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Results for “Complement Activation”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2000

Complement activation promotes muscle inflammation during modified muscle use

Modified muscle use can result in muscle inflammation that is triggered by unidentified events. In the present investigation, we tested whether the activation of the complement system is a component of muscle inflammation that results from changes in muscle loading. Modified rat hindlimb muscle loading was achieved by removing weight-bearing from the hindlimbs for 10 days followed by reloading through normal ambulation. Experimental animals were injected with the recombinant, soluble complement receptor sCR1 to inhibit complement activation. Assays for complement C4 or factor B in sera showed that sCR1 produced large reductions in the capacity for activation of the complement system through both the classical and alternative pathways. Analysis of complement C4 concentration in serum in untreated animals showed that the classical pathway was activated during the first 2 hours of reloading. Analysis of factor B concentration in untreated animals showed activation of the alternative pathway at 6 hours of reloading. Administration of sCR1 significantly attenuated the invasion of neutrophils (-49%) and ED1(+) macrophages (-52%) that occurred in nontreated animals after 6 hours of reloading. The presence of sCR1 also reduced significantly the degree of edema by 22% as compared to untreated animals. Together, these data show that increased muscle loading activated the complement system which then briefly contributes to the early recruitment of inflammatory cells during modified muscle loading.

NASA Discipline Musculoskeletal↗
DOE OSTI2021

Identifying geological structures through microseismic cluster and burst analyses complementing active seismic interpretation

At the Decatur carbon capture and storage site (IL, USA) CO 2 has been injected from 2011–2014 and from 2017 to present near the base of the Lower Mt. Simon Sandstone saline reservoir, resulting in microseismicity. Microseismicity is mainly located in the basement and distributed in distinct spatial clusters. The lack of significant impedance contrasts within the basement makes the interpretation of active-source seismic reflection data challenging, however, recent reprocessing allowed to resolve faults above and at the top of the basement. These faults generally do not coincide with the location of microseismic events and their continuation to the general depth of the seismic events cannot be assumed. This paper shows how the interpretation of the microseismicity can complement structural interpretations of active-source seismic reflection data. In particular, we analyze clusters and bursts (abrupt increases) of microseismicity, identify unresolved, smaller-scale weaknesses and extract statistical parameters. These parameters allow comparisons with the interpreted faults, and with fracture sets intercepted by boreholes. During injection at the Decatur site, the injection pressure was kept far below fracture pressure, nevertheless, seismic events were induced and spread far beyond the expected extent of the CO 2 plume. We argue that local stress transfers related to the CO 2 injection reactivated pre-existing fractures within the critically stressed basement. Finally, we conducted a slip tendency analysis for faults interpreted from active seismic, selected cluster, bursts and nodal planes from focal mechanisms to determine if the interpreted structures are optimally oriented with respect to the stress regime. Our results suggest that the orientation of fractures close to the injection well, generally shows slight deviations from the optimal orientation for slip. This might indicate either slight local deviations of the maximum horizontal stress azimuth from the average direction used in the analysis, or the lack of optimally oriented fractures at this location.

58 GEOSCIENCES↗
DOE OSTI2023

Inhibition of the C1s Protease and the Classical Complement Pathway by 6-(4-Phenylpiperazin-1-yl)Pyridine-3-Carboximidamide and Chemical Analogs

Abstract The classical pathway (CP) is a potent mechanism for initiating complement activity and is a driver of pathology in many complement-mediated diseases. The CP is initiated via activation of complement component C1, which consists of the pattern recognition molecule C1q bound to a tetrameric assembly of proteases C1r and C1s. Enzymatically active C1s provides the catalytic basis for cleavage of the downstream CP components, C4 and C2, and is therefore an attractive target for therapeutic intervention in CP-driven diseases. Although an anti-C1s mAb has been Food and Drug Administration approved, identifying small-molecule C1s inhibitors remains a priority. In this study, we describe 6-(4-phenylpiperazin-1-yl)pyridine-3-carboximidamide (A1) as a selective, competitive inhibitor of C1s. A1 was identified through a virtual screen for small molecules that interact with the C1s substrate recognition site. Subsequent functional studies revealed that A1 dose-dependently inhibits CP activation by heparin-induced immune complexes, CP-driven lysis of Ab-sensitized sheep erythrocytes, CP activation in a pathway-specific ELISA, and cleavage of C2 by C1s. Biochemical experiments demonstrated that A1 binds directly to C1s with a K d of ∼9.8 μM and competitively inhibits its activity with an inhibition constant (K i) of ∼5.8 μM. A 1.8-Å-resolution crystal structure revealed the physical basis for C1s inhibition by A1 and provided information on the structure–activity relationship of the A1 scaffold, which was supported by evaluating a panel of A1 analogs. Taken together, our work identifies A1 as a new class of small-molecule C1s inhibitor and lays the foundation for development of increasingly potent and selective A1 analogs for both research and therapeutic purposes.

