ARF6 CONTROLS LYSOSOMAL TRANSPORT OF APP AND Ap42 PRODUCTION

Alzheimer’s disease (AD) is characterized by the deposition of Beta-Amyloid (AP) peptide plaques in the brain. Ap peptides are generated by the sequential cleavage of the Amyloid Precursor Protein (APP). The AP42 cleavage product is the most neurotoxic form. Previous studies in our lab have uncovered a novel rapid lysosomal APP trafficking pathway that bypasses the early and late endosomal compartments. We set out to characterize this transport pathway using APP constructs with an N-terminal HA-tag, allowing us to label APP at the cell surface with a fluorescently labeled antibody. SN56 cells and mouse cortical neurons were also co-transfected with fluorescently-tagged compartment marker proteins and a panel of endocytosis regulatory proteins bearing dominant negative and constitutively activating mutations. Rapid APP internalization to lysosomes is stimulated by antibody binding and is increased when Arfl activity was inhibited, but decreased when Arfó activity was inhibited. In addition, disruption of either Arfó or Arfl was able to significantly reduce Ap42 secretion into the media. Our findings suggest that rapid APP transport to lysosomes is regulated by Arfó and is an important, and potentially targetable, mechanism that regulates A(342 production, while Arfl regulates secretion of Ap42 into the media

A fast tunable driver of light source for the TRIDENT Pathfinder experiment

TRIDENT (The tRopIcal DEep-sea Neutrino Telescope) is a proposed next-generation neutrino telescope to be constructed in the South China Sea. In September 2021, the TRIDENT Pathfinder experiment (TRIDENT EXplorer, T-REX for short) was conducted to evaluate the in-situ optical properties of seawater. The T-REX experiment deployed three digital optical modules at a depth of 3420 meters, including a light emitter module (LEM) and two light receiver modules (LRMs) equipped with photomultiplier tubes (PMTs) and cameras to detect light signals. The LEM emits light in pulsing and steady modes. It features a fast tunable driver to activate light-emitting diodes (LEDs) that emit nanosecond-width light pulses with tunable intensity. The PMTs in the LRM receive single photo-electron (SPE) signals with an average photon number of approximately 0.3 per 1-microsecond time window, which is used to measure the arrival time distribution of the SPE signals. The fast tunable driver can be remotely controlled in real-time by the data acquisition system onboard the research vessel, allowing for convenient adjustments to the driver's parameters and facilitating the acquisition of high-quality experimental data. This paper describes the requirements, design scheme, and test results of the fast tunable driver, highlighting its successful implementation in the T-REX experiment and its potential for future deep-sea experiments

Biological Effects of Black Phosphorus Nanomaterials on Mammalian Cells and Animals

The remarkable progress of applied black phosphorus nanomaterials (BPNMs) is attributed to BP's outstanding properties. Due to its potential for applications, environmental release and subsequent human exposure are virtually inevitable. Therefore, how BPNMs impact biological systems and human health needs to be considered. In this comprehensive Minireview, the most recent advancements in understanding the mechanisms and regulation factors of BPNMs’ endogenous toxicity to mammalian systems are presented. These achievements lay the groundwork for an understanding of its biological effects, aimed towards establishing regulatory principles to minimize the adverse health impacts

Arf6 controls beta-amyloid production by regulating macropinocytosis of the Amyloid Precursor Protein to lysosomes

Alzheimer\u27s disease (AD) is characterized by the deposition of Beta-Amyloid (Aβ) peptides in the brain. Aβ peptides are generated by cleavage of the Amyloid Precursor Protein (APP) by the β - and γ - secretase enzymes. Although this process is tightly linked to the internalization of cell surface APP, the compartments responsible are not well defined. We have found that APP can be rapidly internalized from the cell surface to lysosomes, bypassing early and late endosomes. Here we show by confocal microscopy and electron microscopy that this pathway is mediated by macropinocytosis. APP internalization is enhanced by antibody binding/crosslinking of APP suggesting that APP may function as a receptor. Furthermore, a dominant negative mutant of Arf6 blocks direct transport of APP to lysosomes, but does not affect classical endocytosis to endosomes. Arf6 expression increases through the hippocampus with the development of Alzheimer\u27s disease, being expressed mostly in the CA1 and CA2 regions in normal individuals but spreading through the CA3 and CA4 regions in individuals with pathologically diagnosed AD. Disruption of lysosomal transport of APP reduces both Aβ40 and Aβ42 production by more than 30 %. Our findings suggest that the lysosome is an important site for Aβ production and that altering APP trafficking represents a viable strategy to reduce Aβ production

Pickering emulsion-enhanced interfacial biocatalysis: tailored alginate microparticles act as particulate emulsifier and enzyme carrier

A robust Pickering emulsion stabilized by lipase-immobilized alginate gel microparticles with a coating of silanized titania nanoparticles is developed for biphasic biocatalysis. The good recyclability and high stability of the proposed interfacial catalysis system have been verified, retaining about 90% of relative enzyme activity in 10 catalytic cycles with operation for 240 h. Meanwhile the Pickering emulsions remain stable during a storage time of one year. The green system can be widely applied to construct powerful platforms for enzyme or microorganism-driven interfacial catalysis

Biologische Effekte von auf schwarzem Phosphor basierenden Nanomaterialien auf Zellen und Tiere

Die bedeutenden Fortschritte bei der Anwendung von auf schwarzem Phosphor basierenden Nanomaterialien (SPNMs) sind auf deren hervorragende Eigenschaften zurückzuführen. Aufgrund der vielfältigen Anwendungsmöglichkeiten dieser Materialien sind die Freisetzung in die Umwelt und eine anschließende Exposition des Menschen praktisch unvermeidlich. Daher muss untersucht werden, wie sich SPNMs auf biologische Systeme und die menschliche Gesundheit auswirken. In dieser umfassenden Übersicht werden die neuesten Erkenntnisse in Bezug auf Wirkungsweise, Mechanismen und Regulierungsfaktoren der endogenen Toxizität von SPNMs in Säugetieren vorgestellt. Diese Ergebnisse bilden die Grundlage für das Verständnis der biologischen Auswirkungen und haben das Ziel, Regulierungsprinzipien zur Minimierung gesundheitsschädlicher Auswirkungen festzulegen