Copper accumulation and the effect of chelation treatment on cerebral amyloid angiopathy compared to parenchymal amyloid plaques
Abstract not provided
Zhu, Xiayoue↗
SEARCH · Search NASA
Results for “plaques”
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.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Silica Nanodepletors: Targeting and Clearing Alzheimer's beta-Amyloid Plaques
Abnormal accumulation of beta-amyloid (A beta) peptide aggregates in the brain is a major hallmark of Alzheimer's disease (AD). A beta aggregates interfere with neuronal communications, ultimately causing neuronal damage and brain atrophy. Much effort has been made to develop AD treatments that suppress A beta aggregate formation, thereby attenuating A beta-induced neurotoxicity. Here, the design of A beta nanodepletors consisting of ultralarge mesoporous silica nanostructures and anti-A beta single-chain variable fragments, with the goal of targeting and eliminating aggregative A beta monomers, is reported. The A beta nanodepletors impart a notable decline in A beta aggregate formation, resulting in significant mitigation of A beta-induced neurotoxicity in vitro. Furthermore, stereotaxic injections of A beta nanodepletors into the brain of an AD mouse model system successfully suppress A beta plaque formation in vivo up to approximate to 30%, suggesting that A beta nanodepletors can serve as a promising antiamylodoisis material.
Jung, Huijin↗
Contrasting roles of rice root iron plaque in retention and plant uptake of silicon, phosphorus, arsenic, and selenium in diverse paddy soils
Abstract Background and aims Iron (Fe) plaque on rice roots is a mixture of Fe oxide and oxyhydroxide minerals thought to protect rice from high levels of arsenic (As) in flooded paddy soils. Silicon (Si), phosphorus (P), and selenium (Se) also exist as oxyanions in rice paddies, but the impacts of Fe plaque on uptake of these nutrients are unknown. Methods We used natural variation in paddy soil chemistry to test how Si, P, As, and Se move from porewater to plaque to plant via multiple techniques. In a pot study, we monitored Fe plaque deposition and porewater chemistry in 5 different soils over time and measured plaque/plant chemistry and Fe plaque mineralogy at harvest. We normalized oxyanion concentrations by Fe to determine the preferential retention on plaque or plant uptake. Results Low phosphorus availability increased root Fe-oxidizing activity, while Fe, Si, P, As, and Se concentrations in plaque were strongly correlated with porewater. Plaque did not appreciably retain Si and Se, and the oxyanions did not compete for adsorption sites on the Fe plaque. Conclusion Root Fe plaque seems to protect rice from As uptake, does not interfere with Si and Se uptake, and roots adapt to maintain P nutrition even with retention of porewater P on plaque.
Agriculture↗
Label-Free In Situ Chemical Characterization of Amyloid Plaques in Human Brain Tissues
The accumulation of amyloid plaques and increased brain redox burdens are neuropathological hallmarks of Alzheimer’s disease. Altered metabolism of essential biometals is another feature of Alzheimer’s, with amyloid plaques representing sites of disturbed metal homeostasis. Despite these observations, metal-targeting disease treatments have not been therapeutically effective to date. A better understanding of amyloid plaque composition and the role of the metals associated with them is critical. To establish this knowledge, the ability to resolve chemical variations at nanometer length scales relevant to biology is essential. Here, we present a methodology for the label-free, nanoscale chemical characterization of amyloid plaques within human Alzheimer’s disease tissue using synchrotron X-ray spectromicroscopy. Our approach exploits a C–H carbon absorption feature, consistent with the presence of lipids, to visualize amyloid plaques selectively against the tissue background, allowing chemical analysis to be performed without the addition of amyloid dyes that alter the native sample chemistry. Using this approach, we show that amyloid plaques contain elevated levels of calcium, carbonates, and iron compared to the surrounding brain tissue. Chemical analysis of iron within plaques revealed the presence of chemically reduced, low-oxidation-state phases, including ferromagnetic metallic iron. The zero-oxidation state of ferromagnetic iron determines its high chemical reactivity and so may contribute to the redox burden in the Alzheimer’s brain and thus drive neurodegeneration. Ferromagnetic metallic iron has no established physiological function in the brain and may represent a target for therapies designed to lower redox burdens in Alzheimer’s disease. Additionally, ferromagnetic metallic iron has magnetic properties that are distinct from the iron oxide forms predominant in tissue, which might be exploitable for the in vivo detection of amyloid pathologies using magnetically sensitive imaging. We anticipate that this label-free X-ray imaging approach will provide further insights into the chemical composition of amyloid plaques, facilitating better understanding of how plaques influence the course of Alzheimer’s disease.
