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At least 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
NASA NTRS2001

Parathyroid hormone enhances fluid shear-induced [Ca2+]i signaling in osteoblastic cells through activation of mechanosensitive and voltage-sensitive Ca2+ channels

Osteoblasts respond to both fluid shear and parathyroid hormone (PTH) with a rapid increase in intracellular calcium concentration ([Ca2+]i). Because both stimuli modulate the kinetics of the mechanosensitive cation channel (MSCC), we postulated PTH would enhance the [Ca2+]i response to fluid shear by increasing the sensitivity of MSCCs. After a 3-minute preflow at 1 dyne/cm2, MC3T3-E1 cells were subjected to various levels of shear and changes in [Ca2+]i were assessed using Fura-2. Pretreatment with 50 nM bovine PTH(1-34) [bPTH(1-34)] significantly enhanced the shear magnitude-dependent increase in [Ca2+]i. Gadolinium (Gd3+), an MSCC blocker, significantly inhibited the mean peak [Ca2+]i response to shear and shear + bPTH(1-34). Nifedipine (Nif), an L-type voltage-sensitive Ca2+ channel (VSCC) blocker, also significantly reduced the [Ca2+]i response to shear + bPTH(1-34), but not to shear alone, suggesting VSCC activation plays an interactive role in the action of these stimuli together. Activation of either the protein kinase C (PKC) or protein kinase A (PKA) pathways with specific agonists indicated that PKC activation did not alter the Ca2+ response to shear, whereas PKA activation significantly increased the [Ca2+]i response to lower magnitudes of shear. bPTH(1-34), which activates both pathways, induced the greatest [Ca2+]i response at each level of shear, suggesting an interaction of these pathways in this response. These data indicate that PTH significantly enhances the [Ca2+]i response to shear primarily via PKA modulation of the MSCC and VSCC.

Non-NASA Center↗
NASA NTRS2000

Parathyroid hormone modulates the response of osteoblast-like cells to mechanical stimulation

Mechanical loading stimulates many responses in bone and osteoblasts associated with osteogenesis. Since loading and parathyroid hormone (PTH) activate similar signaling pathways in osteoblasts, we postulate that PTH can potentiate the effects of mechanical stimulation. Using an in vitro four-point bending device, we found that expression of COX-2, the inducible isoform of cyclooxygenase, was dependent on fluid forces generated across the culture plate, but not physiologic levels of strain in MC3T3-E1 osteoblast-like cells. Addition of 50 nM PTH during loading increased COX-2 expression at both subthreshold and threshold levels of fluid forces compared with either stimuli alone. We also demonstrated that application of fluid shear to MC3T3-E1 cells induced a rapid increase in [Ca(2+)](i). Although PTH did not significantly change [Ca(2+)](i) levels, flow and PTH did produce a significantly greater [Ca(2+)](i) response and increased the number of responding cells than is found in fluid shear alone. The [Ca(2+)](i) response to these stimuli was significantly decreased when the mechanosensitive channel inhibitor, gadolinium, was present. These studies indicate that PTH increases the cellular responses of osteoblasts to mechanical loading. Furthermore, this response may be mediated by alterations in [Ca(2+)](i) by modulating the mechanosensitive channel.

Non-NASA Center↗
NASA NTRS1999

Extracellular signal-regulated kinases 1 and 2 activation in endothelial cells exposed to cyclic strain

The aim of this study was to determine whether extracellular signal-regulated kinases 1/2 (ERK1/ERK2) are activated and might play a role in enhanced proliferation and morphological change induced by strain. Bovine aortic endothelial cells (BAEC) were subjected to an average of 6 or 10% strain at a rate of 60 cycles/min for up to 4 h. Cyclic strain caused strain- and time-dependent phosphorylation and activation of ERK1/ERK2. Peak phosphorylation and activation of ERK1/ERK2 induced by 10% strain were at 10 min. A specific ERK1/ERK2 kinase inhibitor, PD-98059, inhibited phosphorylation and activation of ERK1/ERK2 but did not inhibit the increased cell proliferation and cell alignment induced by strain. Treatment of BAEC with 2,5-di-tert-butyl-1, 4-benzohydroquinone, to deplete inositol trisphosphate-sensitive calcium storage, and gadolinium chloride, a Ca2+ channel blocker, did not inhibit the activation of ERK1/ERK2. Strain-induced ERK1/ERK2 activation was partly inhibited by the protein kinase C inhibitor calphostin C and completely inhibited by the tyrosine kinase inhibitor genistein. These data suggest that 1) ERK1/ERK2 are not critically involved in the strain-induced cell proliferation and orientation, 2) strain-dependent activation of ERK1/ERK2 is independent of intracellular and extracellular calcium mobilization, and 3) protein kinase C activation and tyrosine kinase regulate strain-induced activation of ERK1/ERK2.

