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Results for “germinal center”

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
DOE OSTI2022

A Coarse-Grained Model of Affinity Maturation Indicates the Importance of B-Cell Receptor Avidity in Epitope Subdominance

The elicitation of broadly neutralizing antibodies (bnAbs) is a major goal in the design of vaccines against rapidly-mutating viruses. In the case of influenza, many bnAbs that target conserved epitopes on the stem of the hemagglutinin protein (HA) have been discovered. However, these antibodies are rare, are not boosted well upon reinfection, and often have low neutralization potency, compared to strain-specific antibodies directed to the HA head. Different hypotheses have been proposed to explain this phenomenon. We use a coarse-grained computational model of the germinal center reaction to investigate how B-cell receptor binding valency affects the growth and affinity maturation of competing B-cells. We find that receptors that are unable to bind antigen bivalently, and also those that do not bind antigen cooperatively, have significantly slower rates of growth, memory B-cell production, and, under certain conditions, rates of affinity maturation. The corresponding B-cells are predicted to be outcompeted by B-cells that bind bivalently and cooperatively. We use the model to explore strategies for a universal influenza vaccine, e.g., how to boost the concentrations of the slower growing cross-reactive antibodies directed to the stem. The results suggest that, upon natural reinfections subsequent to vaccination, the protectiveness of such vaccines would erode, possibly requiring regular boosts. Collectively, our results strongly support the importance of bivalent antibody binding in immunodominance, and suggest guidelines for developing a universal influenza vaccine.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

A structural blueprint for interleukin-21 signal modulation

Interleukin-21 (IL-21) plays a critical role in generating immunological memory by promoting the germinal center reaction, yet clinical use of IL-21 remains challenging because of its pleiotropy and association with autoimmune disease. To better understand the structural basis of IL-21 signaling, we determine the structure of the IL-21-IL-21R-γc ternary signaling complex by X-ray crystallography and a structure of a dimer of trimeric complexes using cryo-electron microscopy. Guided by the structure, we design analogs of IL-21 by introducing substitutions to the IL-21-γc interface. These IL-21 analogs act as partial agonists that modulate downstream activation of pS6, pSTAT3, and pSTAT1. These analogs exhibit differential activity on T and B cell subsets and modulate antibody production in human tonsil organoids. These results clarify the structural basis of IL-21 signaling and offer a potential strategy for tunable manipulation of humoral immunity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Priming antibody responses to the fusion peptide in rhesus macaques

Immunodominance of antibodies targeting non-neutralizing epitopes and the high level of somatic hypermutation within germinal centers (GCs) required for most HIV broadly neutralizing antibodies (bnAbs) are major impediments to the development of an effective HIV vaccine. Rational protein vaccine design and non-conventional immunization strategies are potential avenues to overcome these hurdles. Here, we report using implantable osmotic pumps to continuously deliver a series of epitope-targeted immunogens to rhesus macaques over the course of six months to prime and elicit antibody responses against the conserved fusion peptide (FP). GC responses and antibody specificities were tracked longitudinally using lymph node fine-needle aspirates and electron microscopy polyclonal epitope mapping (EMPEM), respectively, to show antibody responses to the FP/N611 glycan hole region were primed, although exhibited limited neutralization breadth. Application of cryoEMPEM delineated key residues for on-target and off-target responses that can drive the next round of structure-based vaccine design.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

mRNA-LNP HIV-1 trimer boosters elicit precursors to broad neutralizing antibodies

Germline-targeting (GT) HIV vaccine strategies are predicated on deriving broadly neutralizing antibodies (bnAbs) through multiple boost immunogens. However, as the recruitment of memory B cells (MBCs) to germinal centers (GCs) is inefficient and may be derailed by serum antibody–induced epitope masking, driving further B cell receptor (BCR) modification in GC-experienced B cells after boosting poses a challenge. Using humanized immunoglobulin knockin mice, we found that GT protein trimer immunogen N332-GT5 could prime inferred-germline precursors to the V3-glycan–targeted bnAb BG18 and that B cells primed by N332-GT5 were effectively boosted by either of two novel protein immunogens designed to have minimum cross-reactivity with the off-target V1-binding responses. The delivery of the prime and boost immunogens as messenger RNA lipid nanoparticles (mRNA-LNPs) generated long-lasting GCs, somatic hypermutation, and affinity maturation and may be an effective tool in HIV vaccine development.

