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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 55 records · Page 3

Functional role of myosin-binding protein H in thick filaments of developing vertebrate fast-twitch skeletal muscle

Myosin-binding protein H (MyBP-H) is a component of the vertebrate skeletal muscle sarcomere with sequence and domain homology to myosin-binding protein C (MyBP-C). Whereas skeletal muscle isoforms of MyBP-C (fMyBP-C, sMyBP-C) modulate muscle contractility via interactions with actin thin filaments and myosin motors within the muscle sarcomere “C-zone,” MyBP-H has no known function. This is in part due to MyBP-H having limited expression in adult fast-twitch muscle and no known involvement in muscle disease. Quantitative proteomics reported here reveal that MyBP-H is highly expressed in prenatal rat fast-twitch muscles and larval zebrafish, suggesting a conserved role in muscle development and prompting studies to define its function. We take advantage of the genetic control of the zebrafish model and a combination of structural, functional, and biophysical techniques to interrogate the role of MyBP-H. Transgenic, FLAG-tagged MyBP-H or fMyBP-C both localize to the C-zones in larval myofibers, whereas genetic depletion of endogenous MyBP-H or fMyBP-C leads to increased accumulation of the other, suggesting competition for C-zone binding sites. Does MyBP-H modulate contractility in the C-zone? Globular domains critical to MyBP-C’s modulatory functions are absent from MyBP-H, suggesting that MyBP-H may be functionally silent. However, our results suggest an active role. In vitro motility experiments indicate MyBP-H shares MyBP-C’s capacity as a molecular “brake.” These results provide new insights and raise questions about the role of the C-zone during muscle development.

59 BASIC BIOLOGICAL SCIENCES↗

The Vertebrate Breed Ontology: Toward Effective Breed Data Standardization

Abstract Background Limited universally-adopted data standards in veterinary medicine hinder data interoperability and therefore integration and comparison; this ultimately impedes the application of existing information-based tools to support advancement in diagnostics, treatments, and precision medicine. Hypothesis/Objectives A single, coherent, logic-based standard for documenting breed names in health, production, and research-related records will improve data use capabilities in veterinary and comparative medicine. Animals No live animals were used. Methods The Vertebrate Breed Ontology (VBO) was created from breed names and related information compiled from the Food and Agriculture Organization of the United Nations, breed registries, communities, and experts, using manual and computational approaches. Each breed is represented by a VBO term that includes breed information and provenance as metadata. VBO terms are classified using description logic to allow computational applications and Artificial Intelligence–readiness. Results VBO is an open, community-driven ontology representing over 19 500 livestock and companion animal breed concepts covering 49 species. Breeds are classified based on community and expert conventions (e.g., cattle breed) and supported by relations to the breed's genus and species indicated by National Center for Biotechnology Information (NCBI) Taxonomy terms. Relationships between VBO terms (e.g., relating breeds to their foundation stock) provide additional context to support advanced data analytics. VBO term metadata includes synonyms, breed identifiers/codes, and attributed cross-references to other databases. Conclusion and Clinical Importance The adoption of VBO as a standard for breed names in databases and veterinary electronic health records enhances veterinary data interoperability and computability, supporting precision medicine.

Veterinary Sciences↗

A model of the vertebrate central command system.

S-RETIC vertebrate command model, discussing computer simulation of reticular formation Golgi anatomy capable of habituation, conditioning, extinction, generalization and error discrimination

Blum, J.↗

The investigation of vertebral injury sustained during aircrew ejection

A series of tests were performed on excised human vertebral segments to determine the static and dynamic response of the thoraco-lumbar spine when loaded in flexion. A total of fifteen tests were performed on eleven specimens. Specimens were obtained from male donors ranging in age from 34 to 60 years. Demographic data pertinent to each specimen and the elapsed time between death of the donor and testing of each corresponding specimen are presented. Only spinal segments comprised of lower thoracic and upper lumbar vertebrae were tested because in aircraft ejection injuries clinical complications in this anatomical region predominate. A complex continuum mathematical model describing the dynamic response of the human spine was formulated, solved, and verified experimentally. Detailed results are presented in figures, tables, and equations.

Benedict, J. V.↗

Comparative anatomy of the vestibular nuclear complex in submammalian vertebrates.

A synopsis of the literature on the natural history of the vestibular nuclear complex (VNC) in lower vertebrates is presented in an attempt to assess the knowledge available. The review discloses that there is considerable descriptive information that is widely dispersed in the literature. However, information about the topology, number, and cellular composition of the cell groups that compose the VNC is sketchy. Major cytological and hodological information is still needed to establish which parts of the VNC actually are homologous.

