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DOE OSTI2019

Structure of interferon-stimulated gene product 15 (ISG15) from the bat species Myotis davidii and the impact of interdomain ISG15 interactions on viral protein engagement

Bats have long been observed to be the hosts and the origin of numerous human diseases. Bats, like all mammals, rely on a number of innate immune mechanisms to combat invading pathogens, including the interferon type I, II and III responses. Ubiquitin-like interferon-stimulated gene product 15 (ISG15) is a key modulator of these interferon responses. Within these pathways, ISG15 can serve to stabilize host proteins modulating innate immune responses and act as a cytokine. Post-translational modifications of viral proteins introduced by ISG15 have also been observed to directly affect the function of numerous viral proteins. Unlike ubiquitin, which is virtually identical across all animals, comparison of ISG15s across species reveals that they are relatively divergent, with sequence identity dropping to as low as ~58% among mammals. In addition to serving as an obstacle to the zoonotic transmission of influenza, these ISG15 species–species differences have also long been shown to have an impact on the function of viral deISGylases. Recently, the structure of the first nonhuman ISG15, originating from mouse, suggested that the structures of human ISG15 may not be reflective of other species. Here, the structure of ISG15 from the bat species Myotis davidii solved to 1.37 Å resolution is reported. Comparison of this ISG15 structure with those from human and mouse not only underscores the structural impact of ISG15 species–species differences, but also highlights a conserved hydrophobic motif formed between the two domains of ISG15. Using the papain-like deISGylase from Severe acute respiratory syndrome coronavirus as a probe, the biochemical importance of this motif in ISG15–protein engagements was illuminated.

Langley, Caroline↗

DOE OSTI2016

Characterizing large river sounds: Providing context for understanding the environmental effects of noise produced by hydrokinetic turbines

Underwaternoise associated with the installation and operation of hydrokinetic turbines in rivers and tidal zones presents a potential environmental concern for fish and marine mammals. Comparing the spectral quality of sounds emitted by hydrokinetic turbines to natural and other anthropogenic sound sources is an initial step at understanding potential environmental impacts. Underwater recordings were obtained from passing vessels and natural underwater sound sources in static and flowing waters. Static water measurements were taken in a lake with minimal background noise. Flowing water measurements were taken at a previously proposed deployment site for hydrokinetic turbines on the Mississippi River, where sounds created by flowing water are part of all measurements, both natural ambient and anthropogenic sources. Vessel sizes ranged from a small fishing boat with 60 hp outboard motor to an 18-unit barge train being pushed upstream by tugboat. As expected, large vessels with large engines created the highest sound levels, which were, on average, 40 dB greater than the sound created by an operating hydrokinetic turbine. As a result, a comparison of sound levels from the same sources at different distances using both spherical and cylindrical sound attenuation functions suggests that spherical model results more closely approximate observed sound attenuation.

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2024

An interpretable model of pre-mRNA splicing for animal and plant genes

Pre-mRNA splicing is a fundamental step in gene expression, conserved across eukaryotes, in which the spliceosome recognizes motifs at the 3' and 5' splice sites (SSs), excises introns, and ligates exons. SS recognition and pairing is often influenced by protein splicing factors (SFs) that bind to splicing regulatory elements (SREs). Here, we describe SMsplice, a fully interpretable model of pre-mRNA splicing that combines models of core SS motifs, SREs, and exonic and intronic length preferences. We learn models that predict SS locations with 83 to 86% accuracy in fish, insects, and plants and about 70% in mammals. Learned SRE motifs include both known SF binding motifs and unfamiliar motifs, and both motif classes are supported by genetic analyses. Our comparisons across species highlight similarities between non-mammals, increased reliance on intronic SREs in plant splicing, and a greater reliance on SREs in mammalian splicing.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2022

Activation mechanism of the mouse cold-sensing TRPM8 channel by cooling agonist and PIP 2