Immunology↗
DOE OSTI2025

A bipartite bacterial virulence factor targets the complement system and neutrophil activation

Abstract The complement system and neutrophils constitute the two main pillars of the host innate immune defense against infection by bacterial pathogens. Here, we identify T-Mac, a novel virulence factor of the periodontal pathogen Treponema denticola that allows bacteria to evade both defense systems. We show that T-Mac is expressed as a pre-protein that is cleaved into two functional units. The N-terminal fragment has two immunoglobulin-like domains and binds with high affinity to the major neutrophil chemokine receptors FPR1 and CXCR1, blocking N -formyl-Met-Leu-Phe- and IL-8-induced neutrophil chemotaxis and activation. The C-terminal fragment functions as a cysteine protease with a unique proteolytic activity and structure, which degrades several components of the complement system, such as C3 and C3b. Murine infection studies further reveal a critical T-Mac role in tissue damage and inflammation caused by bacterial infection. Collectively, these results disclose a novel innate immunity-evasion strategy, and open avenues for investigating the role of cysteine proteases and immunoglobulin-like domains of gram-positive and -negative bacterial pathogens.

Kurniyati, Kurni↗
NASA NTRS2010

Things That Work: Roles and Services of SPDF

The current Heliophysics Science Data Management Policy (HpSDMP) defines the roles of the Space Physics Data Facility (SPDF) project as a heliophysics active Final Archive (aFA), a focus for critical data infrastructure services and a center of excellence for data and ancillary information services. This presentation will highlight (1) select current SPDF activities, (2) the lessons we are continuing to learn in how to usefully serve the the heliophysics science community and (3)SPDF's programmatic emphasis in the coming year. In cooperation with the Heliophysics Virtual discipline Observatories (VxOs), we are working closely with current, and with upcoming missions such as RBSP and MMS, to define effective approaches to ensure the long-term availability and archiving of mission data, as well as how SPDF services can complement active mission capabilities. We are working to make the Virtual Space Physics Observatory (VSPO) service comprehensive in all significant and NASA relevant heliophysics data. We will highlight a new CDAWeb interface, a faster SSCWeb, availability of our data through VxO services such as Autoplot, a new capability to easily access our data from within IDL and continuing improvements to CDF including better handling of leap seconds.

McGuire, R. E.↗
DOE OSTI2026

Longitudinal Plasma Proteomic Profiling Reveals Divergent Immune Responses in Durably Cured and Relapsed Pulmonary Tuberculosis

Background: Predicting the risk of tuberculosis (TB) relapse is vital to improving treatment outcomes. Although clinical risk factors of relapse are well characterized, the biological mechanisms driving relapse, particularly host immune responses, remain poorly understood. Elucidating these mechanisms is necessary to better predict relapse risk. Methods: We conducted a longitudinal, global proteomic study on 60 participants with active pulmonary TB, half who were durably cured and half who relapsed. Plasma was collected at seven time-points: at treatment initiation (baseline), during therapy, and 52 weeks post-baseline. Samples were analyzed by high-resolution LC-MS/MS. Results: 2,418 proteins were identified across all samples, with 1,756 being differentially expressed relative to baseline (unadjusted p < 0.05). 956 proteins were differentially abundant between cured and relapsed participants. Relapsed participants showed heightened humoral immunity throughout treatment, as well as upregulated complement activation and HDL particles. Cured participants exhibited elevated recovery-related pathways by week 4, including downregulated epithelial invasion and upregulated oxygen transport. Conclusions: Heightened humoral and innate immune responses were associated with relapse, whereas recovery signatures were associated with durable cure. These findings advance our understanding of host responses to treatment and provide a basis for developing blood-based biomarkers to identify patients at increased risk of relapse.