Mehler, W. R.↗

Vertebrate gravity sensors as dynamic systems

This paper considers verterbrate gravity receptors as dynamic sensors. That is, it is hypothesized that gravity is a constant force to which an acceleration-sensing system would readily adapt. Premises are considered in light of the presence of kinocilia on hair cells of vertebrate gravity sensors; differences in loading of the sensors among species; and of possible reduction in loading by inclusion of much organic material in otoconia. Moreover, organic-inorganic interfaces may confer a piezoelectric property upon otoconia, which increase the sensitivity of the sensory system to small accelerations. Comparisons with man-made accelerometers are briefly taken up.

Ross, M. D.↗

Earth orbital variations and vertebrate bioevolution

Cause of the Pleistocene-Holocene transition mammalian extinctions at the end of the last age is the subject of debate between those advocating human predation and climate change. Identification of an ambient air temperature (AAT)-uterine blood flow (UBF) coupling phenomenon supports climate change as a factor in the extinctions, and couples the extinctions to earth orbital variations that drive ice age climatology. The AAT-UBF phenomenon couples mammalian bioevolution directly to climate change via effects of environmental heat upon blood flow to the female uterus and damage to developing embryos. Extinctions were in progress during climatic warming before the Younger Dryas event, and after, at times when the AAT-UBF couple would have been operative; however, impact of a sudden short-term cooling on mammals in the process of adapting to smaller size and relatively larger S/V would have been severe. Variations in earth's orbit, and orbital forcing of atmospheric CO2 concentrations, were causes of the succession of Pleistocene ice ages. Coincidence of mammalian extinctions with terminations of the more intense cold stages links mammalian bioevolution to variations in earth's orbit. Earth orbital variations are a driving source of vertebrate bioevolution.

Mclean, Dewey M.↗

Evolution and development of the vertebrate ear

This review outlines major aspects of development and evolution of the ear, specifically addressing issues of cell fate commitment and the emerging molecular governance of these decisions. Available data support the notion of homology of subsets of mechanosensors across phyla (proprioreceptive mechanosensory neurons in insects, hair cells in vertebrates). It is argued that this conservation is primarily related to the specific transducing environment needed to achieve mechanosensation. Achieving this requires highly conserved transcription factors that regulate the expression of the relevant structural genes for mechanosensory transduction. While conserved at the level of some cell fate assignment genes (atonal and its mammalian homologue), the ear has also radically reorganized its development by implementing genes used for cell fate assignment in other parts of the developing nervous systems (e.g., neurogenin 1) and by evolving novel sets of genes specifically associated with the novel formation of sensory neurons that contact hair cells (neurotrophins and their receptors). Numerous genes have been identified that regulate morphogenesis, but there is only one common feature that emerges at the moment: the ear appears to have co-opted genes from a large variety of other parts of the developing body (forebrain, limbs, kidneys) and establishes, in combination with existing transcription factors, an environment in which those genes govern novel, ear-related morphogenetic aspects. The ear thus represents a unique mix of highly conserved developmental elements combined with co-opted and newly evolved developmental elements.

Review↗

Vertebrate development in the environment of space: models, mechanisms, and use of the medaka

With the advent of space travel, it is of immediate interest and importance to study the effects of exposure to various aspects of the altered environment of space, including microgravity, on Earth-based life forms. Initial studies of space travel have focused primarily on the short-term effects of radiation and microgravity on adult organisms. However, with the potential for increased lengths of time in space, it is critical to now address the effects of space on all phases of an organism's life cycle, from embryogenesis to post-natal development to reproduction. It is already possible for certain species to undergo multiple generations within the confines of the Mir Space Station. The possibility now exists for scientists to consider the consequences of even potentially subtle defects in development through multiple phases of an organism's life cycle, or even through multiple generations. In this discussion, we highlight a few of the salient observations on the effects of the space environment on vertebrate development and reproductive function. We discuss some of the many unanswered questions, in particular, in the context of the choice of appropriate models in which to address these questions, as well as an assessment of the availability of hardware already existing or under development which would be useful in addressing these questions.