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
Collagen Fibril Orientation in Tissue Specimens From Atherosclerotic Plaque Explored Using Small Angle X-Ray Scattering
Atherosclerotic plaques can gradually develop in certain arteries. Disruption of fibrous tissue in plaques can result in plaque rupture and thromboembolism, leading to heart attacks and strokes. Collagen fibrils are important tissue building blocks and tissue strength depends on how fibrils are oriented. Fibril orientation in plaque tissue may potentially influence vulnerability to disruption. While X-ray scattering has previously been used to characterize fibril orientations in soft tissues and bones, it has never been used for characterization of human atherosclerotic plaque tissue. This study served to explore fibril orientation in specimens from human plaques using small angle X-ray scattering (SAXS). Additionally, plaque tissue was extracted from human femoral and carotid arteries, and each tissue specimen contained a region of calcified material. Three-dimensional (3D) collagen fibril orientation was determined along scan lines that started away from and then extended toward a given calcification. Fibrils were found to be oriented mainly in the circumferential direction of the plaque tissue at the majority of locations away from calcifications. However, in a number of cases, the dominant fibril direction differed near a calcification, changing from circumferential to longitudinal or thickness (radial) directions. Further study is needed to elucidate how these fibril orientations may influence plaque tissue stress–strain behavior and vulnerability to rupture.
60 APPLIED LIFE SCIENCES↗
Gallionellaceae in rice root plaque: metabolic roles in iron oxidation, nutrient cycling, and plant interactions
On the roots of wetland plants such as rice, Fe(II) oxidation forms Fe(III) oxyhydroxide-rich plaques that modulate plant nutrient and metal uptake. The microbial roles in catalyzing this oxidation have been debated and it is unclear if these iron-oxidizers mediate other important biogeochemical and plant interactions. To investigate this, we studied the microbial communities, metagenomes, and geochemistry of iron plaque on field-grown rice, plus the surrounding rhizosphere and bulk soil. Plaque iron content (per mass root) increased over the growing season, showing continuous deposition. Analysis of 16S rRNA genes showed abundant Fe(II)-oxidizing and Fe(III)-reducing bacteria (FeOB and FeRB) in plaque, rhizosphere, and bulk soil. FeOB were enriched in relative abundance in plaque, suggesting FeOB affinity for the root surface. Gallionellaceae FeOB Sideroxydans were enriched during vegetative and early reproductive rice growth stages, while a Gallionella was enriched during reproduction through grain maturity, suggesting distinct FeOB niches over the rice life cycle. FeRB Anaeromyxobacter and Geobacter increased in plaque later, during reproduction and grain ripening, corresponding to increased plaque iron. Metagenome-assembled genomes revealed that Gallionellaceae may grow mixotrophically using both Fe(II) and organics. The Sideroxydans are facultative, able to use non-Fe substrates, which may allow colonization of rice roots early in the season. FeOB genomes suggest adaptations for interacting with plants, including colonization, plant immunity defense, utilization of plant organics, and nitrogen fixation. Taken together, our results strongly suggest that rhizoplane and rhizosphere FeOB can specifically associate with rice roots, catalyzing iron plaque formation, with the potential to contribute to plant growth.
