GeneLab: Scientific Partnerships and an Open-Access Database to Maximize Usage of Omics Data from Space Biology Experiments

NASA's mission includes expanding our understanding of biological systems to improve life on Earth and to enable long-duration human exploration of space. The GeneLab Data System (GLDS) is NASAs premier open-access omics data platform for biological experiments. GLDS houses standards-compliant, high-throughput sequencing and other omics data from spaceflight-relevant experiments. The GeneLab project at NASA-Ames Research Center is developing the database, and also partnering with spaceflight projects through sharing or augmentation of experiment samples to expand omics analyses on precious spaceflight samples. The partnerships ensure that the maximum amount of data is garnered from spaceflight experiments and made publically available as rapidly as possible via the GLDS. GLDS Version 1.0, went online in April 2015. Software updates and new data releases occur at least quarterly. As of October 2016, the GLDS contains 80 datasets and has search and download capabilities. Version 2.0 is slated for release in September of 2017 and will have expanded, integrated search capabilities leveraging other public omics databases (NCBI GEO, PRIDE, MG-RAST). Future versions in this multi-phase project will provide a collaborative platform for omics data analysis. Data from experiments that explore the biological effects of the spaceflight environment on a wide variety of model organisms are housed in the GLDS including data from rodents, invertebrates, plants and microbes. Human datasets are currently limited to those with anonymized data (e.g., from cultured cell lines). GeneLab ensures prompt release and open access to high-throughput genomics, transcriptomics, proteomics, and metabolomics data from spaceflight and ground-based simulations of microgravity, radiation or other space environment factors. The data are meticulously curated to assure that accurate experimental and sample processing metadata are included with each data set. GLDS download volumes indicate strong interest of the scientific community in these data. To date GeneLab has partnered with multiple experiments including two plant (Arabidopsis thaliana) experiments, two mice experiments, and several microbe experiments. GeneLab optimized protocols in the rodent partnerships for maximum yield of RNA, DNA and protein from tissues harvested and preserved during the SpaceX-4 mission, as well as from tissues from mice that were frozen intact during spaceflight and later dissected on the ground. Analysis of GeneLab data will contribute fundamental knowledge of how the space environment affects biological systems, and as well as yield terrestrial benefits resulting from mitigation strategies to prevent effects observed during exposure to space environments

Bioinformatics challenges and potentialities in studying extreme environments

Cold environments are populated by organisms able to contravene deleterious effects of low temperature by diverse adaptive strategies, including the production of ice binding proteins (IBPs) that inhibit the growth of ice crystals inside and outside cells. We describe the properties of such a protein (EfcIBP) identified in the metagenome of an Antarctic biological consortium composed of the ciliate Euplotes focardii and psychrophilic non-cultured bacteria. Recombinant EfcIBP can resist freezing without any conformational damage and is moderately heat stable, with a midpoint temperature of 66.4 degrees C. Tested for its effects on ice, EfcIBP shows an unusual combination of properties not reported in other bacterial IBPs. First, it is one of the best-performing IBPs described to date in the inhibition of ice recrystallization, with effective concentrations in the nanomolar range. Moreover, EfcIBP has thermal hysteresis activity (0.53 degrees C at 50 mu M) and it can stop a crystal from growing when held at a constant temperature within the thermal hysteresis gap. EfcIBP protects purified proteins and bacterial cells from freezing damage when exposed to challenging temperatures. EfcIBP also possesses a potential N-terminal signal sequence for protein transport and a DUF3494 domain that is common to secreted IBPs. These features lead us to hypothesize that the protein is either anchored at the outer cell surface or concentrated around cells to provide survival advantage to the whole cell consortium

The O/OREOS Mission - Astrobiology in Low Earth Orbit

The O/OREOS (Organism/Organic Exposure to Orbital Stresses) nanosatellite is the first science demonstration spacecraft and flight mission of the NASA Astrobiology Small- Payloads Program (ASP). O/OREOS was launched successfully on November 19, 2010, to a high-inclination (72), 650-km Earth orbit aboard a US Air Force Minotaur IV rocket from Kodiak, Alaska. O/OREOS consists of 3 conjoined cubesat (each 1000 cu.cm) modules: (i) a control bus, (ii) the Space Environment Survivability of Living Organisms (SESLO) experiment, and (iii) the Space Environment Viability of Organics (SEVO) experiment. Among the innovative aspects of the O/OREOS mission are a real-time analysis of the photostability of organics and biomarkers and the collection of data on the survival and metabolic activity for micro-organisms at 3 times during the 6-month mission. We will report on the spacecraft characteristics, payload capabilities and first operational phase of the O/OREOS mission. The science and technology rationale of O/OREOS supports NASAs scientific exploration program by investigating the local space environment as well as space biology relevant to Moon and Mars missions. It also serves as precursor for experiments on small satellites, the International Space Station (ISS), future free-flyers and lunar surface exposure facilities

Sensitization in Transplantation: Assessment of Risk (STAR) 2017 Working Group Meeting Report

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144684/1/ajt14752_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144684/2/ajt14752.pd

Identification of biomarkers for the antiangiogenic and antitumour activity of the superoxide dismutase 1 (SOD1) inhibitor tetrathiomolybdate (ATN-224)