Flight Experiment↗

Models and molecular approaches to assessing the effects of the microgravity environment on vertebrate development

The extent to which gravity, and especially the lack thereof, can affect normal development in higher organisms is poorly understood. Underlying this question is the assumption that normal development depends on the embryo's ability to maintain a programmed temporal and spatial coordination of morphogenetic events. There are several reports documenting the apparently normal development of several vertebrate species, including mammals, under conditions of exposure to space flight during various periods of the development process. Evidence to the contrary also exists and it is therefore likely that some alterations in morphology do occur in a microgravity environment. Although subsequent development may appear overtly normal, more subtle abnormalities result. In all studies, the evaluation is restricted by the few numbers of specimens that can be examined and the relatively insensitive techniques for assessing potentially subtle effects. In the present discussion, we summarize some observations of mammalian development made in microgravity and consider which stages might be expected to be differentially sensitive to altered gravity conditions. While we emphasize mammalian development, we discuss the suitability of another model system for examining such effects in a cross-species context. Furthermore, we consider recent developments in our understanding of the molecular genetic program regulating embryogenesis that could serve as markers for assessing perturbations of development.

Cosmos 1129 Project↗

Modulation by cyclic GMP of the odour sensitivity of vertebrate olfactory receptor cells

Recent evidence has indicated a significant role for the cGMP second messenger system in vertebrate olfactory transduction but no clear functions have been identified for cGMP so far. Here, we have examined the effects of 8-Br-cGMP and carbon monoxide (CO) on odour responses of salamander olfactory receptor neurons using perforated patch recordings. We report that 8-Br-cGMP strongly down-regulates the odour sensitivity of the cells, with a K1/2 of 460 nM. This adaptation-like effect can be mimicked by CO, an activator of soluble guanylyl cyclase, with a K1/2 of 1 microM. Sensitivity modulation is achieved through a regulatory chain of events in which cGMP stimulates a persistent background current due to the activation of cyclic nucleotide-gated channels. This in turn leads to sustained Ca2+ entry providing a negative feedback signal. One consequence of the Ca2+ entry is a shift to the right of the stimulus-response curve and a reduction in saturating odour currents. Together, these two effects can reduce the sensory generator current by up to twenty-fold. Thus, cGMP functions to control the gain of the G-protein coupled cAMP pathway. Another consequence of the action of cGMP is a marked prolongation of the odour response kinetics. The effects of CO/cGMP are long-lasting and can continue for minutes. Hence, we propose that cGMP helps to prevent saturation of the cell's response by adjusting the operational range of the cAMP cascade and contributes to olfactory adaptation by decreasing the sensitivity of olfactory receptor cells to repeated odour stimuli.

NASA Discipline Neuroscience↗

Expression of S100 beta in sensory and secretory cells of the vertebrate inner ear

We evaluated anti-S100 beta expression in the chick (Gallus domesticus) inner ear and determined that: 1) the monomer anti-S100 beta is expressed differentially in the vestibular and auditory perikarya; 2) expression of S100 beta in the afferent nerve terminals is time-related to synapse and myelin formation; 3) the expression of the dimer anti-S100 alpha alpha beta beta and monomer anti-S100 beta overlaps in most inner ear cell types. Most S100 alpha alpha beta beta positive cells express S100 beta, but S100 beta positive cells do not always express S100 alpha alpha beta beta. 4) the expression of S100 beta is diffused over the perikaryal cytoplasm and nuclei of the acoustic ganglia but is concentrated over the nuclei of the vestibular perikarya. 6) S100 beta is expressed in secretory cells, and it is co-localized with GABA in sensory cells. 7) Color thresholding objective quantitation indicates that the amount of S100 beta was higher (mean 22, SD +/- 4) at E19 than at E9 (mean 34, SD +/- 3) in afferent axons. 8) Moreover, S100 beta was unchanged between E11-E19 in the perikaryal cytoplasm, but did change over the nuclei. At E9, 74%, and at E21, 5% of vestibular perikarya were positive. The data suggest that S100 beta may be physically associated with neuronal and ionic controlling cells of the vertebrate inner ear, where it could provide a dual ionic and neurotrophic modulatory function.

