Pugh, A. | Search bioRxiv

bioRxiv2026

The PEARL toolkit: Using sand flies to identify leishmaniasis animal reservoirs

Animal reservoirs remain unknown in emerging and most endemic leishmaniasis foci hindering control efforts. Here, we developed a field-applicable PERL (Phlebotomines Establish Reservoirs of Leishmania) toolkit using individual blood fed sand flies (IBF) to identify leishmaniasis reservoirs. Using IBF, we optimized DNA and RNA co-extraction and parasite detection of [≥]1 parasite/s by kDNA qPCR and ssu rRNA RT-qPCR. We then screened IBF for expression of two parasite genes, sherp and HPB, identified by RNAseq as having low-to-absent expression in IBF given a first Leishmania donovani-infected blood meal (IBF-iBM1) and high expression in specimens provided subsequent uninfected blood meals (IBF-BMS+). Linear discriminant analysis of target gene expression classified iBM1 parasites with a predictive accuracy of ~87% and ~82% in membrane- or naturally-fed on hamsters sand flies, respectively. By determining the blood source in specimens determined as IBF-iBM1, the PERL toolkit provides an innovative and practical approach to identification of leishmaniasis reservoirs.

Molecular Biology↗

bioRxiv2025

Whole-body Loss of FSP27 Impairs Cognitive Function via Disruption of Neuro-Metabolic Pathways

Fat-Specific Protein 27 (FSP27), originally identified for its role in adipocyte lipid metabolism and energy homeostasis, plays a key role in regulating lipolysis and maintaining insulin sensitivity. Beyond adipose tissue, emerging studies have uncovered its involvement in hepatic and skeletal muscle function. More recently, FSP27 has also been implicated in maintaining vascular health through its influence on endothelial signaling. Despite growing insights into FSP27s systemic functions, its involvement in the central nervous system and cognitive regulation have remained unexplored. In this study, we present the first evidence that FSP27 is a critical regulator of cognitive function. Utilizing a global FSP27 knockout (Fsp27-/-) mouse model, we demonstrate that FSP27 deficiency results in significant impairments in learning, memory retention, and spatial awareness. To elucidate the underlying molecular mechanisms, genome-wide transcriptome profiling of brain tissue from Fsp27-/- mice was performed, revealing significant (P<0.05) alterations in gene expression related to neurocognition and metabolic pathways. Notably, FSP27 deletion was associated with genomic instability (P=0.05), downregulation of genes essential for axonal transport (NES=-1.91, FDR q-value=0.21), neuronal plasticity, and brain development (NES=-1.91, FDR q-value=0.28), along with signatures of disrupted systemic metabolism and elevated stress responses (NES=1.81, FDR q-value=0.20) in the brain, the processes tightly linked to cognitive dysfunction. Collectively, these findings establish FSP27 as a molecular node connecting metabolic regulation with cognitive health and identify it as a promising target for therapeutic intervention in neurodegenerative and cognitive disorders. Significance StatementFSP27, previously known for its role in lipid metabolism, is now revealed to be a critical regulator of brain function. Our study provides the first direct evidence that FSP27 supports learning and memory by maintaining neuronal integrity and regulating neurocognitive gene networks. These findings uncover an unexpected metabolic- cognitive link and position FSP27 as a promising molecular target for therapeutic strategies aimed at preventing or treating neurodegenerative and cognitive disorders.

animal behavior and cognition↗