent dynamic weight bearing. Afterward, cortical bone histomorphometry was evaluated at the tibia-fibula synostosis. RESULTS: At the periosteal surface of the tibial diaphysis, alcohol and hindlimb unloading independently decreased the mineralizing perimeter, mineral apposition rate, and bone formation rate. In addition, alcohol, but not hindlimb unloading, increased endocortical bone resorption. The respective detrimental effects of alcohol and hindlimb unloading to inhibit bone formation were additive; there was no interaction between the two variables. CONCLUSIONS: Reduced weight bearing accentuates the detrimental effects of alcohol on cortical bone in adult male rats by further inhibiting bone formation. This finding suggests that reduced physical activity may be a comorbidity factor for osteoporosis in alcohol abusers.

NASA Discipline Cell Biology↗
NASA NTRS2003

Hindlimb unloading has a greater effect on cortical compared with cancellous bone in mature female rats

This study was designed to determine the effects of 28 days of hindlimb unloading (HU) on the mature female rat skeleton. In vivo proximal tibia bone mineral density and geometry of HU and cage control (CC) rats were measured with peripheral quantitative computed tomography (pQCT) on days 0 and 28. Postmortem pQCT, histomorphometry, and mechanical testing were performed on tibiae and femora. After 28 days, HU animals had significantly higher daily food consumption (+39%) and lower serum estradiol levels (-49%, P = 0.079) compared with CC. Proximal tibia bone mineral content and cortical bone area significantly declined over 28 days in HU animals (-4.0 and 4.8%, respectively), whereas total and cancellous bone mineral densities were unchanged. HU animals had lower cortical bone formation rates and mineralizing surface at tibial midshaft, whereas differences in similar properties were not detected in cancellous bone of the distal femur. These results suggest that cortical bone, rather than cancellous bone, is more prominently affected by unloading in skeletally mature retired breeder female rats.

NASA Discipline Musculoskeletal↗
NASA NTRS2002

Effects of major histocompatibility complex class II knockout on mouse bone mechanical properties during development

We investigated the effect of major histocompatibility complex class II (MHC II) knockout on the development of the mouse peripheral skeleton. These C2D mice had less skeletal development at 8, 12 and 16 weeks of age compared to wild-type C57BL/6J (B6) male mice. The C2D mice had decreased femur mechanical, geometric and compositional measurements compared to wild type mice at each of these ages. C2D femur stiffness (S), peak force in 3-pt bending (Pm), and mineral mass (Min-M) were 74%, 64% and 66%, respectively, of corresponding B6 values at 8 weeks of age. Similar differences were measured at 12 weeks (for which C2D femoral S, Pm and Min-M were 71%, 72% and 73%, respectively, of corresponding B6 values) and at 16 weeks (for which C2D femoral S, Pm and Min-M were 80%, 66% and 61%, respectively, of corresponding B6 values). MHC II knockout delays the development of adult bone properties and is accompanied by lower body mass compared to wild-type controls.

Non-NASA Center↗
NASA NTRS2001

Skeletal adaptation to external loads optimizes mechanical properties: fact or fiction

The skeleton adapts to a changing mechanical environment but the widely held concept that bone cells are programmed to respond to local mechanical loads to produce an optimal mechanical structure is not consistent with the high frequency of bone fractures. Instead, the author suggests that other important functions of bone compete with mechanical adaptation to determine structure. As a consequence of competing demands, bone architecture never achieves an optimal mechanical structure. c2001 Lippincott Williams & Wilkins, Inc.

Review, Tutorial↗
NASA NTRS2002

Skeletal unloading and dietary copper depletion are detrimental to bone quality of mature rats

This study was designed to examine the skeletal response to copper depletion and mechanical unloading in mature animals. In a 2 x 2 experimental design, 5.5-mo-old male Sprague-Dawley rats (n = 36) consumed either the control (AIN-93M) or Cu-depletion ((-)Cu) diet beginning 21 d before suspension and throughout the remainder of the study. Half of the rats in each dietary treatment group were either tail-suspended (TS) or kept ambulatory (AMB) for 28 d. Lower bone mineral densities (BMD) of 5th lumbar vertebra (L5) (P < 0.05) and femur were observed with (-)Cu and TS, but no differences were noted in the BMD of the humerus. Mechanical strength in the femur and vertebra decreased in response to TS, but were unaffected by copper depletion. Urinary deoxypyridinoline, an index of bone resorption, was significantly greater in TS rats, but unaltered by (-)Cu. No changes in serum or bone alkaline phosphatase activity, an indicator of bone formation, were observed. Our findings suggest that TS and (-)Cu decreased BMD in unloaded femur and vertebra but had no effect on normally loaded humerus. Bone loss with TS appeared to be related to accelerated bone resorption. Alterations in bone metabolism and bone mechanical properties in the mature skeleton resulting from (-)Cu warrant further investigation.

