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At least 109 records · Page 6
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Spatial Glycomics and Kidney Disease

Glycans are critical for the kidney's physiological and pathological cellular functions, and our ability to reveal their spatial distributions within tissues has helped us reveal how these carbohydrate moieties are involved in many of these processes. This review discusses the role of different types of glycans in kidney biology and disease, common approaches used for glycan imaging, and how glycan imaging has helped us better understand kidney pathology. Here, we mainly focus on emerging methods using mass spectrometry imaging (MSI) because this technology is untargeted and provides complete information on glycan composition compared to the other methods, such as lectin and metabolite labeling, which are targeted and often inform only on the specific part of a glycan structure. We especially focus on protein N-glycosylation, as this is one of the most common post-translational modifications, and these moieties play a vital role in renal structure and function. The recent advancements in MSI of N-glycans we reviewed have provided new insights into the pathophysiology of the kidney and paved the way for clinical application.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2002

Solar Supergranulation Revealed as a Superposition of Traveling Waves

40 years ago two new solar phenomena were described: supergranulation and the five-minute solar oscillations. While the oscillations have since been explained and exploited to determine the properties of the solar interior, the supergranulation has remained unexplained. The supergranules, appearing as convective-like cellular patterns of horizontal outward flow with a characteristic diameter of 30 Mm and an apparent lifetime of 1 day, have puzzling properties, including their apparent superrotation and the minute temperature variations over the cells. Using a 60-day sequence of data from the MDI (Michelson-Doppler Imager) instrument onboard the SOHO (Solar and Heliospheric Observatory) spacecraft, we show that the supergranulation pattern is formed by a superposition of traveling waves with periods of 5-10 days. The wave power is anisotropic with excess power in the direction of rotation and toward the equator, leading to spurious rotation rates and north-south flows as derived from correlation analyses. These newly discovered waves could play an important role in maintaining differential rotation in the upper convection zone by transporting angular momentum towards the equator.

Gizon, L.↗
NASA NTRS2003

Cellular Instabilities and Self-Acceleration of Expanding Spherical Flames

In the present investigation we aim to provide experimental information on and thereby understanding of the generation and propagation of spark-ignited, outwardly propagating cellular flames, with three major focuses. The first is to unambiguously demonstrate the influence of the four most important parameters in inducing hydrodynamic and diffusional-thermal cellularities, namely thermal expansion, flame thickness, non-unity Lewis number, and global activation energy. The second is to investigate the critical state for the onset of cellularity for the stretch-affected, expanding flame. The third is to identify and consequently quantify the phenomena of self-acceleration and possibly auto-turbulization of cellular flames. Due to space limitation the effects of activation energy and the critical state for the onset of cellularity will not be discussed herein. Experiments were conducted using C3H8-air and H2-O2-N2 mixtures for their opposite influences of non-equidiffusivity. The additional system parameters varied were the chamber pressure (p) and the mixture composition including the equivalence ratio (phi). From a sequence of the flame images we can assess the propensity of cell formation, and determine the instantaneous flame radius (R), the flame propagation rate, the global stretch rate experienced by the flame, the critical flame radius at which cells start to grow, and the average cell size.

Law, C. K.↗
NASA NTRS1985

Aerodynamic properties of turbulent combustion fields

Flow fields involving turbulent flames in premixed gases under a variety of conditions are modeled by the use of a numerical technique based on the random vortex method to solve the Navier-Stokes equations and a flame propagation algorithm to trace the motion of the front and implement the Huygens principle, both due to Chorin. A successive over-relaxation hybrid method is applied to solve the Euler equation for flows in an arbitrarily shaped domain. The method of images, conformal transformation, and the integral-equation technique are also used to treat flows in special cases, according to their particular requirements. Salient features of turbulent flame propagation in premixed gases are interpreted by relating them to the aerodynamic properties of the flow field. Included among them is the well-known cellular structure of flames stabilized by bluff bodies, as well as the formation of the characteristic tulip shape of flames propagating in ducts. In its rudimentary form, the mechanism of propagation of a turbulent flame is shown to consist of: (1) rotary motion of eddies at the flame front, (2) self-advancement of the front at an appropriate normal burning speed, and (3) dynamic effects of expansion due to exothermicity of the combustion reaction. An idealized model is used to illustrate these fundamental mechanisms and to investigate basic aerodynamic features of flames in premixed gases. The case of a confined flame stabilized behind a rearward-facing step is given particular care and attention. Solutions are shown to be in satisfactory agreement with experimental results, especially with respect to global properties such as the average velocity profiles and reattachment length.