LC-MS/MS↗
NASA NTRS2016

Enabling Research Tools for Sustained Climate Assessment

The U.S. Global Change Research Program Sustained Assessment process benefits from long-term investments in Earth science research that enable the scientific community to conduct assessment-relevant science. To this end, NASA initiated several research programs over the past five years to support the Earth observation community in developing indicators, datasets, research products, and tools to support ongoing and future National Climate Assessments. These activities complement NASA's ongoing Earth science research programs. One aspect of the assessment portfolio funds four "enabling tools" projects at NASA research centers. Each tool leverages existing capacity within the center, but has developed tailored applications and products for National Climate Assessments. The four projects build on the capabilities of a global atmospheric reanalysis (MERRA-2), a continental U.S. land surface reanalysis (NCA-LDAS), the NASA Earth Exchange (NEX), and a Regional Climate Model Evaluation System (RCMES). Here, we provide a brief overview of each enabling tool, highlighting the ways in which it has advanced assessment science to date. We also discuss how the assessment community can access and utilize these tools for National Climate Assessments and other sustained assessment activities.

Research↗
DOE OSTI2020

Quantitative Protein Corona Composition and Dynamics on Carbon Nanotubes in Biological Environments

When nanoparticles enter biological environments, proteins adsorb to form the "protein corona" which alters nanoparticle biodistribution and toxicity. Herein, we measure protein corona formation on DNA-functionalized single-walled carbon nanotubes (ssDNA-SWCNTs), a nanoparticle used widely for sensing and delivery, in blood plasma and cerebrospinal fluid. We characterize corona composition by mass spectrometry, revealing high-abundance corona proteins involved in lipid binding, complement activation, and coagulation. We investigate roles of electrostatic and entropic interactions driving selective corona formation. Lastly, we study real-time protein binding on ssDNA-SWCNTs, obtaining agreement between enriched proteins binding strongly and depleted proteins binding marginally, while highlighting cooperative adsorption mechanisms. Knowledge of protein corona composition, formation mechanisms, and dynamics informs nanoparticle translation from in vitro design to in vivo application.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Activity-based protein profiling of chitin catabolism

Microbial catabolism of chitin, a highly abundant component of polymeric organic matter worldwide, is a fundamental cog in the carbon and nitrogen cycles that govern CO2 emissions, nutrient dynamics in aquatic systems, and soil vitality. Despite this critical biogeochemical function, we have a poor understanding of the synergy between various microbial chitinases and key accessory enzymes involved in chitin catabolism. We designed and synthesized activity-based probes (ABPs) for profiling active chitinolytic enzymes by modifying the chitin derivatives N-acetyl glucosamine and chitotriose. The ABPs were used to determine the active complement of chitinolytic enzymes produced over time by the soil bacterium Cellvibrio japonicus treated with various C substrates. This approach allowed us to demonstrate the utility of these ABPs in determining the intricate synergy between chitinases and other glycoside hydrolases that microbes employ to catabolize chitin. The strategy can be used to gain molecular level insights that can be used to better understand microbial roles in soil C and N cycling in the face of a changing climate.

Zegeye, Elias↗
DOE OSTI2020

Proteomic assessment of serum biomarkers of longevity in older men

The biological bases of longevity are not well understood, and there are limited biomarkers for the prediction of long life. We used a high-throughput, discovery-based proteomics approach to identify serum peptides and proteins that were associated with the attainment of longevity in a longitudinal study of community-dwelling men age ≥65 years. Baseline serum in 1196 men were analyzed using liquid chromatography–ion mobility–mass spectrometry, and lifespan was determined during ~12 years of follow-up. Men who achieved longevity (≥90% expected survival) were compared to those who died earlier. Rigorous statistical methods that controlled for false positivity were utilized to identify 25 proteins that were associated with longevity. All these proteins were in lower abundance in long-lived men and included a variety involved in inflammation or complement activation. Lower levels of longevity-associated proteins were also associated with better health status, but as time to death shortened, levels of these proteins increased. Pathway analyses implicated a number of compounds as important upstream regulators of the proteins and implicated shared networks that underlie the observed associations with longevity. Overall, these results suggest that complex pathways, prominently including inflammation, are linked to the likelihood of attaining longevity. This work may serve to identify novel biomarkers for longevity and to understand the biology underlying lifespan.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Lipoprotein subfraction patterns throughout gestation in The Gambia: changes in subfraction composition and their relationships with infant birth weights

