1,721,222 research outputs found
Advances in Amyloid-β Clearance in the Brain and Periphery: Implications for Neurodegenerative Diseases
Full text linkThis review examines the role of impaired amyloid-β clearance in the accumulation of amyloid-β in the brain and the periphery, which is closely associated with Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). The molecular mechanism underlying amyloid-β accumulation is largely unknown, but recent evidence suggests that impaired amyloid-β clearance plays a critical role in its accumulation. The review provides an overview of recent research and proposes strategies for efficient amyloid-β clearance in both the brain and periphery. The clearance of amyloid-β can occur through enzymatic or non-enzymatic pathways in the brain, including neuronal and glial cells, blood-brain barrier, interstitial fluid bulk flow, perivascular drainage, and cerebrospinal fluid absorption-mediated pathways. In the periphery, various mechanisms, including peripheral organs, immunomodulation/immune cells, enzymes, amyloid-β-binding proteins, and amyloid-β-binding cells, are involved in amyloid-β clearance. Although recent findings have shed light on amyloid-β clearance in both regions, opportunities remain in areas where limited data is available. Therefore, future strategies that enhance amyloid-β clearance in the brain and/or periphery, either through central or peripheral clearance approaches or in combination, are highly encouraged. These strategies will provide new insight into the disease pathogenesis at the molecular level and explore new targets for inhibiting amyloid-β deposition, which is central to the pathogenesis of sporadic AD (amyloid-β in parenchyma) and CAA (amyloid-β in blood vessels)
Extinction of an evolving jet flame under a linearly-varying flow field
No full textThe effects of an unsteady strain rate on the extinction of diffusion flames are studied experimentally. Experiments are carried out for an evolving jet configuration in which the flow at the tip of vortex is similar to counterflow diffusion flames. A non-reacting flow is used to characterize the flow field of the downward evolving jet flame. Rayleigh scattering images show that the fuel concentration at the jet tip is preserved in the near field, and the velocity at the nozzle exit, measured by LDV, increases linearly. Both buoyancy and curvature effects are also examined using a high-speed shadowgraph system. This transient flow field provides a linearly varying strain history when ignited by a residual flame. Twenty-two strain histories, which have been obtained for various Reynolds numbers and a constant residual temperature at the jet exit, are investigated for the occurrence of extinction of the flame tip. The experimental results show that the extinction point under a linear-varying strain rate is extended with an increase in the slope of the strain rate. An equivalent strain model under a linear-varying strain rate is introduced to complement and validate our experimental results. Although it is noted that an increase in the slope of the strain rate, which implies the flame experiences much more unsteadiness, induces a further extension of the flame extinction point in all the computational results, the initial condition also has a strong influence on the extinction point in the case of steep changes in strain rate. When the appropriate initial condition is selected, the equivalent strain model can predict the experimental extinction point successfully
GRAMMAR COVERINGS OF A DETERMINISTIC PARSER WITH ACTION CONFLICTS
No full textExtended LR parsing of ambiguous grammars is investigated in view of parser transformations. We define a cover grammar of a transformed parser in terms of grammar coverings, and we present a generation method of cover grammars, together with a proof. The method reflects a parser transformation into a cover grammar, which shows the effect of deleting actions in the parser. A general cover grammar for a transformed parser is introduced by the proposed method, and for a meaningful class of parsers, the generation of a reduced cover grammar is presented
Author Correction: ANKS1A regulates LDL receptor-related protein 1 (LRP1)-mediated cerebrovascular clearance in brain endothelial cells
Full text linkExperiments on the transient effect of evolving jet diffusion flames
No full textThe unsteady behavior of diffusion flames was experimentally studied with a jet diffusion flame under a configuration similar to counterflow. We designed and conducted our experiments in such a manner that the Fuel was ejected downward so that various time histories of strain rate with good reproducibility were obtained. The Fuel jet was ignited by means of a residual flame sustained at the nozzle tip, and the developing process was visualized by both Mie scattering and high-speed shadow imaging. The maximum flame temperature was measured by a compensated thermocouple on the flame tip. ri new method was adopted for the time constants. The results show that the history of the strain rate has a significant role in the unsteady behavior of laminar diffusion flames, especially close to flame extinction. Regarding of quenching histories, the extinction strain rates extend as the slope of the strain rate increases, which has riot previously been explored experimentally Even in the non-quenched flame. an unsteady effect is shown based on the fact that there are two maximum flame temperatures at the same strain rate and the one experiencing the higher strain rate is always lower
Reactive ion etching mechanism of RuO2 thin films in oxygen plasma with the addition of CF4, Cl-2, and N-2
