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At least 703 records · Page 39

Biomedical Results of the Space Shuttle Program

The Space Shuttle Program (SSP), which was triumphantly completed by the flight of STS-135 on July 21, 2011, holds a special place in the history of Human Space Exploration. For the first time, a vehicle was built that could perform multiple flights in space and return to Earth. Many important questions regarding the ability of humans to adapt and function in space have been answered during the 30 years since the SSP was launched and many lessons have been learned. The multidisciplinary studies conducted during this program allowed NASA to define the normal responses and potential pathologic changes of the major physiological systems to short-duration space flights. The program significantly contributed to the development of in-flight medical care capabilities and multiple countermeasures. A comprehensive system of preflight, in-flight, and post-flight monitoring of the astronauts was built. It is important to emphasize that the SSP was essential for building the International Space Station (ISS) that significantly expanded the boundaries of space research, allowing for planning of long-term near-terrestrial and extraterrestrial missions. As the program was coming to completion, a decision was made by the NASA Lyndon B. Johnson Space Center Human Research Program senior management to summarize the medico-biological results of the SSP in one comprehensive edition. This was quite an ambitious goal. It required selection of a group of experts in different areas to become the chapters lead authors. These experts were charged with the task of reviewing what was learned in the consequent fields to make the chapters a comprehensive source of information for planning of research, operational activities, and medical care for future missions. We hope that we were able to accomplish this goal and the book will serve as a reliable reference edition for the international space biomedicine community, for new generation of space researchers and Flight Surgeons, as well as for all those interested in space exploration. As space exploration continues, the major question of whether humans are capable of adapting to long-term presence and adequately functioning in space habitats will remain open for a long time. we expect that the comprehensive review of the medico-biological results of the SSP along with the data collected during the missions on the space stations (the Russian space station _Mir_ and ISS) provides a good starting point in seeking the answer to this question.

Diana Risin↗

EMU CO2 Washout Comparative Assessments for the HAB/HAP-E in support of EVA 80

After water was reported in the EMU helmet during ISS US EVA-80, mitigation strategies were created to attempt to arrest the motion of any droplets that enter the helmet for future Extravehicular Activities (EVAs). This included adding absorbent materials into the interior of the helmet. But before a mitigation strategy can be implemented, it must first be proven to be safe. Towards this aim, a computational fluid dynamics (CFD) model was developed to assess the effect that the absorbent material has on the concentration of carbon dioxide in the EMU helmet. Within a small, closed volume such as a helmet, some amount of the carbon dioxide produced by the suit-wearer will be re-inhaled before being cleared from the oral-nasal region. The ability of the suit to remove carbon dioxide is referred to as CO2 washout. Pathological levels of inhaled CO2 (hypercapnia) are associated with dizziness, fatigue, and headaches. The CFD model was built in ANSYS Fluent and adapted to assess CO2 washout in a variety of scenarios grouped into three categories: purge cases, varying metabolic rates, and varying sorbent material configurations. The presence of the sorbent material did not prove detrimental to CO2 washout in the helmet.

Moses Navarro↗

Neuro-behavioral Consequences of Low Dose Radiation Social Isolation and Sex Differences in the Longevity MCAT Mouse Model

The physiological responses to spaceflight elicit wide-ranging consequences and resemble aspects of aging on Earth. Previous studies have shown that oxidative damage via reactive oxygen species (ROS), contributes to aging-related pathologies. Our study uses 1-year old C57BL/6NJ male and female mice (astronaut-relevant age) that underwent exposure to 0.5 gray of gamma radiation together with social isolation and were euthanized 12 weeks after. We used the longevity MCAT mouse model in which human catalase is overexpressed in the mitochondria, for ROS quenching. We aimed to determine whether in older mice quenching ROS, will mitigate the neuro-behavioral consequences of low dose ionizing radiation and/or social isolation and whether the outcomes will differ in males and females. We have performed five mission relevant behavioral tests which focused on performance, memory, physical stance, and stress. We have detected both sex and radiation effects; the older females look physically better are faster and perform better almost in all behavioral tests compared to their male counterparts. On the other hand, they are more sensitive to low dose radiation in many cases, in some cases this effect was indeed mitigated in the MCAT mice, pointing out to the importance of ROS in response to radiation stress and social isolation. We have measured plasma (7- and 90-days post radiation), cytokines, corticosterone and hippocampal cytokine and microglial activation at the end of the experiment. We saw significant changes in the plasma markers due to radiation, sex, and genotype in both short and long post radiation period and detected long term sex and radiation effects in the brain. Our focus is now on applying advanced statistical modeling to corelate the behavioral tests with our recent molecular findings to look for specific biomarkers that could predict behavioral deficits.