Lipoprotein subfraction concentrations have been shown to change as gestation progresses in resource-rich settings. The objective of the current study was to evaluate the impact of pregnancy on different-sized lipoprotein particle concentrations and compositions in a resource-poor setting. Samples were collected from pregnant women in rural Gambia at enrollment (8–20 weeks), 20 weeks, and 30 weeks of gestation. Concentrations of different-sized high-density, low-density, and triglyceride-rich lipoprotein particles (HDL, LDL, and TRL, respectively) were measured by nuclear magnetic resonance in 126 pooled plasma samples from a subset of women. HDL was isolated and the HDL proteome evaluated using mass spectroscopy. Subfraction concentrations from women in The Gambia were also compared to concentrations in women in the U.S. in mid gestation. Total lipoprotein particles and all-sized TRL, LDL, and HDL particle concentrations increased during gestation, with the exception of medium-sized LDL and HDL particles which decreased. Subfraction concentrations were not associated with infant birth weights, though relationships were found between some lipoprotein subfraction concentrations in women with normal versus low birth weight infants (< 2500 kg). HDL’s proteome also changed during gestation, showing enrichment in proteins associated with metal ion binding, hemostasis, lipid metabolism, protease inhibitors, proteolysis, and complement activation. Compared to women in the U.S., Gambian women had lower large- and small-sized LDL and HDL concentrations, but similar medium-sized LDL and HDL concentrations. Most lipoprotein subfraction concentrations increase throughout pregnancy in Gambian women and are lower in Gambian vs U.S. women, the exception being medium-sized LDL and HDL particle concentrations which decrease during gestation and are similar in both cohorts of women. The proteomes of HDL also change in ways to support gestation. These changes warrant further study to determine how a lack of change or different changes could impact negative pregnancy outcomes.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2008

International Space Station Medical Project

The goals and objectives of the ISS Medical Project (ISSMP) are to: 1) Maximize the utilization the ISS and other spaceflight platforms to assess the effects of longduration spaceflight on human systems; 2) Devise and verify strategies to ensure optimal crew performance; 3) Enable development and validation of a suite of integrated physical (e.g., exercise), pharmacologic and/or nutritional countermeasures against deleterious effects of space flight that may impact mission success or crew health. The ISSMP provides planning, integration, and implementation services for Human Research Program research tasks and evaluation activities requiring access to space or related flight resources on the ISS, Shuttle, Soyuz, Progress, or other spaceflight vehicles and platforms. This includes pre- and postflight activities; 2) ISSMP services include operations and sustaining engineering for HRP flight hardware; experiment integration and operation, including individual research tasks and on-orbit validation of next generation on-orbit equipment; medical operations; procedures development and validation; and crew training tools and processes, as well as operation and sustaining engineering for the Telescience Support Center; and 3) The ISSMP integrates the HRP approved flight activity complement and interfaces with external implementing organizations, such as the ISS Payloads Office and International Partners, to accomplish the HRP's objectives. This effort is led by JSC with Baseline Data Collection support from KSC.

Starkey, Blythe A.↗
NASA NTRS2009

Individual Susceptibility to Hypobaric Environments: An Update

Astronauts are at risk for developing decompression sickness (DCS) while exposed to the hypobaric environment of the extravehicular suit in space, in terrestrial hypobaric chambers, and during ascent from neutral buoyancy training dives. There is increasing recognition that DCS risk is different between diving and altitude exposures, with many individual parameters and environmental factors implicated as risk factors for development of DCS in divers but are not recognized as risk factors in altitude exposures. Much of the literature to date has focused on patent foramen ovale (PFO), which has long been considered a major risk factor for DCS in diving exposures, but its link to serious DCS in altitude exposures remains unclear. Knowledge of those risk factors specific to hypobaric DCS may help identify susceptible individuals and aid in astronaut selection, crew assignment, and mission planning. This paper reviews the current literature pertaining to these risk factors, including PFO, anthropometric parameters, gender, menstrual cycle, lifetime diving experience, physical fitness, biochemical levels, complement activation, cigarette smoking, fluid balance, and ambient temperature. Further research to evaluate pertinent risk factors for DCS in altitude exposures is recommended.

