Ho, K. S. | Search bioRxiv

bioRxiv2023

A Mechanism Underpinning the Bioenergetic Metabolism-Regulating Function of Gold Nanocatalysts

Bioenergetic deficits, such as mitochondrial impairments and dysfunction in glucose metabolism, have been identified as significant contributors to neurodegenerative diseases. Nevertheless, identifying safe and effective means to address intracellular bioenergetic deficits remains a significant challenge. This work provides mechanistic insights into the bioenergetic metabolism-regulating function of a suspension of gold (Au) nanocrystals, referred to as CNM-Au8(R), that are synthesized electrochemically in the absence of any surface-capping organic ligands. When neurons are subjected to excitotoxic stressors or toxic peptides, treatment of neurons with CNM-Au8 results in dose-dependent neuronal survival and preservation of neurite networks across multiple neuronal subtypes. CNM-Au8 efficiently catalyzes the conversion of an energetic co-factor, nicotinamide adenine dinucleotide hydride (NADH), into its oxidized, dehydrogenated counterpart (NAD+), which triggers an increase in energy production in the form of adenosine triphosphate (ATP). Detailed kinetic measurements reveal that CNM-Au8-catalyzed NADH oxidation obeys Michaelis-Menten kinetics and exhibits pH-dependent kinetic profiles. CNM-Au8 functions as an NADH-dehydrogenase-mimicking nanozyme that effectively regulates intracellular bioenergetic metabolism. We further utilize photoexcited charge carriers and photothermal transduction, which can be generated through optical excitations of the plasmonic electron oscillations or the interband electronic transitions in CNM-Au8, as unique leverages to modulate reaction kinetics. Benefiting from their bio-compatibility, blood-brain barrier penetrance, tunable optical properties, and enzyme-mimicking functions, CNM-Au8 nanocrystals with deliberately tailored structures and surfactant-free clean surfaces hold great promise for developing next-generation therapeutic agents for neurodegenerative diseases.

neuroscience↗

bioRxiv2018

Limitation of alignment-free tools in total RNA-seq quantification

BackgroundAlignment-free RNA quantification tools have significantly increased the speed of RNA-seq analysis. However, it is unclear whether these state-of-the-art RNA-seq analysis pipelines can quantify small RNAs as accurately as they do with long RNAs in the context of total RNA quantification.\n\nResultWe comprehensively tested and compared four RNA-seq pipelines on the accuracies of gene quantification and fold-change estimation on a novel total RNA benchmarking dataset, in which small non-coding RNAs are highly represented along with other long RNAs. The four RNA-seq pipelines were of two commonly-used alignment-free pipelines and two variants of alignment-based pipelines. We found that all pipelines showed high accuracies for quantifying the expressions of long and highly-abundant genes. However, alignment-free pipelines showed systematically poorer performances in quantifying lowly-abundant and small RNAs.\n\nConclusionWe have shown that alignment-free and traditional alignment-based quantification methods performed similarly for common gene targets, such as protein-coding genes. However, we identified a potential pitfall in analyzing and quantifying lowly-expressed genes and small RNAs with alignment-free pipelines, especially when these small RNAs contain mutations.

bioinformatics↗