Science & Technology - Other Topics↗
DOE OSTI2024

Histopathological characteristics of PRRS and expression profiles of viral receptors in the piglet immune system

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious viral disease that causes significant economic losses to the swine industry worldwide. PRRS virus (PRRSV) infection is a receptor-mediated endocytosis and replication process. The purpose of this study was to determine the localization and expression of four important PRRSV receptors in immunological organs of piglets. After piglets were infected with PRRSV, Hematoxylin and Eosin staining, immunofluorescence, and Western blot were used to perform histopathological examination and receptors distribution analysis. The results showed that PRRSV caused severe damage to the piglets’ immune organs, including atrophy of the thymus and swelling of lymph node. Histopathological lesions were mainly observed in the lung and lymph node and were characterized by interstitial pneumonia, collapsed follicles, exhaustion of germinal centers, and extensive hemorrhage. Immunofluorescence staining and Western blot results showed that the receptors of CD163 and NMHCII-A were mainly distributed in the thymus, hilar lymph nodes, and mesenteric lymph nodes. However, Sn and vimentin receptors were expressed at low levels in the immune organs of piglets. The distribution of the four receptors in the immune organs was more concentrated in the cortex but was more scattered in the medulla. Compared to the control group, the relative expression of the four receptors increased significantly in most immune organs after viral infection. In conclusion, our study examined the distribution and expression of four PRRSV receptors in immunological organs. We observed a significant increase in the expression of Sn, CD163, and vimentin following viral infection. These findings may provide potential targets for future antiviral reagent design or vaccine development.

Chen, Hong↗
NASA NTRS1999

A method for the imbibition and germination of wheat seeds in space

A method was developed for the reliable germination in space of wheat seeds on porous tube nutrient delivery systems. Germination paper strips were loosely rolled into cylinders and two seeds inserted close to the outer edges of each cylinder. This configuration: 1) directed the emerging shoots upward and roots downward, 2) was efficient in wicking moisture from the porous tubes, and 3) provided open areas for oxygen diffusion. Cotton tufts were inserted into the bottom crevices of the cylinders to fix the seeds in a mid-level position and cylinders were then storable (indefinitely) prior to the preprogrammed (on-orbit) initiation of imbibition. This method extends both the upper and lower ends of acceptable moisture levels for successful seed germination, increasing the probability of success for spaceflight applications where moisture availability is more variable than on Earth.

NASA Discipline Life Support Systems↗
NASA NTRS1992

Thermoluminescent dosimetry for LDEF experiment M0006

Experiment M0006 on the Long Duration Exposure Facility had as its objective the investigation of space radiation effects on various electronic and optical components, as well as on seed germination. The Grumman Corporate Research Center provided the radiation dosimetric measurements for M0006, comprising the preparation of thermoluminescent dosimeters (TLD) and the subsequent measurement and analysis of flight exposed and control samples. In addition, various laboratory exposures of TLD's with gamma rays and protons were performed to obtain a better understanding of the flight exposures.

Chang, J. Y.↗
NASA NTRSDate not supplied

Plasma Sanitization of Radish Seeds for International Space Station Growth Experiments

Plant growth in space has long been a topic of key interest to enable sustained human presence. Seeds are common sources for microbial growth and must be sanitized before being sent to space. Current disinfection methods use toxic chemicals that require careful handling and dosing or are ineffective against certain seed types. Low temperature plasma provides an alternative to traditional methods. Plasma produces reactive species and ultraviolet light that reduce contaminants on seeds. NASA’s Kennedy Space Center has explored the treatment of radish seeds with plasma for sanitization and germination. Radio Frequency (RF) and Alternating Current (AC) plasma sources provided continuous treatment of radish seeds in a low-pressure and atmospheric environment, respectively. The seeds were analyzed to compare the presence of bacteria, fungi, and the germination rate. Comparisons between direct and indirect treatments, power supplies, treatment times, and treatment pressures showed the importance of proper dosing of reactive species. Higher powers and longer treatment times have shown larger reductions in microbial contaminants. However, extended direct exposure to high powered plasma can sometimes lead to a reduction in germination rates. Overall, plasma has shown promise as a viable alternative to chemical disinfection techniques. *Work supported by NASA's Kennedy Space Center Engineering and Safety Operations Independent Research and Technology Development.

