Biology subjects

Fernandez, M.

Publications and source records attributed to Fernandez, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Matrix biophysical cues drive transient or prolonged breast cancer dormancy programmes

Breast cancer metastasis can emerge after disease-free periods through the reawakening of dormant disseminated cancer cells. Despite evidence that the extracellular matrix (ECM) modulates this phenomenon, biophysical cues regulating dormancy fate and therapeutic responses remain poorly understood. Here, we engineered stiffness-matched gelatin methacryloyl (GelMA) and alginate-based 3D matrices to disentangle matrix stiffness from adhesion and degradability and uncover their contributions to dormancy. Deep learning-based 3D segmentation revealed that adhesive and degradable matrices supported rounded and proliferative tumour masses, whereas inert matrices favoured single cell dormancy. Within inert matrices, stiffness further determined dormancy fate, with soft matrices activating SOX9-associated transient stem-like dormancy, while stiff matrices reduced cell volume, increased intracellular macromolecular crowding of proteins and induced NR2F1-associated prolonged dormancy marked by autophagy and cellular stress. Transiently dormant cells retrieved from soft matrices retained dormancy memory and failed to form tumours in chicken chorioallantoic membranes, demonstrating persistence of matrix-induced states after removal of biophysical cues. Moreover, patient-derived cells in soft inert matrices recapitulated transient dormant states and exhibited therapy resistance. We demonstrate that tuneable biophysical cues shape distinct dormancy states, linking matrix mechanics to dormancy regulation and therapeutic response.

bioengineering↗

bioRxiv2026

Comparative study on chromatic acclimation in the two Synechococcus species WH8109 and RS9916

Marine Synechococcus cyanobacteria can modify their light-harvesting phycobilisome antennae in response to spectral changes through chromatic acclimation (CA). CA type IV (CA4) involves adjustment of the ratio of the blue-absorbing phycourobilin (PUB) to the green-absorbing phycoerythrobilin (PEB). Although CA4 is associated with a genomic island occurring in two configurations (CA4-A and CA4-B), some strains carrying this island, including Synechococcus sp. WH8109, have been reported to lack CA4 activity. Here, we investigated whether WH8109 undergoes CA4 under blue light (BL) and green light (GL) conditions, using the CA4-positive strain RS9916 as a reference. Whole-cell fluorescence, flow cytometry, isolated phycobilisome analysis, and sequencing of the CA4-B genomic island were used to assess pigment acclimation and identify potential genetic differences. WH8109 showed a stable PUB:PEB ratio of approximately 0.71 under BL and GL, with no detectable changes in PUB content or phycobilisome chromophore composition. In contrast, RS9916 exhibited clear CA4, with PUB:PEB ratios of 1.57 under BL and 0.72 under GL. Sequencing revealed no insertions, deletions, or other sequence anomalies in the WH8109 CA4-B genomic island compared to the public sequence. These results demonstrate that WH8109 does not undergo detectable CA4 under the conditions tested, despite possessing an intact CA4-B genomic island, highlighting a genotype-phenotype discrepancy that warrants further investigation.

microbiology↗

bioRxiv2026

SF3B1 mutation generates novel peptides from long non-coding RNAs

While mRNA alternative splicing caused by somatic mutation in SF3B1 is well-characterized, long non-coding RNAs (lncRNAs) impacted by this mutation are completely unknown. Here, we report long-read sequencing of full-length transcripts from cell lines with and without SF3B1 mutation. We present ALLR (Annotation of human lncRNAs using Long-Read sequencing), a computational workflow to identify and quantify lncRNAs, and to annotate their potential roles in impacting cellular functions. Harnessing matched short-read RNA sequencing and proteomic data, we demonstrate that SF3B1 mutation generates thousands of novel lncRNAs with diverse levels of alternative splicing. Moreover, SF3B1 mutation-associated lncRNAs produce translatable peptides with putative functions, immunogenicity, and potential to bind proteins with impact on cellular signalling networks. 47 lncRNAs could also be detected in primary chronic lymphocytic leukemia (CLL) samples and are associated with significant risks towards adverse disease prognosis, in conjunction with other known CLL risk factors. Our work demonstrates the utility of long-read sequencing for lncRNA research and provides a new territory of functional RNA molecules that SF3B1 mutation may use to impact cancer.