59 BASIC BIOLOGICAL SCIENCES↗
Silenced long non-coding RNA activated by DNA damage elevates microRNA-495-3p to suppress atherosclerotic plaque formation via reducing Krüppel-like factor 5
Objective: Atherosclerosis (AS) is an inflammatory disease and the formation of atherosclerotic plaque plays a critical role in AS progression. We aimed to investigate the effect of long non-coding RNA (lncRNA) activated by DNA damage (NORAD)/microRNA-495-3p (miR-495-3p)/Krüppel-like factor 5 (KLF5) axis on atherosclerotic plaque formation. Methods: The ApoE{sup −/-} mice were fed a high-fat diet to construct AS mouse models and the modeled mice were treated with altered NORAD, miR-495-3p or KLF5. NORAD, miR-495-3p and KLF5 expression in mouse aorta tissues were evaluated, and the levels of inflammatory factors, oxidative stress factors, endothelial function indices and blood lipid in mice were all determined. The atherosclerotic plaque area, lipid deposition area, collagen fibers and CD68 expression in mouse aorta tissues were assessed. The regulatory relation between NORAD and miR-495-3p, and the target relation between miR-495-3p and KLF5 were confirmed. Results: NORAD and KLF5 were increased whereas miR-495-3p was decreased in atherosclerotic mouse aortas. Inhibited NORAD or elevated miR-495-3p suppressed inflammation, oxidative stress, endothelial dysfunction, blood lipid level, atherosclerotic plaque area, collagen fibers and CD68 expression in atherosclerotic mouse aortas. Effects of elevated miR-495-3p on atherosclerotic mice could be reversed by up-regulation of KLF5. NORAD served as a sponge of miR-495-3p and miR-495-3p directly targeted KLF5. Conclusion: Silenced NORAD elevated miR-495-3p to suppress atherosclerotic plaque formation via reducing KLF5. Findings in our research may be helpful for exploring molecular mechanisms of AS.
60 APPLIED LIFE SCIENCES↗
Improved Zika virus plaque assay using Vero/TMPRSS2 cell line
Plaque assay is the gold standard for the quantification of viable cytopathic viruses like Zika virus (ZIKV). Some strains of ZIKV produce plaques that are very difficult to accurately visualize and count on the commonly used Vero cell line. From data generated in our lab, we became curious if Vero/TMPRSS2 cells may be a better alternative; therefore, we compared the plaque forming units of two strains of ZIKV on Vero/TMPRSS2 cells to those produced by Vero cells. We also compared the virus stock titer generated on Vero/TMPRSS2 cells to that generated by the Vero cell line. Although the Vero cells generated higher quantity of ZIKV stocks, the Vero/TMPRSS2 cells produced plaques with significantly improved morphology and visibility and may, therefore, be a better alternative to use for performing plaque assays for strains of ZIKV that are more difficult to titer on regular Vero cells.
60 APPLIED LIFE SCIENCES↗
Effect of oral plaque control on postoperative pneumonia following lung cancer surgery
Abstract Background There have been few studies on the relationship between oral status and postoperative pneumonia (POP) in patients with lung cancer, and whether improving their oral condition assists with a lower incidence of POP before lung cancer surgery remains controversial. This retrospective study was conducted by a stomatologist to assess the effect of controlling oral pathogenic bacteria of patients with lung cancer to prevent POP. Methods A total of 235 patients with lung cancer who underwent lobectomy by open thoracotomy between July 2015 and December 2018 were selected and given the choice of being in the experimental or control group. A total of 122 participants in the experimental group received professional oral plaque control, and 113 participants in the control group did not receive plaque control. All clinical data of participants in both groups were retrospectively studied to determine the incidence of POP at the thirtieth day of discharge from hospital. Results Eight in the experimental group and six in the control group were excluded from the study. It was found that four of 114 patients suffered from POP in the experimental group (incidence = 3.51%). A total of 17 of 107 patients in the control group had pulmonary infection (incidence = 15.89%). Odds ratio was 0.19. The incidence of POP in the experimental group was significantly lower than that of the control group ( P < 0.05). Conclusions Professional oral plaque control is associated with a lower incidence of POP following lung cancer surgery and is therefore a favorable factor for preventing POP, and should be carried out before the surgical treatment of lung cancer. Key points Professional oral plaque control was associated with a lower incidence of POP following lung cancer surgery, and it is recommended this should be carried out before the surgical treatment of lung cancer.