Hsiao, C. C.↗
NASA NTRS2000

Bioenergetics and mitochondrial transmembrane potential during differentiation of cultured osteoblasts

To evaluate the relationship between osteoblast differentiation and bioenergetics, cultured primary osteoblasts from fetal rat calvaria were grown in medium supplemented with ascorbate to induce differentiation. Before ascorbate treatment, the rate of glucose consumption was 320 nmol. h(-1). 10(6) cells(-1), respiration was 40 nmol. h(-1). 10(6) cells(-1), and the ratio of lactate production to glucose consumption was approximately 2, indicating that glycolysis was the main energy source for immature osteoblasts. Ascorbate treatment for 14 days led to a fourfold increase in respiration, a threefold increase in ATP production, and a fivefold increase in ATP content compared with that shown in immature cells. Confocal imaging of mitochondria stained with a transmembrane potential-sensitive vital dye showed that mature cells possessed abundant amounts of high-transmembrane-potential mitochondria, which were concentrated near the culture medium-facing surface. Acute treatment of mature osteoblasts with metabolic inhibitors showed that the rate of glycolysis rose to maintain the cellular energy supply constant. Thus progressive differentiation coincided with changes in cellular metabolism and mitochondrial activity, which are likely to play key roles in osteoblast function.

NASA Center ARC↗
NASA NTRS2007

Simplified Microarray Technique for Identifying mRNA in Rare Samples

Two simplified methods of identifying messenger ribonucleic acid (mRNA), and compact, low-power apparatuses to implement the methods, are at the proof-of-concept stage of development. These methods are related to traditional methods based on hybridization of nucleic acid, but whereas the traditional methods must be practiced in laboratory settings, these methods could be practiced in field settings. Hybridization of nucleic acid is a powerful technique for detection of specific complementary nucleic acid sequences, and is increasingly being used for detection of changes in gene expression in microarrays containing thousands of gene probes. A traditional microarray study entails at least the following six steps: 1. Purification of cellular RNA, 2. Amplification of complementary deoxyribonucleic acid [cDNA] by polymerase chain reaction (PCR), 3. Labeling of cDNA with fluorophores of Cy3 (a green cyanine dye) and Cy5 (a red cyanine dye), 4. Hybridization to a microarray chip, 5. Fluorescence scanning the array(s) with dual excitation wavelengths, and 6. Analysis of the resulting images. This six-step procedure must be performed in a laboratory because it requires bulky equipment.

Almeida, Eduardo↗
DOE OSTI2025

Photothermal Properties of Nanostructured Black Titanium Dioxide for Targeted Cellular and Microbial Elimination

Heterophase black titanium dioxide (hB-TiO 2 ), characterized by broadened near-infrared (NIR) absorption, has emerged as a promising photothermally active nanomaterial. This study focused on the synthesis of nanoscale hB-TiO 2 and its evaluation as a multifunctional agent for photothermal therapy (PTT). The purity and composition of the mixed-phase nanoscale hB-TiO 2 were demonstrated by X-ray diffraction, and the morphology of nanoparticles was imaged by transmission electron microscopy. Extensive additional characterization was conducted to validate the optoelectronic properties. The material was further evaluated in biological systems using NIH 3T3-GFP fibroblasts and the fungus Candida albicans. Nanoscale hB-TiO 2 exhibited good biocompatibility in the absence of laser irradiation and effectively ablated both NIH 3T3-GFP cells and C. albicans following 20 min of laser exposure. This noninvasive treatment strategy leverages NIR-responsive materials to induce localized hyperthermia. The findings provide grounds for the use of selectively induced hyperthermia, which could be employed for the targeted destruction of cells or fungi with minimal impact on surrounding tissue if the material is functionalized with specific targeting groups and delivered to cells or fungal infections.