K W Engeling↗
NASA NTRS2015

Germinating the 2050 Cis-Lunar Econosphere

In early 2013, Marshall Space Flight Center's upper management chartered a diverse team for a six-week 'sprint' to speculate (in a disciplined manner) and paint (with broad brush strokes) a picture of how earth, space, and public/private entities might be operating and relating to each other... in the year 2100. Two 12-person groups of civil servants, one with members having 15 years or less of NASA experience and the other with more senior members, worked independently and then compared and integrated their conclusions. In 2014, the 'Space 2100' team, with some new team members and different group boundaries, ran a longer sprint to a) develop more detailed estimates of the operations and economics of space activities in the vicinity of the Earth and Moon in the 2050 time frame, b) identify evolutionary paths, barriers, and opportunities, and c) suggest actions and philosophies to enable and invigorate progress towards the vision. This paper explores Space 2100's first two sprints and their projections of NASA's role in what will likely be a highly networked, international space industry and cis-lunar infrastructure.

Scott, David W.↗
NASA NTRS2001

Oxytropism: a new twist in pollen tube orientation

Chemical gradients and structural features within the pistil have been previously proposed as factors determining the directionality of pollen tube growth. In this study, we examine the behavior of pollen of eight species germinated in a dynamic oxygen gradient. While the germination rates of some species decreased directly with decreasing oxygen tension, other species showed no decrease in germination at oxygen tensions as low as 2 kPa. In one species, germination was consistently greater at decreased oxygen tensions than at ambient atmospheric levels. In three of the eight species tested, the developing pollen tube showed clear directional growth away from the more-oxygenated regions of the growth medium, while in one species growth was towards the more-oxygenated region. The remaining four species showed random tube growth. The pattern of oxytropic responses among the taxa suggests that this tropic behavior is both widespread and phylogenetically unpredictable.

NASA Discipline Plant Biology↗
NASA NTRS2015

Germinating the 2050 Cis-Lunar Econosphere

In early 2013, the Marshall Space Flight Center (MSFC) Director and MSFC's Office of Strategic Analysis and Communications (OSAC) chartered a diverse team for a six-week "sprint" to speculate (in a disciplined manner) and paint (with broad brush strokes) a picture of how earth, space, and public/private entities might be operating and relating to each other...in the year 2100. Two 12-person groups of civil servants, one with members having 15 years or less of NASA experience and the other with more senior members, worked independently and then compared and integrated their conclusions. In 2014, the "Space 2100" team, with some new team members and different group boundaries, ran a longer sprint to a) develop more detailed estimates of the operations and economics of space activities in the vicinity of the Earth and Moon in the 2050 time frame, b) identify evolutionary steps and viable paths needed to make that a reality, and c) recommend actions to enable and invigorate those steps. This paper explores Space 2100's first two sprints and their projections of NASA's role in what will likely be a highly networked international space industry and cis-lunar infrastructure.

Scott, David W.↗
NASA NTRS2009

Terrestrial Gamma-ray Flash (TGF) Observations with the Gamma-ray Burst Monitor on the Fermi Observatory

Terrestrial Gamma-ray Flashes (TGFs) have now been detected with four different orbiting spacecraft. The latest observations are being made with the scintillation detectors of Gamma-ray Burst Monitor (GBM) on the Fermi Gamma-ray Space Telescope Observatory (Fermi). Although this experiment was designed and optimized for the observation of cosmic gamma-ray bursts (GRBs), it has unprecedented capabilities for TGF observations, surpassing those of the experiment that discovered TGFs, the BATSE experiment on the Compton Gamma-ray Observatory. Launched in June 2008 from the Kennedy Space Center, the Fermi-GBM has been detecting about one TGF every four weeks. The thick bismuth germinate (BGO) scintillation detectors of the GBM have now observed photon energies from TGFs at energies up to approx.40 MeV. Individual photons are detected with an absolute timing accuracy of 2 microsec. Unlike the BATSE instrument, the GBM data system allows higher counting rates to be recorded and deadtime characteristics are well-known and correctable; thus the saturation effects seen with BATSE are avoided. TGF pulses as narrow as approx.0.1ms have been observed with the GBM. Like BATSE (and unlike RHESSI) an on-board trigger is required to detect TGFs. The minimum time window for this trigger is 16ms. A trigger window this wide greatly reduces the number of detected TGFs, since they most often have a much shorter duration than this window, thus reducing the signal-to-background. New on-board trigger algorithms based on detected photon energies are about to be implemented; this should increase the number of TGF triggers. High-energy spectra from TGFs observed with Fermi-GBM will be described.