Jia, Chunling↗
Design and synthesis of astatinated benzothiazole compounds for their potential use in Targeted Alpha Therapy (TAT) strategies to treat Alzheimer's disease-associated amyloid plaques
Alzheimer's disease (AD) is a terminal neurodegenerative disease characterized by the buildup of amyloid fibrils, amorphous aggregates and tauopathies. Several treatment modalities, which rely on various biological processes to reduce disease burden, have been largely ineffective at treating Alzheimer's disease. Targeted alpha therapy (TAT) has demonstrated positive results in the treatment of cancer. Benzothiazole derivatives have been successfully shown to target these plaques and are used in several imaging applications. One such derivative, Flutemetamol (Vizamyl TM ) is an FDA approved diagnostic tool for PET imaging of AD-associated plaques. We report the radiolabeling of benzothiazole derivatives with 211 At, a 7.2 h alpha emitting radionuclide, using a copper catalyzed reaction with a boronic acid precursor molecule. In conclusion, our final compound [ 211 At]3'-At-PIB-OMe had a radiochemical yield of 55% and was found to be stable for at least 3 h in phosphate buffered saline.
62 RADIOLOGY AND NUCLEAR MEDICINE↗
The Importance of Radiation Dose to the Atherosclerotic Plaque in the Left Anterior Descending Coronary Artery for Radiation-Induced Cardiac Toxicity of Breast Cancer Patients?
Radiation-induced acute coronary events (ACEs) may occur as a treatment-related late adverse effect of breast cancer (BC) radiation. However, the underlying mechanisms behind this radiation-induced cardiac disease remain to be determined. The objective of this study was to test the hypothesis that radiation dose to calcified atherosclerotic plaques in the left anterior descending coronary artery (LAD) is a better predictor for ACEs than radiation dose to the whole heart or left ventricle in patients with BC treated with radiation therapy.
62 RADIOLOGY AND NUCLEAR MEDICINE↗
A New Method to Capture the Spatial and Temporal Heterogeneity of Aquatic Plant Iron Root Plaque In Situ
Explore the source record for details and available documents.
99 GENERAL AND MISCELLANEOUS↗
Root size and soil physicochemical properties drive microscale spatial patterns of Fe and As retention in the rice rhizosphere
Background and Aims: Radial oxygen loss from rice roots in flooded soils oxidizes and precipitates dissolved Fe(II), Mn(II), and As(III) into mixed Fe(III), Mn(III/IV), and As(V) as root plaque and in the rhizosphere soil. It is unknown how different soils and root sizes impact the spatial extent of Fe and As retention outside the root. Methods: We imaged cross-sections of 90 roots from 6 different soils using synchrotron μXRF imaging followed by k-means clustering and elliptical averaging to distinguish bulk soil, rhizosphere, plaque, and roots based on As and Fe patterns. Results: We found preferential As retention in the plaque and rhizospheres of most roots except small (< 0.45 mm) roots in silty soils with low P or high As. In contrast, clayey soils had similar As-Fe correlations across plaque, rhizosphere, and bulk soil. Large (> 0.45 mm) roots often had no oxidized rhizosphere region. We obtained an extensive dataset of 256 As and 155 Mn synchrotron μXANES measurements, which revealed that rhizosphere and plaque As was mainly inorganic As(V) and As(III), and Mn oxidation state varied between soils but not between belowground locations. Conclusion: Small roots in coarse-textured soils were less likely to have As retention in the plaque or rhizosphere compared to large roots and fine-textured soils. Furthermore, the unique and extensive data in this study provides new insight into soil and root size impacts on As retention in the rhizosphere. It is essential to investigate a representative number of samples to draw conclusions from XRF imaging.