The transient receptor potential melastatin 8 (TRPM8) channel is the primary molecular transducer responsible for the cool sensation elicited by menthol and cold in mammals. TRPM8 activation is controlled by cooling compounds together with the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP 2 ). Our knowledge of cold sensation and the therapeutic potential of TRPM8 for neuroinflammatory diseases and pain will be enhanced by understanding the structural basis of cooling agonist- and PIP 2 -dependent TRPM8 activation. We present cryo–electron microscopy structures of mouse TRPM8 in closed, intermediate, and open states along the ligand- and PIP 2 -dependent gating pathway. Our results uncover two discrete agonist sites, state-dependent rearrangements in the gate positions, and a disordered-to-ordered transition of the gate-forming S6—elucidating the molecular basis of chemically induced cool sensation in mammals.

Science & Technology - Other Topics↗

DOE OSTI2019

Isolation and Characterization of Akhmeta Virus from Wild-Caught Rodents ( Apodemus spp.) in Georgia

In 2013, a novel orthopoxvirus was detected in skin lesions of two cattle herders from the Kakheti region of Georgia (country); this virus was named Akhmeta virus. Subsequent investigation of these cases revealed that small mammals in the area had serological evidence of orthopoxvirus infections, suggesting their involvement in the maintenance of these viruses in nature. In October 2015, we began a longitudinal study assessing the natural history of orthopoxviruses in Georgia. As part of this effort, we trapped small mammals near Akhmeta (n = 176) and Gudauri (n = 110). Here, we describe the isolation and molecular characterization of Akhmeta virus from lesion material and pooled heart and lung samples collected from five wood mice (Apodemus uralensis and Apodemus flavicollis) in these two locations. The genomes of Akhmeta virus obtained from rodents group into 2 clades: one clade represented by viruses isolated from A. uralensis samples, and one clade represented by viruses isolated from A. flavicollis samples. These genomes also display several presumptive recombination events for which gene truncation and identity have been examined.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2024

From wolves to humans: oral microbiome resistance to transfer across mammalian hosts

The mammalian mouth is colonized by complex microbial communities, adapted to specific niches, and in homeostasis with the host. Individual microbes interact metabolically and rely primarily on nutrients provided by the host, with which they have potentially co-evolved along the mammalian lineages. The oral environment is similar across mammals, but the diversity, specificity, and evolution of community structure in related or interacting mammals are little understood. Here, we compared the oral microbiomes of dogs with those of wild wolves and humans. In dogs, we found an increased microbial diversity relative to wolves, possibly related to the transition to omnivorous nutrition following domestication. This includes a larger diversity of Patescibacteria than previously reported in any other oral microbiota. The oral microbes are most distinct at bacterial species or strain levels, with few if any shared between humans and canids, while the close evolutionary relationship between wolves and dogs is reflected by numerous shared taxa. More taxa are shared at higher taxonomic levels including with humans, supporting their more ancestral common mammalian colonization followed by diversification. Phylogenies of selected oral bacterial lineages do not support stable human-dog microbial transfers but suggest diversification along mammalian lineages (apes and canids). Therefore, despite millennia of cohabitation and close interaction, the host and its native community controls and limits the assimilation of new microbes, even if closely related. Higher resolution metagenomic and microbial physiological studies, covering a larger mammalian diversity, should help understand how oral communities assemble, adapt, and interact with their hosts.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2021

The phylogenetic roots of addiction: compulsive drug seeking, natural and drug-sensitive reward, and the acquisition of learned habits

