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At least 595 records · Page 33

Nanopores and nucleic acids: prospects for ultrarapid sequencing

DNA and RNA molecules can be detected as they are driven through a nanopore by an applied electric field at rates ranging from several hundred microseconds to a few milliseconds per molecule. The nanopore can rapidly discriminate between pyrimidine and purine segments along a single-stranded nucleic acid molecule. Nanopore detection and characterization of single molecules represents a new method for directly reading information encoded in linear polymers. If single-nucleotide resolution can be achieved, it is possible that nucleic acid sequences can be determined at rates exceeding a thousand bases per second.

Review↗

Left-handed Z-DNA: structure and function

Z-DNA is a high energy conformer of B-DNA that forms in vivo during transcription as a result of torsional strain generated by a moving polymerase. An understanding of the biological role of Z-DNA has advanced with the discovery that the RNA editing enzyme double-stranded RNA adenosine deaminase type I (ADAR1) has motifs specific for the Z-DNA conformation. Editing by ADAR1 requires a double-stranded RNA substrate. In the cases known, the substrate is formed by folding an intron back onto the exon that is targeted for modification. The use of introns to direct processing of exons requires that editing occurs before splicing. Recognition of Z-DNA by ADAR1 may allow editing of nascent transcripts to be initiated immediately after transcription, ensuring that editing and splicing are performed in the correct sequence. Structural characterization of the Z-DNA binding domain indicates that it belongs to the winged helix-turn-helix class of proteins and is similar to the globular domain of histone-H5.

Review↗

Growing crops for space explorers on the moon, Mars, or in space

An option in the long-duration exploration of space, whether on the Moon or Mars or in a spacecraft on its way to Mars or the asteroids, is to utilize a bioregenerative life-support system in addition to the physicochemical systems that will always be necessary. Green plants can use the energy of light to remove carbon dioxide from the atmosphere and add oxygen to it while at the same time synthesizing food for the space travelers. The water that crop plants transpire can be condensed in pure form, contributing to the water purification system. An added bonus is that green plants provide a familiar environment for humans far from their home planet. The down side is that such a bioregenerative life-support system--called a controlled environment life-support system (CELSS) in this paper--must be highly complex and relatively massive to maintain a proper composition of the atmosphere while also providing food. Thus, launch costs will be high. Except for resupply and removal of nonrecycleable substances, such a system is nearly closed with respect to matter but open with respect to energy. Although a CELSS facility is small compared to the Earth's biosphere, it must be large enough to feed humans and provide a suitable atmosphere for them. A functioning CELSS can only be created with the help of today's advanced technology, especially computerized controls. Needed are energy for light, possibly from a nuclear power plant, and equipment to provide a suitable environment for plant growth, including a way to supply plants with the necessary mineral nutrients. All this constitutes the biomass production unit. There must also be food preparation facilities and a means to recycle or dispose of waste materials and there must be control equipment to keep the facility running. Humans are part of the system as well as plants and possibly animals. Human brain power will often be needed to keep the system functional in spite of the best computer-driven controls. The particulars of a CELSS facility depend strongly on where it is to be located. The presence of gravity on the Moon and Mars simplifies the design for a facility on those bodies, but a spacecraft in microgravity is a much more challenging environment. One problem is that plants, which are very sensitive to gravity, might not grow and produce food in the virtual absence of gravity. However, the experience with growing super-dwarf wheat in the Russian space station Mir, while not entirely successful because of the sterile wheat heads, was highly encouraging. The plants grew well for 123 days, producing more biomass than had been produced in space before. This was due to the high photon flux available to the plants and the careful control of substrate moisture. The sterile heads were probably due to the failure to remove the gaseous plant hormone, ethylene, from the Mir atmosphere. Since ethylene can easily be removed, it should be possible to grow wheat and other crops in microgravity with the production of viable seeds. On the ground Biosphere-2 taught us several lessons about the design and construction of a CELSS facility, but Bios-3 came much closer to achieving the goals of such a facility. Although stability was never completely reached, Bios-3 was much more stable than Biosphere-2 apparently because every effort was made to keep the system simple and to use the best technology available to maintain control. Wastes were not recycled in Bios-3 except for urine, and inedible plant materials were incinerated to restore CO2 to the atmosphere. Since much meat (about 20% of calories) was imported, closure in the Bios-3 experiments was well below 100%. But then, a practical CELSS on the Moon might also depend on regular resupply from Earth. Several important lessons have been learned from the CELSS research described in this review.

