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22 records · Page 2

Cloning the promoter for transforming growth factor-beta type III receptor. Basal and conditional expression in fetal rat osteoblasts

Transforming growth factor-beta binds to three high affinity cell surface molecules that directly or indirectly regulate its biological effects. The type III receptor (TRIII) is a proteoglycan that lacks significant intracellular signaling or enzymatic motifs but may facilitate transforming growth factor-beta binding to other receptors, stabilize multimeric receptor complexes, or segregate growth factor from activating receptors. Because various agents or events that regulate osteoblast function rapidly modulate TRIII expression, we cloned the 5' region of the rat TRIII gene to assess possible control elements. DNA fragments from this region directed high reporter gene expression in osteoblasts. Sequencing showed no consensus TATA or CCAAT boxes, whereas several nuclear factors binding sequences within the 3' region of the promoter co-mapped with multiple transcription initiation sites, DNase I footprints, gel mobility shift analysis, or loss of activity by deletion or mutation. An upstream enhancer was evident 5' proximal to nucleotide -979, and a silencer region occurred between nucleotides -2014 and -2194. Glucocorticoid sensitivity mapped between nucleotides -687 and -253, whereas bone morphogenetic protein 2 sensitivity co-mapped within the silencer region. Thus, the TRIII promoter contains cooperative basal elements and dispersed growth factor- and hormone-sensitive regulatory regions that can control TRIII expression by osteoblasts.

Non-NASA Center↗

Life Support and Environmental Monitoring International System Maturation Team Considerations

Human exploration of the solar system is an ambitious goal. Future human missions to Mars or other planets will require the cooperation of many nations to be feasible. Exploration goals and concepts have been gathered by the International Space Exploration Coordination Group (ISECG) at a very high level, representing the overall goals and strategies of each participating space agency. The Global Exploration Roadmap published by ISECG states that international partnerships are part of what drives the mission scenarios. It states "Collaborations will be established at all levels (missions, capabilities, technologies), with various levels of interdependency among the partners." To make missions with interdependency successful, technologists and system experts need to share information early, before agencies have made concrete plans and binding agreements. This paper provides an overview of possible ways of integrating NASA, ESA, and JAXA work into a conceptual roadmap of life support and environmental monitoring capabilities for future exploration missions. Agencies may have immediate plans as well as long term goals or new ideas that are not part of official policy. But relationships between plans and capabilities may influence the strategies for the best ways to achieve partner goals. Without commitments and an organized program like the International Space Station, requirements for future missions are unclear. Experience from ISS has shown that standards and an early understanding of requirements are an important part of international partnerships. Attempting to integrate systems that were not designed together can create many problems. Several areas have been identified that could be important to discuss and understand early: units of measure, cabin CO2 levels, and the definition and description of fluids like high purity oxygen, potable water and residual biocide, and crew urine and urine pretreat. Each of the partners is exploring different kinds of technologies. Different specific parameters may important to define or explore possible ranges depending on the system concepts. Early coordination between technology developers can create new possibilities for collaboration, and provide input to determine what combined options may provide the best overall system architecture.

Anderson, Molly↗

Life Support and Environmental Monitoring International System Maturation Team Considerations.

Human exploration of the solar system is an ambitious goal. Future human missions to Mars or other planets will require the cooperation of many nations to be feasible. Exploration goals and concepts have been gathered by the International Space Exploration Coordination Group (ISECG) at a very high level, representing the overall goals and strategies of each participating space agency. The Global Exploration Roadmap published by ISECG states that international partnerships are part of what drives the the mission scenarios. It states "Collaborations will be established at all levels (missions, capabilities, technologies), with various levels of interdependency among the partners." To make missions with interdependency successful, technologists and system experts need to share information early, before agencies have made concrete plans and binding agreements. This paper provides an overview of possible ways of integrating NASA, ESA, and JAXA work into a conceptual roadmap of life support and environmental monitoring capabilities for future exploration missions. Agencies may have immediate plans as well as long term goals or new ideas that are not part of official policy. But relationships between plans and capabilities may influence the strategies for the best ways to achieve partner goals. Without commitments and an organized program like the International Space Station, requirements for future missions are unclear. Experience from ISS has shown that standards and an early understanding of requirements are an important part of international partnerships. Attempting to integrate systems that were not designed together can create many problems. Several areas have been identified that could be important to discuss and understand early: units of measure, cabin CO2 levels, and the definition and description of fluids like high purity oxygen, potable water and residual biocide, and crew urine and urine pretreat. Each of the partners is exploring different kinds of technologies. Different specific parameters may important to define or explore possible ranges depending on the system concepts. Early coordination between technology developers can create new possibilities for collaboration, and provide input to determine what combined options may provide the best overall system architecture.

Anderson, Molly↗

How actin crosslinking and bundling proteins cooperate to generate an enhanced cell mechanical response

Actin-crosslinking proteins organize actin filaments into dynamic and complex subcellular scaffolds that orchestrate important mechanical functions, including cell motility and adhesion. Recent mutation studies have shown that individual crosslinking proteins often play seemingly non-essential roles, leading to the hypothesis that they have considerable redundancy in function. We report live-cell, in vitro, and theoretical studies testing the mechanical role of the two ubiquitous actin-crosslinking proteins, alpha-actinin and fascin, which co-localize to stress fibers and the basis of filopodia. Using live-cell particle tracking microrheology, we show that the addition of alpha-actinin and fascin elicits a cell mechanical response that is significantly greater than that originated by alpha-actinin or fascin alone. These live-cell measurements are supported by quantitative rheological measurements with reconstituted actin filament networks containing pure proteins that show that alpha-actinin and fascin can work in concert to generate enhanced cell stiffness. Computational simulations using finite element modeling qualitatively reproduce and explain the functional synergy of alpha-actinin and fascin. These findings highlight the cooperative activity of fascin and alpha-actinin and provide a strong rationale that an evolutionary advantage might be conferred by the cooperative action of multiple actin-crosslinking proteins with overlapping but non-identical biochemical properties. Thus the combination of structural proteins with similar function can provide the cell with unique properties that are required for biologically optimal responses.

Non-NASA Center↗