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Silva, V.

Publications and source records attributed to Silva, V..

7 recordsLinked to original sources

The richness of little voices: using artificial intelligence to understand early language development

The authors have withdrawn this manuscript because it was realized that the central classification result that we claimed was attributable to a phenomenon of shortcut learning in which the recording conditions for the audios used could have been the main source of information for the classifier, rather than the actual content of the child vocalizations, which was our target. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

neuroscience↗

Sexual dimorphism in the complete connectome of the Drosophila male central nervous system

Sex differences in behaviour exist across all animals, typically under strong genetic regulation. In Drosophila, fruitless/doublesex transcription factors can identify dimorphic neurons but their organisation into functional circuits remains unclear. We present the connectome of the entire Drosophila male central nervous system. This contains 166,691 neurons spanning the brain and nerve cord, fully proofread and annotated including fruitless/doublesex expression and 11,691 types. We provide the first comprehensive comparison between male and female brain connectomes to synaptic resolution, finding 7,205 isomorphic, 114 dimorphic, 262 male-specific and 69 female-specific types. This resource enables analysis of full sensory-to-motor circuits underlying complex behaviours and the impact of dimorphic elements. Sex-specific/dimorphic neurons are concentrated in higher brain centres while the sensory and motor periphery are largely isomorphic. Within higher centres, male-specific connections are organised into hotspots defined by male-specific neurons or arbours. Numerous circuit switches reroute sensory information to form antagonistic circuits controlling opposing behaviours.

neuroscience↗

Molecular Insights into ANPEP in Gastric Adenocarcinoma

Alanyl aminopeptidase (ANPEP) has been implicated in various cancers, but its specific role in gastric adenocarcinoma (GC) remains incompletely understood. This study analyzed ANPEP gene expression in gastric cancer (GC), peritumoral tissue (PTT), metaplasia (M), and normal tissue (N). Total RNA was extracted, libraries were prepared and sequenced on the Illumina NextSeq 500. Data was processed using the nf-core/rnaseq pipeline. Transcript quantifications were imported with tximport and normalized using DESeq2. Differential expression (|log2FC| >2; adj. p < 0.05) and Kruskal-Wallis tests identified key genes. ANPEP was significantly upregulated in GC, PTT, and M compared to normal tissue (p < 0.01), suggesting its involvement in early mucosal transformation and malignant progression. Heatmap analysis revealed upregulation of genes related to immune function and oxidative stress, indicating an immunosuppressive and apoptosis-resistant tumor microenvironment. Correlation analyses identified strong positive associations between ANPEP and genes involved in cytoskeletal remodeling, immune modulation, and metabolic regulation, suggesting that ANPEP supports both the invasive potential of tumor cells and the establishment of an immunosuppressive niche. These findings position ANPEP as a promising biomarker for early detection and a candidate for targeted therapies.

cancer biology↗

Characterization Eclosion Hormone Receptor function reveals differential hormonal control of ecdysis during Drosophila development.

Neuromodulators and peptide hormones play important roles in regulating animal behavior. A well-studied example is ecdysis, which is used by insects to shed their exoskeleton at the end of each molt. Ecdysis is initiated by Ecdysis Triggering Hormone (ETH) and Eclosion Hormone (EH), which interact via positive feedback to coordinate the sequence of behavioral and physiological changes that cause exoskeleton shedding. Whereas the cell types targeted by ETH are well characterized, those targeted by EH have remained largely unknown due to limited characterization of the EH receptor (EHR). A gene encoding an EHR has been described in the oriental fruit fly, B. dorsalis, and in the desert locust, Schistocerca gregaria. However, little is known in these species about its expression pattern and its precise role at ecdysis, and no other insect EHRs are known. Here we analyze CG10738, the Drosophila ortholog of the B. dorsalis gene encoding EHR, and show that expressing it in cells confers sensitivity to EH. In addition, mutations of CG10738 specifically disrupt ecdysis, phenocopying the knockout of the EH gene. Together, these results indicate that CG10738 encodes the Drosophila EHR. As in B. dorsalis, EHR is expressed in the ETH-producing Inka cells; in addition, it is expressed in many known targets of ETH, including the neurons responsible for the secretion of other ecdysis-related peptides, such as CCAP and EH itself. Our results from targeted knockdown and rescue experiments reveal that EHR is required for ecdysis in diverse cell types and that the role of EHR in different targets differs with developmental stage. Our findings indicate extensive convergence of EH and ETH signaling and provide an exemplar of the complex mechanisms by which hormones control animal behavior. AUTHOR SUMMARYHormones and neuromodulators are important regulators of animal behavior. In insects, one of the best studied behaviors influenced by hormones is ecdysis, which allows the animal to shed the remains of its exoskeleton at the end of each molt. Ecdysis is controlled by two key hormones: Ecdysis Triggering Hormone (ETH) and Eclosion Hormone (EH). Whereas most targets of ETH have been identified, those of EH have remained largely unknown due to the limited characterization of its receptor, EHR. Previous studies identified a gene encoding EHR in the oriental fruit fly, Bactrocera dorsalis, and in the desert locust, Schistocerca gregaria, but little is known about its expression pattern or its precise role. Here, we show that CG10738 encodes the Drosophila EHR. We found that EHR is expressed in ETH-producing Inka cells, in neurons that secrete other ecdysis-related peptides, in addition to other neuronal classes and non-neuronal cells. Targeted knockdown and rescue experiments revealed that EHR is essential for ecdysis in various cell types, and that its role can vary depending on the developmental stage. Our findings reveal that the role of EH at ecdysis is complex and provides insights into how hormones and neuromodulators regulate animal behavior.