Irradiation↗
DOE OSTI2024

CT584 Is Not a Protective Vaccine Antigen against Respiratory Chlamydial Challenge in Mice

Background: Chlamydia trachomatis is the most prevalent bacterial sexually transmitted pathogen in humans worldwide. Since chlamydial infection is largely asymptomatic with the potential for serious complications, a preventative vaccine is likely the most viable long-term answer to this public health threat. Cell-free protein synthesis (CFPS) utilizes the cellular protein manufacturing machinery decoupled from the requirement for maintaining cellular viability, offering the potential for flexible, rapid, and decentralized production of recombinant protein vaccine antigens. Methods: Here, we use CFPS to produce the full-length putative chlamydial type three secretion system (T3SS) needle-tip protein, CT584, for evaluation as a vaccine antigen in mouse models. High-speed atomic force microscopy (HS-AFM) (RIBM, Tsukuba, Japan) imaging and computer simulations confirm that CFPS-produced CT584 retains a native-like structure prior to immunization. Female mice were primed with CT584 adjuvanted with CpG-1826 intranasally (i.n.) or CpG-1826 + Montanide ISA 720 intramuscularly (i.m.), followed four weeks later by an i.m. boost before respiratory challenge with 10 4 inclusion forming units (IFU) of Chlamydia muridarum. Results: Immunization with CT584 generated robust antibody responses but weak cell-mediated immunity and failed to protect against i.n. challenge as demonstrated by body weight loss, increased lung weights, and the presence of high numbers of IFUs in the lungs. Conclusion: While CT584 was not a protective vaccine candidate, the speed and flexibility with which CFPS can be used to produce other potential chlamydial antigens make it an attractive technique for antigen production.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1996

Vitamin D endocrine system after short-term space flight

The exposure of the body to microgravity during space flight causes a series of well-documented changes in Ca(2+) metabolism, yet the cellular/molecular mechanisms leading to these changes are poorly understood. There is some evidence for microgravity-induced alterations in the vitamin D endocrine system, which is known to be primarily involved in the regulation of Ca(2+) metabolism. Vitamin D-dependent Ca(2+) binding proteins, or calbindins, are believed to have a significant role in maintaining cellular Ca(2+) homeostasis. We used immunocytochemical, biochemical and molecular approaches to analyze the expression of calbindin-D(sub 28k) and calbindin-D(sub 9k) in kidneys and intestines of rats flown for 9 days aboard the Spacelab 3 mission. The effects of microgravity on calbindins in rats in space vs. 'grounded' animals (synchronous Animal Enclosure Module controls and tail suspension controls) were compared. Exposure to microgravity resulted in a significant decrease in calbindin-D(sub 28k) content in kidneys and calbindin-D(sub 9k) in the intestine of flight and suspended animals, as measured by enzyme-linked immunosorbent assay (ELISA). Immunocytochemistry (ICC) in combination with quantitative computer image analysis was used to measure in situ the expression of calbindins in kidneys and intestine, and insulin in pancreas. There was a large decrease in the distal tubular cell-associated calbindin-D(sub 28k) and absorptive cell-associated calbindin-D(sub 9k) immunoreactivity in the space and suspension kidneys and intestine, as compared with matched ground controls. No consistent differences in pancreatic insulin immunoreactivity between space, suspension and ground controls was observed. There were significant correlations between results by quantitative ICC and ELISA. Western blot analysis showed no consistent changes in the low levels of intestinal and renal vitamin D receptors. These findings suggest that a decreased expression of calbindins after a short-term exposure to microgravity and modelled weightlessness, may affect cellular Ca(2+) homeostasis and contribute to Ca(2+) and bone metabolism disorders induced by space flight.

