Biology subjects

Guerrini, V.

Publications and source records attributed to Guerrini, V..

4 recordsLinked to original sources

bioRxiv2026

Big-team science reveals that patterns of inhibitory control variation in teleost fishes differ from those in mammals and birds

Understanding the evolution of cognition is fundamental to understanding the origins and nature of our own cognitive abilities, with cross-species comparisons providing a cornerstone of this endeavor. Yet, comparative cognition so far has largely focused on endothermic vertebrates, particularly mammals and birds, while ectotherms--representing a substantial proportion of vertebrate diversity--remain relatively understudied. Moreover, variation in experimental methods makes existing data difficult to compare across species. Big-team science offers a way to overcome these limitations by enabling standardized cognitive testing across broad taxonomic scales. Here, we apply this approach to fishes, using inhibitory control as a proof of concept for standardized comparative testing in 444 individuals across 22 teleost species spanning 19 genera. We demonstrate that standardized cognitive testing across such diversity is feasible, while also revealing substantial heterogeneity in the sample. Performance varied markedly among species, but, strikingly, showed only a weak phylogenetic signal, contrasting with patterns previously reported in mammals and birds. In addition, we detected great within-species variation, including differences across research groups, suggesting that performance may reflect not only species-level evolutionary history but also ontogenetic experience and the capacity to adjust decision rules to local conditions. Together, our findings highlight the importance of both evolutionary and environmental sources of cognitive variation and demonstrate that extending standardized comparative approaches beyond traditionally studied endotherms can reveal a more dynamic and complex picture of cognitive evolution across the vertebrate lineage.

animal behavior and cognition↗

bioRxiv2024

Pharmacological inhibition of macrophage triglyceride biosynthesis pathways does not improve Mycobacterium tuberculosis control in infected mice

Triglyceride rich macrophages (foam cells) are a hallmark of necrotic granulomas in tuberculosis, and multiple antimicrobial functions are down-regulated in these cells. In this study, we assessed the ability of two different compounds to reduce triglyceride content and intracellular burden in Mycobacterium tuberculosis (Mtb)-infected macrophages: A-922500 (DGATi), an inhibitor of diacylglycerol acyltransferase 1, an enzyme involved in triglyceride synthesis; and LY2584702 (p70S6Ki), an inhibitor of p70 S6 kinase, a serine/threonine kinase involved in mTORC-1dependent lipid biogenesis. Additionally, we evaluated the adjunctive activity of these inhibitors as host-directed therapies against chronic Mtb infection in C3HeB/FeJ mice. DGATi and p70S6Ki significantly reduced the lipid content and bacillary burden in Mtb-infected human monocyte-derived macrophages. In Mtb-infected mice, each inhibitor reduced the triglyceride content (P[≤] 0.0001) in cells from bronchoalveolar lavage samples. Adjunctive treatment of DGATi with isoniazid and p70S6Ki monotherapy reduced the lipid droplet content (P[≤] 0.05) within lung macrophages of Mtb-infected mice. However, neither inhibitor reduced the lung bacterial burden in Mtb-infected mice alone or in combination with isoniazid, and they did not alter lung inflammation. These findings provide further insights into the role of foam cells in tuberculosis pathogenesis and the utility of interventions targeting these cell populations as adjunctive host-directed therapies.

pharmacology and toxicology↗

bioRxiv2023

Heterogeneity of foam cell biogenesis across diseases

Foam cells are dysfunctional, lipid-laden macrophages associated with chronic inflammation of diverse origin. The long-standing paradigm that foam cells are cholesterol-laden derives from atherosclerosis research. We previously showed that, in tuberculosis, foam cells surprisingly accumulate triglycerides. Here, we utilized bacterial (Mycobacterium tuberculosis), fungal (Cryptococcus neoformans), and human papillary renal cell carcinoma (pRCC) models to address the need for a new explanation of foam cell biogenesis. We applied mass spectrometry-based imaging to assess the spatial distribution of storage lipids relative to foam-cell-rich areas in lesional tissues, and we characterized lipid-laden macrophages generated under corresponding in vitro conditions. The in vivo data and the in vitro findings showed that cryptococcus-infected macrophages accumulate triglycerides, while macrophages exposed to pRCC- conditioned-medium accumulated both triglycerides and cholesterol. Moreover, cryptococcus- and mycobacterium-infected macrophages accumulated triglycerides in different ways. Collectively, the data show that the molecular events underlying foam cell formation are specific to disease and microenvironment. Since foam cells are potential therapeutic targets, recognizing that their formation is disease-specific opens new biomedical research directions.

immunology↗

bioRxiv2020

The anti-tubercular activity of simvastatin is mediated by cholesterol-dependent regulation of autophagy via the AMPK-mTORC1-TFEB axis

Statins, which inhibit both cholesterol biosynthesis and protein prenylation branches of the mevalonate pathway, increase anti-tubercular antibiotic efficacy in animal models. We investigated the mechanism of anti-tubercular action of simvastatin in Mycobacterium tuberculosis-infected human monocytic cells. We found that the anti-tubercular activity of statins was phenocopied by cholesterol-branch but not prenylation-branch inhibitors. Moreover, statin treatment blocked activation of mechanistic target of rapamycin complex 1 (mTORC1), activated AMP-activated protein kinase (AMPK) through increased intracellular AMP:ATP ratios, and favored nuclear translocation of transcription factor EB (TFEB). These mechanisms all induce autophagy, which is anti-mycobacterial. The biological effects of simvastatin on the AMPK-mTORC1-TFEB-autophagy axis were reversed by adding exogenous cholesterol to the cells. Overall, our data demonstrate that the anti-tubercular activity of simvastatin requires inhibiting cholesterol biosynthesis, reveal novel links between cholesterol homeostasis, AMPK-mTORC1-TFEB axis, and intracellular infection control, and uncover new anti-tubercular therapy targets.

immunology↗