Biology subjects

Ribeiro, J.

Publications and source records attributed to Ribeiro, J..

13 recordsLinked to original sources

bioRxiv2026

Two centuries of change in the traits and origins of non-native vertebrates

Globalization is redistributing species worldwide, yet whether the traits and origins of non-native fauna have changed through time remains unclear. We combined global first-record data for non-native species from 1800-2019 with harmonized information on body size, diet, habitat use, native range characteristics, and climatic niche characteristics for 1,910 non-native mammals, birds, reptiles, amphibians, and freshwater fishes. Across most groups, species recorded earlier originated disproportionately from higher latitudes, occupied broader native ranges, and had wider thermal niches. More recent first records increasingly involve species from warmer, lower-latitude regions with smaller and more restricted native distributions. Body size also declined through time in several groups, whereas shifts in diet and habitat use were more taxon-specific. Temporal changes in introduction pathways partly explained these patterns: declines in deliberate release and production-related pathways, together with increases in pet and ornamental pathways, were associated with shifts toward smaller-bodied, lower-latitude, and more range-restricted species. These results indicate that the functional and biogeographic composition of non-native vertebrates has been progressively reshaped over the past two centuries, weakening the historical dominance of widespread temperate species and increasingly incorporating tropical and range-restricted fauna into global redistribution. Anticipating future biological invasions will therefore require attention not only to the number of species being transported, but also to how the characteristics and pathways of transported species are changing through time.

ecology↗

bioRxiv2026

Data-driven forecasts of regional arrivals of non-native vertebrates worldwide

AimTo forecast near-future arrivals of non-native terrestrial and freshwater vertebrates at the regional level. LocationGlobal (geopolitical regions worldwide, including countries and main administrative divisions). MethodsWe compiled first regional record data and assembled functional and macroecological variables for 1,931 non-native vertebrate species. For each region, we identified recently arrived non-native species using retrospective windows of thirty and twenty years ending in 2015 (1986-2015; 1996-2015). We then fitted region-specific random-forest models classifying recently arrived species versus those not yet arrived using as predictors: (i) harmonised species traits (e.g., habitat, diet, body size and native-range attributes) and (ii) spread history, capturing time since first record elsewhere. Predictive performance was evaluated using leave-one-out cross-validation, comparing full models with trait-only and spread-only variants. We also assessed relationships between predictive accuracy, predictor importance, and the geographic positioning and trade connectedness of regions. Finally, we predicted region-specific probabilities of arrival for species not yet recorded. ResultsForecasting accuracy was consistently high across regions and taxa, with AUC values above 0.9 in more than half of the focal regions. Full models substantially outperformed models using either predictor set alone, and spread-history-only models typically exceeded trait-only models. Relative importance of spread-history predictors declined with geographic distance to the focal region, whereas predictability was lower in highly trade-connected regions. Predicted near-future high-risk arrivals were dominated by birds and freshwater fishes and showed strong regional structuring. A small set of species ranked highly across many regions (e.g., birds: Phasianus colchicus, Acridotheres tristis, Amandava amandava, Colinus virginianus, Corvus splendens and Lonchura malacca; fishes: Coregonus peled and Oreochromis mossambicus; mammal: Oryctolagus cuniculus), suggesting substantial unrealised spread potential. Main conclusionsNear-future regional arrivals of non-native vertebrates are predictable from spread history and species traits. This enables scalable, updateable regional watchlists to support prevention, early detection and horizon scanning.

ecology↗

bioRxiv2024

CD47 predominates over CD24 as a macrophage immune checkpoint in cancer.

Macrophages hold tremendous promise as effectors of cancer immunotherapy, but the best strategies to provoke these cells to attack tumors remain unknown. Here, we evaluated the therapeutic potential of targeting two distinct macrophage immune checkpoints: CD47 and CD24. We found that antibodies targeting these antigens could elicit maximal levels of phagocytosis when combined together in vitro. However, to our surprise, via unbiased genome-wide CRISPR screens, we found that CD24 primarily acts as a target of opsonization rather than an immune checkpoint. In a series of in vitro and in vivo genetic validation studies, we found that CD24 was neither necessary nor sufficient to protect cancer cells from macrophage phagocytosis in most mouse and human tumor models. Instead, anti-CD24 antibodies exhibit robust Fc-dependent activity, and as a consequence, they cause significant on-target hematologic toxicity in mice. To overcome these challenges and leverage our findings for therapeutic purposes, we engineered a collection of 77 novel bispecific antibodies that bind to a tumor antigen with one arm and engage macrophages with the second arm. We discovered multiple novel bispecifics that maximally activate macrophage-mediated cytotoxicity and reduce binding to healthy blood cells, including bispecifics targeting macrophage immune checkpoint molecules in combination with EGFR, TROP2, and CD71. Overall, our findings indicate that CD47 predominates over CD24 as a macrophage immune checkpoint in cancer, and that the novel bispecifics we created may be optimal immunotherapies to direct myeloid cells to eradicate solid tumors.

