Metabolic Control Technology: Through the Windows of Space Exploration

As human presence in space will likely extend throughout the solar system, upmass and power constraints will become of paramount importance in considering logistics of transporting experimental animals and humans into space. Life support costs will be a significant part of the mission payload. One solution may be to take advantage of the emerging science of metabolic control, which allows the metabolism of animals to be reduced to a minimal level for a period of time, and allows for subsequent restoration to normal levels. Integration of a hibernation system within deep space mission architecture will solve many problems associated with long-duration space missions, such as payload cost reduction, space flight duration logistics, and demonstrate the potential application of this technology for human astronauts

Environmental Enrichment in the ISS Rodent Habitat Hardware System

Responses of animals exposed to microgravity during in-space experiments were reviewed from NASAs and ESA available video recording archives. These documented observation of animal behavior, as well as the range and level of activities during spaceflight, clearly demonstrate that weightlessness conditions and the extreme novelty of the surroundings exert damaging psychological stresses on the inhabitants. In response to a recognized need for in-flight animals to improve their wellbeing we propose to reduce such stresses by shaping and interrelating structures and surroundings to satisfying vital physiological needs of inhabitants. Rodent Habitat Hardware System based housing facility incorporating a tubing network system, to maintain and monitor rodent health environment with advanced accessories has been proposed. The new tubing configuration was found suitable for further incorporation of innovative monitoring technology and accessories in the animal holding habitat unit which allow to monitor in real-time the most valuable health related biological parameter under weightlessness environment of spaceflight

Adaptation of Organisms by Resonance of RNA Transcription with the Cellular Redox Cycle

Sequence variation in organisms differs across the genome and the majority of mutations are caused by oxidation, yet its origin is not fully understood. It has also been shown that the reduction-oxidation reaction cycle is the fundamental biochemical cycle that coordinates the timing of all biochemical processes in the cell, including energy production, DNA replication, and RNA transcription. We show that the temporal resonance of transcriptome biosynthesis with the oscillating binary state of the reduction-oxidation reaction cycle serves as a basis for non-random sequence variation at specific genome-wide coordinates that change faster than by accumulation of chance mutations. This work demonstrates evidence for a universal, persistent and iterative feedback mechanism between the environment and heredity, whereby acquired variation between cell divisions can outweigh inherited variation

Personalized Risk Assesment for Adverse Drug Reactions and Treatment Failures

As NASA and other space agencies prepare for future long-term space missions beyond the LEO, the cumulative impact of risk factors encountered in space increases substantially rising concerns about astronauts health. Application of on-board medications to mitigate clinical symptoms associated with certain medical conditions and illnesses is the first line of response to ensure sustainable health and performance of crew. Unfortunately, very limited research has been conducted to determine efficacy of the earth-based pharmaceuticals in a microgravity environment. In some instances, orally administered medications taken during flight were reported to be less effective than expected. Evaluation of series of experiments involving astronauts from shuttle flights shows notable individual variability to several pharmaceuticals during flight. These data provide reasonable assumption of perturbation in CYP450 enzymes during spaceflight, which contribute to the hepatic metabolism of the majority of drugs and therefore may have significant effects on therapeutic efficacy and increase treatment-related toxicity. The genes encoding the CYP450 enzymes are highly variable in humans. Inheritable variations of CYP450 hepatic metabolizer enzymes and transport proteins play a crucial role in the inter-individual variability of drug efficiency and risks of adverse drug reactions. Additionally, there are some reports that document changes in the levels of production of drug-metabolizing enzymes in microgravity. Therefore, in order to provide a safe and effective pharmaceutical treatment in space, medications selection should be based not only on the specific efficacy of medications but also on the individual drug sensitivity and flight-induced changes in metabolism of astronauts chosen for a particular mission. To our knowledge, there was no pre-flight drug sensitivity testing on a genetic level for any of the previous manned NASA space missions. Therefore, technologies capable of predicting and managing medication efficacy, side effects, and toxicity of drugs based on individual genetic variability of crew members are increasingly needed. In this report, we present results of testing the market available Personalized Prescribing System (PPS), a comprehensive, non-invasive solution for safer, targeted medication management for every crew member. Statistical accuracy and simplicity of non-invasive sample analysis demonstrate the feasibility of drug sensitivity assessment and record-keeping tool for flight surgeons and astronauts in applying the recommended medications for situations arising in flight. The information on individual drug sensitivity will translate into personalized risk assessment for adverse drug reactions and treatment failures for each drug from the medication kit as well as predefined outcome. This will address the HHCs raised Concern of Clinically Relevant Unpredicted Effects of Medication as recently updated

Advantage of Animal Models with Metabolic Flexibility for Space Research Beyond Low Earth Orbit

As the worlds space agencies and commercial entities continue to expand beyond Low Earth Orbit (LEO), novel approaches to carry out biomedical experiments with animals are required to address the challenge of adaptation to space flight and new planetary environments. The extended time and distance of space travel along with reduced involvement of Earth-based mission support increases the cumulative impact of the risks encountered in space. To respond to these challenges, it becomes increasingly important to develop the capability to manage an organisms self-regulatory control system, which would enable survival in extraterrestrial environments. To significantly reduce the risk to animals on future long duration space missions, we propose the use of metabolically flexible animal models as pathfinders, which are capable of tolerating the environmental extremes exhibited in spaceflight, including altered gravity, exposure to space radiation, chemically reactive planetary environments and temperature extremes.In this report we survey several of the pivotal metabolic flexibility studies and discuss the importance of utilizing animal models with metabolic flexibility with particular attention given to the ability to suppress the organism's metabolism in spaceflight experiments beyond LEO. The presented analysis demonstrates the adjuvant benefits of these factors to minimize damage caused by exposure to spaceflight and extreme planetary environments. Examples of microorganisms and animal models with dormancy capabilities suitable for space research are considered in the context of their survivability under hostile or deadly environments outside of Earth. Potential steps toward implementation of metabolic control technology in spaceflight architecture and its benefits for animal experiments and manned space exploration missions are discussed

