Biology subjects

Souza, R. P.

Publications and source records attributed to Souza, R. P..

4 recordsLinked to original sources

bioRxiv2026

Early dopamine elevation modifies the behavioral consequences of maternal separation in female and male juvenile mice

Alterations in dopaminergic signaling and exposure to early-life stress are both implicated in the developmental origins of psychiatric disorders, yet little is known about how these factors interact during sensitive periods of brain maturation. We investigated whether increased dopamine availability during early postnatal development modifies the behavioral consequences of maternal separation in female and male C57BL/6 mice. From postnatal day (PD) 1 to PD14, mice received L-Dopa plus benserazide, maternal separation (3 h/day), their combination, or the corresponding control conditions. We assessed mice behavior between PD28 and PD32 using novel object recognition, open-field, elevated plus-maze, marble-burying, and forced-swim tests, followed by hippocampal volumetric analysis. Early L-Dopa exposure produced sex- and behavior-specific effects. In females, L-Dopa increased rearing without altering horizontal locomotion and modified open-arm exploration and stress-coping behavior, whereas in males it increased open-arm exploration and reduced climbing frequency. Maternal separation produced distinct effects in females and males and reduced repetitive digging/burying behavior in both sexes. Importantly, maternal separation frequently modified rather than potentiated the effects of L-Dopa. In both sexes, combined maternal separation and L-Dopa opposed several L-Dopa-associated alterations in open-field, elevated plus-maze, and forced-swim behaviors. Recognition memory was largely preserved across experimental conditions. L-Dopa also reduced hippocampal volume selectively in females, whereas hippocampal volume was higher in females exposed to maternal separation plus L-Dopa than in those receiving L-Dopa alone. Multivariate analyses revealed overlapping rather than treatment-specific behavioral clusters, indicating substantial individual heterogeneity and sex-dependent shifts in multidimensional behavioral profiles. Together, these findings demonstrate that transient alterations in dopamine availability and maternal separation interact non-additively during early postnatal development. Their consequences depend on sex, behavioral domain, and developmental timing, supporting a model in which neurochemical and environmental perturbations dynamically shape behavioral trajectories rather than simply producing cumulative developmental damage.

neuroscience↗

bioRxiv2026

Common germline polymorphisms and somatic cancer mutations exhibit non-random positional overlap across the human genome

Germline and somatic mutations have traditionally been studied independently because they arise in distinct biological contexts and are shaped by different selective pressures. Despite these differences, both originate from the same molecular processes of DNA damage, replication error, and DNA repair. Yet this separation has limited the opportunity of investigation of genomic loci recurrently mutated across both mutational landscapes. Identifying such mutational co-occurrences may provide unique insights into the principles governing recurrent mutation. Here, we show that common germline polymorphisms and cancer-associated somatic SNVs recur at identical genomic positions across the human genome, sharing the same nucleotide substitutions more frequently than expected by chance. This recurrence persists within coding regions, is only minimally explained by the canonical hotspot contexts evaluated here (CpG islands and microsatellites), and is associated with a mutational signature profile enriched for the ubiquitous clock-like SBS5 signature together with DNA repair-associated signatures. Importantly, this overlap pattern is not shared across other germline variation: rare (AF<1%) and clinically classified variants exhibit significantly less overlap than expected. Together, these findings support the existence of intrinsically vulnerable genomic loci and provide a framework for investigating the mechanisms underlying recurrent mutation.

bioinformatics↗

bioRxiv2026

Negative emotional visual stimuli alter specific improvised dance biomechanics in professional dancers

Dance is a core form of human-environment interaction and a powerful medium for emotional expression, yet dancers are routinely exposed to environmental affective cues that may shape their movement. We tested whether a negative emotional context induced immediately before improvisation alters dance biomechanics. Twenty professional dancers performed two 3-min improvised dances. Between dances, they viewed either Neutral or Negatively valenced pictures from the International Affective Picture System (IAPS; 2 min 40 s, 5 s per image). Eye tracking verified attention to the visual stream. Mood was assessed at four time points (PT1-PT4) using the Brazilian Mood Scale (BRAMS), and full-body, three-dimensional kinematics were captured at 300 Hz using a 9-camera optoelectronic system (Qualisys) and processed to measure global movement amplitude and expansion. Negative IAPS exposure increased tension, depression, fatigue, and decreased vigor from PT2 to PT3. Biomechanically, the Negative Stimulus dancers showed a significant reduction in global movement amplitude after negative IAPS exposure, with reduced movement amplitude of the body extremities. In contrast, global movement expansion remained unchanged; that is, the extremities were not positioned closer or farther from the pelvis. Neutral images produced no mood change and no measurable modulation of movement amplitude or expansion. Together, these results support the hypothesis that improvised dance carries biomechanical signatures of the dancers current affective state, beyond the intended expressive content, and provide an automated motion-capture workflow for studying emotion-movement coupling in spontaneous dance. HighlightsNegative visual context shifted dancers mood toward negative affect Negative images reduced movement amplitude in improvised dance Movement expansion remained stable despite mood induction Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/711707v2_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@dabb85org.highwire.dtl.DTLVardef@4d2ebdorg.highwire.dtl.DTLVardef@137bb12org.highwire.dtl.DTLVardef@1dadaf7_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2019

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 210 loci underlying cardiac conduction

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality1,2. We performed multi-ancestry (N=293,051) and European only (N=271,570) genome-wide association (GWAS) meta-analyses for the PR interval, discovering 210 loci of which 149 are novel. Variants at all loci nearly doubled the percentage of heritability explained, from 33.5% to 62.6%. We observed enrichment for genes involved in cardiac muscle development/contraction and the cytoskeleton highlighting key regulation processes for atrioventricular conduction. Additionally, 19 novel loci harbour genes underlying inherited monogenic heart diseases suggesting the role of these genes in cardiovascular pathology in the general population. We showed that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease risk, including distal conduction disease, AF, atrioventricular pre-excitation, non-ischemic cardiomyopathy, and coronary heart disease. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.

genetics↗