Covalent attachment of ubiquitin, a small globular polypeptide, to protein substrates is a key post-translational modification that determines the fate, function, and turnover of most cellular proteins. Ubiquitin modification exists as mono- or polyubiquitin chains involving multiple ways how ubiquitin C-termini are connected to lysine, perhaps other amino acid side chains, and N-termini of proteins, often including branching of the ubiquitin chains. Understanding this enormous complexity in protein ubiquitination, the so-called ‘ubiquitin code’, in combination with the ∼1000 enzymes involved in controlling ubiquitin recognition, conjugation, and deconjugation, calls for novel developments in analytical techniques. Here, we review different headways in the field mainly driven by mass spectrometry and chemical biology, referred to as “ubiquitomics”, aiming to understand this system’s biological diversity.
Ubiquitylation and ISGylation are protein post-translational modifications (PTMs) and two of the main events involved in the activation of pattern recognition receptor (PRRs) signals allowing the host defense response to viruses. As with similar viruses, SARS-CoV-2, the virus causing COVID-19, hijacks these pathways by removing ubiquitin and/or ISG15 from proteins using a protease called PLpro, but also by interacting with enzymes involved in ubiquitin/ISG15 machinery. These enable viral replication and avoidance of the host immune system. In this review, we highlight potential points of therapeutic intervention in ubiquitin/ISG15 pathways involved in key host–pathogen interactions, such as PLpro, USP18, TRIM25, CYLD, A20, and others that could be targeted for the treatment of COVID-19, and which may prove effective in combatting current and future vaccine-resistant variants of the disease.
Dielectric thin films are a fundamental part of solid-state devices providing the means for advanced structures and enhanced operation. Charged dielectrics are a particular kind in which embedded charge is used to create a static electric field which can add functionality and improve the performance of adjacent electronic materials. To date, the charge concentration has been limited to intrinsic defects present after dielectric synthesis, unstable corona charging, or complex implantation processes. While such charging mechanisms have been exploited in silicon surface passivation and energy harvesters, an alternative is presented here. Solid-state cations are migrated into SiO2 thin films using a gateless and implantation-free ion injecting method, which can provide greater long-term durability and enable fine charge tailoring. We demonstrate the migration kinetics and the stability of potassium, rubidium, and caesium cations inside of SiO2 thin films, showing that the ion concentration within the film can be tuned, leading to charge densities between 0.1-10 x 1012 qcm-2. A comprehensive model of ion injection and transport is presented along a detailed investigation of the kinetics of alkali cations. Integrating ionic charge into dielectrics to produce controlled electric fields can enable new architectures where field effect is exploited for improved electron devices.
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