Our rational faculties permit us humans to maximize the utility of our actions. We perform a fundamental type of cost-benefit analysis in which we frame a problem, assign values to the different paths, and then choose from among a set of available options, the course that promises the most favorable outcome. So why then does addiction appear to be so impervious to the associated costs, so unaffected by undesired consequences, and ultimately so resistant to cognitive oversight? The answer may likely be found in the fact that the drivers for compulsive drug seeking and drug taking are located in affective brain circuits, circuits that are structured and patterned by learning with repeated activation. These deep processes exhibit significant resistance to control by our cognitive faculties. The general consensus is that addiction arises from mechanisms that overvalue the magnitude of reward, discount the associated risks, and thereby bias individuals towards compulsive pursuit of addictive drugs. Behavioral disruption and dependence appear to arise at the intersection of a number of connected but separate phenomena: expectations for the occurrence of specific events, behaviors that seek encounters with them, the ability to notice and learn nonrandom, co-occurring conditions, the prediction and valuation of consequences, the forming of enduring memories, and the drivers of focused behavior through compulsion, habits, and acquired routines. It is important to recognize that each one of these individual faculties are present and well developed across the entire phylogenetic tree of bilateral metazoans. The goal of this special volume is dedicated to exploring the degree to which inherent elements can account for addiction and addiction-associated phenomena. In much of the literature on addiction, the underlying processes are often viewed as distinctly mammalian, arising, in part, from the strong cognitive capacities of this taxon. Some phenomena may even be regarded to exist only in primates, or even solely in humans. This supposition arises from the fact that studies are conducted almost exclusively in mammals and primates, while evolutionary antecedents of the behavior are rarely considered. A more comprehensive perspective that examines drug reward and reinforcement in a wider range of organisms demonstrates that many of the component traits are actually well developed across the greater metazoan lineage, and they may well predate the emergence of a mammalian clade by a wide margin. The collection of papers assembled here supports the notion that the capacity to associate cues and quences has not arisen in mammals de novo. Rather, the neural mechanisms for detecting contingencies and for predicting future outcomes are very deeply rooted across broad phylogenetic divisions. Our understanding of an ability to associate paired events has been enriched by work in invertebrate preparations in both classical and operant conditioning scenarios [Cook and Carew, 1986, 1989a, 1989b]. The ability to learn allows us to connect cues and behavioral actions to their associated consequences. Pavlovian conditioning enriches surrounding cues with predictive value. Outcomes with positive valence generate appetitive responses and approach to the associated cues, while those perceived as aversive bring cue avoidance and withdrawal. Humans are not the only life forms capable of such short- and long-term modulations of behavior

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2014

Avian Diagnostic and Therapeutic Antibodies

A number of infectious agents have the potential of causing significant clinical symptomology and even death, but despite this, the number of incidence remain below the level that supports producing a vaccine. Therapeutic antibodies provide a viable treatment option for many of these diseases. We proposed that antibodies derived from West Nile Virus (WNV) immunized geese would be able to treat WNV infection in mammals and potential humans. We demonstrated that WNV specific goose antibodies are indeed successful in treating WNV infection both prophylactically and therapeutically in a golden hamster model. We demonstrated that the goose derived antibodies are non-reactogenic, i.e. do not cause an inflammatory response with multiple exposures in mammals. We also developed both a specific pathogen free facility to house the geese during the antibody production phase and a patent-pending purification process to purify the antibodies to greater than 99% purity. Therefore, the success of these study will allow a cost effective rapidly producible therapeutic toward clinical testing with the necessary infrastructure and processes developed and in place.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2017

Industrializing Offshore Wind Power with Serial Assembly and Lower-cost Deployment - Final Report