genomics↗

bioRxiv2026

Integrating dedicated and opportunistic surveys to estimate seasonal common dolphin density off mainland Portugal

1. Common dolphins (Delphinus delphis) are the most abundant cetaceans off mainland Portugal and a species of conservation and bycatch concern, so reliable abundance estimates are a management priority. Yet no single survey provides adequate spatiotemporal coverage: dedicated programmes offer sparse snapshots, while opportunistic programmes are spatially constrained by their routes. Integrating them is methodologically demanding, and the existing methods that do so in a single model estimate the density of animal groups, not of the individual animals that management often requires. 2. We develop a spatiotemporal marked log-Gaussian Cox process that integrates four structurally distinct surveys through a shared intensity surface, comprising environmental covariates, a latent spatial field, and survey-specific detection functions. Group size enters as a zero-truncated negative binomial mark with its own spatiotemporal field. We apply it to a dedicated aerial survey and three opportunistic ship-based programmes off mainland Portugal, comprising 162,514 km of on-effort transects and 1,756 sightings of 17,000 animals. We fit the model in a Bayesian framework with integrated nested Laplace approximations, yielding seasonally resolved group and animal density surfaces across the Portuguese Exclusive Economic Zone, and abundance estimates with fully propagated uncertainty. 3. Predicted animal density concentrated over the shelf and upper slope in every season, peaking northwest, and increased in shallower, cooler, more productive waters and over steeper seabed. Abundance nearly doubled from summer (77,000 [95% credible interval: 60,000, 98,000]) to winter (146,000 [99,000, 208,000]). Seasons shared 56% of the spatial field's variance, so effort from any programme in any season informed all others, and the seasonal contrast remained estimable despite uneven coverage. 4. Synthesis and applications. Our framework allows managers to combine dedicated surveys with existing platforms of opportunity to estimate animal density by season. Because group size is modelled explicitly, densities are estimated in animals rather than groups, as required for bycatch risk assessment and marine spatial planning. Because each survey enters through its own observation model, the approach accommodates programmes that differ in platform and protocol and transfers to any species or region where several surveys each cover part of a population.

ecology↗

bioRxiv2026

Calcineurin B-mediated Ca2+ sensing translates stress signal intensity into the assembly of phase-separated condensates at PERK complexes.

Endoplasmic reticulum (ER) stress activates protein kinase RNA-like ER kinase (PERK), which initially promotes adaptive responses but remains the only active UPR branch during prolonged stress, mediating both early cytoprotective and chronic pro-apoptotic signaling. Recently, we identified translocon-generated Ca2+ microdomains that promote PERK phosphorylation during early UPR, revealing a mechanism by which local Ca2+ signals regulate UPR activation. However, the molecular mechanism linking these Ca2+ microdomains to PERK activation remains elusive. Previously, we showed that calcineurin (CN), a Ca2+ -dependent heterodimer composed of catalytic (CNA) and regulatory (CNB) subunits, exerts a non-canonical pro-survival function by promoting PERK autophosphorylation. Here, using super-resolution microscopy, CRISPR-Cas9 editing, in silico analyses, and optogenetic droplet assays, we identify CNB as a local Ca2+ sensor that couples translocon-generated Ca2+ signals to liquid condensate assembly, thereby promoting adaptive PERK phosphorylation. These findings establish CNB-mediated condensate assembly as a mechanism that translates local Ca2+ signals into spatially organized early adaptive PERK signaling.

cell biology↗

bioRxiv2026

A U1-U3 snRNA-snoRNA interaction couples SF3B1 mutation to chromatin-state rewiring and genome instability

