Characterization of Physiological Changes in Roots Grown in Spaceflight Conditions: A Comparison of Nutrient Delivery Technologies.

The best strategy for providing food and maintaining the environment on long-duration space missions is a bioregenerative life support system based on the growth of higher plants. Before such a system can be implemented, a better understanding of plant growth in space will have to be achieved. Little is known about the role of gravity-dependent physical processes in normal physiological function. A series of ground-based and spaceflight experiments was conducted to examine root oxygen availability in microgravity nutrient delivery systems. In spaceflight experiments Arabidopsis thaliana (L.) Heynh. plants were analyzed for changes in root medium redox potential and root alcohol dehydrogenase (ADH) activity, localization, and expression. These experiments showed ADH activity and expression increased by 89% and 136% respectively, without any change in localization. Ground experiments demonstrated the increase in ADH activity in spaceflight roots was achieved by a 28% decrease in oxygen availability. Metabolic and growth pattern changes in spaceflight roots suggested that root orientation could be directed toward oxygen (oxytropism). Both gravity sensing and agravitropic Pisum sativum L. roots reoriented toward oxygen when grown in a microrhizotron that maintains an oxygen gradient over the whole range of subambient oxygenation, although the rate of reorientation declined as oxygen concentrations decreased. Ground-based experiments to evaluate technologies for growing plants in space were conducted by comparing root system morphology, ADH activity, nutrient content, and general plant growth parameters of Triticum aestivum L. cv Yecora Rojo and Brassica rapa L. A system that maintains a nutrient solution inside of a porous hydrophilic ceramic tube was compared with two passive substrate systems now used for spaceflight research (solidified agar-gel and phenolic foam media). Plants performed best on the porous tube because the roots grow on the tube surface in contact with air and nutrient solution. Oxygenation is important for normal root function in space, as on earth. Two obstacles restricting development of plant nutrient delivery technologies are a limited knowledge of the requirements of plants in space, and an incomplete understanding of plants in general. Information concerning the changes in oxygenation during spaceflight should allow scientists and engineers to address these problems

A non-invasive method for measuring preimplantation embryo physiology

Author Posting. © Cambridge University Press, 2000. This article is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Zygote 8 (2000): 15-24, doi:10.1017/S0967199400000782.The physiology of the early embryo may be indicative of embryo vitality and therefore methods for non-invasively monitoring physiological parameters from embryos could improve preimplantation diagnoses. The self-referencing electrophysiological technique is capable of non-invasive measurement of the physiology of individual cells by monitoring the movement of ions and molecules between the cell and the surrounding media. Here we use this technique to monitor gradients of calcium, potassium, oxygen and hydrogen peroxide around individual mouse preimplantation embryos. The calcium-sensitive electrode in self-referencing mode identified a region of elevated calcium concentration ([similar]0.25 pmol) surrounding each embryo. The calcium gradient surrounding embryos was relatively steep, such that the region of elevated calcium extended into the medium only 4 [mu]m from the embryo. By contrast, using an oxygen-sensitive electrode an extensive gradient of reduced dissolved oxygen concentration was measured surrounding the embryo and extended tens of micrometres into the medium. A gradient of neither potassium nor hydrogen peroxide was observed around unperturbed embryos. We also demonstrate that monitoring the physiology of embryos using the self-referencing technique does not compromise their subsequent development. Blastocysts studied with the self-referencing technique implanted and developed to term at the same frequency as did unexamined, control embryos. Therefore, the self-referencing electrode provides a valuable non-invasive technique for studying the physiology and pathophysiology of individual embryos without hindering their subsequent development.A portion of this work was funded by an NIH R21 #RR 12718–02 to D.L.K. and P.J.S.S., KO81099 to D.L.K. and NIH P41 RR01395 to P.J.S.S

Mouse and human islets survive and function after coating by biosilicification

Inorganic materials have properties that can be advantageous in bioencapsulation for cell transplantation. Our aim was to engineer a hybrid inorganic/soft tissue construct by inducing pancreatic islets to grow an inorganic shell. We created pancreatic islets surrounded by porous silica, which has potential application in the immunoprotection of islets in transplantation therapies for type 1 diabetes. The new method takes advantage of the islet capsule surface as a template for silica formation. Mouse and human islets were exposed to medium containing saturating silicic acid levels for 9-15 min. The resulting tissue constructs were then cultured for up to 4 wk under normal conditions. Scanning electron microscopy and energy dispersive X-ray spectroscopy was used to monitor the morphology and elemental composition of the material at the islet surface. A cytokine assay was used to assess biocompatibility with macrophages. Islet survival and function were assessed by confocal microscopy, glucose-stimulated insulin release assays, oxygen flux at the islet surface, expression of key genes by RT-PCR, and syngeneic transplant into diabetic mice