A team of engineers and contractors has developed a method to move offshore wind installation toward lower cost, faster deployment, and lower environmental impact. A combination of methods, some incremental and some breaks from past practice, interact to yield multiple improvements. Three designs were evaluated based on detailed engineering: 1) a 5 MW turbine on a jacket with pin piles (base case), 2) a 10 MW turbine on a conventional jacket with pin piles, assembled at sea, and 3) a 10 MW turbine on tripod jacket with suction buckets (caissons) and with complete turbine assembly on-shore. The larger turbine, assembly ashore, and the use of suction buckets together substantially reduce capital cost of offshore wind projects. Notable capital cost reductions are: changing from 5 MW to 10 MW turbine, a 31% capital cost reduction, and assembly on land then single-piece install at sea an additional 9% capital cost reduction. An estimated Design 4) estimates further cost reduction when equipment and processes of Design 3) are optimized, rather than adapted to existing equipment and process. Cost of energy for each of the four Designs are also calculated, yielding approximately the same percentage reductions. The methods of Design 3) analyzed here include accepted structures such as suction buckets used in new ways, innovations conceived but previously without engineering and economic validation, combined with new methods not previously proposed. Analysis of Designs 2) and 3) are based on extensive engineering calculations and detailed cost estimates. All design methods can be done with existing equipment, including lift equipment, ports and ships (except that design 4 assumes a more optimized ship). The design team consists of experienced offshore structure designers, heavy lift engineers, wind turbine designers, vessel operators, and marine construction contractors. Comparing the methods based on criteria of cost and deployment speed, the study selected the third design. That design is, in brief: a conventional turbine and tubular tower is mounted on a tripod jacket, in turn atop three suction buckets. Blades are mounted on the tower, not on the hub. The entire structure is built in port, from the bottom up, then assembled structures are queued in the port for deployment. During weather windows, the fully-assembled structures are lifted off the quay, lashed to the vessel, and transported to the deployment site. The vessel analyzed is a shear leg crane vessel with dynamic positioning like the existing Gulliver, or it could be a US-built crane barge. On site, the entire structure is lowered to the bottom by the crane vessel, then pumping of the suction buckets is managed by smaller service vessels. Blades are lifted into place by small winches operated by workers in the nacelle without lift vessel support. Advantages of the selected design include: cost and time at sea of the expensive lift vessel are significantly reduced; no jack up vessel is required; the weather window required for each installation is shorter; turbine structure construction is continuous with a queue feeding the weather-dependent installation process; pre-installation geotechnical work is faster and less expensive; there are no sound impacts on marine mammals, thus minimal spotting and no work stoppage Industrializing Offshore Wind Power 6 of 96 9 for mammal passage; the entire structure can be removed for decommissioning or major repairs; the method has been validated for current turbines up to 10 MW, and a calculation using simple scaling shows it usable up to 20 MW turbines.

17 WIND ENERGY↗

DOE OSTI2022

Rapidly Deployable Acoustic Monitoring and Localization System Based on a Low-Cost Wave Buoy Platform

The primary objective of this project is to develop a cost-effective, fit-for-purpose environmental monitoring system, “NoiseSpotter®,” that characterizes, classifies, and provides accurate location information for anthropogenic and natural sounds in near real-time. NoiseSpotter was developed to support the evaluation of potential acoustic effects of marine energy (ME) projects. By utilizing a compact array of three acoustic particle motion sensors, NoiseSpotter triangulates individual bearings to provide sound source localization to within 5% accuracy, allowing the ability to discern ME device sounds relative to other confounding sounds in the environment, while providing location estimates to nearby marine mammals for environmental mitigation purposes. The ME industry needs proven solutions to meet environmental impact assessment needs. The NoiseSpotter® includes off-the-shelf, modular components that are easy to assemble and disassemble. Its acoustic particle motion sensors are commercially available and the data logger and real-time telemetry system is designed to be plug-and-play. The entire system is relatively compact and can be deployed from small vessels. NoiseSpotter’s near real-time capability enables operational monitoring of ME sounds, particularly during early stages of technology adoption to facilitate mitigation of potential noise effects. Widespread adoption of the technology for acoustic monitoring of ME devices requires that it be cost effective; hence the anticipated commercial cost of system hardware is $35,000. This project contributes to reducing barriers to ME testing through support of scientific research focused on reducing or mitigating environmental risks and lowering costs and complexity of environmental monitoring. This project has developed an acoustic monitoring system, NoiseSpotter® (U.S. Patent No. 11,156,734 and U.S. Registered Trademark No. 6,442,313), to detect and characterize baseline noise and sounds from ME operations and support geolocation of detected sounds. The intended outcome of the project is to mitigate concerns about the potential for ME device noise to alter marine mammal or fish behavior. NoiseSpotter® enables cost-effective, near real-time acoustic monitoring of an operational ME device relative to ambient environmental noise and provides a technical basis for ME developers seeking to navigate the permitting process in an efficient manner.