NASA Discipline Cell Biology↗
NASA NTRS1998

Mouse osteoblastic cell line (MC3T3-E1) expresses extracellular calcium (Ca2+o)-sensing receptor and its agonists stimulate chemotaxis and proliferation of MC3T3-E1 cells

The calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays key roles in extracellular calcium ion (Ca2+o) homeostasis in parathyroid gland and kidney. Osteoblasts appear at sites of osteoclastic bone resorption during bone remodeling in the "reversal" phase following osteoclastic resorption and preceding bone formation. Bone resorption produces substantial local increases in Ca2+o that could provide a signal for osteoblasts in the vicinity, leading us to determine whether such osteoblasts express the CaR. In this study, we used the mouse osteoblastic, clonal cell line MC3T3-E1. Both immunocytochemistry and Western blot analysis, using an antiserum specific for the CaR, detected CaR protein in MC3T3-E1 cells. We also identified CaR transcripts in MC3T3-E1 cells by Northern analysis using a CaR-specific riboprobe and by reverse transcription-polymerase chain reaction with CaR-specific primers, followed by nucleotide sequencing of the amplified products. Exposure of MC3T3-E1 cells to high Ca2+o (up to 4.8 mM) or the polycationic CaR agonists, neomycin and gadolinium (Gd3+), stimulated both chemotaxis and DNA synthesis in MC3T3-E1 cells. Therefore, taken together, our data strongly suggest that the osteoblastic cell line MC3T3-E1 possesses both CaR protein and mRNA very similar, if not identical, to those in parathyroid and kidney. Furthermore, the CaR in these osteoblasts could play a key role in regulating bone turnover by stimulating the proliferation and migration of such cells to sites of bone resorption as a result of local release of Ca2+o.

Non-NASA Center↗
NASA NTRS1998

Extracellular calcium (Ca2+(o))-sensing receptor in a murine bone marrow-derived stromal cell line (ST2): potential mediator of the actions of Ca2+(o) on the function of ST2 cells

The calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays key roles in extracellular calcium ion (Ca2+(o)) homeostasis by mediating the actions of Ca2+(o) on parathyroid gland and kidney. Bone marrow stromal cells support the formation of osteoclasts from their progenitors as well as the growth of hematopoietic stem cells by secreting humoral factors and through cell to cell contact. Stromal cells also have the capacity to differentiate into bone-forming osteoblasts. Bone resorption by osteoclasts probably produces substantial local increases in Ca2+(o) that could provide a signal for stromal cells in the immediate vicinity, leading us to determine whether such stromal cells express the CaR. In this study, we used the murine bone marrow-derived, stromal cell line, ST2. Both immunocytochemistry and Western blot analysis, using an antiserum specific for the CaR, detected CaR protein in ST2 cells. We also identified CaR transcripts in ST2 cells by Northern analysis using a CaR-specific probe and by RT-PCR with CaR-specific primers, followed by nucleotide sequencing of the amplified products. Exposure of ST2 cells to high Ca2+(o) (4.8 mM) or to the polycationic CaR agonists, neomycin (300 microM) or gadolinium (100 microM), stimulated both chemotaxis and DNA synthesis in ST2 cells. Therefore, taken together, our data strongly suggest that the bone marrow-derived stromal cell line, ST2, possesses both CaR protein and messenger RNA that are very similar if not identical to those in parathyroid and kidney. Furthermore, as ST2 cells have the potential to differentiate into osteoblasts, the CaR in stromal cells could participate in bone turnover by stimulating the proliferation and migration of such cells to sites of bone resorption as a result of local, osteoclast-mediated release of Ca2+(o) and, thereafter, initiating bone formation after their differentiation into osteoblasts.