No full textIn this study, we thoroughly investigated the reactive ion etching mechanism of RuO2 film in oxygen plasma with the addition of CF4, Cl-2, and N-2. The etch rate of RuO2 was examined as functions of flow rates of input gases, substrate temperature, DC bias applied to the substrate, and pressure. The concentrations of the etching species in the plasma were determined using optical emission spectroscopy (OES) and a quadrupole mass spectrometer (QMS). The etch products were determined with a QMS and the etched surface of RuO2 film was examined with X-ray photoelectron spectroscopy (XPS). RuO4 and RuO3, which are formed by the reactions between RuO2 film and oxygen radicals, are the only etch products regardless of the kind of additive gas. The additive gases (CF4, Cl-2, and N-2) are not directly involved in the chemical reaction with the RuO2 film, but they increase the concentration of oxygen radicals and accordingly, appreciably increase the etch rate of the RuO2 films. The etch rate is limited by the formation rate of the etch products, which is enhanced by the bombardment of energetic ions. Therefore, the etch rate depends not only on the concentration of oxygen radicals, but also on the nux and energy of the ions bombarding the film surface. In this study, for the first time, we introduced the use of the O-2/N-2 plasma system in RuO2 etching.The authors acknowledge the support of Hyundai Electronics Co., Ltd
Comprehensive Single-Cell Transcriptomic Atlas of the Mouse Pons and Medulla
No full textThe pons and medulla, key regions of the hindbrain within the brainstem, regulate a wide range of complex behaviors, ranging from motor control to autonomic regulation and reflexes. As the central hub of neural projections and gut-to-brain communication, the cellular diversity that supports these functions remains ambiguous. To address this, we integrated eight single-cell and single-nucleus RNA sequencing (sc/snRNA-seq) datasets from mouse brains. We constructed a large-scale single-cell atlas encompassing 318,522 single cells from different sub-regions of the pons and medulla. Using a rigorous metadata standardization and annotation approach, we identified 45 cell types that span major populations and exhibit subtype-specific variability. We observed high diversity among neuronal populations, while non-neuronal cells were dominated by glial and vascular cells, each with unique transcriptional profiles. This atlas serves as the foundational resource for exploring region-specific cellular diversity in the pons and medulla, enabling comparative analyses for future studies
Gut-brain axis and environmental factors in Parkinson's disease: bidirectional link between disease onset and progression
No full textParkinson's disease has long been considered a disorder that primarily affects the brain, as it is defined by the dopaminergic neurodegeneration in the substantia nigra and the brain accumulation of Lewy bodies containing alpha-synuclein protein. In recent decades, however, accumulating research has revealed that Parkinson's disease also involves the gut and uncovered an intimate and important bidirectional link between the brain and the gut, called the "gut-brain axis." Numerous clinical studies demonstrate that gut dysfunction frequently precedes motor symptoms in Parkinson's disease patients, with findings including impaired intestinal permeability, heightened inflammation, and distinct gut microbiome profiles and metabolites. Furthermore, alpha-synuclein deposition has been consistently observed in the gut of Parkinson's disease patients, suggesting a potential role in disease initiation. Importantly, individuals with vagotomy have a reduced Parkinson's disease risk. From these observations, researchers have hypothesized that alpha-synuclein accumulation may initiate in the gut and subsequently propagate to the central dopaminergic neurons through the gut-brain axis, leading to Parkinson's disease. This review comprehensively examines the gut's involvement in Parkinson's disease, focusing on the concept of a gut-origin for the disease. We also examine the interplay between altered gut-related factors and the accumulation of pathological alpha-synuclein in the gut of Parkinson's disease patients. Given the accessibility of the gut to both dietary and pharmacological interventions, targeting gut-localized alpha-synuclein represents a promising avenue for developing effective Parkinson's disease therapies
Copolymerization of propylene and styene with highly active Mg(OEt)2/TiCl4/Phthalic Anhydride Catalyst
No full textNanoplastics exacerbate Parkinson's disease symptoms in C. elegans and human cells
Full text linkThe increasing prevalence of nanoplastics in our environment due to the widespread use of plastics poses potential health risks that are not yet fully understood. This study examines the physiological and neurotoxic effects of these minuscule nanoplastic particles on the nematode Caenorhabditis elegans as well as on human cells. Here, we find that 25 nm polystyrene nanoplastic particles can inhibit animal growth and movement at very low concentrations, with varying effects on their surface groups. Furthermore, these nanoplastic particles not only accumulate in the digestive tract but also penetrate further into extraintestinal tissues. Such nanoplastics significantly compromise the integrity of the intestinal barrier, leading to “leaky gut” conditions and cause mitochondrial fragmentation in muscles, which possibly explains the observed movement impairments. A striking discovery was that these nanoplastics exacerbate symptoms similar to those of Parkinson's disease (PD), including dopaminergic neuronal degeneration, locomotor dysfunction, and accumulation of α-Synuclein aggregates. Importantly, our study demonstrates that the detrimental effects of nanoplastics on the aggregation of α-Synuclein extend to both C. elegans and human cell models of PD. In conclusion, our research highlights the potential health hazards linked to the physicochemical properties of nanoplastics, underlining the urgency of understanding their interactions with biological systems. Environmental implication: The escalating prevalence of nanoplastics in the environment due to widespread plastic usage raises potential health risks. Studies conducted on C. elegans indicate that even low concentrations of 25 nm polystyrene nanoplastics can impair growth and movement. These particles accumulate in the digestive system, compromising the intestinal barrier, causing “leaky gut”, as well as inducing Parkinson's-like symptoms. Importantly, in both C. elegans and human cell models of Parkinson's disease, such nanoplastics penetrate tissues or cells and increase α-Synuclein aggregates. This underscores the urgent need to understand the interactions of nanoplastics with biological systems and highlights potential environmental and health consequences
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