Biology subjects

Flores, G.

Publications and source records attributed to Flores, G..

3 recordsLinked to original sources

bioRxiv2026

Inducible lipid storage and steatosis in the human choroid plexus associated with age and adiposity

Cells that store lipids for other cells or organs can contain "giant" or large lipid droplets (LLDs) greater than 2 {micro}m in diameter. In this study, human postmortem choroid plexus was evaluated for lipid droplets. Staining with hematoxylin and eosin (H&E), the lipophilic dye Oil red O, and anti-adipophilin antibodies established the presence of LLDs exceeding 10 {micro}m in diameter in choroid plexus epithelial cells (CPECs). Manual annotation of H&E stains from 105 cases revealed a significant association between age and the percentage of CPECs containing LLDs (reaching up to 69%) and involving LLDs in our largest annotated category (>5 {micro}m in diameter). The LLD association with age was replicated and extended to a total of 245 cases using a trained convolutional neural network, which further showed significant associations with body mass index at time of death (increasing with BMI), sex (higher in females >65 years old), and a near-significant association with Alzheimers Disease (lower in AD). Like HepG2 and derived hepatocytes, excess fatty acids in culture media readily induced LLDs and steatosis in human embryonic stem cell-derived CPECs. Akin to hepatocytes for the human body, we propose that CPECs store lipids for the human brain and become steatotic in the setting of excess adiposity.

pathology↗

bioRxiv2026

Engineering an in vitro model of demyelinated spinal cord tissue

Demyelinating diseases are a group of complex neurodegenerative disorders characterized by damage to the myelin, the protective sheath that insulates and supports efficient nerve signal conduction. Such a loss of myelin causes the formation of lesions not only in the brain but also often in the spinal cord (SC). Despite the high prevalence of SC lesions among patients, existing models mostly focus on those in the brain, inadequately capture the unique anatomical and physiological features of SC pathology. In this study, we developed a robust, reproducible in vitro model of SC demyelination by combining microwell technology and piezoelectric scaffolds to engineer human neural stem cell (hNSC)-derived nerve tissues featuring aligned, myelinated, extended axons up to 2000 {micro}m in length. We utilized distinct chemical treatments to induce demyelination with or without axonal degeneration: a cuprizone cocktail, a copper chelator combined with inflammatory cytokines, and lysophosphatidylcholine (LPC). Electrophysiological assessments validated the physiological relevance of our model, demonstrating impaired signal transmission and neural connectivity akin to in vivo demyelination pathology. Our versatile platform thus provides a valuable tool for elucidating SC demyelination pathophysiology and exploring potential therapeutic interventions.

bioengineering↗

bioRxiv2019

Comparative genomics guides elucidation of vitamin B12 biosynthesis in novel human associated Akkermansia

BackgroundAkkermansia muciniphila is a mucin-degrading bacterium found in the gut of most healthy humans and is considered a next-generation probiotic. However, knowledge of the genomic and physiological diversity of human associated Akkermansia is limited, as only one species has been formally described. ResultsTo begin to fill this knowledge gap, we reconstructed 35 high-quality metagenome assembled genomes from children and combined them with 40 other publicly available genomes from adults and mice for comparative genomic analysis. We identified at least four species-level phylogroups (AmI-AmIV) with distinct functional potentials. Most notably, we identified the presence of putative cobalamin (vitamin B12) biosynthesis genes within the AmII (n=26/28) and AmIII (n=2/2) phylogroups. To test these predictions, 10 novel strains of Akkermansia were isolated from adults and screened for essential vitamin B12 biosynthesis genes via PCR. Two strains of the AmII phylogroup were positive for the presence of vitamin B12 biosynthesis genes, while all AmI strains, including the type strain A. muciniphila MucT, were negative. To demonstrate vitamin B12 biosynthesis, we measured the production of acetate, succinate, and propionate in the presence and absence of vitamin supplementation in representative strains of the AmI and AmII phylogroups since cobalamin is a cofactor in propionate metabolism. Results show that the Akkermansia AmII strain produced acetate and propionate in the absence of supplementation, which is indicative of de novo vitamin B12 biosynthesis. In contrast, acetate and succinate were the main fermentation products for the AmI strains when vitamin B12 was not supplied in the culture medium. ConclusionsWe identified Akkermansia strains as potentially important vitamin B12 biosynthetic bacteria in the human gut. This novel physiological trait of human associated Akkermansia may impact how these bacteria interact with the human host and other members of the human gut microbiome.

genomics↗