Biology subjects

Aguado, F. J.

Publications and source records attributed to Aguado, F. J..

3 recordsLinked to original sources

bioRxiv2026

Reduced food accessibility enhances value-based decision-making in rats

Finding nutrients regularly is critical for survival; therefore, most animals invest a large portion of their time and energy in securing access to food. Food acquisition activates the brain's reward system, enhancing motivation and thereby increasing chances to succeed again in the future. However, little is known about the effect of food accessibility on cognition. We hypothesize that reducing food accessibility by requiring laboratory animals to get it with effort, will expose them to daily learning challenges, enhance reward system engagement and consequently have a positive impact on cognitive performance. To test whether effortful access to food confers cognitive benefits, one group of rats was housed with a food dispenser specifically designed to reduce food accessibility (Low Accessibility, LA). The comparison group had free access to food at any time (High Accessibility, HA). Both groups were trained in a value-based task in which they were required to choose between two options and, through trial and error, learn which option was more likely to deliver a reward. We found that both groups learned the task structure similarly. However, the LA group showed a higher proportion of optimal choices throughout training, indicating better task performance. We also found that LA rats were more sensitive to the outcomes of previous decisions. Collectively, our findings suggest that reducing food accessibility improves value-based decision-making, potentially by increasing sensitivity to action outcomes, highlighting a previously underappreciated link between food acquisition demands and cognitive performance.

animal behavior and cognition↗

bioRxiv2023

Concurrent D-loop cleavage by Mus81 and Yen1 yields half-crossover precursors

Homologous recombination involves the formation of branched DNA molecules that may interfere with chromosome segregation. To resolve these persistent joint molecules, cells rely on the activation of structure-selective endonucleases (SSEs) during the late stages of the cell cycle. However, the premature activation of SSEs compromises genome integrity, due to untimely processing of replication/recombination intermediates. Here, we employed a biochemical approach to demonstrate that the budding yeast SSEs Mus81 and Yen1 possess the ability to cleave the central recombination intermediate known as the displacement loop or D-loop. Moreover, we confirm that, consistently with previous genetic data, the simultaneous action of Mus81 and Yen1, followed by ligation, is sufficient to recreate the formation of a half-crossover precursor in vitro. Our results provide not only mechanistic explanation for the formation of a half-crossover, but also highlight the critical importance for precise regulation of these SSEs to prevent chromosomal rearrangements.

molecular biology↗

bioRxiv2020

Canonical and novel non-canonical activities of the Holliday junction resolvase Yen1

Yen1 and GEN1 are members of the Rad2/XPG family of nucleases that were identified as the first canonical nuclear Holliday junction (HJ) resolvases in budding yeast and humans due to their ability to introduce two symmetric, coordinated incisions on opposite strands of the HJ, yielding nicked DNA products that could be readily ligated. While GEN1 has been extensively characterized in vitro, much less is known about the biochemistry of Yen1. Here, we have performed the first in-depth characterization of purified Yen1. We confirmed that Yen1 resembles GEN1 in many aspects, including range of substrates targeted, position of most incisions they produce or monomeric state in solution. However, we have also observed unexpected alternative processing of substrates, such as nicked HJs and a different conformational preference on intact HJs. Moreover, we demonstrate that Yen1 is endowed with additional nuclease activities, like a nick-specific 5-3 exonuclease or HJ arm-chopping that could apparently blur its classification as a canonical HJ resolvase. Despite this, we show that Yen1 fulfills the requirements of a canonical HJ resolvase and hypothesize that its wider array of nuclease activities might contribute to its function in the removal of persistent recombination or replication intermediates.

molecular biology↗