Biology subjects

Pinto, B.

Publications and source records attributed to Pinto, B..

8 recordsLinked to original sources

bioRxiv2025

Distinct spatial distribution of potentiated dendritic spines in encoding- and recall-activated hippocampal neurons

Experimental advancements in neuroscience have identified cellular engrams -- ensembles of neurons whose activation is necessary and sufficient for memory retrieval. Synaptic plasticity, including long-term potentiation, is key to memory encoding and recall, but the relationship between learning-induced dendritic spine potentiation and neuron-wide activation remains unclear. Here, we employ a post-synaptic translation-dependent potentiation reporter (SA-PSD{Delta}Venus) and a neuronal activation reporter (ESARE-dTurquoise) to determine their spatiotemporal correlation in the mouse hippocampal CA1 following contextual fear conditioning (CFC). Potentiated spines were enriched in activated neurons, with distribution varying across CA1 layers at different phases of memory: potentiated spines were more frequent in activated neurons in stratum oriens and stratum lacunosum moleculare after CFC (encoding), while recall-activated neurons showed a larger number of potentiated spines in the stratum radiatum. These findings demonstrate that the relative weight and spatial distribution of potentiated synaptic inputs to hippocampal CA1 pyramidal neurons changes between the encoding and retrieval phases of memory.

neuroscience↗

bioRxiv2025

Gene Loss DB: A curated database for gene loss in vertebrate species.

Molecular databases are essential resources for both experimental and computational biologists. The rapid increase in high-quality genome assemblies has led to a surge in publications describing secondary gene loss events associated with lineage-specific adaptations across diverse vertebrate groups. This growing volume of information underscores the urgent need for organized, searchable, and curated resources that facilitate data discovery, allow detection of broad evolutionary patterns, and support downstream analyses. Currently, no existing database compiles manually curated and validated information on published secondary gene loss events. Here, we introduce the Gene Loss Database (GLossDB), a platform designed to centralize and present this data in an easy-to-search and user-friendly format (https://geneloss.org/). GLossDB compiles gene loss events alongside supporting evidence, including the inferred mechanism of gene loss (exon deletion, gene deletion, loss of function mutation), the type of data used to support inactivation (genomic, transcriptomic, single/multiple individual sequence reads, synteny maps) and, when available, whether the event is shared across all lineages within a taxon. Each entry also includes a short excerpt from the original publication to provide context. This information is structured in the database to be searchable by species, gene, taxa, or by GO-terms linked to the gene in question. The initial release of GLossDB focuses on cetaceans, a lineage with numerous gene loss events linked to aquatic adaptations. This first collection comprises 1866 gene loss events identified across 57 cetacean species. In addition, the database includes 1321 gene loss events from other taxa, which were also reported in the same studies and collected simultaneously.

bioinformatics↗

bioRxiv2025

Parallel erosion of a testis-specific Na+/K+ ATPase in three mammalian lineages sheds light into the evolution of spermatozoa energetics

Understanding how extant physiological landscapes arise from novel genetic interactions is key to elucidating phenotypic evolution. Sperm cells exemplify a striking case of functional compartmentalization shaped by molecular adjustments, notably regarding energy metabolism. Here, we examine the impact of gene duplication and loss on the evolution of sperm energetics in mammals. Our findings reveal that the acquisition of an exclusive mechanism controlling the sperm plasma membrane Na+ gradient, critical for glucose uptake, emerged in the ancestor of mammals through gene duplication, which originated the Na+/K+ ATPase transporting subunit alpha 4 transporter (Atp1a4). Furthermore, we demonstrate that testis-specific expression of Atp1a4 was acquired after the divergence from monotremes. Notably, we identify three independent pseudogenization events of Atp1a4, including in pangolins, the naked mole-rat (Heterocephalus glaber) and toothed whales. The recurrent loss of function in Atp1a4 coincides with the erosion of the testis-specific glycolytic pathway in these lineages. Furthermore, enrichment analysis of striped dolphin (Stenella coeruleoalba) and naked mole-rat testis transcriptomes also suggests significant alterations in sperm capacitation processes. Overall, we show that the elaboration of a sodium-dependent glucose uptake wiring was a key innovation in the energetic landscape governing mammalian spermatozoa, with secondary gene loss in three separate lineages pointing to drastic alterations in motility and capacitation processes. Our findings illustrate how metabolic pathways co-shaped by gene duplication and erosion define extant physiological phenotypes. SignificanceThe sperm cell exhibits a distinct morphology, characterized by exceptional functional and energetic compartmentalization between the midpiece and the flagellum. Here, we demonstrate that the evolution of a sodium-dependent glucose uptake mechanism, driven by gene duplication and giving rise to Atp1a4, was a key innovation promoting efficient glucose usage in mammalian sperm. Additionally, we identify independent losses of Atp1a4 in three lineages--pangolins, naked mole-rats, and toothed whales--coinciding with the reduction of glucose-dependent pathways, such as glycolysis. Our findings highlight how gene expansion and erosion shape metabolic pathways, offering insights into the genetic innovations underlying physiological diversity in reproductive biology.

evolutionary biology↗

bioRxiv2024

Alterations of Pleiotropic Neuropeptide-Receptor gene couples in Cetacea

BackgroundHabitat transitions have considerable consequences in organism homeostasis, as they require the adjustment of several concurrent physiological compartments to maintain stability and adapt to a changing environment. Within the range of molecules with a crucial role in the regulation of different physiological processes, neuropeptides are key agents. Here, we examined the coding status of several neuropeptides and their receptors with pleiotropic activity in Cetacea. ResultsAnalysis of 202 mammalian genomes, including 41 species of Cetacea, exposed an intricate mutational landscape compatible with gene sequence modification and loss. Specifically for Cetacea, in the twelve genes analysed we have determined patterns of loss ranging from species-specific disruptive mutations (e.g., Neuropeptide FF-Amide Peptide Precursor; NPFF) to complete erosion of the gene across the cetacean stem lineage (e.g., Somatostatin Receptor 4; SSTR4). ConclusionsImpairment of some of these neuromodulators, may have contributed to the unique energetic metabolism, circadian rhythmicity and diving response displayed by this group of iconic mammals.