Fishman, Gerald J.↗
NASA NTRS1989

Springback in root gravitropism

Conditions under which a gravistimulus of Merit corn roots (Zea mays L.) is withdrawn result in a subsequent loss of gravitropic curvature, an effect which we refer to as springback.' This loss of curvature begins within 1 to 10 minutes after removal of the gravistimulus. It occurs regardless of the presence or absence of the root cap. It is insensitive to inhibitors of auxin transport (2,3,5-triiodobenzoic acid, naphthylphthalamic [correction of naphthylphthalmaic] acid) or to added auxin (2,4-dichlorophenoxyacetic acid). Springback is prevented if a clinostat treatment is interjected to neutralize gravistimulation during germination, which suggests that the change in curvature is a response to a memory' effect carried over from a prior gravistimulation.

NASA Discipline Plant Biology↗
NASA NTRS1991

Gene activity during germination of spores of the fern, Onoclea sensibilis: RNA and protein synthesis and the role of stored mRNA

Pattern of 3H-uridine incorporation into RNA of spores of Onoclea sensibilis imbibed in complete darkness (non-germinating conditions) and induced to germinate in red light was followed by oligo-dT cellulose chromatography, gel electrophoresis coupled with fluorography and autoradiography. In dark-imbibed spores, RNA synthesis was initiated about 24 h after sowing, with most of the label accumulating in the high mol. wt. poly(A) -RNA fraction. There was no incorporation of the label into poly(A) +RNA until 48 h after sowing. In contrast, photo-induced spores began to synthesize all fractions of RNA within 12 h after sowing and by 24 h, incorporation of 3H-uridine into RNA of irradiated spores was nearly 70-fold higher than that into dark-imbibed spores. Protein synthesis, as monitored by 3H-arginine incorporation into the acid-insoluble fraction and by autoradiography, was initiated in spores within 1-2 h after sowing under both conditions. Autoradiographic experiments also showed that onset of protein synthesis in the cytoplasm of the germinating spore is independent of the transport of newly synthesized nuclear RNA. One-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis of 35S-methionine-labelled proteins revealed a good correspondence between proteins synthesized in a cell-free translation system directed by poly(A) +RNA of dormant spores and those synthesized in vivo by dark-imbibed and photo-induced spores. These results indicate that stored mRNAs of O. sensibilis spores are functionally competent and provide templates for the synthesis of proteins during dark-imbibition and germination.

NASA Discipline Number 29-20↗
NASA NTRS1998

Influence of gravity and light on the developmental polarity of Ceratopteris richardii fern spores

The polarity of germinating single-celled spores of the fern Ceratopteris richardii Brogn. is influenced by gravity during a time period prior to the first cellular division designated a "polarity-determination window". After this window closes, control of polarity is seen in the downward (with respect to gravity) migration of the nucleus along the proximal face of the spore and the subsequent downward growth of the primary rhizoid. When spores are germinated on a clinostat the direction of nuclear migration and subsequent primary rhizoid growth is random. However, in each case the direction of nuclear migration predicts the direction of rhizoid elongation. Although it is the most obvious movement, the downward migration is not the first movement of the nucleus. During the polarity-determination window, the nucleus moves randomly within a region centered behind the trilete marking. While the polarity of many fern spores has been reported to be controlled by light, spores of C. richardii are the first documented to have their polarity influenced by gravity. Directional white light also affects the polarity of these spores, but this influence is slight and is secondary to that of gravity.