radiation↗

Murine Host-gut Microbiota Interactions are Modulated During Spaceflight

The rodent habitat on the International Space Station has provided critical insight into the impact of spaceflight on mammalian physiology. These effects include dysfunction of carbohydrate, steroid and lipid metabolism, and immune response, as well as induction of symptoms characteristic of liver disease, insulin resistance, osteopenia and myopathy, which are anticipated to intensify over long-duration spaceflight. Although these physiological responses can involve the microbiome, the host-microorganism interactions during spaceflight are still largely unknown. NASA GeneLab curates a wide range of space research data and the current work harnesses GeneLab multi’omic data from recent Rodent Research studies to explore changes to gut microbiota during spaceflight and their associations with host physiology when compared to ground controls. Using a hybrid analysis of DNA barcoding and whole genome shotgun data, an array of bacteria, fungi and nematodes could be identified at species level, and significant differences in relative abundances associated with spaceflight. Functional prediction based on differential abundance of species and metagenome gene inventories as well as metatranscriptomic gene expression at the host-gut microbiome interface implicate microbiota interactions could contribute to spaceflight pathology. Harnessing carefully curated publicly available data, such as from Genelab, to generate multi‘omic space science discoveries can help decipher the complex host-microbiome interactions that influence both health on Earth and the feasibility of long-duration spaceflight.

Microbiome↗

EMU CO2 Washout Comparative Assessments for the HAB/HAP-E in Support of EVA 80

After water was reported in the Extravehicular Mobility Unit (EMU) helmet during ISS US EVA 80, mitigation strategies were created to attempt to arrest the motion of any droplets that enter the helmet for future Extravehicular Activities (EVAs). This included adding absorbent materials into the interior of the helmet. But before a mitigation strategy can be implemented, it must first be proven to be safe. Towards this aim, a computational fluid dynamics (CFD) model was developed to assess the effect that the absorbent material has on the concentration of carbon dioxide in the EMU helmet. Within a small, closed volume such as a helmet, some amount of the carbon dioxide produced by the suit-wearer will be re-inhaled before being cleared from the oral-nasal region. The ability of the suit to remove carbon dioxide is referred to as CO2 washout. Pathological levels of inhaled CO2 (hypercapnia) are associated with dizziness, fatigue, and headaches. The CFD model was built in ANSYS Fluent and adapted to assess CO2 washout in a variety of scenarios grouped into three categories: ventilation cases, varying metabolic rates, and varying sorbent material configurations. The presence of the sorbent material did not prove detrimental to CO2 washout in the helmet.

Moses Navarro↗

Examining the Effects of 4He Exposure on the Gut-Brain Axis

Beyond low earth orbit, space radiation poses significant risks to astronaut health. Previous studies have shown that the microbial composition of the gastrointestinal (GI) microbiome changes upon exposure to high linear energy transfer radiation. Interestingly, radiation-induced shifts in GI microbiota composition are linked to various neuropsychological disorders. Herein, we aimed to study changes in GI microbiota and behaviors of rats exposed to whole-body radiation (0, 5, or 25 cGy 4 He, 250 MeV/n) at approximately 6 months of age. Fecal samples were collected 24 hours prior to 4 He radiation and 24 hours and 7 days post-exposure for quantitative PCR analyses to assess fecal levels of spore-forming bacteria (SFB), Bifidobacterium, Lactobacillus, and Akkermansia. Rats were also tested in the social odor recognition memory (SORM) test at 7 days following 4 He exposure. A subset of rats was euthanized 90 minutes following completion of the SORM test, and GI tissue from small intestine to colon were prepared for examining overall histological changes and immunohistochemical staining for serotonin (5-HT). No notable pathological changes were observed in GI tissues. Akkermansia spp. and SFB were significantly decreased the 25 cGy group at 24 hours and 7 days post-exposure compared to pre-exposure, respectively. Bifidobacterium and Lactobacillus spp. showed no significant changes. 5-HT production was significantly higher in the proximal small intestine and the cecum in the 25 cGy group compared to the sham group. The 25 cGy group exhibited deficits in recognition in SORM testing at 7 days post-exposure. Taken together, these results suggest a connection between GI microbiome 3 composition, serotonin production, and neurobehavioral performance, and that this connection may be disrupted upon exposure to 25 cGy of 4 He ions