36 MATERIALS SCIENCE↗
Molecular Imaging of Matrix Metalloproteinase-2 in Atherosclerosis Using a Smart Multifunctional PET/MRI Nanoparticle
Matrix metalloproteinases from macrophages are important intraplaque components that play pivotal roles in plaque progression and regression. This study sought to develop a novel multifunctional positron emission tomography (PET) and magnetic resonance imaging (MRI) contrast agents based on MMP-2 cleavable nanoparticles to noninvasive assessment of MMP-2 activity in mouse carotid atherosclerotic plaques. Macrophage-rich vascular lesions were induced by carotid ligation plus high-fat diet and streptozotocin-induced diabetes in CL57/BL6 mice. To render iron oxide nanoparticles (IONP) specific for the extracellular MMP-2, the magnetic nanoparticle base material has been derivatized with 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) for the nuclear tracer 64 Cu labeling and the MMP-2-cleavable peptide modified with polyethylene glycol 2000, yielding a multi-modality reporter ( 64 Cu-NOTA-IONP@MMP2c-PEG2K, MMP2cNPs) for PET/MR imaging. Small animal PET imaging and biodistribution data revealed that MMP2cNPs exhibited remarkable plaque uptake (3.06 ± 0.87% ID/g and 1.83 ± 0.28% ID/g at 4 and 12 h, respectively). And MMP2cNPs were rapidly cleared from the contralateral normal carotid artery, resulting in excellent plaque-to-normal carotid artery contrasts. Furthermore, in vivo MRI showed a preferential accumulation of MMP2cNPs in atherosclerotic lesions compared with the non-cleavable reference compound, MMP2ncNPs. In addition, histological analyses revealed iron accumulations in the carotid atherosclerotic plaque, in colocalization with MMP-2 expression and macrophages. Using a combination of innovative imaging modalities, in this study, we demonstrate the feasibility of applying the novel smart MMP2cNPs as a PET/MR hybrid imaging contrast agent for detection of MMP-2 in atherosclerotic plaque in vivo.
60 APPLIED LIFE SCIENCES↗
Functional and genetic markers of niche partitioning among enigmatic members of the human oral microbiome
Abstract Introduction Microbial residents of the human oral cavity have long been a major focus of microbiology due to their influence on host health and intriguing patterns of site specificity amidst the lack of dispersal limitation. However, the determinants of niche partitioning in this habitat are yet to be fully understood, especially among taxa that belong to recently discovered branches of microbial life. Results Here, we assemble metagenomes from tongue and dental plaque samples from multiple individuals and reconstruct 790 non-redundant genomes, 43 of which resolve to TM7, a member of the Candidate Phyla Radiation, forming six monophyletic clades that distinctly associate with either plaque or tongue. Both pangenomic and phylogenomic analyses group tongue-specific clades with other host-associated TM7 genomes. In contrast, plaque-specific TM7 group with environmental TM7 genomes. Besides offering deeper insights into the ecology, evolution, and mobilome of cryptic members of the oral microbiome, our study reveals an intriguing resemblance between dental plaque and non-host environments indicated by the TM7 evolution, suggesting that plaque may have served as a stepping stone for environmental microbes to adapt to host environments for some clades of microbes. Additionally, we report that prophages are widespread among oral-associated TM7, while absent from environmental TM7, suggesting that prophages may have played a role in adaptation of TM7 to the host environment. Conclusions Our data illuminate niche partitioning of enigmatic members of the oral cavity, including TM7, SR1, and GN02, and provide genomes for poorly characterized yet prevalent members of this biome, such as uncultivated Flavobacteriaceae.
60 APPLIED LIFE SCIENCES↗
A Solvatochromic Near Infrared Fluorophore Sensitive to the Full Amyloid Beta Aggregation Pathway
Alzheimer's disease has long been associated with the aggregation of amyloid beta peptides (Aβ42) into macroscale plaques, although specific neurodegenerative agents have not been definitively identified. Much evidence has pointed to the soluble nanoscale oligomers that form early in the Aβ42 aggregation pathway, but there is little understanding of these structures, their mechanisms of formation, or how they grow into plaques. Here, we show that a solvatochromic fluorophore with near-infrared (NIR) emission can track synthetic Aβ42 aggregation through environment-sensitive spectral shifts from the earliest time points through plaque formation. This azide-functionalized phosphine oxide azetidine rhodol (Phazr-N3) shows large polarity-dependent changes in fluorescence emission, with maxima shifting from 630 nm in toluene to 703 nm in aqueous buffer, and a maximum quantum yield of 62%. Upon induction of Aβ42 aggregation, we observe immediate solvatochromic changes in Phazr-N3 fluorescence, with multiple apparent phases over 12 h, and which culminate before the onset of any major fluorescence changes of conformation-specific aggregation fluorophore thioflavin T. Solution anisotropy measurements show a low micromolar affinity of Phazr-N3 for disordered, free Aβ42 in solution, and real-time measurements are consistent with rapid liquid-liquid phase separation and slow dehydration of the growing aggregate. Spectral imaging of synthetic plaques stained in the presence of live cells and lipid-binding protein albumin shows over 4000-fold Phazr-N3 fluorescence intensity above background under no-wash conditions, and over 100-fold intensity above coplated microglial cells or a large excess of albumin. This use of a solvatochromic probe with structure-independent binding to free Aβ42 offers real-time, minimally invasive insight into the full Aβ42 aggregation pathway.