NASA Discipline Musculoskeletal↗
NASA NTRS2001

The skeletal structure of insulin-like growth factor I-deficient mice

The importance of insulin-like growth factor I (IGF-I) for growth is well established. However, the lack of IGF-I on the skeleton has not been examined thoroughly. Therefore, we analyzed the structural properties of bone from mice rendered IGF-I deficient by homologous recombination (knockout [k/o]) using histomorphometry, peripheral quantitative computerized tomography (pQCT), and microcomputerized tomography (muCT). The k/o mice were 24% the size of their wild-type littermates at the time of study (4 months). The k/o tibias were 28% and L1 vertebrae were 26% the size of wild-type bones. Bone formation rates (BFR) of k/o tibias were 27% that of the wild-type littermates. The k/o bones responded normally to growth hormone (GH; 1.7-fold increase) and supranormally to IGF-I (5.2-fold increase) with respect to BFR. Cortical thickness of the proximal tibia was reduced 17% in the k/o mouse. However, trabecular bone volume (bone volume/total volume [BV/TV]) was increased 23% (male mice) and 88% (female mice) in the k/o mice compared with wild-type controls as a result of increased connectivity, increased number, and decreased spacing of the trabeculae. These changes were either less or not found in L1. Thus, lack of IGF-I leads to the development of a bone structure, which, although smaller, appears more compact.

NASA Discipline Musculoskeletal↗
NASA NTRS1996

Expression of spicule matrix protein gene SM30 in embryonic and adult mineralized tissues of sea urchin Hemicentrotus pulcherrimus

We have isolated a cDNA clone for spicule matrix protein, SM30, from sea urchin Hemicentrotus pulcherrimus and have studied the expression of this gene in comparison with that of another spicule matrix protein gene, SM50. In cultured micromeres as well as in intact embryos transcripts of SM30 were first detectable around the onset of spicule formation and rapidly increased with the growth of spicules, which accompanied accumulation of glycosylated SM30 protein(s). When micromeres were cultured in the presence of Zn2+, spicule formation and SM30 expression were suppressed, while both events resumed concurrently after the removal of Zn2+ from the culture medium. Expression of SM50, in contrast, started before the appearance of spicules and was not sensitive to Zn2+. Differences were also observed in adult tissues; SM30 mRNA was detected in spines and tube feet but not in the test, while SM50 mRNA was apparent in all of these mineralized tissues at similar levels. These results strongly suggest that the SM30 gene is regulated by a different mechanism to that of the SM50 gene and that the products of these two genes are differently involved in sea urchin biomineralization. A possible role of SM30 protein in skeleton formation is discussed.

NASA Discipline Musculoskeletal↗
NASA NTRS1986

Photoactivable analogs for labeling 25-hydroxyvitamin D3 serum binding protein and for 1,25-dihydroxyvitamin D3 intestinal receptor protein

3-Azidobenzoates and 3-azidonitrobenzoates of 25-hydroxyvitamin D3 as well as 3-deoxy-3-azido-25-hydroxyvitamin D3 and 3-deoxy-3-azido-1,25-dihydroxyvitamin D3 were prepared as photoaffinity labels for vitamin D serum binding protein and 1,25-dihydroxyvitamin D3 intestinal receptor protein. The compounds prepared were easily activated by short- or long-wavelength uv light, as monitored by uv and ir spectrometry. The efficacy of the compounds to compete with 25-hydroxyvitamin D3 or 1,25-dihydroxyvitamin D3 for the binding site of serum binding protein and receptor, respectively, was studied to evaluate the vitamin D label with the highest affinity for the protein. The presence of an azidobenzoate or azidonitrobenzoate substituent at the C-3 position of 25-OH-D3 significantly decreased (10(4)- to 10(6)-fold) the binding activity. However, the labels containing the azido substituent attached directly to the vitamin D skeleton at the C-3 position showed a high affinity, only 20- to 150-fold lower than that of the parent compounds with their respective proteins. Therefore, 3-deoxy-3-azidovitamins present potential ligands for photolabeling of vitamin D proteins and for studying the structures of the protein active sites.