NASA Discipline Musculoskeletal↗
NASA NTRS1996

Yeast respond to hypotonic shock with a calcium pulse

We have used the transgenic AEQUORIN calcium reporter system to monitor the cytosolic calcium ([Ca2+]cyt) response of Saccharomyces cerevisiae to hypotonic shock. Such a shock generates an almost immediate and transient rise in [Ca2+]cyt which is eliminated by gadolinium, a blocker of stretch-activated channels. In addition, this transient rise in [Ca2+]cyt is initially insensitive to 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), an extracellular calcium chelator. However, BAPTA abruptly attenuates the maintenance of that transient rise. These data show that hypotonic shock generates a stretch-activated channel-dependent calcium pulse in yeast. They also suggest that the immediate calcium influx is primarily generated from intracellular stores, and that a sustained increase in [Ca2+]cyt depends upon extracellular calcium.

NASA Discipline Plant Biology↗
NASA NTRS1995

Preservation of auditory and vestibular function after surgical removal of bilateral vestibular schwannomas in a patient with neurofibromatosis type 2

The outcome of acoustic neuroma (vestibular schwannoma) surgery continues to improve rapidly. Advances can be attributed to several fields, but the most important contributions have arisen from the identification of the genes responsible for the dominant inheritance of neurofibromatosis types 1 (NF1) and 2 (NF2) and the development of magnetic resonance imaging with gadolinium enhancement for the early anatomic confirmation of the pathognomonic, bilateral vestibular schwannomas in NF2. These advances enable early diagnosis and treatment when the tumors are small in virtually all subjects at risk for NF2. The authors suggest that advising young NF2 patients to wait until complications develop, especially hearing loss, before diagnosing and operating for bilateral eighth nerve schwannomas may not always be in the best interest of the patient. To the authors' knowledge, this is the first reported case of preservation of both auditory and vestibular function in a patient after bilateral vestibular schwannoma excision.

Case Reports↗
NASA NTRS1994

Chronic, intermittent loading alters mechanosensitive channel characteristics in osteoblast-like cells

The effects of chronic, intermittent strain on the mechanosensitive cation (SA-cat) channels in UMR-106.01 osteoblast-like osteosarcoma cells were studied using patch-clamp techniques. Chronically strained cells demonstrated significantly larger increases in whole cell conductance when subjected to additional mechanical strain than nonstrained controls (69.0 +/- 15.1 vs. 14.1 +/- 3.1%; P < 0.001). This increase could be blocked by the SA-cat channel inhibitor, gadolinium, and corresponded to a three- to fivefold increase in SA-cat channel activity. Chronic strain increased the number of open channels in response to stretch and induced spontaneous SA-cat channel activity in 33% of the patches of strained cells. Graded increases in negative patch pressure demonstrated that SA-cat channels in chronically strained cells were activated at significantly lower levels of mechanical perturbation than nonstrained controls. These data suggest that chronic, cyclic strain reduces the activation threshold of the SA-cat channel and further strengthen our hypothesis that this channel may act as a mechanotransducer for the activation of bone remodeling by physical strain.

NASA Discipline Musculoskeletal↗
NASA NTRS2004

Allograft tolerance induced by donor apoptotic lymphocytes requires phagocytosis in the recipient

Cell death through apoptosis plays a critical role in regulating cellular homeostasis. Whether the disposal of apoptotic cells through phagocytosis can actively induce immune tolerance in vivo, however, remains controversial. Here, we report in a rat model that without using immunosuppressants, transfusion of apoptotic splenocytes from the donor strain prior to transplant dramatically prolonged survival of heart allografts. Histological analysis verified that rejection signs were significantly ameliorated. Splenocytes from rats transfused with donor apoptotic cells showed a dramatically decreased response to donor lymphocyte stimulation. Most importantly, blockade of phagocytosis in vivo, either with gadolinium chloride to disrupt phagocyte function or with annexin V to block binding of exposed phosphotidylserine to its receptor on phagocytes, abolished the beneficial effect of transfused apoptotic cells on heart allograft survival. Our results demonstrate that donor apoptotic cells promote specific allograft acceptance and that phagocytosis of apoptotic cells in vivo plays a crucial role in maintaining immune tolerance.

