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Freitas, B.

Publications and source records attributed to Freitas, B..

7 recordsLinked to original sources

Song as a behavioural pre-mating barrier in early population divergence: Insights from the Canary Islands Chaffinch

Acoustic signaling is key to individual and species recognition, playing a major role in sexual and social communication. Since reproductive isolation is often maintained through pre-mating mechanisms, song can be an early isolating trait leading to assortative mating, promoting reproductive divergence, and potentially contributing to speciation. However, whether song differences alone are sufficient to prevent interbreeding or if other traits also contribute, remains a matter of debate. Playback experiments provide a more direct way to test the role of song as a reproductive barrier. Here, we use playback experiments to test the hypothesis that song acts as a pre-mating barrier in two recently diverged populations of an island passerine, the Canary Islands Chaffinch (Fringilla canariensis palmae), which inhabit ecologically distinct laurel and pine forests within the island of La Palma. Assuming that male song has diverged in the two habitats, we tested if territorial males from a given habitat responded differently to songs from intruding males from their own habitat or from the other habitat type, using a closely related mainland species as a control. We found that probability of response was weaker to songs of the closely related species and to the different-habitat birds than to songs of the same-habitat birds, but differences for the latter were weak. The intensity of response followed the same pattern. Overall, song divergence between laurel and pine forest chaffinches does not appear strong enough to cause clear behavioural discrimination against individuals from the alternative habitat. Other factors such as morphological and ecological divergence associated with adaptation to local resources might better explain population differentiation. However, testing female responses will be essential to determine whether songs convey lineage-specific information that may elicit assortative mating.

evolutionary biology↗

Dormant viral pathways underlie space-induced neural senescence: a neuroprotective strategy for spaceflight and neurological diseases

Long-duration spaceflight is associated with neurological symptoms in astronauts, yet the underlying molecular mechanisms remain unclear. Using human brain organoids cultured aboard the International Space Station, we analyzed three independent spaceflights to demonstrate that exposure to the space environment triggers Space-Induced Neural Senescence (SINS), characterized by chromatin remodeling, mitochondrial dysfunction, and activation of viral-like transcriptional programs in the absence of infection. Multi-omics analyses identified upregulation of endogenous LINE-1 (L1) retroelements, whose activity was markedly enhanced in organoids lacking MECP2, a known L1 repressor implicated in Rett syndrome. The resulting accumulation of cytoplasmic L1 DNA elicited an IL-6-mediated inflammatory and neurotoxic response, which was reversed by reverse transcriptase inhibitors (RTi) such as lamivudine or stavudine. Parallel preclinical experiments in Mecp2-deficient mice confirmed that RTi treatment restored neuronal morphology, synaptogenesis, function, cognition, and survival. These findings reveal that the space environment reactivates dormant genomic retroelements, providing an unexpected mechanistic insight into astronaut neurobiology and identifying a potential therapeutic strategy for both space-induced and terrestrial neurological conditions. Our pioneering study demonstrates the value of space-enabling research in accelerating drug discovery and disease treatment on Earth.

neuroscience↗

Worldwide soundscape ecology patterns across realms

Abstract and keywordsO_ST_ABSAimC_ST_ABSThe urgency for remote, reliable, and scalable biodiversity monitoring amidst mounting human pressures on ecosystems has sparked worldwide interest in Passive Acoustic Monitoring (PAM), which can track life underwater and on land. However, we lack a unified methodology to report this sampling effort and a comprehensive overview of PAM coverage to gauge its potential as a global research and monitoring tool. To remediate this, we created the Worldwide Soundscapes project, a collaborative network and growing database comprising metadata from 409 datasets across all realms (terrestrial, marine, freshwater, and subterranean). LocationWorldwide, 12 200 sites, all ecosystems. Time period1991 to present. Major taxa studiedAll soniferous taxa. MethodsWe synthesise sampling coverage across spatial, temporal, and ecological scales using metadata describing sampling locations, deployment schedules, focal taxa, and recording parameters. We explore global trends in biological, anthropogenic, and geophysical sounds based on 168 recordings from twelve ecosystems across all realms. ResultsTerrestrial sampling is spatially denser (45 sites/Mkm2) than aquatic sampling (0.3 and 1.8 sites/Mkm2 in oceans and fresh water) with only two subterranean datasets. Although diel and lunar cycles are well-covered in all realms, only marine datasets (56%) comprehensively sample all seasons. Across twelve ecosystems, biological sounds show contrasting diel patterns, decline with distance from the equator and negatively correlate with anthropogenic sounds. Main conclusionsPAM can inform macroecology studies as well as global conservation and phenology syntheses, but representation can be improved by expanding terrestrial taxonomic scope, sampling coverage in the high seas and subterranean ecosystems, and spatio-temporal replication in freshwater habitats. Overall, this global PAM network holds promise to support global biodiversity research and monitoring efforts.

ecology↗

The acoustic adaptation hypothesis across terrestrial vertebrates: a meta-analysis