NASA Discipline Musculoskeletal↗
NASA NTRS1989

Secular change in chert distribution: a reflection of evolving biological participation in the silica cycle

In the modern oceans, the removal of dissolved silica from sea water is principally a biological process carried out by diatoms, with lesser contributions from radiolaria, silicoflagellates, and sponges. Because such silica in sediments is often redistributed locally during diagenesis to from nodular or bedded chert, stratigraphic changes in the facies distribution of early diagenetic chert provide important insights into the development of biological participation in the silica cycle. The abundance of chert in upper Proterozoic peritidal carbonates suggests that at this time silica was removed from seawater principally by abiological processes operating in part of the margins of the oceans. With the evolution of demosponges near the beginning of the Cambrian Period, subtidal biogenetic cherts became increasingly common, and with the Ordovician rise of radiolaria to ecological and biogeochemical prominence, sedimented skeletons became a principal sink for oceanic silica. Cherts of Silurian to Cretaceous age share many features of facies distribution and petrography but they differ from Cenozoic siliceous deposits. These differences are interpreted to reflect the mid-Cretaceous radiation of diatoms and their subsequent rise to domination of the silica cycle. Biogeochemical cycles provide an important framework for the paleobiological interpretation of the organisms that participate in them.

Non-NASA Center↗
NASA NTRS1993

Calcified microbes in Neoproterozoic carbonates: implications for our understanding of the Proterozoic/Cambrian transition

Tidal flat and lagoonal dolostones of the Neoproterozoic Draken Formation, Spitsbergen, exhibit excellent preservation of carbonate fabrics, including heavily calcified microfossils. The crust-forming cyanobacterium Polybessurus is preserved locally by carbonate precipitated on and within sheaths in mildly evaporitic upper intertidal to supratidal environments. In contrast, calcified filaments in columnar stromatolites reflect subtidal precipitation. Filament molds in dolomicrites independently document extremely early lithification. The presence of heavily calcified cyanobacteria in Draken and other Proterozoic carbonates constrains potential explanations for the widespread appearance of calcified microorganisms near the Proterozoic-Cambrian boundary. We propose that the rarity of Proterozoic examples principally reflects the abundance and wide distribution of carbonate crystals precipitated on the sea floor or in the water column. Cyanobacterial sheaths would have competed effectively as sites for carbonate nucleation and growth only where calcitic and/or aragonitic nuclei were absent. In this view, the Proterozoic-Cambrian expansion of calcified microfossils primarily reflects the emergence of skeletons as principal agents of carbonate deposition.

Non-NASA Center↗
NASA NTRS2003

Neural crest contributions to the lamprey head

The neural crest is a vertebrate-specific cell population that contributes to the facial skeleton and other derivatives. We have performed focal DiI injection into the cranial neural tube of the developing lamprey in order to follow the migratory pathways of discrete groups of cells from origin to destination and to compare neural crest migratory pathways in a basal vertebrate to those of gnathostomes. The results show that the general pathways of cranial neural crest migration are conserved throughout the vertebrates, with cells migrating in streams analogous to the mandibular and hyoid streams. Caudal branchial neural crest cells migrate ventrally as a sheet of cells from the hindbrain and super-pharyngeal region of the neural tube and form a cylinder surrounding a core of mesoderm in each pharyngeal arch, similar to that seen in zebrafish and axolotl. In addition to these similarities, we also uncovered important differences. Migration into the presumptive caudal branchial arches of the lamprey involves both rostral and caudal movements of neural crest cells that have not been described in gnathostomes, suggesting that barriers that constrain rostrocaudal movement of cranial neural crest cells may have arisen after the agnathan/gnathostome split. Accordingly, neural crest cells from a single axial level contributed to multiple arches and there was extensive mixing between populations. There was no apparent filling of neural crest derivatives in a ventral-to-dorsal order, as has been observed in higher vertebrates, nor did we find evidence of a neural crest contribution to cranial sensory ganglia. These results suggest that migratory constraints and additional neural crest derivatives arose later in gnathostome evolution.

Non-NASA Center↗
NASA NTRS1995

Terminal Proterozoic reorganization of biogeochemical cycles

The Proterozoic aeon (2,500-540 million years ago) saw episodic increases in atmospheric oxygen content, the evolution of multicellular life and, at its close, an enormous radiation of animal diversity. These profound biological and environmental changes must have been linked, but the underlying mechanisms have been obscure. Here we show that hydrocarbons extracted from Proterozoic sediments in several locations worldwide are derived mainly from bacteria or other heterotrophs rather than from photosynthetic organisms. Biodegradation of algal products in sedimenting matter was therefore unusually complete, indicating that organic material was extensively reworked as it sank slowly through the water column. We propose that a significant proportion of this reworking will have been mediated by sulphate-reducing bacteria, forming sulphide. The production of sulphide and consumption of oxygen near the ocean surface will have inhibited transport of O2 to the deep ocean. We find that preservation of algal-lipid skeletons improves at the beginning of the Cambrian, reflecting the increase in transport by rapidly sinking faecal pellets. We suggest that this rapid removal of organic matter will have increased oxygenation of surface waters, leading to a descent of the O2-sulphide interface to the sea floor and to marked changes in the marine environment, ultimately contributing to the Cambrian radiation.