Review↗

Nutrition and muscle loss in humans during spaceflight

The protein loss in humans during spaceflight is partly due to a normal adaptive response to a decreased work load on the muscles involved in weight bearing. The process is mediated by changes in prostaglandin release, secondary to the decrease in tension on the affected muscles. On missions, where there is a high level of physical demands on the astronauts, there tends to be an energy deficit, which adds to the muscle protein loss and depletes the body fat reserves. While the adaptive response is a normal part of homeostasis, the additional protein loss from an energy deficit can, in the long run, have a negative effect on health and capability of humans to live and work in space and afterward return to Earth.

NASA Program Biomedical Research and Countermeasur↗

Biomarkers of exposure, sensitivity and disease

PURPOSE: This review is to evaluate the use of biomarkers as an indication of past exposure to radiation or other environmental insults, individual sensitivity and risk for the development of late occurring disease. OVERVIEW: Biomarkers can be subdivided depending on their applications. Markers of exposure and dose can be used to reconstruct and predict past accidental or occupational exposures when limited or no physical measurements were available. Markers of risk or susceptibility can help identify sensitivity individuals that are at increased risk for development of spontaneous disease and may help predict the increased risk in sensitive individuals associated with environmental or therapeutic radiation exposures. Markers of disease represent the initial cellular or molecular changes that occur during disease development. Each of these types of biomarkers serves a unique purpose. OUTLINE: This paper concentrates on biomarkers of dose and exposure and provides a brief review of biomarkers of sensitivity and disease. The review of biomarkers of dose and exposure will demonstrate the usefulness of biomarkers in evaluation of physical factors associated with radiation exposure, such as LET, doserate and dose distribution. It will also evaluate the use of biomarkers to establish relationships that exist between exposure parameters such as energy deposition, environmental concentration of radioactive materials, alpha traversals and dose. In addition, the importance of biological factors on the magnitude of the biomarker response will be reviewed. Some of the factors evaluated will be the influence of species, tissue, cell types and genetic background. The review will demonstrate that markers of sensitivity and disease often have little usefulness in dose-reconstruction and, by the same token, many markers of dose or exposure may not be applicable for prediction of sensitivity or risk.

Non-NASA Center↗

If walls could talk

The plant cell wall is very complex, both in structure and function. The wall components and the mechanical properties of the wall have been implicated in conveying information that is important for morphogenesis. Proteoglycans, fragments of polysaccharides and the structural integrity of the wall may relay signals that influence cellular differentiation and growth control. Furthering our knowledge of cell wall structure and function is likely to have a profound impact on our understanding of how plant cells communicate with the extracellular environment.

Review↗

Protein machines and self assembly in muscle organization

The remarkable order of striated muscle is the result of a complex series of protein interactions at different levels of organization. Within muscle, the thick filament and its major protein myosin are classical examples of functioning protein machines. Our understanding of the structure and assembly of thick filaments and their organization into the regular arrays of the A-band has recently been enhanced by the application of biochemical, genetic, and structural approaches. Detailed studies of the thick filament backbone have shown that the myosins are organized into a tubular structure. Additional protein machines and specific myosin rod sequences have been identified that play significant roles in thick filament structure, assembly, and organization. These include intrinsic filament components, cross-linking molecules of the M-band and constituents of the membrane-cytoskeleton system. Muscle organization is directed by the multistep actions of protein machines that take advantage of well-established self-assembly relationships. Copyright 1999 John Wiley & Sons, Inc.

NASA Discipline Musculoskeletal↗

Applications of amorphous track models in radiation biology

The average or amorphous track model uses the response of a system to gamma-rays and the radial distribution of dose about an ion's path to describe survival and other cellular endpoints from proton, heavy ion, and neutron irradiation. This model has been used for over 30 years to successfully fit many radiobiology data sets. We review several extensions of this approach that address objections to the original model, and consider applications of interest in radiobiology and space radiation risk assessment. In the light of present views of important cellular targets, the role of target size as manifested through the relative contributions from ion-kill (intra-track) and gamma-kill (inter-track) remains a critical question in understanding the success of the amorphous track model. Several variations of the amorphous model are discussed, including ones that consider the radial distribution of event-sizes rather than average electron dose, damage clusters rather than multiple targets, and a role for repair or damage processing.

