Biology subjects

Alonso, D.

Publications and source records attributed to Alonso, D..

17 recordsLinked to original sources

bioRxiv2026

Aberrant chromatin looping by NUP98-HOXA9 is constrained by CTCF and facilitated by cohesin

The acute myeloid leukemia (AML) fusion protein NUP98-HOXA9 (NHA9) drives leukemogenesis by promoting aberrant chromatin loop formation through phase separation, yet the mechanisms underlying these interactions remain unclear. To address this, we dissect the interplay between NHA9 and individual loop extrusion factors using in situ Hi-C, CUT&RUN, RNA-seq, and Auxin-inducible degradation of CTCF or RAD21. CTCF was found to be dispensable for NHA9 loop formation, although CTCF binding constrained a subset of loops that emerged only upon CTCF depletion. In contrast, cohesin played a distance-dependent role where short-range NHA9 loops formed independently of RAD21, while long-range loops were strongly cohesin-dependent. Despite this requirement, RAD21 showed minimal enrichment at NHA9 loop anchors, indicating that NHA9 does not function as a canonical cohesin barrier. Instead, these findings support a non-canonical model in which cohesin transiently facilitates interactions between distal NHA9-bound loci, which are subsequently stabilized through NHA9 phase separation. Together, this work reveals a distinct mechanism of oncogenic chromatin looping in which NUP98-HOXA9 cooperates with canonical loop extrusion machinery to reprogram genome architecture in AML.

Molecular Biology↗

bioRxiv2026

A quantitative approach to species occupancy across communities: the co-occurrence-occupancy curve

Species tolerating the same environmental conditions can potentially colonize and thrive in the same habitats and eco-regions. Are any pair of those species equally probable to co-occur in the same community? Can we quantify the propensity of two species to co-occur together? Here, we focus on a simple but largely overlooked community-level pattern: the co-occurrence-occupancy curve, which relates the tendency of species to co-occur with others to their total occupancy across sites. We first define this empirical curve and then derive its expected shape under a random null model that assumes site equivalence and species independence. Building on these results, we introduce the Species Association Index (SAI), an occupancy-standardized measure that quantifies the tendency of a species to associate with others independently of its overall frequency of occurrence. The SAI enables meaningful comparisons among species with contrasting occupancies and provides a transparent benchmark against which departures from neutrality can be assessed. We illustrate the approach using two contrasting systems--tropical rain forest trees on Barro Colorado Island and organisms from Mediterranean rocky shores--highlighting both the generality of the co-occurrence-occupancy framework and its limitations.

ecology↗

bioRxiv2026

Trait dimensionality in experimental and natural ecological communities

Classical niche theory predicts that species with more similar traits experience stronger competition, and thus, trait dimensionality, here defined as the number of independent traits per species in a community, plays a critical role in coexistence. Despite this, current studies often assume that communities are structured by only a few key traits. Here, we leveraged a theoretical framework that integrates phylogenetic information with repeated instances of community assembly to estimate the number of ecologically relevant traits required to support observed species richness in experimental and natural plant communities. We found that the inferred trait dimensionality is surprisingly high, often exceeding species richness, suggesting that many traits contribute to coexistence. Furthermore, we explored drivers of grassland trait dimensionality, and it depends in complex ways on area, species pool size, and latitude. Our findings indicate that local coexistence may rely on a larger number of traits than previously assumed, challenging low-dimensional trait-based views of community structure.

ecology↗

bioRxiv2025

The structure of pairwise competition is responsible for sudden regime shifts in a microbe-plasmid model

Plasmids play a crucial role in bacterial communities by facilitating the horizontal transfer of genetic material, particularly genes that confer resistance to different stressor agents. In this work, we introduce a microbe-plasmid model to study the conditions under which a plasmid-carrying bacterial strain can invade its corresponding plasmid-free counterpart, as well as those under which it can be eradicated from the population through potential intervention strategies. We reveal the variety of dynamic regimes of the model depending on the parameter values. In particular, we show that a heterogeneous structure of the competition between the two strains drives the possibility of coexistence of stationary states (i.e. bistability) which creates conditions for sudden regime shifts and hysteresis. We explore the implications of our results for the potential eradication of plasmid-mediated antibiotic resistance.

ecology↗

bioRxiv2025

RAS-PI3K Pathway in CAFs Shapes Physicochemical Properties of Tumor ECM and restrains Tumor progression

Cancer-associated fibroblasts display extensive functional plasticity, yet the signaling mechanisms that stabilize distinct CAF states remain poorly understood. Here, we identify stromal RAS-PI3K signaling as a key regulator of myofibroblastic CAF identity and matrix competence in lung cancer. Genetic disruption of the RAS-PI3K interaction in fibroblasts preserved upstream responsiveness to activating cues but impaired cytoskeletal remodeling, contractile execution and acquisition of a matrix-remodeling CAF program. As a result, RAS-PI3K-deficient CAFs generated extracellular matrices with defective collagen and fibronectin organization, reduced stiffness, altered microstructural properties and broad compositional remodeling of the matrisome, including changes in ECM glycoproteins and glycosylation-associated enzymes. These altered matrices failed to efficiently provide directional, adhesive and proliferative cues to tumor cells, attenuated EMT-associated programs and increased sensitivity to cisplatin plus pemetrexed. In vivo, fibroblast-specific RAS-PI3K disruption reduced tumor burden, decreased tumor cell proliferation, prolonged survival and improved chemotherapy response. Loss of RAS-PI3K signaling did not simply suppress CAF activation, but redirected CAFs toward a STAT3/NF-{kappa}B-linked immunomodulatory state associated with IL6, CXCL12 and PDGFR induction. Functionally, this altered stromal state promoted iNOS-associated macrophage features and was accompanied in vivo by reduced macrophage accumulation and increased CD8 T cell infiltration. These findings establish RAS-PI3K signaling as a stromal state-control mechanism that couples myofibroblastic matrix competence to tumor-supportive microenvironmental function while restraining alternative immunomodulatory CAF programs.

