The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its localization, degradation, and toxicity.

Missense mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease (PD); however, pathways regulating LRRK2 subcellular localization, function, and turnover are not fully defined. We performed quantitative mass spectrometry-based interactome studies to identify 48 novel LRRK2 interactors, including the microtubule-associated E3 ubiquitin ligase TRIM1 (tripartite motif family 1). TRIM1 recruits LRRK2 to the microtubule cytoskeleton for ubiquitination and proteasomal degradation by binding LRRK2911-919, a nine amino acid segment within a flexible interdomain region (LRRK2853-981), which we designate the "regulatory loop" (RL).

Agnostic Framework for the Classification/Identification of Organisms Based on RNA Post-Transcriptional Modifications.

We propose a novel approach for building a classification/identification framework based on the full complement of RNA post-transcriptional modifications (rPTMs) expressed by an organism at basal conditions. The approach relies on advanced mass spectrometry techniques to characterize the products of exonuclease digestion of total RNA extracts. Sample profiles comprising identities and relative abundances of all detected rPTM were used to train and test the capabilities of different machine learning (ML) algorithms.

Comparative Analysis of Radiotherapy Linear Accelerator Downtime and Failure Modes in the UK, Nigeria and Botswana.

The lack of radiotherapy linear accelerators (linacs) in low- and middle-income countries (LMICs) has been recognised as a major barrier to providing quality cancer care in these regions, together with a shortfall in the number of highly qualified personnel. It is expected that additional challenges will be faced in operating precise, high-technology radiotherapy equipment in these environments, and anecdotal evidence suggests that linacs have greater downtime and higher failure rates of components than their counterparts in high-income countries. To guide future developments, such as the design of a linac tailored for use in LMIC environments, it is important to take a data-driven approach to any re-engineering of the technology.

High-resolution ion mobility spectrometry-mass spectrometry of isomeric/isobaric ribonucleotide variants.

In this report, we explored the benefits of cyclic ion mobility (cIM) mass spectrometry in the analysis of isomeric post-transcriptional modifications of RNA. Standard methyl-cytidine samples were initially utilized to test the ability to correctly distinguish different structures sharing the same elemental composition and thus molecular mass. Analyzed individually, the analytes displayed characteristic arrival times (t ) determined by the different positions of the modifying methyl groups onto the common cytidine scaffold.