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Malave, A.

Publications and source records attributed to Malave, A..

2 recordsLinked to original sources

Exposure to perfluorooctanoic acid accelerates Drosophila melanogaster juvenile development and disrupts mitochondrial metabolism

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants with poorly understood sublethal effects on insects. Perfluorooctanoic acid (PFOA), one of the most widely distributed legacy PFAS is increasingly recognized for altering organismal physiology beyond traditional toxicity endpoints. Here, we use the fruit fly Drosophila melanogaster as a model to examine how PFOA exposure during larval (juvenile) development reshapes insect life-history progression and metabolic homeostasis. Our studies reveal that at environmentally relevant concentrations (nM to low {micro}M), PFOA induces precocious expression of developmentally-regulated genes and leads to metabolic changes that persist into adulthood. At higher concentrations used to probe mechanism, PFOA accelerates larval development, disrupts mitochondrial membrane potential, and increases whole-organism metabolic heat production - results that suggest altered mitochondrial energetic efficiency. Consistent with this tradeoff, PFOA-exposed larvae that develop faster under permissive conditions exhibit heightened sensitivity to environmental stressors, including elevated temperature and reduced food hydration. Together, these findings demonstrate that PFOA disrupts metabolic and developmental processes in a dose- and context-dependent manner, highlighting sublethal effects that may influence insect resilience under environmental stress. SYNOPSIS STATEMENTHere we describe how PFOA alters the growth, development, and metabolism of the fruit fly Drosophila melanogaster. Specifically, we find that PFOA accelerates Drosophila juvenile growth while also rendering exposed larvae sensitive to environmental stress. These observations suggest that widespread PFOA contamination may impair the developmental fitness of insect populations.

pharmacology and toxicology↗

Transcranial Focused Ultrasound of the Human Subgenual Anterior Cingulate Reconfigures Resting State Connectivity: A Sham-Controlled fMRI Study

Transcranial focused ultrasound stimulation (tFUS) can modulate human brain activity, but its impact on large-scale functional connectivity (FC) in vivo remains incompletely characterized. Here we asked whether brief tFUS to the subgenual anterior cingulate cortex (sgACC) modulates its FC with other brain regions. In a sham-controlled, within-subject study of healthy adults (N = 16), we measured resting-state blood-oxygen-level dependent (BOLD) activity with functional magnetic resonance imaging (fMRI) before, during, and after five minutes of tFUS (i.e., five 20-second sonications followed by 40 second pauses). Subject-level sgACC-whole-brain FC was analyzed with a linear mixed-effects model (fixed: time, condition, timexcondition; random: subject). tFUS increased sgACC-whole brain connectivity after sonication relative to sham. A smaller, non-significant trend was observed during sonication. Baseline-controlled analyses were employed to rule out the possibility that the observed increase in FC was due to a "regression to the mean" effect. Interestingly, network-level analysis revealed a clear disassociation in the evolution of resting-state FC across the 15 minute recordings: during sham sessions, the sgACCs connectivity with the default mode network (DMN) increased, while FC with other networks was largely unchanged. On the other hand, active tFUS led to a notable increase in FC with non-DMN networks (especially the cognitive control network), while connectivity with the DMN was stable. These results provide whole-brain evidence that tFUS reconfigures network dynamics in the human brain, motivating clinical applications to disorders characterized by dysregulated brain activity.

neuroscience↗