Biology subjects

Esparza, M.

Publications and source records attributed to Esparza, M..

4 recordsLinked to original sources

bioRxiv2026

Neonatal social communication and single genes predict the variability of post-pubertal social behavior in a mouse model of paternal 15q11-13 duplication

Mental illnesses associated with high-risk copy number variations (CNVs) are characterized by incomplete penetrance and variable severity, with their underlying mechanisms remaining inadequately understood. We hypothesized that such phenotypic variability is evident from the neonatal stage and is, at least in part, attributable to individual differences in the expression levels of CNV-encoded genes in the brain. We conducted an analysis of the quantitative and functional structure of neonatal social communication, assessed post-pubertal social interaction, and evaluated the brain expression levels of genes within the same cohort of a mouse model of paternal human 15q11-13 duplication, a high-risk factor variably associated with neurodevelopmental disorders. Subsequently, computational methods were utilized to identify predictive variables for the variability of post-pubertal social interaction. Mice harboring the 15q11-13 duplication exhibited distinctive call sequences characterized by diverse connections, which lacked the incentive value necessary for effective social communication with mother mice. The neonatal call sequences and the expression levels of Magel2, along with, to a lesser extent, Herc2 and Ndn, in the prefrontal cortex of the 15q11-13 duplication model were predictive of post-pubertal social interaction. Our findings demonstrate that variability in post-pubertal social interaction--a dimensional characteristic of neurodevelopmental disorders--can be predicted by the variability of neonatal social communication and is influenced by the expression levels of specific CNV-encoded genes in the prefrontal cortex. This computational approach has the potential to predict the developmental trajectories of various dimensions of mental illness among CNV carriers in humans and to identify CNV-encoded driver genes in preclinical models, thereby providing potential mechanistic bases for the development of gene-based therapeutic strategies.

neuroscience↗

bioRxiv2025

Tbx1 heterozygosity in the oligodendrocyte lineage has distinct effects on myelinated axons in the fimbria and on behaviors related to neurodevelopmental disorders in mice.

Constitutive heterozygosity of Tbx1, a T-box transcription factor gene located within the 22q11.2 deletion region, results in behavioral deficits and altered composition of myelinated axons in the fimbria, together with reduced levels of an oligodendrocyte precursor cell (OPC) marker, in mice. However, the cellular origins of these effects and the extent to which axonal changes causally contribute to behavioral impairments remain unclear. We hypothesized that Tbx1 deficiency specifically within the oligodendrocyte lineage contributes to myelin and behavioral phenotypes. To test this hypothesis, we first demonstrated through in vitro siRNA knockdown that Tbx1 regulates both OPCs and mature oligodendrocytes. Subsequently, we assessed the impact of Tbx1 heterozygosity initiated in OPCs on behavioral and myelin phenotypes in male conditional PdgfrCre;Tbx1+/flox mice. These mice exhibited Cre-mediated recombination in Pdgfr-expressing brain regions and in the OPC progeny within the fimbria. At one month of age, the mutants displayed a higher rate of spontaneous alternation at the longest inter-trial interval in the T-maze compared to their wild-type littermates--an effect that was dissipated at two months. No significant phenotypic abnormalities were observed in conditional PdgfrCre;Tbx1+/flox mice regarding neonatal ultrasonic vocalizations, social interaction, novel object approach, anxiety-like behavior (elevated plus maze), or open-field locomotion and thigmotaxis. Electron microscopic analysis revealed a compositional shift in myelinated axons within the fimbria of adult male mutants, characterized by an increased number of myelinated axons in the 300-800 nm diameter range and a decreased number in the [~]1,200 nm and [~]1,400 nm ranges, with myelin thickness remaining unchanged across diameters. These findings indicate that Tbx1 heterozygosity in the oligodendrocyte lineage leads to a selective shift towards smaller myelinated axons in the fimbria and a transiently higher level of capacity for working memory and cognitive flexibility. However, it does not replicate the full spectrum of myelination abnormalities or the broader cognitive and social deficits observed in constitutive Tbx1 heterozygotes, suggesting that Tbx1 deficiency in non-oligodendrocyte lineage cells may lead to altered myelination and neurodevelopmental behavioral impairments.

neuroscience↗

bioRxiv2025

Quantitative evaluation of the role of the microenvironment in the phenotype, metabolism, and drug resistance of PDAC tumor organoids

Tumor organoids are powerful tools to study cancer. However, the clinical translation of organoid-based studies depends on how closely the organoid scaffolding material recapitulates the tumor extracellular matrix (ECM). We present a quantitative analysis of the effect of scaffold composition on the phenotype, tissue remodeling, metabolism, and drug resistance of pancreatic ductal adenocarcinoma (PDAC) organoids. We grew PDAC organoids within hydrogels made of Matrigel, collagen-I, or a mixture of collagen-I and Matrigel. Our results show that 1) PDAC organoids grown in Matrigel-only are phenotypically and metabolically similar to low-physiological two-dimensional PDAC cultures; 2) collagen-containing hydrogels, and especially so those grown in hydrogels of mixed collagen-Matrigel composition, accurately reproduce invasive tumors that underwent epithelial-to-mesenchymal transition (EMT) regarding phenotype, tissue remodeling, metabolic activity, and drug resistance. In summary, our work illustrates the importance of three-dimensional (3D) matrix composition for PDAC growth and postulates that organoids grown in collagen-Matrigel hydrogels are the most adequate for studying the biology of invasive PDAC tumors.

bioengineering↗

bioRxiv2018

Pattern of severe injuries in Spanish children: boys and falls are alarmingly overrepresented

Background: Taking into account that injury is one of the main causes of child fatalities in developed countries, and that boys are more likely to suffer it than girls, we have explored a database of pediatric patients with severe injuries to determine whether sex and age influence the pattern of these fatalities, and the magnitude of this.\n\nMethod: Observational study of the demographic and clinical characteristics of 227 patients from a Spanish pediatric reference hospital, all of them admitted with a diagnosis of trauma.\n\nResult: Falls are the most frequent type of trauma (60.7%), followed by pedestrian traffic collisions (15%). Boys are over-represented in falls (72% vs 28% in girls) and pedestrian traffic injuries (61% vs 39 %). In boys, falls are mainly observed in public roads and during leisure activities (53.8%) whereas in girls at home (55.2%). In a logistic regression, sex and age are statistically significant predictors of severe trauma, boys (OR = 1.59) and the adolescent age group (OR = 3.7) showed the highest odds.\n\nConclusion: We have observed a clear gender-biased pattern of injury-related events: falls are the leading cause of injuries, with 2.5 boys for every girl. Falls mostly happened during outdoor leisure activities in boys and at home in girls. Pedestrian traffic injuries also show significant differences between sexes, emphasizing the role of cognitive and cultural factors in childrens behavior.

epidemiology↗