Carli B Jones↗

EMU CO2 Washout Comparative Assessments for the HAB/HAP-E in Support of EVA 80

After water was reported in the Extravehicular Mobility Unit (EMU) helmet during ISS US EVA 80, mitigation strategies were created to attempt to arrest the motion of any droplets that enter the helmet for future Extravehicular Activities (EVAs). This included adding absorbent materials into the interior of the helmet. But before a mitigation strategy can be implemented, it must first be proven to be safe. Towards this aim, a computational fluid dynamics (CFD) model was developed to assess the effect that the absorbent material has on the concentration of carbon dioxide in the EMU helmet. Within a small, closed volume such as a helmet, some amount of the carbon dioxide produced by the suit-wearer will be re-inhaled before being cleared from the oral-nasal region. The ability of the suit to remove carbon dioxide is referred to as CO2 washout. Pathological levels of inhaled CO2 (hypercapnia) are associated with dizziness, fatigue, and headaches. The CFD model was built in ANSYS Fluent and adapted to assess CO2 washout in a variety of scenarios grouped into three categories: ventilation cases, varying metabolic rates, and varying sorbent material configurations. The presence of the sorbent material did not prove detrimental to CO2 washout in the helmet.

Moses Navarro↗

Efficient Oculometric Assessment of Altered Neural Function

Eye movements have long been known to shed light on the locus and nature of serious brain injuries and pathologies. Recent scientific findings linking eye movements and higher-order psychometric performance and recent technical advances in eye-tracking precision have enabled the harnessing of an assortment of oculometrics as sensitive and reliable biomarkers of mild neural impairment across a wide range of stressors and brain regions. Oculometrics is, therefore, a promising new tool for the assessment of spaceflight effects on sensorimotor performance and on the effectiveness of candidate countermeasures, even with small sample populations

eye movements↗

Oculometric Biomarkers of Visuomotor Deficits in Clinically Asymptomatic Patients With Systemic Lupus Erythematosus Undergoing Long-Term Hydroxychloroquine Treatment

Introduction: This study examines a set of oculomotor measurements, or “oculometric” biomarkers, as potential early indicators of visual and visuomotor deficits due to retinal toxicity in asymptomatic Systemic Lupus Erythematosus (SLE) patients on long-term hydroxychloroquine (HCQ) treatment. The aim is to identify subclinical functional impairments that are otherwise undetectable by standard clinical tests and to link them to structural retinal changes. Methods: We measured oculomotor responses in a cohort of SLE patients on chronic HCQ therapy using a previously established behavioral task and analysis technique. We also examined the relationship between oculometrics, OCT measures of retinal thickness, and standard clinical perimetry measures of visual function in our patient group using Bivariate Pearson Correlation and a Linear Mixed-Effects Model (LMM). Results: Significant visual and visuomotor deficits were found in 12 asymptomatic SLE patients on long-term HCQ therapy compared to a cohort of 17 age-matched healthy controls. Notably, six oculometrics were significantly different. The median initial pursuit acceleration was 22%, steady-state pursuit gain 16%, proportion smooth 7%, and target speed responsiveness 31% lower, while catch-up saccade amplitude was 46% and fixation error 46% larger. Excluding the two patients with diagnosed mild toxicity, four oculometrics, all but fixation error and proportion smooth, remained significantly impaired compared to controls. Across our population of 12 patients (24 retinae), we found that pursuit latency, initial acceleration, steady-state gain, and fixation error were linearly related to retinal thickness even when age was accounted for, while standard measures of clinical function (Mean Deviation and Pattern Standard Deviation) were not. Discussion: Our data show that specific oculometrics are sensitive early biomarkers of functional deficits in SLE patients on HCQ that could be harnessed to assist in the early detection of HCQ-induced retinal toxicity and other visual pathologies, potentially providing early diagnostic value beyond standard visual field and OCT evaluations.