NASA Discipline Regulatory Physiology↗
NASA NTRS2012

A Reversible Thermally Driven Pump for Use in a Sub-Kelvin Magnetic Refrigerator

A document describes a continuous magnetic refrigerator that is suited for cooling astrophysics detectors. This refrigerator has the potential to provide efficient, continuous cooling to temperatures below 50 mK for detectors, and has the benefits over existing magnetic coolers of reduced mass because of faster cycle times, the ability to pump the cooled fluid to remote cooling locations away from the magnetic field created by the superconducting magnet, elimination of the added complexity and mass of heat switches, and elimination of the need for a thermal bus and single crystal paramagnetic materials due to the good thermal contact between the fluid and the paramagnetic material. A reliable, thermodynamically efficient pump that will work at 1.8 K was needed to enable development of the new magnetic refrigerator. The pump consists of two canisters packed with pieces of gadolinium gallium garnet (GGG). The canisters are connected by a superleak (a porous piece of VYCOR glass). A superconducting magnetic coil surrounds each of the canisters. The configuration enables driving of cyclic thermodynamic cycles (such as the sub-Kelvin Active Magnetic Regenerative Refrigerator) without using pistons or moving parts.

Miller, Franklin K.↗
NASA NTRS2012

A Superfluid Pulse Tube Refrigerator Without Moving Parts for Sub-Kelvin Cooling

A report describes a pulse tube refrigerator that uses a mixture of He-3 and superfluid He-4 to cool to temperatures below 300 mK, while rejecting heat at temperatures up to 1.7 K. The refrigerator is driven by a novel thermodynamically reversible pump that is capable of pumping the He-3 He-4 mixture without the need for moving parts. The refrigerator consists of a reversible thermal magnetic pump module, two warm heat exchangers, a recuperative heat exchanger, two cold heat exchangers, two pulse tubes, and an orifice. It is two superfluid pulse tubes that run 180 out of phase. All components of this machine except the reversible thermal pump have been demonstrated at least as proof-of-concept physical models in previous superfluid Stirling cycle machines. The pump consists of two canisters packed with pieces of gadolinium gallium garnet (GGG). The canisters are connected by a superleak (a porous piece of VYCOR glass). A superconducting magnetic coil surrounds each of the canisters.

Miller, Franklin K.↗
NASA NTRS2013

Micromachined Active Magnetic Regenerator for Low-Temperature Magnetic Coolers

A design of an Active Magnetic Regenerative Refrigeration (AMRR) system has been developed for space applications. It uses an innovative 3He cryogenic circulator to provide continuous remote/distributed cooling at temperatures in the range of 2 K with a heat sink at about 15 K. A critical component technology for this cooling system is a highly efficient active magnetic regenerator, which is a regenerative heat exchanger with its matrix material made of magnetic refrigerant gadolinium gallium garnet (GGG). Creare Inc. is developing a microchannel GGG regenerator with an anisotropic structured bed for high system thermal efficiency. The regenerator core consists of a stack of thin, single-crystal GGG disks alternating with thin polymer insulating layers. The insulating layers help minimize the axial conduction heat leak, since GGG has a very high thermal conductivity in the regenerator s operating temperature range. The GGG disks contain micro channels with width near 100 micrometers, which enhance the heat transfer between the circulating flow and the refrigerant bed. The unique flow configuration of the GGG plates ensures a uniform flow distribution across the plates. The main fabrication challenges for the regenerator are the machining of high-aspect-ratio microchannels in fragile, single-crystal GGG disks and fabrication and assembly of the GGG insulation layers. Feasibility demonstrations to date include use of an ultrashort- pulse laser to machine microchannels without producing unacceptable microcracking or deposition of recast material, as shown in the figure, and attachment of a thin insulation layer to a GGG disk without obstructing the flow paths. At the time of this reporting, efforts were focused on improving the laser machining process to increase machining speed and further reduce microcracking.