evolutionary biology↗

bioRxiv2022

Convergent Decay of Skin-specific Gene Modules in Pangolins

The Mammalia skin exhibits a rich spectrum of evolutionary adaptations. The pilosebaceous unit, composed of the hair shaft, follicle, and the sebaceous gland, is the most striking synapomorphy. The evolutionary diversification of mammals across different ecological niches was paralleled by the appearance of an ample variety of skin modifications. Pangolins, order Pholidota, exhibit keratin-derived scales, one of the most iconic skin appendages. This formidable armor is intended to serve as a deterrent against predators. Surprisingly, while pangolins have hair on their abdomens, the occurrence of sebaceous and sweat glands is contentious. Here, we explore various molecular modules of skin physiology in four pangolin genomes, including that of sebum production. We show that genes driving wax monoester formation - Awat1/2, show patterns of inactivation in the stem pangolin branch; while the triacylglycerol synthesis gene Dgat2l6 seems independently eroded in the African and Asian clades. In contrast, Elovl3 implicated in the formation of specific neutral lipids required for skin barrier function, is intact and expressed in the skin. An extended comparative analysis shows that genes involved in skin pathogen defense and structural integrity of keratinocyte layers also show inactivating mutations: associated with both ancestral and independent pseudogenization events. Finally, we deduce that the suggested absence of sweat glands is not paralleled by the inactivation of the ATP-binding cassette transporter Abcc11, as previously described in Cetacea. Our findings reveal the sophisticated, convergent and complex history of gene retention and loss as key mechanisms in the evolution of the highly modified mammalian skin phenotypes.

evolutionary biology↗

bioRxiv2020

Grazing results in mobilization of spherulous cells and re-allocation of secondary metabolites to the surface in the sponge Aplysina aerophoba

On the sea floor, prey and predator commonly engage in a chemical warfare. Here, sponges thrive due to their specific and diverse chemical arsenal. Yet, some animals use these chemically-defended organisms as food and home. Most research on sponge chemical ecology has characterized crude extracts and investigated defences against generalist predators like fish. Consequently, we know little about intraindividual chemical dynamics and responses to specialist grazers. Here, we studied the response of the sponge Aplysina aerophoba to grazing by the opistobranch Tylodina perversa, in comparison to mechanical damage, at the cellular (via microscopy) and chemical level (via matrix-assisted laser desorption/ionization imaging mass spectrometry). We characterized the distribution of two major brominated compounds in A. aerophoba, aerophobin-2 and aeroplysinin-1, and identified a generalized wounding response that was similar in both wounding treatments: (i) brominated compound-carrying cells (spherulous cells) accumulated at the wound and (ii) secondary metabolites reallocated to the sponge surface. Upon mechanical damage, the wound turned dark due to oxidized compounds, causing T. perversa deterrence. During grazing, T. perversas way of feeding prevented oxidation. Thus, the sponge has not evolved a specific response to this specialist predator, but rather relies on rapid regeneration and flexible allocation of constitutive defences.

ecology↗

bioRxiv2020

Mosaic expression of X-linked PCDH19 Protein by in Utero Electroporation in Rats Replicates Human Cortical and Hippocampal Developmental Abnormalities, Associated Core Behaviors Related to Autism, and Cognitive Impairment.

PCDH19 gene-related epilepsy or epileptic encephalopathy, early infantile, 9 (EIEE9) is an infantile onset epilepsy syndrome characterized by psychiatric (including autistic) sensory and cognitive impairment of varying degrees. EIEE9 is caused by X-linked PCDH19 protein loss of function. Due to random X-chromosome inactivation, EIEE9-affected females present a mosaic population of healthy and Pcdh19-mutant cells. Unfortunately, no mouse models recapitulate to date both the brain histological and behavioural deficits present in people with EIEE9. Thus, the search for a proper understanding of the disease, and possible future treatment is hampered. By inducing a focal mosaicism of Pcdh19 expression using in utero electroporation in rat, we found here that Pcdh19 signaling in specific brain areas is implicated in neuronal migration, as well as in core behaviors related to autism and cognitive function.

neuroscience↗

bioRxiv2017

Impeding transcription of expanded microsatellite repeats by deactivated Cas9

Transcription of expanded microsatellite repeats is associated with multiple human diseases, including myotonic dystrophy, Fuchs endothelial corneal dystrophy, and C9orf72-ALS/FTD. Eliminating or reducing production of RNA and proteins arising from these expanded loci holds therapeutic benefit. Here, we tested the hypothesis that a deactivated form of the Cas9 enzyme impedes transcription across expanded microsatellites. We observed a repeat length-, PAM-, and strand-dependent reduction in the abundance of repeat-containing RNAs upon targeting dCas9 directly to repeat sequences. Aberrant splicing patterns were rescued in DM1 cells, and production of RAN peptides characteristic of DM1, DM2, and C9orf72-ALS/FTD cells was drastically decreased. Systemic delivery of dCas9/gRNA by adeno-associated virus led to reductions in pathological RNA foci, rescue of chloride channel 1 protein expression, and decreased myotonia. These observations suggest that transcription of microsatellite repeat-containing RNAs is more sensitive to perturbation than transcription of other RNAs, indicating potentially viable strategies for therapeutic intervention.

molecular biology↗