The First Swift Ultra-Violet/Optical Telescope GRB Afterglow Catalog

We present the first Swift Ultra-Violet/Optical Telescope (UVOT) gamma-ray burst (GRB) afterglow catalog. The catalog contains data from over 64,000 independent UVOT image observations of 229 GRBs first detected by Swift, the High Energy Transient Explorer 2 (HETE2), the INTErnational Gamma-Ray Astrophysics Laboratory (INTEGRAL), and the Interplanetary Network (IPN). The catalog covers GRBs occurring during the period from 2005 Jan 17 to 2007 Jun 16 and includes ~86% of the bursts detected by the Swift Burst Alert Telescope (BAT). The catalog provides detailed burst positional, temporal, and photometric information extracted from each of the UVOT images. Positions for bursts detected at the 3-sigma-level are provided with a nominal accuracy, relative to the USNO-B1 catalog, of ~0.25 arcseconds. Photometry for each burst is given in three UV bands, three optical bands, and a 'white' or open filter. Upper limits for magnitudes are reported for sources detected below 3-sigma. General properties of the burst sample and light curves, including the filter-dependent temporal slopes, are also provided. The majority of the UVOT light curves, for bursts detected at the 3-sigma-level, can be fit by a single power-law, with a median temporal slope (alpha) of 0.96, beginning several hundred seconds after the burst trigger and ending at ~1x10^5 s. The median UVOT v-band (~5500 Angstroms) magnitude at 2000 s for a sample of "well" detected bursts is 18.02. The UVOT flux interpolated to 2000 s after the burst, shows relatively strong correlations with both the prompt Swift BAT fluence, and the Swift X-ray flux at 11 hours after the trigger.Comment: 60 pages, 17 figures, 8 tables, accepted for publication by the Astrophysical Journa

Ion-selective electrode biochip for applications in a liquid environment

Physiological sensing conducted in a liquid environment requires electrodes with long lifetime. The development of a robust ion-selective electrode–based biochip in a lab-on-a-chip platform is described. To compare electrode lifetime, which is driven by the transducer layer, electrochemical measurements were performed in a custom-made flow-cell chamber. The results of potentiometric measurement of cationic analytes demonstrate the electrodes to have a near-Nernstian slope profile even after they are stored for almost a month in liquid medium. The electrodes also achieved H2O2 amperometric sensitivity (1.25 and 3.32 µAmM-1cm-2 for PEDOT:PSS and PEDOT:CaSO4 respectively) and lower detection limit (2.21 µM, 8.4 µM, 3.44 µM, for H+, NH4+, Ca2+ respectively) comparable to that of wire-type electrodes. Furthermore, the lifetime is dependent on the electrodeposition method of the conductive polymer, and the transducer layer must be modified to fit the analyte types. These results indicate that extended lifetime of microfabricated ion-selective electrodes in a multiplex format can be realized by optimizing the microfabricated electrode surface functionalization

The interplay between lncRNAs, RNA-binding proteins and viral genome during SARS-CoV-2 infection reveals strong connections with regulatory events involved in RNA metabolism and immune response