Wang, Zeming↗
MicroRNA-22 inhibition promotes the development of atherosclerosis via targeting interferon regulator factor 5
Atherosclerosis is generally accepted as a chronic inflammatory disease and is the most important pathological process underlying the cardiovascular diseases. MiR-22 exerts an important role in tumorgenesis, obesity and NAFLD development, as well as cardiovascular diseases. However, a certain role of miR-22 in the pathogenesis of atherosclerosis remains undetermined. Here, we showed that miR-22 exhibited a negative association with the deteriorated atherosclerotic plaque and showed significant downregulated expression in macrophages. Next, treatment of ApoE deficiency (ApoE{sup −/-}) mice with miR-22 inhibitors which were then subjected to high fat diet (HFD) for 12 weeks were performed to investigate the function of miR-22 on atherogenesis. The results exhibited that miR-22 inhibition dramatically promoted atherosclerotic plaques but attenuated plaque stabilization which were accompanied by decreased smooth muscle cell and collagen content, but increased macrophage infiltration and lipid accumulation. More importantly, the in vivo and in vitro experiments suggested that miR-22 inhibition accelerated inflammatory response and foam cell formation. Mechanistically, we demonstrated interferon regulator factor 5 (IRF5) was an important target of miR-22 and it was required for the regulation of inflammation mediated by miR-22 inhibition. Collectively, these evidences revealed that miR-22 inhibition promoted the atherosclerosis progression through activation of IRF5.
60 APPLIED LIFE SCIENCES↗
Phage K gp102 Drives Temperature-Sensitive Antibacterial Activity on USA300 MRSA
There is widespread interest in using obligately lytic bacteriophages (“phages”) to treat human bacterial infections. Among Staphylococcus aureus infections, the USA300 lineage is a frequent cause of invasive disease. We observed that phage K, a model S. aureus myophage, exhibits temperature-sensitive growth on USA300 strains, with the wild-type phage providing poorer growth suppression in broth and forming smaller and fainter plaques at 37 °C vs. 30 °C. We isolated 65 mutants of phage K that had improved plaquing characteristics at 37 °C when compared to the parental phage. In all 65 mutants, this phenotype was attributable to loss-of-function (LoF) mutations in gp102, which encodes a protein of unknown function that has homologs only among the Herelleviridae (SPO1-like myophages infecting gram-positive bacteria). Additional experiments with representative mutants consistently showed that the temperature-sensitive plaque phenotype was specific to USA300 MRSA strains and that Gp102 disruption was correlated with improved suppression of bacterial growth in broth and improved antibacterial activity in a mouse model of upper respiratory tract infection. The same genotype and in vitro phenotypes could be replicated in close relatives of phage K. Gp102 disruption did not have a detectable effect on adsorption but did delay cell culture lysis relative to wild-type under permissive infection conditions, suggesting that gp102 conservation might be maintained by selective pressure for more rapid replication. Expression of gp102 on a plasmid was toxic to both an MSSA and a USA300 MRSA strain. Molecular modeling predicts a protein with two helix-turn-helix domains that displays some similarity to DNA-binding proteins such as transcription factors. While its function remains unclear, gp102 is a conserved gene that is important to the infection process of Kayvirus phages, and it appears that the manner in which USA300 strains defend against them at 37 °C can be overcome by gp102 LoF mutations.
59 BASIC BIOLOGICAL SCIENCES↗