cancer biology↗

bioRxiv2024

Unbiased discovery of antibody therapies that stimulate macrophage-mediated destruction of B-cell lymphoma

Macrophages are critical effectors of antibody therapies for lymphoma, but the best targets for this purpose remain unknown. Here, we sought to define a comprehensive repertoire of cell surface antigens that can be targeted to stimulate macrophage-mediated destruction of B-cell lymphoma. We developed a high-throughput assay to screen hundreds of antibodies for their ability to provoke macrophages to attack B-cell lymphoma cells. Across both mouse and human systems, we identified multiple unappreciated targets of opsonization as well as putative immune checkpoints. We used this information to engineer a compendium of 156 bispecific antibodies, and we identified dozens of bispecifics that dramatically stimulate macrophage-mediated cytotoxicity of lymphoma cells. Among these, a bispecific comprising a SIRP decoy domain and a CD38-targeting arm (WTa2d1xCD38) exhibited maximal efficacy while minimizing the risk of hematologic toxicity. This bispecific stimulated robust anti-tumor responses in multiple xenograft models of aggressive B-cell lymphoma. Our approach can be directly applied to other cancers to rapidly discover bispecific antibodies that leverage anti-tumor responses by macrophages or other innate immune cells.

immunology↗

bioRxiv2024

Zebrafish Avatar-test predicts patient's tumor response to chemotherapy in breast cancer: a co-clinical study towards personalized medicine

Chemotherapy remains the mainstay in most high-risk breast cancer (BC) settings, with several equivalent options of treatment. However, the efficacy of each treatment varies between patients and there is currently no test to determine which option will be the most effective for each individual patient. Here, we developed a fast in-vivo test for BC therapy screening: the zebrafish patient derived xenograft model (zAvatars), where in-vivo results can be obtained in just 10 days. To determine the predictive value of the BC zAvatars we performed a clinical study, where zAvatars were treated with the same therapy as the donor-patient and their response to therapy was compared. Our data shows a 100% correlation between patients clinical response to treatment and its matching zAvatar. Altogether, our results suggest that the zAvatar model constitutes a promising in-vivo assay to optimize cancer treatments in truly personalized manner.

cancer biology↗

bioRxiv2024

Small non-coding RNA content in plasma-derived extracellular vesicles distinguish ataxic SCA3 mutation carriers from pre-ataxic and control subjects

Spinocerebellar ataxia type 3 (SCA3), a neurodegenerative disorder caused by a CAG expansion in the ATXN3 gene, is the most common spinocerebellar ataxia subtype worldwide. Currently, there is no therapy to stop or prevent disease progression. Promising therapeutic strategies are emerging, but their translation into clinical practice requires sensitive and reliable biomarkers. Blood circulating extracellular vesicles constitute a promising source of biomarkers with potential to track alterations of the central nervous system due to their ability to cross the blood brain barrier. Here, we perform sequencing analysis of small RNAs from plasma-derived extracellular vesicles from SCA3 mutation carriers (10 pre-ataxic and 10 ataxic) and 12 control subjects to identify potential RNA biomarker candidates for this disease. Data showed that plasma-derived extracellular vesicles from ataxic SCA3 mutation carriers are enriched in mitochondrial, nuclear, and nucleolar RNA biotypes compared to pre-ataxic and control subjects. Moreover, ataxic mutation carriers could be discriminated from control and pre-ataxic subjects based on the miRNAs or piRNAs content, but not tRNA. Furthermore, we identified a subset of differentially expressed miRNAs and piRNAs that clearly differentiate ataxic mutation carriers from pre-ataxic and control subjects. These findings open new avenues for further investigation on the role of these RNAs in the pathogenesis of SCA3 and their potential as biomarkers for this disease.

neuroscience↗

bioRxiv2022

Changes in adenosine and neurotrophic signaling in the SOD1G93A mouse model of amyotrophic lateral sclerosis: modulation by chronic caffeine intake

Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of corticospinal tract motor neurons. Previous studies showed that adenosine-mediated neuromodulation is disturbed in ALS and that vascular endothelial growth factor (VEGF) has a neuroprotective function in ALS mouse models. We evaluated how adenosine (A1R and A2AR) and VEGF (VEGFA, VEGFB, VEGFR-1 and VEGFR-2) system markers are altered in the cortex and spinal cord of pre-symptomatic and symptomatic SOD1G93A mice. We then assessed if/how chronic treatment of SOD1G93A mice with a widely consumed adenosine receptor antagonist, caffeine, modulates VEGF system and/or the levels of Brain-derived Neurotrophic Factor (BDNF), known to be under control of A2AR. We found out decreases in A1R and increases in A2AR levels even before disease onset. Concerning the VEGF system, we detected increases of VEGFB and VEGFR-2 levels in the spinal cord at pre-symptomatic stage, which reverses at the symptomatic stage, and decreases of VEGFA levels in the cortex, in very late disease states. Chronic treatment with caffeine rescued cortical A1R levels in SOD1G93A mice, bringing them to control levels, while rendering VEGF signaling nearly unaffected. In contrast, BDNF levels were significantly affected in SOD1G93A mice treated with caffeine, being decreased in the cortex and increased in spinal the cord. Altogether, these findings suggest an early dysfunction of the adenosinergic system in ALS and highlights the possibility that the negative influence of caffeine previously reported in ALS animal models results from interference with BDNF rather than with the VEGF signaling molecules.

neuroscience↗

bioRxiv2022

GCNA is a histone binding protein required for spermatogonial stem cell maintenance

Recycling and de-novo deposition of histones during DNA replication is a critical challenge faced by eukaryotic cells and is coordinated by histone chaperones. However, little is known about how tissue-specific histone chaperones function to maintain tissue homeostasis. Here we show that Germ Cell Nuclear Acidic protein (GCNA), a germ cell specific protein in adult mice, can bind histones and purified GCNA exhibits histone chaperone activity. GCNA associates with the DNA replication machinery and supports progression through S-phase in murine spermatogonial stem cells (SSCs). Whilst GCNA is dispensable for embryonic germ cell development, it is required for the maintenance of the SSC pool and for long-term production of sperm. Our work describes the role of a germ cell specific histone chaperone in SSCs maintenance in mice. These findings provide a mechanistic basis for the male infertility observed in patients carrying mutations in the GCNA locus.

physiology↗

bioRxiv2021

A high-throughput 3D bioprinted cancer cell migration and invasion model with versatile and broad biological applicability

Understanding the underlying mechanisms of migration and metastasis is a key focus of cancer research. There is an urgent need to develop in vitro 3D tumor models that can mimic physiological cell-cell and cell-extracellular matrix interactions, with high reproducibility and that are suitable for high throughput (HTP) drug screening. Here, we developed a HTP 3D bioprinted migration model using a bespoke drop-on-demand bioprinting platform. This HTP platform coupled with tunable hydrogel systems enables (i) the rapid encapsulation of cancer cells within in vivo tumor mimicking matrices, (ii) in situ and real-time measurement of cell movement, (iii) detailed molecular analysis for the study of mechanisms underlying cell migration and invasion, and (iv) the identification of novel therapeutic options. This work demonstrates that this HTP 3D bioprinted cell migration platform has broad applications across quantitative cell and cancer biology as well as drug screening.

cell biology↗

bioRxiv2020

Precise, high-throughput production of multicellular spheroids with a bespoke 3D bioprinter

3D in vitro cancer models are important therapeutic and biological discovery tools, yet formation of multicellular spheroids in a throughput and highly controlled manner to achieve robust and statistically relevant data, remains challenging. Here, we developed an enabling technology consisting of a bespoke drop-on-demand 3D bioprinter capable of high-throughput printing of 96-well plates of spheroids. 3D-multicellular spheroids are embedded inside a tissue-like matrix with precise control over size and cell number. Application of 3D bioprinting for high-throughput drug screening was demonstrated with doxorubicin. Measurements showed that IC50 values were sensitive to spheroid size, embedding and how spheroids conform to the embedding, revealing parameters shaping biological responses in these models. Our study demonstrates the potential of 3D bioprinting as a robust high-throughput platform to screen biological and therapeutic parameters. Significance StatementIn vitro 3D cell cultures serve as more realistic models, compared to 2D cell culture, for understanding diverse biology and for drug discovery. Preparing 3D cell cultures with defined parameters is challenging, with significant failure rates when embedding 3D multicellular spheroids into extracellular mimics. Here, we report a new 3D bioprinter we developed in conjunction with bioinks to allow 3D-multicellular spheroids to be produced in a high-throughput manner. High-throughput production of embedded multicellular spheroids allowed entire drug-dose responses to be performed in 96-well plate format with statistically relevant numbers of data points. We have deconvoluted important parameters in drug responses including the impact of spheroid size and embedding in an extracellular matrix mimic on IC50 values.

