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Varela, S.

Publications and source records attributed to Varela, S..

4 recordsLinked to original sources

Optimistic and pessimistic cognitive judgement bias modulates the stress response and cancer progression in zebrafish

Cognitive judgement bias in decision-making under ambiguity occurs both in animals and humans, with some individuals interpreting ambiguous stimulus as positive (optimism) and others as negative (pessimism). We hypothesize that judgement bias is a personality trait and that individuals with a pessimistic bias would be more reactive to stressors and therefore more susceptible to stress-related diseases than optimistic ones. Here, we show that zebrafish judgment bias is a consistent behavioral trait over time, and that pessimistic and optimistic fish express phenotype-specific neurogenomic responses to stress. Furthermore, both phenotypes show differential activation of the hypothalamic-pituitary-interrenal axis in response to chronic stress, suggesting that optimists have a lower stress reactivity. Accordingly, optimists seem to be more resilient to disease than pessimists, as shown by a lower tumorigenesis in a zebrafish melanoma line [Tg(mtifa:HRAS-GFP)]. Together these results indicate that judgement bias is paralleled by differences in the stress response with implications for disease resilience.

animal behavior and cognition↗

Single-nucleus and spatial landscape of the sub-ventricular zone in human glioblastoma

The sub-ventricular zone (SVZ) is the most well-characterized neurogenic area in the mammalian brain. We previously showed that in 65% of patients with glioblastoma (GBM), the SVZ is a reservoir of cancer stem-like cells that contribute to treatment resistance and emergence of recurrence. Here, we built a single-nucleus RNA-sequencing-based microenvironment landscape of the tumor mass (T_Mass) and the SVZ (T_SVZ) of 15 GBM patients and 2 histologically normal SVZ (N_SVZ) samples as controls. We identified a mesenchymal signature in the T_SVZ of GBM patients: tumor cells from the T_SVZ relied on the ZEB1 regulatory network, whereas tumor cells in the T_Mass relied on the TEAD1 regulatory network. Moreover, the T_SVZ microenvironment was predominantly characterized by tumor-supportive microglia, which spatially co-exist and establish heterotypic interactions with tumor cells. Lastly, differential gene expression analyses, predictions of ligand-receptor and incoming/outgoing interactions, and functional assays revealed that the IL-1{beta}/IL-1RAcP and Wnt-5a/Frizzled-3 pathways are therapeutic targets in the T_SVZ microenvironment. Our data provide insights into the biology of the SVZ in GBM patients and identify specific targets of this microenvironment.

cancer biology↗

Early Jurassic origin of avian endothermy and thermophysiological diversity in Dinosauria

A fundamental question in dinosaur evolution is how they adapted to substantial long-term shifts in Earth System during the Mesozoic and when they developed environmentally independent, avian-style acclimatization due to the evolution of an endothermic physiology. Combining fossil occurrences with macroevolutionary and paleoclimatic models, we unveil distinct evolutionary pathways in the main dinosaur lineages: ornithischians and theropods diversified across broader climatic landscapes, trending toward cooler niches. An Early Jurassic shift to colder climates in Theropoda suggests an early adoption of endothermic thermophysiology. Conversely, sauropodomorphs exhibited prolonged climatic conservatism associated with higher thermal conditions. Paleo-biome mapping emphasizes temperature, rather than plant productivity, as the primary driver of this pattern, suggesting poikilothermic physiology with a stronger dependence on higher temperatures in sauropods since the Early Jurassic. One-Sentence SummaryDinosaur climatic evolution reveals early endothermy emergence in theropods, ornithischians but heterotherm sauropodomorphs.

paleontology↗

Bioregionalization: From Wallace and Humboldt to deep-time paleoregion dynamics

Bioregionalization methods allow us to classify and map biogeographic units using data on species composition and traits. Here, we reviewed the evolution of the field during the last 70 years, seeking to summarize its history, and identify gaps and future avenues for research. Our results show that the aim of the studies using bioregionalization methods changed in time. First, bioregionalization were used to unveil the drivers of the observed spatial patterns of biodiversity on Earth, and to understand the role of dispersal limitations on the evolutionary history of clades, but recently, these methods are mostly used for conservation management. Further, data used to map biodiversity regions, the ones that we are now defining conservation strategies, are taxonomically and geographically biased, with a large percentage of the papers using vertebrate data from developed continents/countries. Finally, we show how key papers in the field, the ones with most citations, heavily depend on expert criteria and non-reproducible workflows, preventing direct comparison of maps of bioregions from different papers. Following our findings, we identified 3 gaps for the advance in the field, 1) We need to move beyond maps of vertebrate composition. Ideally, we need to increase the taxonomic diversity of the studies, but also to add other type of information, like data on species traits, genetic diversity, or phylogenetic distances. 2) we need reproducible and standardized methods 3) we need to further explore the temporal dimension of bioregions, to understand how they evolved through time.

ecology↗