NASA Discipline Radiation Health↗

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↗

Gravity and space flight: effects on nutritional status

The final decade of the millennium has seen an enormous amount of on-orbit life sciences research, including both short- and long-duration flight research. Life sciences dedicated Space Shuttle flights have made intensive research opportunities available to study on the acute adaptation to weightlessness. The NASA/Mir Science Program combined resources of the USA and Russia to provide the first long-duration flight opportunities for the United States since the Skylab program of the early 1970s. Many of the results of these studies are still being evaluated, and in some cases data are still being collected to assess long-term readaptation to gravity after several months in weightlessness. The surge in life sciences research during this decade serves as a preamble to the opportunities to be provided by the latest addition to the Earth-orbiting structures--the International Space Station.

short duration↗

Artificial gravity considerations for a mars exploration mission

Artificial gravity (AG), as a means of preventing physiological deconditioning of astronauts during long-duration space flights, presents certain special challenges to the otolith organs and the adaptive capabilities of the CNS. The key issues regarding the choice of AG acceleration, radius, and rotation rate are reviewed from the viewpoints of physiological requirements and human factors disturbances. Head movements and resultant Coriolis forces on the rotating platform may limit the usefulness of economical short centrifuges for other than brief periods of intermittent stimulation.

Review↗

Mechanosensitive channels in bacteria as membrane tension reporters

The purpose of this short review is to discuss recent data on the molecular structure and mechanism of gating of MscL, a mechanosensitive channel of large conductance from Escherichia coli. MscL is the first isolated molecule shown to convert mechanical stress of the membrane into a simple response, the opening of a large aqueous pore. The functional complex appears to be a stable homo-pentamer of 15-kDa subunits, the gating transitions in which are driven by stretch forces conveyed through the lipid bilayer. We have measured the open probability of MscL and the kinetics of transitions as a function of membrane tension. The parameters extracted from the single-channel current recordings and dose-response curves such as the energy difference between the closed, open, and intermediate conducting states, and the transition-related changes in protein dimensions suggest a large conformational rearrangement of the channel complex. The estimations show that in native conditions MscL openings could be driven primarily by forces of osmotic nature. The thermodynamic and spatial parameters reasonably correlate with the available data on the structure of a single MscL subunit and multimeric organization of the complex. Combined with the functional analysis of mutations, these data give grounds to hypotheses on the nature of the channel mechanosensitivity.

Review↗

Peroxide-modified titanium dioxide: a chemical analog of putative Martian soil oxidants

Hydrogen peroxide chemisorbed on titanium dioxide (peroxide-modified titanium dioxide) is investigated as a chemical analog to the putative soil oxidants responsible for the chemical reactivity seen in the Viking biology experiments. When peroxide-modified titanium dioxide (anatase) was exposed to a solution similar to the Viking labeled release (LR) experiment organic medium, CO2 gas was released into the sample cell headspace. Storage of these samples at 10 degrees C for 48 hr prior to exposure to organics resulted in a positive response while storage for 7 days did not. In the Viking LR experiment, storage of the Martian surface samples for 2 sols (approximately 49 hr) resulted in a positive response while storage for 141 sols essentially eliminated the initial rapid release of CO2. Heating the peroxide-modified titanium dioxide to 50 degrees C prior to exposure to organics resulted in a negative response. This is similar to, but not identical to, the Viking samples where heating to approximately 46 degrees C diminished the response by 54-80% and heating to 51.5 apparently eliminated the response. When exposed to water vapor, the peroxide-modified titanium dioxide samples release O2 in a manner similar to the release seen in the Viking gas exchange experiment (GEx). Reactivity is retained upon heating at 50 degrees C for three hours, distinguishing this active agent from the one responsible for the release of CO2 from aqueous organics. The release of CO2 by the peroxide-modified titanium dioxide is attributed to the decomposition of organics by outer-sphere peroxide complexes associated with surface hydroxyl groups, while the release of O2 upon humidification is attributed to more stable inner-sphere peroxide complexes associated with Ti4+ cations. Heating the peroxide-modified titanium dioxide to 145 degrees C inhibited the release of O2, while in the Viking experiments heating to this temperature diminished but did not eliminated the response. Although the thermal stability of the titanium-peroxide complexes in this work is lower than the stability seen in the Viking experiments, it is expected that similar types of complexes will form in titanium containing minerals other than anatase and the stability of these complexes will vary with surface hydroxylation and mineralogy.

Review↗