Alzheimer's disease (AD) is marked by cytoplasmic proteinopathies, primarily involving misfolded Tau protein. Pathogenic Tau species, such as soluble oligomers and fibrils, disrupt RNA metabolism, though the mechanisms are unclear. Recent research indicates that RNA has a crucial role in Tau aggregation. Our study builds on this by noting significant co-deposition of RNA-Binding Proteins (RBPs) with Tau in AD and Frontotemporal dementia (FTLD) brains. Using molecular and cellular techniques, we investigate the interaction between RNA dynamics and Tau aggregation, focusing on the localization and aggregation of Tau and RBPs, particularly Musashi (MSI), within neuronal nuclei. Through cyto-fluorometric, biochemical, and cellular assays, we reveal the importance of Tau/RBP interplay in primary cortical neurons expressing wild-type and mutant Tau. Pathogenic Tau oligomers alter MSI protein localization and function, causing cytoplasmic and nuclear aggregation. Mass spectrometry of the MSI1 nuclear interactome in Tau models shows disrupted RNA metabolism pathways, including ribosomal biogenesis, RNA splicing, and protein folding. Moreover, RNA immunoprecipitation assay revealed a remarkable impact of mutant P301L Tau on MSI1 ability to bind RNA targets. These findings highlight potential targets for early neurodegenerative therapeutic interventions.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to evolve, with mutations leading to the emergence of new variants. JN.1, a subvariant of omicron BA.2.86, has demonstrated marked immune escape and is now included in updated vaccine formulations. While reduced sensitivity has been reported for antibody assays using ancestral spike protein subunits to detect omicron-induced responses, the performance of full-length spike-based assays against omicron sublineages remains unclear. We aimed to compare the sensitivity of ELISA and Luminex assays using full-length spike proteins from the ancestral Wuhan strain and the JN.1 variant. Methods: Wuhan and JN.1 full-length spike protein constructs were designed and expressed in Expi293F mammalian cells. In-house ELISAs based on previously validated protocols were used to measure anti-spike IgG levels. Additionally, a Luminex-based assay for anti-spike antibody detection was developed and validated. Both assays were applied to the following sample groups: pre-pandemic samples (designated “gold standard negatives”); PCR confirmed 2020 positives (“gold standard wildtype positives”); PCR confirmed 2024 positives (“gold standard omicron positives”); 2022 vaccinated individuals with verbal confirmed infection (“gold standard hybrid positives”); and 2024 household samples (“unknowns”). Results: Wuhan spike protein showed a sensitivity of 100% (95% CI: 0.88–1.0) in detecting omicron-specific antibodies using gold standard omicron positives with JN.1 spike protein as a reference assay. Overall, across all samples, in ELISA, the Wuhan antigen had a sensitivity of 0.93 (95% CI: 0.89–0.95) and a specificity of 0.98 (95% CI: 0.94–0.99). The JN.1 antigen showed a sensitivity of 0.91 (95% CI: 0.87–0.94) and a specificity of 0.97 (95% CI: 0.93–0.99). In Luminex, sensitivity was 0.95 (95% CI: 0.91–0.97) for Wuhan and 0.94 (95% CI: 0.91–0.96) for JN.1. Specificity for both antigens in Luminex was 0.98 (95% CI: 0.94–0.99). Conclusions: Both ELISA and Luminex assays showed comparable sensitivity and specificity for both Wuhan and JN.1 antigens, indicating that mutations in the JN.1 variant do not significantly impact assay performance. This suggests preserved antigenic recognition across variants.

Background: Wastewater and Environmental Surveillance (WES) has become a useful public health tool as an early-warning system revealing emergence/re-emergence of pathogenic diseases and spread of antimicrobial resistance (AMR). We characterized the taxonomic composition, relative abundance, and antibiotic resistance genes (ARGs) of wastewater-identified bacterial pathogens across socioeconomically and epidemiologically diverse sewerage catchments in Nairobi, Kenya—a key East African urban city representing a low- and middle-income country (LMIC). Results: Metagenomic analysis of Nairobi’s wastewater revealed distinct bacterial and antimicrobial resistance (AMR) profiles. Campylobacteraceae (52.5% ± 17.9%) and Bacteroidaceae (19.8% ± 9.9%) dominated the communities. While Arcobacter cryaerophilus was ubiquitous, Bacteroides fragilis and A. suis abundances varied by neighborhood socioeconomic status. We detected critical clinical pathogens—including Escherichia coli, Vibrio cholerae, Mycobacterium tuberculosis, and the ESKAPE species—alongside 207 distinct ARGs conferring resistance to 11 antibiotic classes. Both taxonomic and ARG compositions showed high spatial heterogeneity, with maximum variation in low-income areas. Temporal analysis captured shifting pathogen dynamics, and metagenomic abundances for Vibrio cholerae and Klebsiella pneumoniae were validated via qPCR. Conclusions: Our findings underscore the utility of WES as a scalable, non-invasive public health tool. By capturing community-level pathogen composition and AMR dynamics, WES bypasses the limitations of clinical diagnostic access, providing a vital early-warning system for underserved urban populations. To maximize its public health utility, environmental genomic signals must serve as actionable triggers for coordinated One Health responses, including targeted clinical diagnostics, localized antimicrobial stewardship reviews, proactive risk communication, and prioritized sanitation infrastructure upgrades.