Mutations in spliceosome factors such as SF3B1 are recurrent across human diseases, including myelodysplastic syndromes and leukemia1-4, yet splicing defects alone do not fully explain the widespread chromatin alterations and genome instability in mutant cells5. Here, by comprehensively mapping snRNA-directed RNA-RNA interactions, we identify two previously unrecognized interaction motifs in U1 snRNA beyond canonical 5' splice-site pairing6,7. These motifs enable U1 RNA to i) bind intronic and other chromatin-associated RNA (caRNA) regions outside of splice sites, and ii) base pair specifically with snoRNA. We uncover a U1-U3 snRNA-snoRNA interaction that recruits the H3K36 methyltransferase SETD2 to caRNA, promoting gene-body H3K36me3 and antagonizing H3K27me3 to modulate chromatin accessibility. The snRNA-snoRNA interface is essential for this previously unrecognized layer of chromatin and transcriptional regulation mediated through SETD2. SF3B1 mutation enhances U1-U3 binding and increases the association of the U1-U3 complex with caRNA, driving chromatin-accessibility remolding, R-loop formation, DNA damage, and copy-number abnormalities that promote tumorigenesis. A U1-specific 2'-O-methoxyethyl antisense oligonucleotide that selectively blocks U1-U3 pairing suppresses these genomic abnormalities, reduces leukemic infiltration, and prolongs survival in xenograft and patient-derived models, establishing pathological snRNA-snoRNA rewiring as a critical driver of SF3B1-mutant leukemogenesis.

cell biology↗

bioRxiv2026

Time to Potential Collision: A Dynamic Approach To Study Vessel-Whale Close Encounters

Vessel-whale collisions are a growing global concern and remain challenging to quantify. Therefore, the use of proxies, such as Close Encounters (CEs) that comprise Surprise Encounters (SEs) and Near-Miss Events (NMEs), has been proposed and widely employed to assess collision risk. To better understand this risk in the Eastern North Atlantic, where maritime traffic is intensive, this study aimed to redefine and quantify CEs, and to assess detectability-related variables that may affect CE identification. CEs were assessed using a cetacean occurrence dataset collected between 2012 and 2024 on board cargo ships and oceanographic vessels. CEs thresholds were redefined based on Time to Potential Collision (TPC), rather than distance alone (as described in literature), to allow a more dynamic, risk-based, and speed-sensitive approach. In total, 1226 sightings of whales (baleen, sperm, and beaked whales) were recorded, of which 37.4% were classified as SEs and 2.0% as NMEs. The sperm whale, Physeter macrocephalus, was the species most frequently involved in CEs (13.9% of all CEs), followed by the Cuviers beaked whale, Ziphius cavirostris (11.8%). A Generalized Additive Model was used to assess the influence of detectability-related variables (i.e., meteorological conditions, whale taxa, vessel characteristics, and Marine Mammals Observers (MMOs) experience) on TPC. Significantly lower TPC values were observed with beaked whales, cargo ships, poor visibility conditions, and less experienced MMOs. The results of this study provide an CEs assessment in this region and contribute to the ongoing efforts to standardize CE quantification, by using TPC as a metric. This work also highlights the importance of decreased speeds and the presence of experienced MMOs on board to increase detection probability and TPC, thereby potentially minimizing collision risk.

ecology↗

bioRxiv2026

Montreal Urban Observatory: research platform to monitor urban forest ecosystems for global change adaptation and health

As urban populations grow, cities are increasingly seen not only as drivers of climate change but also as critical arenas for implementing mitigation and adaptation strategies. Urban forests and green infrastructure play a vital role in shaping environmental quality and human health, yet access to these benefits remains inequitable. The Montreal Urban Observatory was designed to investigate the complex relationships among biodiversity, ecosystem functioning, and human health. Twenty-five permanent plots were established across the Island of Montreal, strategically located along gradients in vegetation cover, population density, and mean household income. Interdisciplinary research within the Observatory focuses on themes including urban forest structure and function, abiotic conditions, biodiversity, ecological interactions, natures contributions to people, related human health outcomes, and developing novel methodological approaches. The Observatory supports long-term, cross-scale monitoring and fosters collaborative research on urban social-ecological systems, thus contributing to global initiatives to enhance urban sustainability and equity through nature-based solutions. Early results confirm the relevance of the main gradients for several organisms and response variables, from microbes to trees and abiotic factors. For example, sampling all trees, public and private, within a radius of 200m centered on each plot revealed significant differences in the diversity and structure of private and public trees, including an overwhelming dominance of Thuya occidentalis not captured in commonly used public tree inventories.