neuroscience↗

Optogenetic Central Amygdala Stimulation is Highly Reinforcing and Strongly Outcompetes Fentanyl Self-Administration in Male, but not Female, Rats

The central nucleus of the amygdala plays a key role in many aspects of substance use disorders, in particular biasing behaviors toward one drug or natural reward over another, yet the role of this region in opioid self-administration remains unclear. Here, we report that pharmacological inactivation of the central amygdala reduces fentanyl self-administration, while intra-central amygdala opioid receptor antagonism dose-dependently increases fentanyl self-administration. We tested whether optogenetic activation of the central amygdala would increase motivation for fentanyl in rats with a long fentanyl self-administration history. While pairing fentanyl delivery with optogenetic central amygdala activation increased fentanyl self-administration, optoactivation itself was highly reinforcing and, in choice settings, was pursued over fentanyl despite mounting effort requirements, delays, and sporadic reward availability. Of note, under free response conditions, these effects were limited to male rats; while female rats avidly responded for optogenetic activation of the central amygdala, this activation was less effective in enhancing fentanyl intake, and it was not preferred over fentanyl. In contrast, under discrete trial choice which precluded independent regulation of intake of the two options, both females and males preferred optoactivation to fentanyl. These results demonstrate that optogenetic stimulation of neural activity within the anterior central amygdala does not appear to potentiate the reinforcing effects of fentanyl, but is itself highly reinforcing regardless of sex, and, in male rats can robustly outcompete fentanyl. In contrast, in females, fentanyl intake is relatively insensitive to competing opportunities for optoactivation, except when opportunities to obtain drug or optoactivation are sparse.

neuroscience↗

Climate variables and urbanization drive changes in the distribution of S. mansoni competent snails in Brazil: novel results from a counterfactual analysis

Schistosomiasis is a neglected tropical disease caused by Schistosoma parasites. Schistosoma are obligate parasites of freshwater Biomphalaria snails, so controlling snail populations is critical to reducing transmission risk. As snails are sensitive to environmental conditions, we expect their distribution is significantly impacted by global change. Here, we leveraged machine learning, remote sensing, and 30 years of snail occurrence records to map the historical and current distribution of competent Biomphalaria throughout Brazil. We identified key features influencing the distribution of suitable habitat and determined how Biomphalaria habitat has changed with climate and urbanization over the last three decades. Our models show that climate change has driven broad shifts in snail host range, whereas expansion of urban and peri-urban areas has driven localized increases in habitat suitability. Elucidating change in Biomphalaria distribution - while accounting for non-linearities that are difficult to detect from local case studies - can help inform schistosomiasis control strategies.

ecology↗

3D quantification of zebrafish cerebrovascular architecture by automated image analysis of light sheet fluorescence microscopy datasets

Zebrafish transgenic lines and light sheet fluorescence microscopy allow in-depth insights into vascular development in vivo and 3D. However, robust quantification of the zebrafish cerebral vasculature in 3D remains a challenge, and would be essential to describe the vascular architecture. Here, we report an image analysis pipeline that allows 3D quantification of the total or regional zebrafish brain vasculature. This is achieved by landmark- or object-based inter-sample registration and extraction of quantitative parameters including vascular volume, surface area, density, branching points, length, radius, and complexity. Application of our analysis pipeline to a range of sixteen genetic or pharmacological manipulations shows that our quantification approach is robust, allows extraction of biologically relevant information, and provides novel insights into vascular biology. To allow dissemination, the code for quantification, a graphical user interface, and workflow documentation are provided. Together, we present the first 3D quantification approach to assess the whole 3D cerebrovascular architecture in zebrafish.

bioinformatics↗