eye movements↗

Mitochondrial apoptotic sensor

Mitochondria are central to the intrinsic apoptotic pathway of programmed cell death. Commitment to cell death occurs upon mitochondrial outer membrane permeabilization, and dysregulation of this vital apoptotic control point is implicated in various pathologies. Provided herein are novel sensors which can detect, in real time and with great sensitivity, the release of protons from intact mitochondria caused by mitochondrial outer membrane permeabilization. Embodiments include graphene based ion-sensitive field effect transistors.

59 BASIC BIOLOGICAL SCIENCES↗

Spectroscopy imaging and analysis of live cells

Disclosed herein are systems, methods, systems and devices for measurement and visualization of chemical dynamics in living cells or tissues for diagnostic pathology. Devices can be open- or closed-channel microfluidic membrane devices for long-term IR spectroscopy of live adherent cells and ultimately for rapidly identifying time-dependent spectral features indicative of chemical abnormality in individual cells.

Holman, Hoi-Ying N.↗

Products and methods for organ protection with noble nanoparticles

Products and methods for redirecting the pathological biochemical process of accumulation of reduced pyridine nucleotides under deleterious hypoxia conditions toward the reduction of the precursor salt and the biosynthesis of biologically compatible, antioxidant noble metal nanoparticles and the simultaneous restoring of the tissue redox state are provided. The products and methods have application in the treatment of hypoxia and hypoxia-related diseases and disorders. Such products and methods are also useful in organ transplantation and recovery, in screening of anti-hypoxia agents, and in detecting elevated levels of the reducing equivalents of the redox state, for example, NADH, NADPH, GSH, and TrxSH 2 , in cells, tissues, or organs.

Rozhkova, Elena A.↗

Apple Bitter Rot: Biology, Ecology, Omics, Virulence Factors, and Management of Causal Colletotrichum Species

ABSTRACT Apple bitter rot is caused by various Colletotrichum spp. that threaten apple production globally resulting in millions of dollars in damage annually. The fungus causes a decline in fruit quality and yield, eventually rotting the fruit and rendering it inedible. The pathogen is difficult to keep out of orchards because of its broad host range and transmissibility by rain splash and insects. Once the disease manifests, pathogen identification is difficult due to evolving taxonomy and similar morphology between species. Current management strategies are threatened by an increase in fungicide resistance and regulations on many multisite fungicides, leading to a pressing need for new management options for control. This review aims to summarise the most current knowledge regarding the biology, virulence factors, ecology, omics and emerging management strategies for Colletotrichum species that cause apple bitter rot. Taxonomy Colletotrichum species—Domain Eukaryota, Kingdom Fungi, Phylum Ascomycota, Class Sordariomycetes, Order Glomerellales, Family Glomerellaceae, Genus Colletotrichum . Biology Hemibiotrophic pathogen with a wide host range that establishes a biotrophic interaction where it penetrates host plants using appressoria followed by a switch to necrotrophy causing rot symptoms. Toxins Cercosporin, colletotrichins, colletotric acid, ferricrocin. Host Range The host range varies by species but largely occurs on dicotyledonous plants and is less prevalent on monocots as well as gymnosperms, ferns, mosses and animals (e.g., insects). Disease Symptoms Symptoms often manifest as flat to sunken necrotic areas on fruit. Lesions on leaves and fruit can have concentric rings with abundant pathogen sporulation. Disease Control Colletotrichum spp. are primarily managed by single‐site quinone outside inhibitor (Qol), methyl benzimidazole carbamate (MBC), demethylation inhibitor (DMI) fungicides, and multisite dithiocarbamate and phthalimide fungicides. Susceptibility may vary with species, strain specificity, or geographic region. Other management options include clean stock production, cultural practices, resistance breeding, and biological control through the introduction of protective or competing microorganisms.