Chen, Weibo↗
NASA NTRS2014

Implementation of an Ultra-Bright Thermographic Phosphor for Gas Turbine Engine Temperature Measurements

The overall goal of the Aeronautics Research Mission Directorate (ARMD) Seedling Phase II effort was to build on the promising temperature-sensing characteristics of the ultrabright thermographic phosphor Cr-doped gadolinium aluminum perovskite (Cr:GAP) demonstrated in Phase I by transitioning towards an engine environment implementation. The strategy adopted was to take advantage of the unprecedented retention of ultra-bright luminescence from Cr:GAP at temperatures over 1000 C to enable fast 2D temperature mapping of actual component surfaces as well as to utilize inexpensive low-power laser-diode excitation suitable for on-wing diagnostics. A special emphasis was placed on establishing Cr:GAP luminescence-based surface temperature mapping as a new tool for evaluating engine component surface cooling effectiveness.

temperature↗
NASA NTRS2014

Temperature and Pressure Sensors Based on Spin-Allowed Broadband Luminescence of Doped Orthorhombic Perovskite Structures

Systems and methods that are capable of measuring pressure or temperature based on luminescence are discussed herein. These systems and methods are based on spin-allowed broadband luminescence of sensors with orthorhombic perovskite structures of rare earth aluminates doped with chromium or similar transition metals, such as chromium-doped gadolinium aluminate. Luminescence from these sensors can be measured to determine at least one of temperature or pressure, based on either the intense luminescence of these sensors, even at high temperatures, or low temperature techniques discussed herein.

Eldridge, Jeffrey I.↗
NASA NTRS2017

Fabrication of Lightweight Radiation Shielding Composite Materials by Field Assisted Sintering Technique (FAST)

Advances in radiation shielding technologies are needed to protect humans and electronic components from all threats of space radiation over long durations. In this paper, we report on the use of the innovative and novel fabrication technology known as Field Assisted Sintering Technology (FAST) to fabricate lightweight material with enhanced radiation shielding strength to safeguard humans and electronics suitable for next generation space exploration missions. The base materials we investigated were aluminum (Al), the current standard material for space hardware, and Ultra-High Molecular Weight Polyethylene (UHMWPE), which has high hydrogen content and resistance to nuclear reaction from neutrons, making it a good shielding material for both gamma radiation and particles. UHMWPE also has high resistance to corrosive chemicals, extremely low moisture sensitivity, very low coefficient of friction, and high resistance to abrasion. We reinforced the base materials by adding high density (ie, high atomic weight) metallic material into the composite. These filler materials included: boron carbide (B4C), tungsten (W), tungsten carbide (WC) and gadolinium (Gd).

Prasad, Narasimha↗
NASA NTRS2018

Percolation Behaviour in the Magnetic Permeability and Electrical Conductivity in Conducting Magnetic - Insulating Non Magnetic Binary Composites

Experimental results of the complex magnetic permeability (µ) and the electrical conductivity (σ) of a granular paramagnetic Gadolinium Gallium Garnet (GGG: 0.3–26 vol%) and Teflon (PTFE) system are presented and discussed in relation to previously published (conductivity) and unpublished (permeability) studies on granular Fe3O4 – talc and Ni – talc wax systems. In these systems plots of the real conductivity (σ'(sub m)) against the volume fraction (φ) lie on characteristic sigmoid curves that when fitted to the Two Exponent Phenomenological Percolation Equation (TEPPE) confirm the existence of “percolation microstructures” with critical volume fractions (φ(sub c)). The plots of the real and imaginary permeability (µ'(sub m)) and (µ"(sub m)) satisfactorily fit to the TEPPE using the φ(sub c) obtained in each case from the “conductivity” measurements. In all three cases the conductivity results gave the exponent t > 2, and the permeability results gave t < 1.

David S McLachlan↗
NASA NTRS2019

Development of a Flight-Worthy 10 to 4 K Continuous Adiabatic Demagnetization Refrigerator

The cryogenics and fluids branch at NASA's Goddard Space Flight Center is currently developing a high-efficiency, vibration-free, flight-worthy Continuous Adiabatic Demagnetization Refrigerator (CADR) that consist of two modular units: one that lifts ~6 microW at 50 mK while rejecting its heat to a 4 K thermal sink, and another unit that provides a constant 4 K cooling stage while rejecting its heat to a thermal sink at 10 K. The two units are linked together via a 4 K common platform. This paper discusses the status report on the thermodynamic performance of the 4 -10 K ADR. This ADR utilizes an Nb3Sn superconducting magnet and Gadolinium Gallium Garnet (GGG) as its refrigerant. Results show that an idealized cycle, one where its hold time at 4 K is equal to the recycle time, can lift 13 mW at 4 K with a hold time of 132 seconds.

CADR↗