Biology subjects

Jara, C.

Publications and source records attributed to Jara, C..

4 recordsLinked to original sources

bioRxiv2026

Galectin-8 regulates primary cilium in hypothalamic neurons through anL-type calcium channel/Aurora kinaseA/HDAC6 pathway impacting body energy balance

OBJETIVEFood intake, energy expenditure, and metabolic homeostasis depend on hypothalamic neurons responses to peripheral signals, such as leptin, involving the primary cilium (PC). The PC is crucial for signal transduction and is dynamically regulated by assembly/disassembly or reabsorption of its microtubules-based axoneme. Absence or reduction in the length of PC is associated with obesity and type-2 diabetes (T2D). In other cellular systems, PC reabsorption is primarily regulated by calcium-mediated activation of the Aurora kinase A (AurkA)/histone deacetylase C6 (HDAC6) axis, which promotes axonemal disassembly. Here, we explore the role of Galectin-8 (Gal-8), a glycan-binding protein, in regulating PC structure and signaling related to metabolic parameters in hypothalamic neurons. METHODSGal-8 effects were assessed in hypothalamic Clu-177 cells by analyzing the PC presence and length by immunofluorescence, PC dynamics, and intracellular calcium changes by in vivo cell imaging, activation of FAK, Src, AurkA, HDAC6 and STAT3 by immunoblot, and Gal-8 interactions with {beta}1-integrins by pull-down assays. Gal-8-KO mice were used to evaluate PC length in hypothalamic neurons, metabolic phenotype, and responses to Gal-8 intranasal administration. RESULTSIn Clu-177 cells, Gal-8 induced PC reabsorption and reduced responsiveness to leptin signaling towards STAT3 activation. PC reabsorption involves glycan-mediated Gal-8 interactions with a5b1 and a3b1 integrins, activation of FAK and Src leading to calcium influx through L-type calcium channels (LTCC), and subsequent AurkA/HDAC6 axis activation. Gal-8-KO mice showed longer PC in hypothalamic neurons, higher STAT3 activation, decreased body weight and food intake, improved glucose tolerance, higher locomotor activity, and a glycolytic respiratory exchange rate (RER). Daily intranasal Gal-8 administration for 4 days restored hypothalamic PC length and STAT3 signaling, as well as RER in Gal-8-KO mice to the level of WT mice. CONCLUSIONSEndogenous Gal-8 is required to maintain PC structure and leptin signaling in hypothalamic neurons, impacting body weight, energy balance, and glucose homeostasis. The mechanism involves calcium influx via LTCC downstream of b1-integrin/FAK/Src signaling and subsequent AurkA/HDAC6 axis activation. Both Gal-8 and the AurkA/HDAC6 axis may offer new therapeutic opportunities for treating metabolic diseases characterized by ciliogenesis impairment, including obesity and type-2 diabetes.

cell biology↗

bioRxiv2026

Pretend Comprehension Enhances Social and Exploratory Behaviors in Human Toddlers and Adults.

Pretend play is a hallmark behavior in childhood where children create nonliteral meanings. Empirical data supporting the role of social cognition and the decoupling from literality are still scarce during early development. Here we examined how the comprehension of pretense modulates visual exploration in 19-month-old toddlers (n = 44) and adults (n = 65) when they were exposed to short videos with an actress performing either real actions (e.g., eating jelly) or pretend actions (e.g., pretending to eat with imaginary food), while varying the complexity of those actions. We analyzed participants exploration of the actresss face as exploitation of social information. We showed that all observers paid more attention to the face in pretend episodes than in real ones, measured as longer total looking time in adults and more fixations and revisits to the face in both age groups. We also found more gaze shifts (a measure of information sampling) between the face and the moving hand in pretense across age groups, mainly at the initial stages of the actions. Additionally, analyses of the scanpaths structure using gaze entropy revealed less order in the exploration of pretend movies at both ages. Both social and visual trajectory effects emerged mostly in complex pretense actions. Together, our results indicate that from its developmental origins, the comprehension of pretense relies on social inferential processes linked with information seeking and exploration.

animal behavior and cognition↗

bioRxiv2025

Metabolic Adaptations of Prostate Cancer Cells Under Chronic Fructose Stimulation

BackgroundDietary sugars, particularly fructose, are increasingly implicated in cancer progression through their impact on tumor metabolism. However, the specific metabolic adaptations driven by fructose in prostate cancer (PCa) remain unexplored. MethodsWe investigated the metabolic consequences of chronic fructose exposure in androgen-sensitive (LNCaP) and androgen-independent (PC-3) PCa cell lines. We evaluated the expression, localization, and function of the fructose transporter Glut-5 and assessed metabolic fluxes, enzyme expression, lipid accumulation, and global metabolite profiles using molecular, imaging, and metabolomic approaches. ResultsGlut-5 was primarily localized to early endosomes under basal and fructose-stimulated conditions, suggesting a non-canonical role potentially consistent with transceptor function. Chronic fructose exposure significantly upregulated Glut-5 expression and enhanced fructose uptake, but did not alter substantially its subcellular localization. Functionally, fructose reduced lactate production and mitochondrial ATP output, indicating a metabolic shift away from glycolysis and oxidative phosphorylation. In LNCaP cells, fructose induced robust activation of de novo lipogenesis (DNL), evidenced by upregulation of FASN and G6PD, increased lipid droplet accumulation, and enhanced levels of key fatty acid metabolites (e.g., TG, EPA, DHA). In contrast, PC-3 cells exhibited a distinct metabolic response, characterized by increased ceramide and amino acid metabolites. Notably, pharmacological inhibition of lipid metabolism using etomoxir abrogated proliferation in both cell lines under fructose stimulation. ConclusionsThese findings reveal that fructose promotes a metabolic reprogramming in PCa cells that is cell type- and AR-dependent, enhancing lipogenesis and potentially contributing to tumor progression. Our study identifies Glut-5-mediated fructolysis and lipid metabolic pathways as key vulnerabilities in PCa, offering potential avenues for metabolic intervention.

cell biology↗

bioRxiv2019

H7N6 Low Pathogenic Avian Influenza outbreak in commercial turkey farms in Chile caused by a native South American Lineage

In December of 2016, low pathogenic avian influenza (LPAI) caused by an H7N6 subtype was confirmed in a grow-out turkey farm located in Valparaiso Region, Chile. Depopulation of exposed animals, zoning, animal movement control and active surveillance were implemented to contain the outbreak. Two weeks later, a second turkey grow-out farm located 70 km north of the first site was also infected by H7N6 LPAI, which subsequently spilled over to one backyard poultry flock. The virus involved in the outbreak shared a close genetic relationship with viruses collected from Chilean aquatic birds viruses. The A/turkey/Chile/2017(H7N6) LPAI virus belonged to a native South American lineage. Based on the H7 and most of the internal genes phylogenies, these viruses were also closely related to the viruses that caused a highly pathogenic avian influenza outbreak in Chile in 2002. Results from this study help understand the regional dynamics of influenza outbreaks, highlighting the importance of local native viruses circulating in the natural reservoir hosts.

epidemiology↗