16 TIDAL AND WAVE POWER↗

DOE OSTI2021

Arabidopsis thaliana EARLY RESPONSIVE TO DEHYDRATION 7 Localizes to Lipid Droplets via Its Senescence Domain

Lipid droplets (LDs) are neutral-lipid-containing organelles found in all kingdoms of life and are coated with proteins that carry out a vast array of functions. Compared to mammals and yeast, relatively few LD proteins have been identified in plants, particularly those associated with LDs in vegetative (non-seed) cell types. Thus, to better understand the cellular roles of LDs in plants, a more comprehensive inventory and characterization of LD proteins is required. Here, we performed a proteomics analysis of LDs isolated from drought-stressed Arabidopsis leaves and identified EARLY RESPONSIVE TO DEHYDRATION 7 (ERD7) as a putative LD protein. mCherry-tagged ERD7 localized to both LDs and the cytosol when ectopically expressed in plant cells, and the protein’s C-terminal senescence domain (SD) was both necessary and sufficient for LD targeting. Phylogenetic analysis revealed that ERD7 belongs to a six-member family in Arabidopsis that, along with homologs in other plant species, is separated into two distinct subfamilies. Notably, the SDs of proteins from each subfamily conferred targeting to either LDs or mitochondria. Further, the SD from the ERD7 homolog in humans, spartin, localized to LDs in plant cells, similar to its localization in mammals; although, in mammalian cells, spartin also conditionally localizes to other subcellular compartments, including mitochondria. Disruption of ERD7 gene expression in Arabidopsis revealed no obvious changes in LD numbers or morphology under normal growth conditions, although this does not preclude a role for ERD7 in stress-induced LD dynamics. Consistent with this possibility, a yeast two-hybrid screen using ERD7 as bait identified numerous proteins involved in stress responses, including some that have been identified in other LD proteomes. Collectively, these observations provide new insight to ERD7 and the SD-containing family of proteins in plants and suggest that ERD7 may be involved in functional aspects of plant stress response that also include localization to the LD surface.

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2021

Detection Technologies for Reactive Oxygen Species: Fluorescence and Electrochemical Methods and Their Applications

Reactive oxygen species (ROS) have been found in plants, mammals, and natural environmental processes. The presence of ROS in mammals has been linked to the development of severe diseases, such as diabetes, cancer, tumors, and several neurodegenerative conditions. The most common ROS involved in human health are superoxide (O 2 •-), hydrogen peroxide (H 2 O 2 ), and hydroxyl radicals (•OH). Organic and inorganic molecules have been integrated with various methods to detect and monitor ROS for understanding the effect of their presence and concentration on diseases caused by oxidative stress. Among several techniques, fluorescence and electrochemical methods have been recently developed and employed for the detection of ROS. This literature review intends to critically discuss the development of these techniques to date, as well as their application for in vitro and in vivo ROS detection regarding free-radical-related diseases. Moreover, important insights into and further steps for using fluorescence and electrochemical methods in the detection of ROS are presented.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2013

Design and implementation of a marine animal alert system to support Marine Renewable Energy

Power extracted from fast moving tidal currents has been identified as a potential commercial-scale source of renewable energy. Device developers and utilities are pursuing deployment of prototype tidal turbines to assess technology viability, site feasibility, and environmental interactions. Deployment of prototype turbines requires permits from a range of regulatory authorities. Ensuring the safety of marine animals, particularly those under protection of the Endangered Species Act of 1973 (ESA) and the Marine Mammal Protection Act of 1972 has emerged as a key regulatory challenge for initial MHK deployments. The greatest perceived risk to marine animals is from strike by the rotating blades of tidal turbines. Development of the marine mammal alert system (MAAS) was undertaken to support monitoring and mitigation requirements for tidal turbine deployments. The prototype system development focused on Southern Resident killer whales (SRKW), an endangered population of killer whales that frequents Puget Sound and is intermittently present in the part of the sound where deployment of prototype tidal turbines is being considered. Passive acoustics were selected as the primary means because of the vocal nature of these animals. The MAAS passive acoustic system consists of two-stage process involving the use of an energy detector and a spectrogram-based classifier to distinguish between SKRW’s calls and noise. A prototype consisting of two 2D symmetrical star arrays separated by 20 m center to center was built and evaluated in the waters of Sequim Bay using whale call playback.