ecology↗

bioRxiv2026

Southern South American Maize Landraces: A Source of Phenotypic Diversity

Maize (Zea mays L.) is a globally important crop for food, feed, and industrial uses. Modern breeding increasingly targets traits beyond yield, including stress tolerance, nutritional quality, and pest resistance. Progress toward these goals is constrained by the narrow genetic diversity of commercial varieties, a consequence of the repeated use of a limited number of inbred lines. Maize landraces therefore represent valuable reservoirs of genetic and phenotypic diversity. Northern Argentina is one of the southernmost regions of maize landrace cultivation and comprises two main centers of diversity: Northeastern Argentina (NEA; <2000 m.a.s.l.) and Northwestern Argentina (NWA; >2000 m.a.s.l.). Despite their potential relevance, phenotypic characterization of these landraces remains limited, particularly for biochemical traits, which, although less visible, play key roles in biomass accumulation, defense against pathogens and herbivores, tolerance to environmental stress, and quality attributes such as flavor. Here, we evaluated 17 phenotypic traits, including morphological traits, leaf biochemical compounds (such as pigments, carbohydrates, and phenolics), and salt stress tolerance, in 19 maize landrace accessions from Northern Argentina. Substantial variation was detected across all traits, both within and among accessions, indicating that each accession harbors a distinct phenotypic profile. While no significant differences were observed between regions, redundancy analysis revealed associations between phenotypic variation and collection-site altitude. These findings highlight the value of Argentine maize landraces as sources of biochemical and stress-related traits and support their conservation and use in breeding programs aimed at broadening the genetic base of cultivated maize. Main ConclusionMaize landraces from Southern South America show high within and between accession phenotypic variability, while differences between regions of origin are associated with altitude.

plant biology↗

bioRxiv2025

Phospho-signalling deregulation of the mTOR pathway in fibroblasts from LRRK2 Parkinson s patients

Activating mutations at the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent genetic cause of Parkinsons Disease (PD). Using in-depth mass-spectrometry, here we analysed the impact of LRRK2 mutations on the proteome and phospho-proteome of skin fibroblasts from a large LRRK2 clinical cohort from Spain. The cohort encompassed G2019S LRRK2-associated PD (L2PD) (n=15), G2019S LRRK2 non-manifesting carriers (L2NMCs) (n=13), idiopathic PD (iPD) (n=12), and control subjects (n=14) (total n=54). The proteome analysis revealed 89 differential proteins in G2019S L2PD (58 down/ 31 up) and 168 in G2019S L2NMCs (127 down / 41 up) compared to controls. Most of these proteome changes involved deficits in proteins related to mitochondrial energy and ribosomal protein synthesis. At the phospho-proteome level, we identified 394 differential phospho-sites in G2019S L2PD (188 hyper / 206 hypo), 367 in G2019S L2NMCs (215 hyper / 152 hypo), and 428 in iPD (214 hyper / 214 hypo) compared with controls. These phospho-proteomic changes included hyper-phosphorylated proteins associated with the mTOR and Rho GTPase pathways. Notably, the top hyper-phosphorylated hit in G2019S carriers was pThr37/46 4E-BP1, a key effector of the mTOR pathway controlling protein synthesis, and this protein was also deregulated in iPD. In summary, our study uncovers peripheral deregulation of mTOR phospho-signalling associated with LRRK2 mutations, which is related to deficits in mitochondrial and ribosomal proteins, and affects converging pathways altered in iPD.

neuroscience↗

bioRxiv2025

The coloNISation: spatio-temporal metabarcoding surveys in ports reveal homogenised communities with high genetic diversity and connectivity of non-indigenous species

