Biology subjects

Santana, A.

Publications and source records attributed to Santana, A..

3 recordsLinked to original sources

bioRxiv2026

PREMATURE BIRTH AND CESAREAN SECTION AFFECT NEONATAL CD4+ T CELL GENE EXPRESSION AND CELLULAR FUNCTION

Premature birth and cesarean section are associated with increased morbidity and inflammatory diseases. However, their impact on neonatal immunity remains incompletely defined. To explore how gestational age and mode of delivery contribute to early immune programming, we analyzed CD4+ T cells, central regulators of adaptive responses, from preterm neonates and full-term neonates born by cesarean section or vaginal delivery. We performed transcriptomic profiling (mRNA-seq) and functional assessment of T cell activation, proliferation, and cytokine production following stimulation. The mode of delivery emerged as a key factor for CD4+ T cell transcriptome and function. CD4+ T cells from full-term neonates born by vaginal delivery exhibited an immune activation signature, produced higher levels of multiple cytokines, and showed reduced proliferative capacity. In contrast, prematurity was associated with modest changes in basal gene expression relative to full-term cesarean section neonates. CD4+ T cells from preterm neonates displayed enhanced proliferation and increased secretion of inflammatory cytokines (IL-13, TNF, IL-6, and IL-17F) upon stimulation, consistent with heightened responsiveness. Collectively, our findings show that CD4+ T cells from preterm neonates exhibit augmented inflammatory potential, which becomes more regulated at term. Mode of delivery further contributes to this developmental trajectory: cesarean section is associated with a restrained functional profile, whereas vaginal delivery is associated with a mild immune activation signature and increased responsiveness. These results support a model in which neonatal CD4+ T cell trajectories are established during fetal life and further modulated at birth, highlighting the layered influence of perinatal factors on immune development. Summary sentenceNeonatal CD4+ T cell trajectories are established during fetal life and further shaped at birth by the mode of delivery, influencing early immune responsiveness.

immunology↗

bioRxiv2023

Somatotopic organization among parallel sensory pathways that promote a grooming sequence in Drosophila

Mechanosensory neurons located across the body surface respond to tactile stimuli and elicit diverse behavioral responses, from relatively simple stimulus location-aimed movements to complex movement sequences. How mechanosensory neurons and their postsynaptic circuits influence such diverse behaviors remains unclear. We previously discovered that Drosophila perform a body location-prioritized grooming sequence when mechanosensory neurons at different locations on the head and body are simultaneously stimulated by dust (Hampel et al., 2017; Seeds et al., 2014). Here, we identify nearly all mechanosensory neurons on the Drosophila head that individually elicit aimed grooming of specific head locations, while collectively eliciting a whole head grooming sequence. Different tracing methods were used to reconstruct the projections of these neurons from different locations on the head to their distinct arborizations in the brain. This provides the first synaptic resolution somatotopic map of a head, and defines the parallel-projecting mechanosensory pathways that elicit head grooming.

neuroscience↗

bioRxiv2020

Lysosomal dysfunction impairs mitochondrial quality control and predicts neurodegeneration in TBCKE

Biallelic variants in TBC1-domain containing kinase (TBCK) cause intellectual disability in children. It remains unclear how variants in TBCK lead to a neurodevelopmental disorder and what biological factors modulate the variability of clinical severity. Previous studies showed increased autophagosomes in patients sharing the truncating (p.R126X) Boricua homozygous TBCK variant, who exhibit a severe and progressive neurodegenerative phenotype. Since defects in mitophagy are linked to neurodegenerative disorders, we tested whether mitophagy and mitochondrial function are altered in TBCK-/- fibroblasts. Our data shows significant accumulation of mitophagosomes, reduced mitochondrial respiratory capacity, and mtDNA depletion. Furthermore, mitochondrial dysfunction correlates with the severity of the neurological phenotype. Since effective mitophagy and degradation of mitophagosomes ultimately depends on successful lysosomal degradation, we also tested lysosomal function. Our data shows that lysosomal proteolytic function is significantly reduced in TBCK-/- fibroblasts. Moreover, acidifying lysosomal nanoparticles rescue the mitochondrial respiratory defects, suggesting that impaired mitochondrial quality control secondary to lysosomal dysfunction, may play an important role in the pathogenicity of this rare neurodevelopmental disorder and predict the degree of disease progression and neurodegeneration.

genetics↗