killer whales↗

NASA NTRS1972

Application of various elastic thin shell theories to blood flow problems

Some existing theories, on elastic thin shells, are reviewed to ascertain their influence on the computation of phase velocities in fluid filled cylinders representing certain aspects of the behavior of arteries and veins in vivo. For physiologically meaningful parameters, including moderately large in plane prestrain that occurs in mammals, the results suggest that with one exception, the small differences in the formulations exercise little influence on the phase velocities. However, it is demonstrated that inclusion of the forces induced by the rotation of the hydrostatic pressure is essential or significantly erroneous torsional wave speeds result. Also the introduction of moderate implane prestrains that are present in living mammals is shown to lead to nonselfadjoint differential equations of motion, whose biorthogonal eigenvectors differ slightly from each other.

Source record↗

NASA NTRS1989

Gravity and animal embryos

Out of more than 4,500 rat hours in space there was only one experimental attempt (Cosmos 1129) at mating with an apparent absence of fertilization, implantation and subsequent development to term and partuition. Portions of this process were successfully flown, however, including the major portion of organogenesis in the rat (Cosmos 1524). These observations show that the cellular and molecular events underlying morphogenesis and differentiation in a small mammal can proceed normally in-utero under microgravity and other conditions encountered during short-duration flight. However, it is not known whether this situation will hold for larger mammals over several generations during extended missions that venture outside of near Earth. Furthermore, it is not understood why the previous attempt at obtaining copulation, fertilization and implantation in orbit failed but may be related to limitations of the rat habitat for meeting the preconditions for reproductive behavior. With respect to mammalian development it is important to appreciate that fertilization and development occur internally within the female and take a long time to complete and their success will, therefore, be contingent upon the maternal response to the space environment. One process central to development (the establishment of cell lines) is initiated prior to implantation by environmental asymmetries preceived by progenitor cells. These asymmetries appear to result from the formation of asymmetric cell-cell contacts and the concommitant development of an electrical axis across the progenitor cells. Other asymmetries were also documented. It is not known whether any of the known asymmetries perceived by progenitor cells are influenced by gravity vectors and/or by the maternal response to microgravity and other conditions encountered in space.

Wiley, Lynn M.↗

NASA NTRS1992

The neurochemical basis of photic entrainment of the circadian pacemaker

Circadian rhythmicity in mammals is controlled by the action of a light-entrainable hypothalamus, in association with two cell clusters known as the supra chiasmatic nuclei (SCN). In the absence of temporal environmental clues, this pacemaker continues to measure time by an endogenous mechanism (clock), driving biochemical, physiological, and behavioral rhythms that reflect the natural period of the pacemaker oscillation. This endogenous period usually differs slightly from 24 hours (i.e., circadian). When mammals are maintained under a 24 hour light-dark (LD) cycle, the pacemaker becomes entrained such that the period of the pacemaker oscillation matches that of the LD cycle. Potentially entraining photic information is conveyed to the SCN via a direct retinal projection, the retinohypothalamic tract (RHT). RHT neurotransmission is thought to be mediated by the release of excitatory amino acids (EAA) in the SCN. In support of this hypothesis, recent experiments using nocturnal rodents have shown that EAA antagonists block the effects of light on pacemaker-driven behavioral rhythms, and attenuate light induced gene expression in SCN cells. An understanding of the neurochemical basis of the photic entrainment process would facilitate the development of pharmacological strategies for maintaining synchrony among shift workers in environments, such as the Space Station, which provide unreliable or conflicting temporal photic clues.

