Development of a Sensitive and Reliable Meso Scale Discovery-Based Electrochemiluminescence Immunoassay to Quantify TDP-43 in Human Biofluids.

Transactive response DNA-binding protein of 43 kDa (TDP-43) is a major component of pathological inclusions in various neurodegenerative disorders, including amyotrophic lateral sclerosis and frontotemporal lobar degeneration. The detection of TDP-43 in biofluids is crucial for the development of diagnostic and prognostic indicators of disease and therapeutic development for TDP-43-related proteinopathies. Despite its potential as a biomarker for numerous neurological disorders, the lack of a sensitive and reproducible TDP-43 assay hinders progress in TDP-43-based therapy development, underscoring the need for an effective and standardized method for accurate quantification.

Ciliary intrinsic mechanisms regulate dynamic ciliary extracellular vesicle release from sensory neurons.

Extracellular vesicles (EVs) are submicron membranous structures and key mediators of intercellular communication. Recent research has highlighted roles for cilia-derived EVs in signal transduction, underscoring their importance as bioactive extracellular organelles containing conserved ciliary signaling proteins. Members of the transient receptor potential (TRP) channel polycystin-2 (PKD-2) family are found in ciliary EVs of the green algae Chlamydomonas and the nematode Caenorhabditis elegans and in EVs in the mouse embryonic node and isolated from human urine.

Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes.

Therapeutic use of tiny extracellular vesicles (EVs) requires understanding cargo loading mechanisms. Here, we used a modular proximity label approach to identify EV cargo associated with the transient potential channel (TRP) polycystin PKD-2 of . Polycystins are conserved receptor-TRP channel proteins affecting cilium function; dysfunction causes polycystic kidney disease in humans and mating deficits in .

RESTRICTED DATA MANAGEMENT: THE CURRENT PRACTICE AND THE FUTURE.

Many organizations across the world that manage restricted data have adapted the Five Safes framework (safe data, safe projects, safe people, safe setting, safe output) for their management of restricted and confidential data. While the Five Safes have been well integrated throughout the data life cycle, organizations encounter several challenges with regard to safe data management. In this paper, we review current practices for restricted data management, and discuss challenges and future directions.