Rhoten, William B.↗
NASA NTRS1985

Pattern formation by particles settling in viscous flows

Results are reported of several simulations of the motions of small objects in two-dimensional cellular flows performed to study the evolution of the distributions of particle flows over time in processes such as sedimentation. Stream functions are defined in the form of a Hamiltonian system for the particle motions, with inertial and particle acceleration being neglected. Conditions are found for which the particles will become trapped in an oscillatory motion or the particle orbits attain an oscillary motion. Various simulation images are provided to illustrate the usefulness of the technique for modeling fractal swarms.

Smith, L. A.↗
NASA NTRS1998

Space Tissue Loss Configuration B (STL-B)

The goal of these experiments was to determine the effect of microgravity on the early development of the fish medaka. There were two objectives for this flight series. The primary objective was to assess the effects of microgravity on different stages of development and to ascertain whether the relevant developmental questions can be addressed at the gross morphological level or if the issues involve more subtle questions about regulation at the molecular and cellular levels. The secondary objective was the assessment of the utility of flight hardware with the capabilities to perform embryological studies. We have been able to take advantage of the flight testing phase of the STL-B hardware to also study the effects of microgravity on the early development of the fish, Medaka. Our initial studies involved monitoring the early Medaka development and raising flight embryos for breeding. Images of the developing embryos were collected either via video which was either taken by the astronauts or broadcast to Earth. Sample video images were digitized and stored on a hard drive resident within the on-board STL-B unit. Embryos were fixed at specific intervals, returned to Earth and are being analyzed for the timing and location of molecular events associated with controlling the morphological pattern for the onset of adult structures.

Source record↗
NASA NTRS1995

Development of the Fish Medaka in Microgravity

The goal of these experiments was to determine the effect of microgravity on the early development of the fish medaka. There were two objectives for this flight series. The primary objective was to assess the effects of microgravity on different stages of development and to ascertain whether the relevant developmental questions can be addressed at the gross morphological level or if the issues involve more subtle questions about regulation at the molecular and cellular levels. The secondary objective was the assessment of the utility of flight hardware with the capabilities to perform embryological studies. We have been able to take advantage of the flight testing phase of the STL-B hardware to also study the effects of microgravity on the early development of the fish, Medaka. Our initial studies involved monitoring the early Medaka development and raising flight embryos for breeding. Images of the developing embryos were collected either via video which was either taken by the astronauts or broadcast to Earth. Sample video images were digitized and stored on a hard drive resident within the on-board STL-B unit. Embryos were fixed at specific intervals, returned to Earth and are being analyzed for the timing and location of molecular events associated with controlling the morphological pattern for the onset of adult structures.

Wolgemuth, Debra J.↗
NASA NTRS2016

Biomolecular Analysis Capability for Cellular and Omics Research on the International Space Station

International Space Station (ISS) assembly complete ushered a new era focused on utilization of this state-of-the-art orbiting laboratory to advance science and technology research in a wide array of disciplines, with benefits to Earth and space exploration. ISS enabling capability for research in cellular and molecular biology includes equipment for in situ, on-orbit analysis of biomolecules. Applications of this growing capability range from biomedicine and biotechnology to the emerging field of Omics. For example, Biomolecule Sequencer is a space-based miniature DNA sequencer that provides nucleotide sequence data for entire samples, which may be used for purposes such as microorganism identification and astrobiology. It complements the use of WetLab-2 SmartCycler"TradeMark", which extracts RNA and provides real-time quantitative gene expression data analysis from biospecimens sampled or cultured onboard the ISS, for downlink to ground investigators, with applications ranging from clinical tissue evaluation to multigenerational assessment of organismal alterations. And the Genes in Space-1 investigation, aimed at examining epigenetic changes, employs polymerase chain reaction to detect immune system alterations. In addition, an increasing assortment of tools to visualize the subcellular distribution of tagged macromolecules is becoming available onboard the ISS. For instance, the NASA LMM (Light Microscopy Module) is a flexible light microscopy imaging facility that enables imaging of physical and biological microscopic phenomena in microgravity. Another light microscopy system modified for use in space to image life sciences payloads is initially used by the Heart Cells investigation ("Effects of Microgravity on Stem Cell-Derived Cardiomyocytes for Human Cardiovascular Disease Modeling and Drug Discovery"). Also, the JAXA Microscope system can perform remotely controllable light, phase-contrast, and fluorescent observations. And upcoming confocal microscopy capability will allow for optical sectioning of biological tissues to determine microanatomical localization of biomarkers. Furthermore, NASA's geneLAB effort addresses integration of genomic, epigenomic, transcriptomic, proteomic and metabolomic datasets, by applying an innovative open source science platform for multi-investigator high throughput utilization of the ISS. In sum, the expanding ISS capability for analysis of biomolecules is enabling innovative research in a broad spectrum of areas such as cellular and molecular biology, biotechnology, tissue engineering, biomedicine, and Omics, providing manifold benefits for humanity.