Non-NASA Center↗
NASA NTRS1992

Gene activity during germination of spores of the fern, Onoclea sensibilis. Cell-free translation analysis of mRNA of spores and the effect of alpha-amanitin on spore germination

Poly(A)-RNA fractions of dormant, dark-imbibed (non-germinating) and photoinduced (germinating) spores of Onoclea sensibilis were poor templates in the rabbit reticulocyte lysate protein synthesizing system, but the translational efficiency of poly(A)+RNA was considerably higher than that of unfractionated RNA. Poly(A)+RNA isolated from photoinduced spores had a consistently higher translational efficiency than poly(A)+RNA from dark-imbibed spores. Analysis of the translation products by one-dimensional polyacrylamide gel electrophoresis showed no qualitative differences in the mRNA populations of dormant, dark-imbibed, and photoinduced spores. However, poly(A)+RNA from dark-imbibed spores appeared to encode in vitro fewer detectable polypeptides at a reduced intensity than photoinduced spores. A DNA clone encoding the large subunit of maize ribulose bisphosphate carboxylase hybridized at strong to moderate intensity to RNA isolated from dark-imbibed spores, indicating the absence of mRNA degradation. Although alpha-amanitin did not inhibit the germination of spores, the drug prevented the elongation of the rhizoid and protonemal initial with a concomitant effect on the synthesis of poly(A)+RNA. These results are consistent with the view that some form of translational control involving stored mRNA operates during dark-imbibition and photoinduced germination of spores.

NASA Discipline Number 29-20↗
NASA NTRS2000

A pollen-specific novel calmodulin-binding protein with tetratricopeptide repeats

Calcium is essential for pollen germination and pollen tube growth. A large body of information has established a link between elevation of cytosolic Ca(2+) at the pollen tube tip and its growth. Since the action of Ca(2+) is primarily mediated by Ca(2+)-binding proteins such as calmodulin (CaM), identification of CaM-binding proteins in pollen should provide insights into the mechanisms by which Ca(2+) regulates pollen germination and tube growth. In this study, a CaM-binding protein from maize pollen (maize pollen calmodulin-binding protein, MPCBP) was isolated in a protein-protein interaction-based screening using (35)S-labeled CaM as a probe. MPCBP has a molecular mass of about 72 kDa and contains three tetratricopeptide repeats (TPR) suggesting that it is a member of the TPR family of proteins. MPCBP protein shares a high sequence identity with two hypothetical TPR-containing proteins from Arabidopsis. Using gel overlay assays and CaM-Sepharose binding, we show that the bacterially expressed MPCBP binds to bovine CaM and three CaM isoforms from Arabidopsis in a Ca(2+)-dependent manner. To map the CaM-binding domain several truncated versions of the MPCBP were expressed in bacteria and tested for their ability to bind CaM. Based on these studies, the CaM-binding domain was mapped to an 18-amino acid stretch between the first and second TPR regions. Gel and fluorescence shift assays performed with CaM and a CaM-binding synthetic peptide further confirmed MPCBP binding to CaM. Western, Northern, and reverse transcriptase-polymerase chain reaction analysis have shown that MPCBP expression is specific to pollen. MPCBP was detected in both soluble and microsomal proteins. Immunoblots showed the presence of MPCBP in mature and germinating pollen. Pollen-specific expression of MPCBP, its CaM-binding properties, and the presence of TPR motifs suggest a role for this protein in Ca(2+)-regulated events during pollen germination and growth.

NASA Discipline Plant Biology↗
NASA NTRS1998

The development of spaceflight experiments with Arabidopsis as a model system in gravitropism studies

Experiments with Arabidopsis have been developed for spaceflight studies in the European Space Agency's Biorack module. The Biorack is a multiuser facility that is flown on the United States Space Shuttle and serves as a small laboratory for studying cell and developmental biology in unicells, plants, and small invertebrates. The purpose of our spaceflight research was to investigate the starch-statolith model for gravity perception by studying wild-type (WT) and three starch-deficient mutants of Arabidopsis. Since spaceflight opportunities for biological experimentation are scarce, the extensive ground-based testing described in this paper is needed to ensure the success of a flight project. Therefore, the specific aims of our ground-based research were: (1) to modify the internal configuration of the flight hardware, which originally was designed for large lentil seeds, to accommodate small Arabidopsis seeds; (2) to maximize seed germination in the hardware; and (3) to develop favorable conditions in flight hardware for the growth and gravitropism of seedlings. The hardware has been modified, and growth conditions for Arabidopsis have been optimized. These experiments were successfully flown on two Space Shuttle missions in 1997.

STS-84 Shuttle Project↗