Large commercial ports facilitate the introduction of non-indigenous species (NIS), while smaller harbours and marinas contribute to their regional spread. Harbour networks are thus important drivers of introductions. Despite extensive research effort on NIS in recent years, no study has yet assessed genetic connectivity among harbours considering whole-community composition. Here, we analysed spatio-temporal patterns of metazoan communities over one year in four medium-size harbours along the NW Mediterranean coast sampled by deploying standardised biological collectors. Using cytochrome c oxidase subunit I (COI) metabarcoding, we identified 1,770 metazoan molecular operational taxonomic units (MOTUs), of which 82 were classified as NIS based on a custom database of Mediterranean NIS. Despite their lower species count compared to natives, NIS accounted for 34-70% of reads in harbours. The southernmost harbour had the highest NIS number of reads, likely due to its proximity to aquaculture facilities. While we observed some variation in the spatial structure of metazoan communities across harbours, NIS showed consistently low differentiation values, sharing significantly more MOTUs among sites. Seasonal patterns influenced both NIS and the rest of the community. Haplotype diversity was significantly higher in NIS, which also exhibited lower genetic differentiation across harbours compared to native species, indicating NIS spread via local boating and likely recurrent introductions. These findings highlight distinct dynamics between NIS and native species in artificial environments, emphasising the importance of continued monitoring in harbour networks to manage coastal NIS proliferation. HIGHLIGHTSCOI metabarcoding of standardised collectors detected over 1,700 MOTUs of marine metazoans in ports over a year. Less than 4% were NIS MOTUs, but they comprised 34-71 % of the reads. NIS were more homogeneously distributed among ports than other MOTUs. NIS showed higher genetic variability but lower genetic differentiation than native species. Different dynamics underpin NIS and native assemblages in port communities. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/688838v1_ufig1.gif" ALT="Figure 1000"> View larger version (32K): org.highwire.dtl.DTLVardef@fa0a5corg.highwire.dtl.DTLVardef@1be29ccorg.highwire.dtl.DTLVardef@1aa4e85org.highwire.dtl.DTLVardef@91842_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2025

Spatiotemporal data integration for marine megafauna SDMs in dynamic environments: A point process approach

Species distribution models (SDMs) are widely used to predict where and when species occur, but the data available to fit them often resolve space and time unevenly. Designed surveys, such as line-transect distance-sampling surveys, provide structured spatial coverage and the detection information needed to estimate detectability, but logistical and funding constraints often limit them to short, infrequent periods. Opportunistic or citizen-science records are collected more frequently across the year, but from areas shaped by observer access and interest rather than survey design, and usually without comparable detection information. As a result, models built from either source alone tend to capture spatial structure or temporal dynamics well, but not both, limiting predictions for mobile species in dynamic environments. Here, we present a general framework, based on a log-Gaussian Cox process (LGCP) fitted using integrated nested Laplace approximations (INLA), that links multiple data sources to a shared spatiotemporal measure of species density through source-specific observation models: a detection function for survey transects, and spatial constraints reflecting the footprint of opportunistic effort. We apply the framework to cetacean line-transect surveys and whale-watching records. In a simulation with one month of survey data and twelve months of opportunistic data, the integrated model recovered spatiotemporal distribution patterns well (median correlation with the true pattern = 0.91) and estimated monthly abundance with a mean error of +10.7%, outperforming single-source models. In a case study of common dolphins (Delphinus delphis) off mainland Portugal, integration improved the spatial accuracy of predictions, although weak covariate effects limited the temporal variation the model could resolve. These results show that integration adds the most value when the two data sources resolve complementary aspects of distribution, in this case broad spatial structure from the survey and temporal replication from whale-watching, while temporal predictions remain limited when covariates carry weak seasonal signal. The framework is general and can be extended to other taxa, systems, and combinations of structured and opportunistic data by substituting the relevant observation models.

ecology↗

bioRxiv2025

Acute Pericentral Liver Injury Induces a Novel Transient Hepatocyte Population

The liver exhibits robust regenerative capacity in response to injury, a property shaped by its essential metabolic and detoxification roles. While the mechanisms of regeneration following chronic liver injury have been extensively studied, the response during the early phases of acute injury remains poorly understood. Here, we employed a pericentral model of acute liver injury using carbon tetrachloride (CCl4) to investigate the initial hepatocyte response to damage. Through integration of single-nucleus multiome-sequencing, lineage tracing, spatial transcriptomics, and immunostaining, we identified a novel, transient population of damage-responsive SOX9+ pericentral hepatocytes. This population does not exhibit progenitor-like behavior but instead potentially mediates key aspects of early tissue repair. Specifically, SOX9+ pericentral hepatocytes engage in interactions with hepatic stellate cells and display migratory features associated with wound closure. Moreover, these cells exhibit an immune-related transcriptional signature and colocalize with liver macrophages at injury sites, suggesting a role in modulating immune responses. Our findings highlight a previously underappreciated function of SOX9 as a stress-responsive regulator of hepatocyte behavior and intercellular crosstalk during the early stages of acute liver injury.

cell biology↗

bioRxiv2025

Tuning the gate and the gear: The LRRC26 (γ1) subunit modulates intrinsic gating and voltage-sensor coupling of the BK channel