Guinart-Ramirez, Y.↗
NASA NTRS2002

Biosensors for Real-Time Monitoring of Radiation-Induced Biologic Effects in Space

This proposal seeks to develop cellular biosensors based on dendritic polymers. Nanoscale polymer structures less than 20 nm in diameter will be used as the basis of the sensor/actuators. The structures will be designed to target into specific cells of an astronaut and be able to monitor health issues such as the exposure to radiation or infectious agents. Multiple components can be assembled on the polymers including target directors, analytical devices (such as molecular probes), magnetic particles and metals, and imaging agents. The design and assembly of these devices has been pioneered at the Center for Biologic Nanotechnology in the University of Michigan. These molecules would also be able to administer therapeutics in response to the needs of the astronaut, and act as actuators to remotely manipulate an astronaut as necessary to ensure their safety. The reporting will be accomplished either through fluorescence signal monitoring, with the use of multispectral analysis for signal interpretation, or through functional MRI. These nanosensors coupled to NEMS devices could facilitate the success and increase the safety of extended space flight.

Baker, James R., Jr.↗
DOE OSTI2025

Prediction of α $IIb$ $β$ 3 integrin structures along its minimum free energy activation pathway

The adhesion protein integrin is a transmembrane heterodimer that plays a pivotal role in cellular processes such as cell signaling and cell migration. To execute its function, integrin undergoes extensive conformational changes from a bent-closed to an extended-open state. Resolving the structures across these changes remains a challenge with both experimental and computational methods, but it is crucial for understanding the activation mechanism of integrin. We address this challenge for the platelet integrin α IIb β 3 by employing finite temperature string method with structures of the images along the initial guess path generated by a multiscale data-driven framework. The full-length all-atom structures along the resulting minimum free energy path between the inactive bent-closed and active extended-open states of α IIb β 3 integrin are consistent with a variety of experimentally resolved structures. Changes in these predicted structures along the path show that the extension and separation of the α and β subunits from the bent-closed to the extended-open state require correlated movements between the subdomain pairs in α IIb β 3 . Furthermore, these results provide new insights into integrin activation mechanism, and the predicted structures have potential applications in guiding the design of integrin-targeting therapeutics.

Dasetty, Siva [University of Chicago, IL (United S↗
DOE OSTI2025

Integrating N -glycan and CODEX imaging reveal cell-specific protein glycosylation in healthy human lung

Identifying cell-specific glycan structures in human lungs is critical for understanding the chemistry and mechanisms that guide cell–cell and cell–matrix interactions and determining nuanced functions of specific glycosylation. Our dual-modality omics platform, which uses matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to profile glycan chemistry at 50 μm × 50 μm scale, combined with co-detection by indexing (CODEX) to provide cell identification from the exact same tissue section, is a significant step in this direction. It enabled us to detect, differentiate, and reveal chemical properties of N-glycans in the various cell types of a human lung, suggesting the cell-specific function of distinct carbohydrate moieties. This innovative technological combination bridges the gap between the specific protein glycosylation and their cellular origin, paving the way for targeted studies in the lungs and many other human tissues where glycans mediate cell–cell recognition events.