Law, Jennifer↗
NASA NTRSDate not supplied

COSMIR-H: an Airborne Hyperspectral Microwave Sounder for Thermodynamic Sensing of the Planetary Boundary Layer

The NASA Planetary Boundary Layer (PBL) Incubation Study Team Report lists hyperspectral microwave (HMW) sensors as one of the “essential components” of a future global PBL observing system. HMW sensors will provide profiles of the PBL thermodynamic (temperature and water vapor) structure in synergy with passive infrared sounders and to complement active measurements (e.g., lidar and radar). While many simulation studies have been performed showing the benefit of HMW observations, measurements are needed to demonstrate the efficacy of hyperspectral retrievals. The Conical Scanning Millimeter-wave Imaging Radiometer (CoSMIR) is an airborne sensor that is currently being modified with digital spectrometers to create a HMW sounder with 4-MHz spectral resolution at 50.0-58.0 GHz and 175-191 GHz. The new CoSMIR-Hyperspectral (CoSMIRH) will collect measurements in July 2024 on the highaltitude NASA ER-2 aircraft. These measurements will advise on current knowledge gaps in HMW sounding and inform decisions on future spaceborne HMW sensors

radiometry↗
NASA NTRS2002

Interactions between muscle and the immune system during modified musculoskeletal loading

Interactions between the immune system and skeletal muscle may play a significant role in modulating the course of muscle injury and repair after modified musculoskeletal loading. Current evidence indicates that activation of the complement system is an early event during modified loading, which then leads to inflammatory cell invasion. However, the functions of those inflammatory cells are complex and they seem to be capable of promoting additional injury and repair. Recent findings implicate an early invading neutrophil population in increasing muscle damage that is detected by the presence of muscle membrane lesions. Macrophages that invade subsequently serve to remove cellular debris, and seem to promote repair. However, macrophages also have the ability to increase damage in muscle in which there is an impaired capacity to generate nitric oxide. In vivo and in vitro evidence indicates that muscle-derived nitric oxide can serve an important role in protecting muscle from membrane damage by invading inflammatory cells. Collectively, these findings indicate that the dynamic balance between inflammatory cells, the complement system, and muscle-derived free radicals can play important roles in the secondary damage of muscle during modified musculoskeletal loading.

Review↗
NASA NTRS2010

NASA Education Activities on the International Space Station: A National Laboratory for Inspiring, Engaging, Educating and Employing the Next Generation

The International Space Station (ISS) National Lab Education Project has been created as a part of the ISS National Lab effort mandated by the U.S. Congress The project seeks to expand ISS education of activities so that they reach a larger number of students with clear educational metrics of accomplishments. This paper provides an overview of several recent ISS educational payloads and activities. The expected outcomes of the project, consistent with those of the NASA Office of Education, are also described. NASA performs numerous education activities as part of its ISS program. These cover the gamut from formal to informal educational opportunities in grades Kindergarten to grade 12, Higher Education (undergraduate and graduate University) and informal educational venues (museums, science centers, exhibits). Projects within the portfolio consist of experiments performed onboard the ISS using onboard resources which require no upmass, payloads flown to ISS or integrated into ISS cargo vehicles, and ground based activities that follow or complement onboard activities. Examples include ground based control group experiments, flight or experiment following lesson plans, ground based activities involving direct interaction with ISS or ground based activities considering ISS resources in their solution set. These projects range from totally NASA funded to projects which partner with external entities. These external agencies can be: other federal, state or local government agencies, commercial entities, universities, professional organizations or non-profit organizations. This paper will describe the recent ISS education activities and discuss the approach, outcomes and metrics associated with the projects.

Severance, Mark T.↗
NASA NTRS2012

2012 Robotics Activities at JPL

The Robotics Section of the Jet Propulsion Laboratory (JPL), California Institute of Technology, is engaged in a full spectrum of flight project and research activities. This paper will provide an overview of these efforts, and discuss the recent accomplishments and future directions of them. Specific activities will be high- lighted based on their level of accomplishment, impact on the community, maturity, or novelty. Robotics activities on flight projects are a significant subset of the full effort for these large missions. Complementing flight activities is a diverse set of research efforts for NASA and other U.S. Government agencies. Future directions will be motivated by NASA and other sponsor objectives, as well as success experienced in these current endeavours.

planetary exploration↗