Non-NASA Center↗
NASA NTRS1989

Incorporation of measured photosynthetic rate in a mathematical model for calculation of non-structural saccharide concentration

A simple mathematical model for calculating the concentration of mobile carbon skeletons in the shoot of soya bean plants [Glycine max (L.) Merrill cv. Ransom] was built to examine the suitability of measured net photosynthetic rates (PN) for calculation of saccharide flux into the plant. The results suggest that either measurement of instantaneous PN overestimated saccharide influx or respiration rates utilized in the model were underestimated. If neither of these is the case, end-product inhibition of photosynthesis or waste respiration through the alternative pathway should be included in modelling of CH2O influx or efflux; and even if either of these is the case, the model output at a low coefficient of leaf activity indicates that PN still may be controlled by either end-product inhibition or alternative respiration.

NASA Program CELSS↗
NASA NTRS1994

Ammonium and nitrate uptake by soybean during recovery from nitrogen deprivation

Soybean [Glycine max (L.) Merrill] plants that had been subjected to 15 d of nitrogen deprivation were resupplied for 10 d with 1.0 mol m-3 nitrogen provided as NO3-, NH4+, or NH4(+) + NO3- in flowing hydroponic culture. Plants in a fourth hydroponic system received 1.0 mol m-3 NO3- during both stress and resupply periods. Concentrations of soluble carbohydrates and organic acids in roots increased 210 and 370%, respectively, during stress. For the first day of resupply, however, specific uptake rates of nitrogen, determined by ion chromatography as depletion from solution, were lower for stressed than for non-stressed plants by 43% for NO3- resupply, by 32% for NH4(+) + NO3- resupply, and 86% for NH4+ resupply. When specific uptake of nitrogen for stressed plants recovered to rates for non-stressed plants at 6 to 8 d after nitrogen resupply, carbohydrates and organic acids in their roots had declined to concentrations lower than those of non-stressed plants. Recovery of nitrogen uptake capacity of roots thus does not appear to be regulated simply by the content of soluble carbon compounds within roots. Solution concentrations of NH4+ and NO3- were monitored at 62.5 min intervals during the first 3 d of resupply. Intermittent 'hourly' intervals of net influx and net efflux occurred. Rates of uptake during influx intervals were greater for the NH4(+)-resupplied than for the NO3(-)-resupplied plants. For NH4(+)-resupplied plants, however, the hourly intervals of efflux were more numerous than for NO3(-)-resupplied plants. It thus is possible that, instead of repressing NH4+ influx, increased accumulation of amino acids and NH4+ in NH4(+)-resupplied plants inhibited net uptake by stimulation of efflux on NH4+ absorbed in excess of availability of carbon skeletons for assimilation. Entry of NH4+ into root cytoplasm appeared to be less restricted than translocation of amino acids from the cytoplasm into the xylem.

NASA Discipline Number 61-10↗
NASA NTRS2000

Invited review: what do we know about the effects of spaceflight on bone?

This review of the peer-reviewed literature focuses on the effects of spaceflight on bone. Studies performed in humans and laboratory animals have revealed abnormalities in bone and mineral metabolism that suggest that long-duration spaceflight will have detrimental effects on the skeleton. However, because of large gaps in our knowledge, it is not presently possible to estimate the magnitude of the health risk, individual variations in risk, effective countermeasures, or mechanism(s) of action. Specific recommendations are made for future research to ascertain risk and develop appropriate countermeasures.

NASA Discipline Musculoskeletal↗
NASA NTRS1999

Mechanical signaling in the development of postmenopausal osteoporosis

Estrogen deficiency results in increased bone turnover and net bone loss in rats as well as humans. The respective roles of bone turnover and mechanical strain in mediating estrogen deficiency-induced cancellous bone loss were investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in long bones. However, cancellous bone was preferentially lost in the metaphysis, a site that experiences low strain energy during normal physical activity. No bone loss was observed in the epiphysis, a site experiencing higher strain energy, despite a similar increase in bone turnover. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased or decreased in long bones of ovariectomized rats by treadmill exercise or functional unloading, respectively. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing weight bearing accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in unloaded limbs and prevented bone loss in the loaded limbs. These results suggest that estrogen alters the mechanosensory (mechanostat) set point for skeletal adaptation, effectively reducing the minimum strain energy levels at which bone is added. Additionally, these studies suggest that physical activity as well as endocrine status play an important role in maintenance of the female skeleton during aging.

Non-NASA Center↗