Rea, Michael A.↗

NASA NTRS1994

Proposed law of nature linking impacts, plume volcanism, and Milankovitch cycles to terrestrial vertebrate mass extinctions via greenhouse-embryo death coupling

A greenhouse-physiological coupling killing mechanism active among mammals, birds, and reptiles has been identified. Operating via environmental thermal effects upon the maternal core-skin blood flow critical to the survival and development of embryos, it reduces the flow of blood to the uterine tract. Today, during hot summers, this phenomena kills embryos on a vast, global scale. Because of sensitivity of many mammals to modern heat, a major modern greenhouse could reduce population numbers on a global scale, and potentially trigger population collapses in the more vulnerable parts of the world. In the geological past, the killing mechanism has likely been triggered into action by greenhouse warming via impact events, plume volcanism, and Earth orbital variations (Milankovitch cycles). Earth's biosphere is maintained and molded by the flow of energy from the solar energy source to Earth and on to the space energy sink (SES). This SES energy flow maintains Earth's biosphere and its living components, as open, intermediate, dissipative, nonequilibrium systems whose states are dependent upon the rate of energy flowing through them. Greenhouse gases such as CO2 in the atmosphere influence the SES energy flow rate. Steady-state flow is necessary for global ecological stability (autopoiesis). Natural fluctuations of the C cycle such as rapid releases of CO2 from the mantle, or oceans, disrupt steady-state SES flow. These fluctuations constantly challenge the biosphere; slowdown of SES energy flow drives it toward thermodynamical equilibrium and stagnation. Fluctuations induced by impact event, mantle plume volcanism, and Milankovitch cycles can grow into structure-breaking waves triggering major perturbations of Earth's C cycle and mass extinctions. A major C cycle perturbation involves readjustment of the outer physiochemical spheres of the Earth: the atmosphere, hydrosphere, and lithosphere; and by necessity, the biosphere. A greenhouse, one manifestation of a major C cycle perturbation, is the most dangerous natural phenomenon that life on Earth can experience. Greenhouse conditions existed during the KT mass extinctions of 65 m.y. ago, and the Pleistocene-Holocene (P-H) mammalian extinctions of 10,000-12,000 yr ago. Coupling climatology to reproductive physiology via effects of ambient air temperature upon uterine blood flow to developing embryos accounts for the extinctions via established physiological principles.

Mclean, D. M.↗

NASA NTRS1994

US experiments flown on the Soviet biosatellite Cosmos 2044. Volume 1: Mission description, experiments K-7-01 - K-7-15

Cosmos 2044 was launched on September 15, 1989, containing radiation dosimetry experiments and a biological payload including two young male rhesus monkeys, ten adult male Wistar rats, insects, amphibians, protozoa, cell cultures, worms, plants and fish. The biosatellite was launched from the Plesetsk Cosmodrome in the Soviet Union for a mission duration of 14 days, as planned. The major research objectives were: (1) Study adaptive response mechanisms of mammals during flight; (2) Study physiological mechanisms underlying vestibular, motor system and brain function in primates during early and later adaptation phases; (3) Study the tissue regeneration processes of mammals; (4) Study the development of single-celled organisms, cell cultures and embryos in microgravity; (5) Study radiation characteristics during the mission and investigate doses, fluxes and spectra of cosmic radiation for various types of shielding. American and Soviet specialists jointly conducted 29 experiments on this mission including extensive preflight and post flight studies with rhesus monkeys, and tissue processing and cell culturing post flight. Biosamples and data were subsequently transferred to the United States. The U.S. responsibilities for this flight included development of flight and ground-based hardware, the preparation of rat tissue sample procedures, the verification testing of hardware and experiment procedures, and the post flight analysis of biospecimens and data for the joint experiments. The U.S. investigations included four primate experiments, 24 rat experiments, and one radiation dosimetry experiment. Three scientists investigated tissue repair during flight for a subgroup of rats injured preflight by surgical intervention. A description of the Cosmos 2044 mission is presented in this report including preflight, on-orbit and post flight activities. The flight and ground-based bioinstrumentation which was developed by the U.S. and U.S.S.R. is also described, along with the associated preflight testing of the U.S. hardware.

Connolly, James P.↗