Acoustic communication plays a prominent role in various ecological and evolutionary processes involving social interactions. The properties of acoustic signals are thought to be influenced not only by the interaction between signaller and receiver but also by the acoustic characteristics of the environment through which the signal is transmitted. This conjecture forms the core of the so-called "acoustic adaptation hypothesis" (AAH), which posits that vegetation structure affects frequency and temporal parameters of acoustic signals emitted by a signaller as a function of their acoustic degradation properties. Specifically, animals in densely vegetated closed habitats are expected to produce longer acoustic signals with lower repetition rates and lower frequencies (minimum, mean, maximum, and peak) compared to the ones inhabiting less vegetated open habitats. To date, this hypothesis has received mixed results, with the level of support depending on the taxonomic group and the methodology used. We conducted a systematic literature search of empirical studies testing for an effect of vegetation structure on acoustic signalling and assessed the generality of the AAH using a meta-analytic approach based on 371 effect sizes from 75 studies and 57 taxa encompassing birds, mammals and amphibians. Overall, our results do not provide consistent support for the AAH, neither in within-species comparisons (suggesting no overall phenotypically plastic response of acoustic signalling to vegetation structure) nor in among-species comparisons (suggesting no overall evolutionary response). However, when considering birds only, we found a weak support for the AAH in within-species comparisons, which was mainly driven by studies that measured frequency bandwidth, suggesting that this variable may exhibit a phenotypically plastic response to vegetation structure. For among-species comparisons in birds, we also found support for the AAH, but this effect was not significant after excluding comparative studies that did not account for phylogenetic non-independence. Collectively, our synthesis does not support a universal role of vegetation structure in the evolution of acoustic communication. We highlight the need for more empirical work on currently under-studied taxa such as amphibians, mammals, and insects. Furthermore, we propose a framework for future research on the AAH. We specifically advocate for a more detailed and quantitative characterization of habitats to identify frequencies with the highest detection probability and to determine if frequencies with greater detection distances are preferentially used. Finally, we stress that empirical tests of the AAH should focus on signals which are selected for increased transmission distance.

evolutionary biology↗

Acquired Cross-resistance in Small Cell Lung Cancer due to Extrachromosomal DNA Amplification of MYC paralogs

Small cell lung cancer (SCLC) presents as a highly chemosensitive malignancy but acquires cross-resistance after relapse. This transformation is nearly inevitable in patients but has been difficult to capture in laboratory models. Here we present a pre-clinical system that recapitulates acquired cross-resistance in SCLC, developed from 51 patient-derived xenografts (PDXs). Each model was tested for in vivo sensitivity to three clinical regimens: cisplatin plus etoposide, olaparib plus temozolomide, and topotecan. These functional profiles captured hallmark clinical features, such as the emergence of treatment-refractory disease after early relapse. Serially derived PDX models from the same patient revealed that cross-resistance was acquired through a MYC amplification on extrachromosomal DNA (ecDNA). Genomic and transcriptional profiles of the full PDX panel revealed that this was not unique to one patient, as MYC paralog amplifications on ecDNAs were recurrent among cross-resistant models derived from patients after relapse. We conclude that ecDNAs with MYC paralogs are recurrent drivers of cross-resistance in SCLC. SIGNIFICANCESCLC is initially chemosensitive, but acquired cross-resistance renders this disease refractory to further treatment and ultimately fatal. The genomic drivers of this transformation are unknown. We use a population of PDX models to discover that amplifications of MYC paralogs on ecDNA are recurrent drivers of acquired cross-resistance in SCLC.

cancer biology↗

Reduced synaptic activity and dysregulated extracellular matrix pathways are common phenotypes in midbrain neurons derived from sporadic and mutation-associated Parkinson's disease patients

Several mutations that cause Parkinsons disease (PD) have been identified over the past decade. These account for 15-25% of PD cases; the rest of the cases are considered sporadic. Currently, it is accepted that PD is not a single monolithic disease but rather a constellation of diseases with some common phenotypes. While rodent models exist for some of the PD-causing mutations, research on the sporadic forms of PD is lagging due to a lack of cellular models. In our study, we differentiated PD patient-derived dopaminergic (DA) neurons from induced pluripotent stem cells (iPSCs) of several PD-causing mutations as well as from sporadic PD patients. Strikingly, we observed a common neurophysiological phenotype: Neurons derived from PD patients had a severe reduction in the rate of synaptic currents compared to those derived from healthy controls. While the relationship between mutations in genes such as the SNCA and LRRK2 and a reduction in synaptic transmission has been investigated before, here we show evidence that the pathogenesis of the synapses in neurons is a general phenotype in PD. Analysis of RNA sequencing results displayed changes in gene expression in different synaptic mechanisms as well as other affected pathways such as extracellular matrix-related pathways. Some of these dysregulated pathways are common to all PD patients (monogenic or idiopathic). Our data, therefore, shows changes that are central and convergent to PD and suggests a strong involvement of the tetra-partite synapse in PD pathophysiology.

neuroscience↗

Data-Driven Prediction of CRISPR-Based Transcription Regulation for Programmable Control of Metabolic Flux

Multiplex and multi-directional control of metabolic pathways is crucial for metabolic engineering to improve product yield of fuels, chemicals, and pharmaceuticals. To achieve this goal, artificial transcriptional regulators such as CRISPR-based transcription regulators have been developed to specifically activate or repress genes of interest. Here, we found that by deploying guide RNAs to target on DNA sites at different locations of genetic cassettes, we could use just one synthetic CRISPR-based transcriptional regulator to simultaneously activate and repress gene expressions. By using the pairwise datasets of guide RNAs and gene expressions, we developed a data-driven predictive model to rationally design this system for fine-tuning expression of target genes. We demonstrated that this system could achieve programmable control of metabolic fluxes when using yeast to produce versatile chemicals. We anticipate that this master CRISPR-based transcription regulator will be a valuable addition to the synthetic biology toolkit for metabolic engineering, speeding up the \"design-build-test\" cycle in industrial biomanufacturing as well as generating new biological insights on the fates of eukaryotic cells.

synthetic biology↗