Biology subjects

Gaca, M.

Publications and source records attributed to Gaca, M..

4 recordsLinked to original sources

bioRxiv2025

Modeling metabolic disease susceptibility and resilience in genetically diverse mice

Model organisms have provided critical insights into the basic biology of metabolic disorders, however, one of the greatest limitations to translation has been the absence of the genetic heterogeneity that is characteristic of human populations. We examined metabolic health across three genetically diverse mouse strains fed control (low fat, no sucrose) or unhealthy (high fat, high sucrose) diets and observed a wide range of metabolic responses from overt type 2 diabetes in NZO/HlLtJ mice, to obesity and glucose intolerance in C57BL/6J mice, to complete resilience in CAST/EiJ mice. Analysis of multi-tissue gene expression revealed strain- and tissue-specific responses to diet, with strongest responses in white adipose tissue and pancreatic islets. In pancreatic islets, diet response was limited to just NZO mice, which showed high levels of inflammation and associated {beta} cell dysfunction. Adipose tissue was responsive to diet across all three strains and revealed both common and strain-specific changes in inflammatory and metabolic pathways. Using a complementary outbred mouse resource, we mapped genetic loci associated with strain-specific diet responses, including a monocyte regulatory locus on mChr19. This multi-strain approach to modeling metabolic disease revealed a prominent role of white adipose tissue and lipid-associated inflammation in the determination of individual disease risk in response to unhealthy diets.

physiology↗

bioRxiv2024

Transcripts with high distal heritability mediate genetic effects on complex metabolic traits

Although many genes are subject to local regulation, recent evidence suggests that complex distal regulation may be more important in mediating phenotypic variability. To assess the role of distal gene regulation in complex traits, we combined multi-tissue transcriptomes with physiological outcomes to model diet-induced obesity and metabolic disease in a population of Diversity Outbred mice. Using a novel high-dimensional mediation analysis, we identified a composite transcriptome signature that summarized genetic effects on gene expression and explained 30% of the variation across all metabolic traits. The signature was heritable, interpretable in biological terms, and predicted obesity status from gene expression in an independently derived mouse cohort and multiple human studies. Transcripts contributing most strongly to this composite mediator frequently had complex, distal regulation distributed throughout the genome. These results suggest that trait-relevant variation in transcription is largely distally regulated, but is nonetheless identifiable, interpretable, and translatable across species.

genetics↗

bioRxiv2024

Understanding functional brain reorganisation for naturalistic piano playing in novice pianists

Learning to play the piano is a unique complex task, integrating multiple sensory modalities and higher-order cognitive functions. Longitudinal neuroimaging studies on adult novice musicians show training-related functional changes in music perception tasks. The reorganisation of brain activity while actually playing an instrument was studied only on a very short time-frame of a single fMRI session, and longer interventions have not yet been performed. Thus, our aim was to investigate the dynamic complexity of functional brain reorganisation while playing the piano within the first half year of musical training. We scanned twenty-four novice keyboard learners (female, 18-23yo) using fMRI while they played increasingly complex musical pieces after 1, 6, 13 and 26 weeks of training. Playing music evoked responses bilaterally in the auditory, inferior frontal and supplementary motor areas, and the left sensorimotor cortex. The effect of training over time, however, invoked widespread changes encompassing the right sensorimotor cortex, cerebellum, superior parietal cortex, anterior insula and hippocampus, among others. As the training progressed, the activation of these regions decreased while playing music. Post-hoc analysis revealed region-specific time-courses for independent auditory and motor regions of interest. These results suggest that while the primary sensory, motor and frontal regions are associated with playing music, the training decreases the involvement of higher-order cognitive control and integrative regions, and basal ganglia. Moreover, training might affect distinct brain regions in different ways, providing evidence in favour of the dynamic nature of brain plasticity. Significance statementMastering the piano is a unique process requiring a collaboration of multiple brain regions. However, associated brain activation changes are not well understood. Using functional MRI, we showed that playing the piano activated brain areas associated with movement and auditory processing. However, as the novice pianists progressed through their training, the activation of other brain regions, involved in memory retrieval, auditory-motor integration, or the processing of musical syntax, was gradually reduced. Our findings suggest that musical training is an optimisation process, with higher-order cognitive networks being activated more strongly at the beginning and their activity decreasing with increased proficiency.

neuroscience↗

bioRxiv2020

Lenticular nucleus volume predicts performance in real-time strategy game - cross-sectional and training approach using voxel-based morphometry

It is unclear why some people learn faster than others. We performed two independent studies in which we investigated the neural basis of real-time strategy (RTS) gaming and neural predictors of RTS games skill-acquisition. In the first (cross-sectional) study we found that experts in the RTS game StarCraft II (SC2) had a larger lenticular nucleus volume than non-RTS players. We followed a cross validation procedure where we used the volume of regions identified in the first study to predict the quality of learning a new, complex skill (SC2) in a sample of individuals who were naive to RTS games (second training study). Our findings provide new insights into how the volume of lenticular nucleus, which is associated with motor as well as cognitive functions, can be utilized to predict successful skill-learning, and be applied to a much broader context than just video games, e.g. contributing to optimizing cognitive training interventions.

neuroscience↗