Veličković, Dušan [Pacific Northwest National Labo↗
NASA NTRS1994

Climatic, eustatic, and tectnoic controls on Quarternary deposits and landforms, Red Sea coast, Egypt

The degree to which local climatic variations, eustatic sea level fluctuations, and tectonic uplift have influenced the development of Quaternary marine and fluvial landforms and deposits along the Red Sea coast, Eastern Desert, was investigated using a combination of remote sensing and field data, age determinations of corals, and numerical simulations. False color composites generated from Landsat Thematic Mapper and SPOT image data, digital elevation models derived from sterophotogrammetric analysis of SPOT data, and field observations document that a approximately 10-km wide swath inland from the coast is covered in many places with coalescing alluvial fans of Quaternary age. Wadis cutting through the fans exhibit several pairs of fluvial terraces, and wadi walls expose alluvium interbedded with corraline limestone deposits Further, three distinct coral terraces are evident along the coatline. Climatic, eustatic, and tectonic uplift controls on the overall system were simulated using a cellular automata algorithm with the following characteristics: (1) uplift as a function of position and time, as defined by the elevations and ages of corals; (2) climatic variations driven by insolation changes associated with Milankovitch cycles; (3) sea level fluctuations based on U/Th ages of coral terraces and eustatic data; and (4) parametrized fluvial erosion and deposition. Results imply that the fans and coralline limestones were generated in a setting in which the tectonic uplift rate decreased over the Quarternary to negligible values at present. Coralline limestones formed furing eustatic highstands when alluvium was trapped uspstream and wadis filled with debris. During lowstands, wadis cut into sedimentary deposits; coupled with continuing uplift, fans were dissected, leaving remnant surfaces, and wadi-related terraces were generated by down cutting. Only landforms from the past three to four eustatic sea level cycles (i.e., approximately 300 to 400 kyr) are likely to have survived erosion and deposition associated with fluvial processes.

Arvidson, Raymond↗
NASA NTRS1999

Directional Solidification of Pure Succinonitrile and a Succinonitrile-Acetone Alloy

An experimental study of the horizontal Bridgman growth of pure succinonitrile (SCN) and of a succinonitrile-1.0 mol.% acetone alloy (SCN-1.0 mol.% ACE) has been performed. Experiments involving both a stationary thermal field (no-growth case) and a translating thermal field (growth case) were conducted. Growth rates of 2 and 40 micrometers/s were investigated. For the pure SCN experiments, the velocity field in the melt was estimated using video images of seed particles in the melt. Observations of the seed particles indicate that a primary longitudinal convective cell is formed. The maximum velocity of two different particles which traveled along similar paths was the same and equal to 1.49 +/- 0.01 mm/s. The general accuracy of velocity measurements is estimated to be +/- 0.08 mm/s, though the data shows consistency to within +/- 0.02 mm/s. The shape of the solid/liquid interface was also quantitatively determined. The solid/liquid interface was stable (non-dendritic and non-cellular) but not flat; rather it was significantly distorted by the influence of convection in (he melt and, for the growth case, by the moving temperature boundary conditions along the ampoule. It was found that the interface shape and position were highly dependent on the alignment of the ampoule in the apparatus. Consequently, the ampoule was carefully aligned for all experiments. The values for front location agree with those determined in previous experiments. For the alloy experiments, the solid/liquid interface was determined to be unstable at growth rates greater than 2.8 micrometers/s, but stable for the cases of no-growth and growth at 2 micrometers/s. When compared to the shape of the pure SCN interface, the alloy interface forms closer to the cold zone, indicating that the melting temperature decreased due to the alloying element. Extensive temperature measurements were performed on the outside of the ampoule containing pure SCN. The resulting thermal profiles are presented in detail in the results section. It is intended that the interface shape, thermal boundary condition and velocity data presented in this paper be used to test numerical simulations.

Simpson, James E.↗