Association of auxiliary subunits ({beta}1-4 and {gamma}1-4) with the pore-forming subunit of the calcium- and voltage-activated potassium (BK) channel provides functional diversity. {gamma}1 promotes a significant leftward shift of the voltage activation curve, ensuring the adequate functioning of secretory glands, allowing the BK channel to release K+ at the cells resting Ca2+ concentration. Given its physiological importance, it is crucial to elucidate the mechanisms of {gamma}1 action. However, structural and functional studies have yielded conflicting conclusions regarding the modulation of BK channels by {gamma}1. Here, using macroscopic, single-channel, and gating current measurements, we demonstrate that at zero mV {gamma}1 increases 92-fold the equilibrium constant that defines the closed- open transition by destabilizing the channels closed configuration and enhancing the coupling between the voltage sensor and the pore domain, without affecting voltage-sensor activation. These results suggest that {gamma}1 not only causes an increase in the energetic coupling between the voltage sensors and the pore but mainly enhances the channel opening reaction. TeaserThe {gamma}1 subunit favors the BK channel pore opening by destabilizing its closed configuration.

biophysics↗

bioRxiv2025

PHYSICOCHEMICAL PROPERTIES OF ENHANCED AND RECOVERED VENEZUELAN CRUDE OIL TREATED WITH BIOCOMPATIBLE PHARMACEUTICAL FORMULATION: SIMULATION OF THE ROLE OF WATER AND IONIC CONTENT.

In this work, the hydrogen bonding interaction of water and ethanol with Polysorbate 80 (P-80, Tween 80) is simulated, in relation to its role in oil upgrading and recovery, using real theoretical and experimental studies. The theoretical physicochemical results obtained were compared with other experimental results derived from the treatment of improved and recovered oil after mixing Biocompatible Pharmaceutical Formulations (BPF) of these three compounds and oil produced in Venezuela. The Spartan 16 program was used to build the molecular structures and simulate the interactions with the semi-empirical PM3 method, to compare them with two real experiments. These two experiments were performed as follows: in the first, the mixture consists of a surfactant, (Z)-Sorbitan mono-9-octadecenoate poly(oxy-1,2-ethanediyl) or polyoxoethylene (20) sorbitan mono-oleate (Polysorbate 80), which is mixed with the hydrocarbon, and then completely fluidized with the addition of ethyl alcohol or ethanol.Water and ions (<100 ppm) present in this experiment are contained in oil and ethanol as contaminants (approximately 1.73-1.30% of total water). In the second experiment, the BPF ratios were 10:5:0.1:0.01 for oil:water with 17,800 ppm NaCl:P-80:ethanol (approximately 33.09% of total water and 1.78% w/v NaCl). The simulations were performed taking into account both real experiments. The simulated interactive products were characterized by the following parameters: energy, minimum conformational energy, solvation energy, aqueous energy, HOMO energy, LUMO energy, {Delta}E, dipole moment, polarizability, electrostatic potential map (EPM) and electron density.A theoretical parametric relationship (sio Index, "stability in oil Index") is developed to evaluate the stability of the molecular forms generated within the hydrocarbon. The following theoretical experiments were performed: First, successive interactions of water with P-80 from position 1 to position 21. Second, successive interactions from position 1 to position 21 of P-80 of water and ethanol, 1 to 1. Third, successive interactions with P-80 of 21 ethanol molecules on the final product of the first experiment. These theoretical results were compared with some experimental results obtained using Oil Mixtures. The results obtained and compared in both experimental series (theoretical and real) allow to distinguish the role of P-80, Ethanol, Water and ions for the improvement and recovery of the treated oil. It is concluded that the formulation that does not contain added water and sodium chloride is supposed to use the contaminating water present in the petroleum and the water contained in the ethanol (<5%).This formulation has very little effect on the resulting Density of the improved Oil, but it greatly decreases the resulting Viscosity in the Crude Oil. The formulation that contains more than 30% added Water decreases the Density while the Viscosity of the Crude Oil responds proportionally to the Water retained in it. This difference in the results could be interpreted as a different proportion and chemical composition as a consequence of a different structural relationship between these components and a different conformation of the nanoparticle generated within the Oil, in each case. In this sense, the hypothesis is established that there would be an intermediate molecular form that could improve both Viscosity and Density.

biophysics↗

bioRxiv2025

Seasonal and interannual variation of common dolphin densities in Portuguese waters