Rationale: Viral infections are complex processes based on an intricate network of molecular interactions. The infectious agent hijacks components of the cellular machinery for its profit, circumventing the natural defense mechanisms triggered by the infected cell. The successful completion of the replicative viral cycle within a cell depends on the function of viral components versus the cellular defenses. Non-coding RNAs (ncRNAs) are important cellular modulators, either promoting or preventing the progression of viral infections. Among these ncRNAs, the long non-coding RNA (lncRNA) family is especially relevant due to their intrinsic functional properties and ubiquitous biological roles. Specific lncRNAs have been recently characterized as modulators of the cellular response during infection of human host cells by single stranded RNA viruses. However, the role of host lncRNAs in the infection by human RNA coronaviruses such as SARS-CoV-2 remains uncharacterized. Methods: In the present work, we have performed a transcriptomic study of a cohort of patients with different SARS-CoV-2 viral load and analyzed the involvement of lncRNAs in supporting regulatory networks based on their interaction with RNA-binding proteins (RBPs). Results: Our results revealed the existence of a SARS-CoV-2 infection-dependent pattern of transcriptional up-regulation in which specific lncRNAs are an integral component. To determine the role of these lncRNAs, we performed a functional correlation analysis complemented with the study of the validated interactions between lncRNAs and RBPs. This combination of in silico functional association studies and experimental evidence allowed us to identify a lncRNA signature composed of six elements - NRIR, BISPR, MIR155HG, FMR1-IT1, USP30-AS1, and U62317.2 - associated with the regulation of SARS-CoV-2 infection. Conclusions: We propose a competition mechanism between the viral RNA genome and the regulatory lncRNAs in the sequestering of specific RBPs that modulates the interferon response and the regulation of RNA surveillance by nonsense-mediated decay (NMD)

Targeted prevention in primary care aimed at lifestyle-related diseases:a study protocol for a non-randomised pilot study

Background: The consequences of lifestyle-related disease represent a major burden for the individual as well as for society at large. Individual preventive health checks to the general population have been suggested as a mean to reduce the burden of lifestyle-related diseases, though with mixed evidence on effectiveness. Several systematic reviews, on the other hand, suggest that health checks targeting people at high risk of chronic lifestyle-related diseases may be more effective. The evidence is however very limited. To effectively target people at high risk of lifestyle-related disease, there is a substantial need to advance and implement evidence-based health strategies and interventions that facilitate the identification and management of people at high risk. This paper reports on a non-randomized pilot study carried out to test the acceptability, feasibility and short-term effects of a healthcare intervention in primary care designed to systematically identify persons at risk of developing lifestyle-related disease or who engage in health-risk behavior, and provide targeted and coherent preventive services to these individuals. Methods: The intervention took place over a three-month period from September 2016 to December 2016. Taking a two-pronged approach, the design included both a joint and a targeted intervention. The former was directed at the entire population, while the latter specifically focused on patients at high risk of a lifestyle-related disease and/or who engage in health-risk behavior. The intervention was facilitated by a digital support system. The evaluation of the pilot will comprise both quantitative and qualitative research methods. All outcome measures are based on validated instruments and aim to provide results pertaining to intervention acceptability, feasibility, and short-term effects. Discussion: This pilot study will provide a solid empirical base from which to plan and implement a full-scale randomized study with the central aim of determining the efficacy of a preventive health intervention. Trial registration: Registered at Clinical Trial Gov (Unique Protocol ID: TOFpilot2016). Registered 29 April 2016. The study adheres to the SPIRIT guidelines

Space radiation damage rescued by inhibition of key spaceflight associated miRNAs

Our previous research revealed a key microRNA signature that is associated with spaceflight that can be used as a biomarker and to develop countermeasure treatments to mitigate the damage caused by space radiation. Here, we expand on this work to determine the biological factors rescued by the countermeasure treatment. We performed RNA-sequencing and transcriptomic analysis on 3D microvessel cell cultures exposed to simulated deep space radiation (0.5 Gy of Galactic Cosmic Radiation) with and without the antagonists to three microRNAs: miR-16-5p, miR-125b-5p, and let-7a-5p (i.e., antagomirs). Significant reduction of inflammation and DNA double strand breaks (DSBs) activity and rescue of mitochondria functions are observed after antagomir treatment. Using data from astronaut participants in the NASA Twin Study, Inspiration4, and JAXA missions, we reveal the genes and pathways implicated in the action of these antagomirs are altered in humans. Our findings indicate a countermeasure strategy that can potentially be utilized by astronauts in spaceflight missions to mitigate space radiation damage.This article is published as McDonald, J.T., Kim, J., Farmerie, L. et al. Space radiation damage rescued by inhibition of key spaceflight associated miRNAs. Nat Commun 15, 4825 (2024). https://doi.org/10.1038/s41467-024-48920-y. Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted

Researching COVID to Enhance Recovery (RECOVER) Adult Study Protocol: Rationale, Objectives, and Design

IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. METHODS: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. DISCUSSION: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options