bioengineering↗

bioRxiv2020

shani mutation in mouse affects splicing of Spata22 and leads to impaired meiotic recombination

Recombination is crucial for chromosome pairing and segregation during meiosis. SPATA22, along with its direct binding partner and functional collaborator, MEIOB, is essential for the proper repair of double-strand breaks (DSBs) during meiotic recombination. Here we describe a novel point-mutated allele (shani) of mouse Spata22 that we isolated in a forward genetic screen. shani mutant mice phenocopy Spata22-null and Meiob-null mice: mutant cells appear to form DSBs and initiate meiotic recombination, but are unable to complete DSB repair, leading to meiotic prophase arrest, apoptosis and sterility. shani mutants show precocious loss of DMC1 foci and improper accumulation of BLM-positive recombination foci, reinforcing the requirement of SPATA22-MEIOB for the proper progression of meiotic recombination events. The shani mutation lies within a Spata22 coding exon and molecular characterization shows that it leads to incorrect splicing of the Spata22 mRNA, ultimately resulting in no detectable SPATA22 protein. We propose that the shani mutation alters an exonic splicing enhancer element (ESE) within the Spata22 transcript. The affected DNA nucleotide is conserved in most tetrapods examined, suggesting that the splicing regulation we describe here may be a conserved feature of Spata22 regulation.

genetics↗

bioRxiv2018

Past-future information bottleneck framework for simultaneously sampling biomolecular reaction coordinate, thermodynamics and kinetics

The ability to rapidly learn from high-dimensional data to make reliable bets about the future outcomes is crucial in many contexts. This could be a fly avoiding predators, or the retina processing gigabytes of data almost instantaneously to guide complex human actions. In this work we draw parallels between such tasks, and the efficient sampling of complex biomolecules with hundreds of thousands of atoms. For this we use the Predictive Information Bottleneck (PIB) framework developed and used for the first two classes of problems, and re-formulate it for the sampling of biomolecular structure and dynamics, especially when plagued with rare events. Our method considers a given biomolecular trajectory expressed in terms of order parameters or basis functions, and uses a deep neural network to learn the minimally complex yet most predictive aspects of this trajectory, viz the PIB. This information is used to perform iterative rounds of biased simulations that enhance the sampling along the PIB to gradually improve its accuracy, directly obtaining associated thermodynamic and kinetic information. We demonstrate the method on two test-pieces, including benzene dissociation from the protein lysozyme, where we calculate the dissociation pathway and timescales slower than milliseconds. Finally, by performing an analysis of residues contributing to the PIB, we predict the critical mutations in the system which would be most impactful on the stability of the crucial but ephemeral transition state. We believe this work marks a big step forward in the use of predictive artificial intelligence ideas for the sampling of biomolecules.

biophysics↗

bioRxiv2018

MEIOB and SPATA22 resemble RPA subunits and interact with the RPA complex to promote meiotic recombination

Homologous recombination is a conserved DNA repair process mandatory for chromosome segregation during meiosis. RPA, a ubiquitous complex essential to recombination, is thought to play a similar role during mitotic and meiotic recombination. MEIOB, a meiosis-specific factor with unknown molecular function, ressembles a RPA subunit. Here we use in vivo approaches to show that in mouse spermatocytes, DMC1 and RAD51 appear to be normally loaded in the absence of MEIOB but are prematurely lost from unrepaired recombination sites. This loss correlates with an accumulation of the BLM helicase on meiotic chromosomes. We also show that MEIOB alters the immunodetection of RPA subunits at meiotic recombination sites. Using electron microscopy and purified proteins, we demonstrate that the MEIOB-SPATA22 complex associates with and modifies the conformation of RPA-coated ssDNA. Finally, we identify structural homology between MEIOB, SPATA22 and RPA subunits, and show that MEIOB and SPATA22 interact through C-terminal OB-fold containing domains (OBCDs) like RPA subunits. Moreover, MEIOB and SPATA22 cooperate to interact with RPA through their OBCDs. Our results suggest that MEIOB, SPATA22 and RPA work together to ensure proper processing of meiotic recombination intermediates.

cell biology↗