Modelling a species ecology and abundance provides important insights into its habitat preferences, population trends and distribution. This can be used to inform conservation efforts, highlighting populations at risk of extinction and regions in need of protection. Here, we studied how environmental factors relate to common dolphins (Delphinus delphis) densities in the waters off mainland Portugal. We analyzed an opportunistic dataset collected using European Seabirds At Sea (ESAS) methodology with distance sampling, spanning from 2004 to 2020. There were 1151 sightings of common dolphins, 737 of which were during effort. Detection functions were fitted to model the dolphins detectability as a function of the distance to the track line. We used smooths of static (depth, slope, and distance to the coast, 200m and 1000m isobaths) and dynamic (sea surface temperature, salinity, chlorophyll-a concentration with and without a time lag, zooplankton, and sardine biomass) environmental factors, relating them to counts corrected for detectability and survey effort, to fit habitat-based Density Surface Models. We then predicted and mapped common dolphin densities seasonally (winter, spring, summer autumn) throughout the sample years. The results show how different environment variables relate to dynamic common dolphin densities. In general, common dolphins had higher densities in coastal environments, especially during the summer due to high productivity and lower sea surface temperature in shelf waters, associated with seasonal upwelling. During the summer, there were predicted local peaks in common dolphin densities, in areas with high zooplankton and chlorophyll-a concentration. In the other seasons, its range expands to more offshore waters, with less local density peaks. The interannual variation of this species densities is mostly explained by the annual sardine biomass. Overall, this brings important insights into this species conservation and potential impacts from anthropogenic activities, such as climate change and overfishing.

ecology↗

bioRxiv2025

Oncogene Silencing via ecDNA Micronucleation

Extrachromosomal DNA (ecDNA) contributes to cancer genome instability by enabling high-copy oncogene amplification, intratumoural heterogeneity and rapid genetic change. Micronuclei (MN) are frequently observed in chromosomally unstable cancers, yet their origins and relevance in ecDNA-driven tumours remain incompletely understood. Here, we investigate the relationship between ecDNA segregation errors and MN formation. We find that ecDNA frequently localizes to MN and represents a prominent source of MN content in ecDNA-positive cancer cells. Mitotic clustering of oncogene-bearing ecDNAs is associated with asymmetric inheritance and mis-segregation into MN. Transfer of oncogenes from ecDNA into MN is accompanied by reduced transcriptional output. Single-MN sequencing shows that individual MN are enriched for ecDNA to a degree that exceeds expectations from stochastic mis-segregation and that in MN oncogenes originating from multiple distinct ecDNAs coalesce. Using live-cell imaging, we observe that cells inheriting ecDNA-positive MN show limited proliferative capacity and an increased likelihood of cell death. In neuroblastoma patients with MYCN-amplified ecDNA, higher frequencies of ecDNA-positive MN at diagnosis are associated with improved event-free and overall survival. Together, these findings link ecDNA mis-segregation to MN formation and reduced cellular fitness, suggesting that ecDNA-positive MN may reflect a state of impaired oncogenic ecDNA function with potential relevance for clinical outcome.

cancer biology↗

bioRxiv2025

Development of novel high-affinity nanobodies against EGFR for cancer therapy

The epidermal growth factor receptor (EGFR) is a member of a family of transmembrane tyrosine kinase receptors that plays a pivotal role in regulating diverse cellular processes such as cell proliferation, survival, migration, and differentiation. Aberrant activation of EGFR signaling has been implicated in various pathological conditions, particularly cancer, making it an attractive target for therapeutic intervention. While several anti-EGFR monoclonal antibodies have been developed and demonstrated their clinical value for the treatment of various solid tumors, smaller antibody fragments such as nanobodies (Nb) offer distinct advantages over conventional antibodies, including reduced immunogenicity and enhanced tumor penetration. In this paper, we report the isolation and characterization of two novel high-affinity Nb targeting EGFR. These Nb were identified and characterized using ELISA, flow cytometry, microscopy, and SPR. Furthermore, these Nb and bivalent Nb engineered from them were tested for their effects on cancer cell proliferation. We demonstrate that the novel Nb exhibit high affinity and potent anti-tumor activity in vitro in their bivalent form, positioning them as promising candidates for cancer treatment.

molecular biology↗