Tetrathiomolybdate (choline salt; ATN-224), a specific, high-affinity copper binder, is currently being evaluated in several phase II cancer trials. ATN-224 inhibits CuZn superoxide dismutase 1 (SOD1) leading to antiangiogenic and antitumour effects. The pharmacodynamics of tetrathiomolybdate has been followed by tracking ceruloplasmin (Cp), a biomarker for systemic copper. However, at least in mice, the inhibition of angiogenesis occurs before a measurable decrease in systemic copper is observed. Thus, the identification and characterisation of other biomarkers to follow the activity of ATN-224 in the clinic is of great interest. Here, we present the preclinical evaluation of two potential biomarkers for the activity of ATN-224: (i) SOD activity measurements in blood cells in mice and (ii) levels of endothelial progenitor cells (EPCs) in bonnet macaques treated with ATN-224. The superoxide dismutase activity in blood cells in mice is rapidly inhibited by ATN-224 treatment at doses at which angiogenesis is maximally inhibited. Furthermore, ATN-224 dosing in bonnet macaques causes a profound and reversible decrease in EPCs without significant toxicity. Thus, both SOD activity measurements and levels of EPCs may be useful biomarkers of the antiangiogenic activity of ATN-224 to be used in its clinical development

The O/OREOS Mission - Astrobiology in Low Earth Orbit

The O/OREOS (Organism/Organic Exposure to Orbital Stresses) nanosatellite is the first science demonstration spacecraft and flight mission of the NASA Astrobiology Small- Payloads Program (ASP). O/OREOS was launched successfully on November 19, 2010, to a high-inclination (72), 650-km Earth orbit aboard a US Air Force Minotaur IV rocket from Kodiak, Alaska. O/OREOS consists of 3 conjoined cubesat (each 1000 cu.cm) modules: (i) a control bus, (ii) the Space Environment Survivability of Living Organisms (SESLO) experiment, and (iii) the Space Environment Viability of Organics (SEVO) experiment. Among the innovative aspects of the O/OREOS mission are a real-time analysis of the photostability of organics and biomarkers and the collection of data on the survival and metabolic activity for micro-organisms at 3 times during the 6-month mission. We will report on the spacecraft characteristics, payload capabilities and first operational phase of the O/OREOS mission. The science and technology rationale of O/OREOS supports NASAs scientific exploration program by investigating the local space environment as well as space biology relevant to Moon and Mars missions. It also serves as precursor for experiments on small satellites, the International Space Station (ISS), future free-flyers and lunar surface exposure facilities

Treatment of bipolar disorder: a complex treatment for a multi-faceted disorder

Background: Manic-depression or bipolar disorder (BD) is a multi-faceted illness with an inevitably complex treatment. Methods: This article summarizes the current status of our knowledge and practice of its treatment. Results: It is widely accepted that lithium is moderately useful during all phases of bipolar illness and it might possess a specific effectiveness on suicidal prevention. Both first and second generation antipsychotics are widely used and the FDA has approved olanzapine, risperidone, quetiapine, ziprasidone and aripiprazole for the treatment of acute mania. These could also be useful in the treatment of bipolar depression, but only limited data exists so far to support the use of quetiapine monotherapy or the olanzapine-fluoxetine combination. Some, but not all, anticonvulsants possess a broad spectrum of effectiveness, including mixed dysphoric and rapid-cycling forms. Lamotrigine may be effective in the treatment of depression but not mania. Antidepressant use is controversial. Guidelines suggest their cautious use in combination with an antimanic agent, because they are supposed to induce switching to mania or hypomania, mixed episodes and rapid cycling. Conclusion: The first-line psychosocial intervention in BD is psychoeducation, followed by cognitive-behavioral therapy. Other treatment options include Electroconvulsive therapy and transcranial magnetic stimulation. There is a gap between the evidence base, which comes mostly from monotherapy trials, and clinical practice, where complex treatment regimens are the rule

Inferential framework for non-stationary dynamics:theory and applications

An extended Bayesian inference framework is presented, aiming to infer time-varying parameters in non-stationary nonlinear stochastic dynamical systems. The convergence of the method is discussed. The performance of the technique is studied using, as an example, signal reconstruction for a system of neurons modeled by FitzHugh–Nagumo oscillators: it is applied to reconstruction of the model parameters and elements of the measurement matrix, as well as to inference of the time-varying parameters of the non stationary system. It is shown that the proposed approach is able to reconstruct unmeasured (hidden) variables of the system, to determine the model parameters, to detect stepwise changes of control parameters for each oscillator and to track the continuous evolution of the control parameters in the adiabatic limit

Activity and activity coefficient of Iron Oxides in the liquid FeO-Fe2O3-CaO-SiO2 slag systems at intermediate oxygen partial pressures

At present, there is a scarcity of data on the activities of iron oxides in the FeO-Fe2O3-CaO-SiO2 slag system at intermediate oxygen partial pressures and temperatures relevant to sulfide smelting and nonferrous metallurgy. The present study provides relevant data at temperatures between 1573 and 1673 K and partial pressures of oxygen between 10-9 and 10-4 atm. The experiments were carried out by equilibrating the slag in a CO-CO2 gas mixture in a platinum crucible, after which the phases of all the experimental samples, including the platinum foil, were analyzed by electron probe microanalysis (EPMA). Where only liquid phase or liquid phase and tridymite (SiO2) were observed, wet chemical analysis was used to determine the ratio of (mass pct Fe2+)/(mass pct Fe3+). Activity and activity coefficients for FeO (liquid) and FeO1.33 (solid) were calculated. Tendencies of the effect of the (CaO/SiO2) ratio, temperature, and oxygen partial pressure on these thermochemical quantities are discussed in this article