Investigating the frequency of neural autoantibodies in refractory focal epilepsy.

Objectives: There have been conflicting reports about the frequency of neural autoantibodies in epilepsy cohorts, which is confounded by the lack of clear distinction of epilepsy from acute symptomatic seizures due to encephalitis. The aim of this study was to determine the frequency of neural autoantibodies in a well characterised population of refractory focal epilepsy of known and unknown cause.

Methods: Cases were recruited from epilepsy outpatient clinics at the Princess Alexandra, Mater, Royal Brisbane and Women's and Cairns Base Hospitals from 2021 - 2023.

Untargeted Metabolic Phenotyping by LC-MS.

Untargeted analysis by LC-MS is a valuable tool for metabolic profiling (metabonomics/metabolomics), and applications of this technology have grown rapidly over the past decade. LC-MS offers advantages of speed, sensitivity, relative ease of sample preparation, and large dynamic range compared to other platforms in this role. However, like any analytical approach, there are still drawbacks and challenges that have to be overcome, some of which are being addressed by advances in both column chemistries and instrumentation.

Quality Control and Validation Issues in LC-MS-Based Metabolomics.

Metabolic profiling performed using untargeted metabolomics of different, complex biological samples aims to apply agnostic/holistic, hypothesis-free, analysis of the small molecules that are present in the analyzed sample. This approach has been the center of major investments and dedicated efforts from the research community for many years. However, limitations and challenges remain, particularly with regard to the validation and the quality of the obtained results.

Metabolic Profiling: A Perspective on the Current Status, Challenges, and Future Directions.

Metabolic profiling continues to develop, and research is now conducted on this topic globally in hundreds of laboratories, from small groups up to national centers and core facilities. Here we briefly provide a perspective on the current status and challenges facing metabolic phenotyping (metabonomics/metabolomics) and consider future directions for this important area of biomarker and systems biology research.

Spontaneous base flipping helps drive Nsp15's preferences in double stranded RNA substrates.

Coronaviruses evade detection by the host immune system with the help of the endoribonuclease Nsp15, which regulates levels of viral double stranded RNA by cleaving 3' of uridine (U). While prior structural data shows that to cleave double stranded RNA, Nsp15's target U must be flipped out of the helix, it is not yet understood whether Nsp15 initiates flipping or captures spontaneously flipped bases. We address this gap by designing fluorinated double stranded RNA substrates that allow us to directly relate a U's sequence context to both its tendency to spontaneously flip and its susceptibility to cleavage by Nsp15.