NASA Discipline Number 40-10↗

Effect of Ex Vivo Ionizing Radiation on Static and Fatigue Properties of Mouse Vertebral Bodies

For a variety of medical and scientific reasons, human bones can be exposed to a wide range of ionizing radiation levels. In vivo radiation therapy (0.05 kGy) is used in cancer treatment, and ex vivo irradiation (25-35 kGy) is used to sterilize bone allografts. Ionizing radiation in these applications has been shown to increase risk of fracture, decrease bone quality and degrade collagen integrity. Past studies have investigated the deleterious effects of radiation on cortical or trabecular bone specimens individually, but to date no studies have examined whole bones containing both cortical and trabecular tissue. Furthermore, a clear relationship between the dose and the mechanical and biochemical response of bone's extracellular matrix has yet to be established for doses ranging from cancer therapy to allograft sterilization (0.05-35 kGy). To gain insight into these issues, we conducted an ex vivo radiation study to investigate non-cellular (i.e. matrix) effects of ionizing radiation dose on vertebral whole bone mechanical properties, over a range of radiation doses (0.05-35 kGy), with a focus on any radiation-induced changes in collagen. With underlying mechanisms of action in mind, we hypothesized that any induced reductions in mechanical properties would be associated with changes in collagen integrity. METHODS: 20-week old female mice were euthanized and the lumbar spine was dissected using IACUC approved protocols. The lumbar vertebrae (L1- S1) were extracted from the spine via cuts through adjacent intervertebral discs, and the endplates, posterior processes, surrounding musculature, and soft tissues were removed (approx. 1.5mm diameter, approx. 2mm height). Specimens were randomly assigned to one of five groups for ex vivo radiation exposure: x-ray irradiation at 0.05, 1, 17, or 35 kGy, or a 0 kGy control. Following irradiation, the vertebrae were imaged using microcomputed tomography (micro-CT) and then subjected to either monotonic compressive loading to failure or uniform cyclic compressive loading. During cyclic testing, samples were loaded in force control to a force level that corresponded to a strain of 0.46%, as determined in advance by a linearly elastic micro-CT-based finite element analysis for each specimen. Tests were stopped at imminent fracture, defined as a rapid increase in strain. The main outcome for the monotonic test was the strength (maximum force); for cyclic testing it was the fatigue life (log of the number of cycles of loading at imminent failure). A fluorometric assay was used on the S1 vertebrae to measure the number of non-enzymatic collagen crosslinks[4]. A one-way ANOVA was performed on mechanical properties and collagen crosslinks; means were compared with controls using Dunnett's method, with a Tukey-Kramer post-hoc analysis when significance was found (p < or = 0.05). RESULTS: Compared to the unirradiated control group, the concentration of non-enzymatic collagen crosslinks was significantly increased for all irradiated groups (p < 0.0001), and being higher by at least 50% (Figure 1a). By contrast, the radiation effects on the collagen were only evident at the higher doses. For irradiation exposures of 17 kGy or more, strength decreased substantially as the radiation level was increased, but no effect was evident below 17 kGy (Figure 1b). There was no significant change in the stiffness or maximum displacement for any radiation dose (p>0.05). The finite element analysis prescribed force level for cyclic loading exceeded the measured (monotonic) strength of the 17 and 35 kGy irradiated groups (mean +/- SD, 20.6 +/- 5.6 N; 13.2 +/- 3.7 N, respectively) and therefore these groups were eliminated from the fatigue study. The fatigue life for the 0.05 and 1 kGy groups were similar to each other and were not statistically significantly different from the control group (Figure 1c).

radiation↗

Ionizing Radiation from Ex Vivo Sterilization Diminishes Fatigue but Not Static Murine Vertebral Body Mechanics

For a variety of medical and scientific reasons, human bones can be exposed to ionizing radiation. At relatively high doses (30,000±5,000 Gy), ex vivo ionizing radiation is commonly used to sterilize bone allografts. However, ionizing radiation in these applications has been shown to increase risk of fracture clinically and decrease bone quality. Previously, we observed a significant decrease in compressive static strength and fatigue life of ex vivo whole bones exposed to x-ray radiation at 17,000 Gy and above; no changes in compressive mechanical properties were observed for radiation doses of 1,000 Gy and below. The gap in doses between no mechanical change (1,000 Gy) and significant mechanical degradation (17,000 Gy) is large, and it is unclear at what dose mechanical integrity begins to diminish in whole bones, and if its effects differ in response to static versus cyclic mechanical loading. This is a major clinical concern, as trabecular and cortical bone allografts are commonly used in structural, load-bearing applications. To gain insight into the effect of ionizing radiation from 1,000-17,000 Gy, we conducted an ex vivo radiation study on the static and fatigue mechanical properties of the vertebral whole bone. Our objectives were to: (1) quantify the effect of exposure to ex vivo ionizing radiation on the mechanical integrity (compressive static and fatigue) of whole bones; and (2) evaluate, if there are observed differences in mechanics, if they differ in magnitude for static versus cyclic properties. The results of this study will give insight into the need for changes in protocols for bone allograft radiation sterilization procedures.

bone mechanics↗