Boeckman, Nathanial J. [Plant Pathology Laboratory↗

Mondo: integrating disease terminology across communities

Precision medicine aims to enhance diagnosis, treatment, and prognosis by integrating multimodal data at the point of care. However, challenges arise due to the vast number of diseases, differing methods of classification, and conflicting terminological coding systems and practices used to represent molecular definitions of disease. This lack of interoperability artificially constrains the potential for diagnosis, clinical decision support, care outcome analysis, as well as data linkage across research domains to support the development or repurposing of therapeutics. There is a clear and pressing need for a unified system for managing disease entities⁠—including identifiers, synonyms, and definitions. To address these issues, we created the Mondo disease ontology—a community-driven, open-source, unified disease classification system that harmonizes diverse terminologies into a consistent, computable framework. Mondo integrates key medical and biomedical terminologies, including Online Mendelian Inheritance in Man (OMIM), Orphanet, Medical Subject Headings (MeSH), National Cancer Institute Thesaurus (NCIt), and more, to provide a comprehensive and accurate representation of disease concepts with fully provenanced and attributed links back to the sources. Mondo can be used as the handle for curation of gene–disease associations utilized in diagnostic applications, research applications such as computational phenotyping, and in clinical coding systems in clinical decision support by pointing the clinician to the numerous knowledge resources linked to the Mondo identifier. Mondo's community-centric approach, stewarded by the Monarch Initiative's expertise in ontologies, ensures that the ontology remains adaptable to the evolving needs of biomedical research and clinical communities, as well as the knowledge providers.

biomedical informatics↗

A haplotype‐resolved reference genome of Quercus alba sheds light on the evolutionary history of oaks

Summary White oak ( Quercus alba ) is an abundant forest tree species across eastern North America that is ecologically, culturally, and economically important. We report the first haplotype‐resolved chromosome‐scale genome assembly of Q. alba and conduct comparative analyses of genome structure and gene content against other published Fagaceae genomes. We investigate the genetic diversity of this widespread species and the phylogenetic relationships among oaks using whole genome data. Despite strongly conserved chromosome synteny and genome size across Quercus , certain gene families have undergone rapid changes in size, including defense genes. Unbiased annotation of resistance (R) genes across oaks revealed that the overall number of R genes is similar across species – as are the chromosomal locations of R gene clusters – but, gene number within clusters is more labile. We found that Q. alba has high genetic diversity, much of which predates its divergence from other oaks and likely impacts divergence time estimations. Our phylogenetic results highlight widespread phylogenetic discordance across the genus. The white oak genome represents a major new resource for studying genome diversity and evolution in Quercus . Additionally, we show that unbiased gene annotation is key to accurately assessing R gene evolution in Quercus .

Larson, Drew A. [Department of Biology Indiana Uni↗

Jasmonate primes plant responses to extracellular ATP

SUMMARYExtracellular ATP (eATP) signaling in Arabidopsis thaliana is mediated by the purinoceptor P2K1. Previous studies have clarified that the downstream transcriptional responses to eATP involve jasmonate (JA)‐based signaling components such as the JA receptor (COI1) and JA‐responsive bHLH transcription factors (MYCs). However, the specific contributions of JA itself on eATP signaling are unexplored. Here, we report that JA primes plant responses to eATP through P2K1. Our findings show that JA treatment significantly upregulates P2K1 transcription, corroborating our observation that JA facilitates eATP‐induced cytosolic calcium elevation and transcriptional reprogramming in a JA signaling‐dependent manner. Additionally, we find that salicylic acid pre‐treatment represses eATP‐induced plant response. These results suggest that JA accumulation during biotic or abiotic stresses potentiates eATP signaling, enabling plants to better cope with subsequent stress events.

Jewell, Jeremy B. [Institute of Biological Chemist↗