Environmental Enrichment in the ISS Rodent Habitat Hardware System

Responses of animals exposed to microgravity during in-space experiments were observed via available video recording stored in the NASA Ames Life Sciences Data Archive. These documented observations of animal behavior, as well as the range and level of activities during spaceflight, demonstrate that weightlessness conditions and the extreme novelty of the surroundings may exert damaging psychological stresses on the inhabitants. In response to a recognized need for in-flight animals to improve their wellbeing we propose to reduce such stresses by shaping and interrelating structures and surroundings to satisfying vital physiological needs of inhabitants. A Rodent Habitat Hardware System (RHHS) based housing facility incorporating a tubing network system, to maintain and monitor rodent health environment with advanced accessories has been proposed. Placing mice in a tubing-configured environment creates more natural space-restricted nesting environment for rodents, thereby facilitating a more comfortable transition to living in microgravity. A sectional tubing structure of the RHHS environment will be more beneficial under microgravity conditions than the provision of a larger space area that is currently utilized. The new tubing configuration was found suitable for further incorporation of innovative monitoring technology and accessories in the animal holding habitat unit which allow to monitor in real-time monitoring of valuable health related biological parameters under weightlessness environment of spaceflight

A protein model exhibiting three folding transitions

We explain the physical basis of a model for small globular proteins with water interactions. The water is supposed to access the protein interior in an "all-or-none" manner during the unfolding of the protein chain. As a consequence of this mechanism (somewhat speculative), the model exhibits fundamental aspects of protein thermodynamics, as cold, and warm unfolding of the polypeptide chain, and hence decreasing the temperature below the cold unfolding the protein folds again, accordingly the heat capacity has three characteristic peaks. The cold and warm unfolding has a sharpness close to a two-state system, while the cold folding is a transition where the intermediate states in the folding is energetical close to the folded/unfolded states, yielding a less sharp transition. The entropy of the protein chain causes both the cold folding and the warm unfolding.Comment: 13 pages LaTeX, 4 Postscript figure

Perancangan Online Virtual Gallery Dengan Memanfaatkan Teknologi HTML5

Visual Communication Design is a Department in Information Technology Faculty. Annually, this study program conducts several exhibition events. However, there is a big problem in it that is no storage to store files of student works that usually are often damaged or vanished. By this research the researcher created an Online Virtual Gallery with the newest technology called HTML5 that use to store the files, such as: drawings, paintings, sketches, videos, games, etc. For the result, this research produced a virtual container that able to accommodate the works of DKV student, so that by this application expectantly could be help the student to store their exhibition files

Highly Anomalous Energetics of Protein Cold Denaturation Linked to Folding-Unfolding Kinetics

Despite several careful experimental analyses, it is not yet clear whether protein cold-denaturation is just a “mirror image” of heat denaturation or whether it shows unique structural and energetic features. Here we report that, for a well-characterized small protein, heat denaturation and cold denaturation show dramatically different experimental energetic patterns. Specifically, while heat denaturation is endothermic, the cold transition (studied in the folding direction) occurs with negligible heat effect, in a manner seemingly akin to a gradual, second-order-like transition. We show that this highly anomalous energetics is actually an apparent effect associated to a large folding/unfolding free energy barrier and that it ultimately reflects kinetic stability, a naturally-selected trait in many protein systems. Kinetics thus emerges as an important factor linked to differential features of cold denaturation. We speculate that kinetic stabilization against cold denaturation may play a role in cold adaptation of psychrophilic organisms. Furthermore, we suggest that folding-unfolding kinetics should be taken into account when analyzing in vitro cold-denaturation experiments, in particular those carried out in the absence of destabilizing conditions

Local Cooperativity in an Amyloidogenic State of Human Lysozyme Observed at Atomic Resolution

The partial unfolding of human lysozyme underlies its conversion from the soluble state into amyloid fibrils observed in a fatal hereditary form of systemic amyloidosis. To understand the molecular origins of the disease, it is critical to characterize the structural and physicochemical properties of the amyloidogenic states of the protein. Here we provide a high-resolution view of the unfolding process at low pH for three different lysozyme variants, the wild-type protein and the mutants I56T and I59T, which show variable stabilities and propensities to aggregate in vitro. Using a range of biophysical techniques that includes differential scanning calorimetry and nuclear magnetic resonance spectroscopy, we demonstrate that thermal unfolding under amyloidogenic solution conditions involves a cooperative loss of native tertiary structure, followed by progressive unfolding of a compact, molten globule-like denatured state ensemble as the temperature is increased. The width of the temperature window over which the denatured ensemble progressively unfolds correlates with the relative amyloidogenicity and stability of these variants, and the region of lysozyme that unfolds first maps to that which forms the core of the amyloid fibrils formed under similar conditions. Together, these results present a coherent picture at atomic resolution of the initial events underlying amyloid formation by a globular protein