cancer biology↗

bioRxiv2024

Association analyses reveal both anthropic and environmental selective events during eggplant domestication

Eggplant (Solanum melongena) is one of the four most important Solanaceous crops, widely cultivated and consumed in Asia, the Mediterranean basin, and Southeast Europe. We studied the Genome-wide association (GWA) of historical genebank phenotypic data on a genotyped worldwide collection of 3,449 eggplant accessions. Overall, 334 significant associations for key agronomic traits were detected. Significant correlations were obtained between different types of phenotypic data, some of which were not obvious, such as between fruit size/yield and fruit color components, suggesting simultaneous anthropic selection for genetically unrelated traits. Anthropic selection of traits like leaf prickles, fruit color, and yield, acted on distinct genomic regions in the two domestication centers (India and Southeast Asia), further confirming the multiple domestication of eggplant. To discriminate anthropic from environmental selection in domestication centers, we conducted a Genotype-Environment Association (GEA) on a subset of georeferenced accessions from the Indian subcontinent. The population structure in this area revealed four genetic clusters, corresponding to a latitudinal gradient, and environmental factors explained 31% of the population structure when the effect of spatial distances was removed. GEA and outlier association (OA) identified 305 candidate regions under environmental selection, containing genes for abiotic stress responses, plant development, and flowering transition. Finally, in the Indian domestication center anthropic and environmental selection acted largely independently, and on different genomic regions. These data allow a better understanding of the different effects of environmental and anthropic selection during domestication of a crop, and the different world regions where some traits were initially selected by humans.

genomics↗

bioRxiv2024

Present and future suitability of invasive and urban vectors through an environmentally-driven Mosquito Reproduction Number

1Temperature and water availability significantly influence mosquito population dynamics. Weve devised a method, integrating experimental data with insights from mosquito and thermal biology, to calculate the basic reproduction number (RM) for urban mosquito species, Aedes albopictus and Aedes aegypti. RM represents the number of female mosquitoes produced by one female during her lifespan, indicating suitability for growth. Environmental conditions, including temperature, rainfall and human density influence RM by altering key mosquito life cycle traits. Validation using data from Spain and Europe confirms the approachs reliability. Our analysis suggests that temperature increases may not uniformly benefit Ae. albopictus proliferation but could boost Ae. aegypti expansion. We suggest using vector RM maps, leveraging climate and environmental data, to predict areas susceptible to invasive mosquito population growth. These maps aid in resource allocation for intervention strategies, supporting effective vector surveillance and management efforts.

ecology↗

bioRxiv2024

Convergent evolution of plant prickles is drivenby repeated gene co-option over deep time

An enduring question in evolutionary biology concerns the degree to which episodes of convergent trait evolution depend on the same genetic programs, particularly over long timescales. Here we genetically dissected repeated origins and losses of prickles, sharp epidermal projections, that convergently evolved in numerous plant lineages. Mutations in a cytokinin hormone biosynthetic gene caused at least 16 independent losses of prickles in eggplants and wild relatives in the genus Solanum. Strikingly, homologs promote prickle formation across angiosperms that collectively diverged over 150 million years ago. By developing new Solanum genetic systems, we leveraged this discovery to eliminate prickles in a wild species and an indigenously foraged berry. Our findings implicate a shared hormone-activation genetic program underlying evolutionarily widespread and recurrent instances of plant morphological innovation.

evolutionary biology↗

bioRxiv2024

Translational T-box riboswitches bind tRNA by modulating conformational flexibility

T-box riboswitches, paradigmatic non-coding RNA elements involved in genetic regulation in most Gram-positive bacteria, are adept at monitoring amino acid metabolism through direct interactions with specific tRNAs. T-box riboswitches assess tRNA aminoacylation status, subsequently regulating the transcription or translation of downstream genes involved in amino acid metabolism. Here we present single-molecule FRET studies of the Mycobacterium tuberculosis IleS T-box riboswitch, a model of T-box translational regulation. The data supports a two-step binding model where the tRNA anticodon is recognized first, followed by interactions with the NCCA sequence. Specifically, after anticodon recognition, tRNA in the partially bound state can transiently dock into the discriminator domain, resembling the fully bound state, even in the absence of the tRNA NCCA-discriminator interactions. Establishment of the NCCA-discriminator interactions significantly stabilizes the fully bound state. Collectively, the data suggests higher conformational flexibility in translation-regulating T-box riboswitches, compared to transcription-regulating ones, and supports a conformational selection model for NCCA recognition. Furthermore, it was found that the conserved RAG sequence is pivotal in maintaining specific interactions with the tRNA NCCA sequence by preventing sampling of an aberrant conformational state, while Stem IIA/B-linker interactions impact the conformational dynamics and the stability of both the partially bound and fully bound states. The present study provides a critical kinetic basis for how specific sequences and structural elements in T-box riboswitches enable the binding efficiency and specificity required to achieve gene regulation.

biophysics↗

bioRxiv2023

Andes virus genome mutations that are likely associated with animal-model attenuation and human person-to-person transmission

STRUCTURED ABSTRACTO_ST_ABSAbstractC_ST_ABSWe performed whole-genome sequencing with bait-enrichment techniques to analyze Andes virus (ANDV), a cause of human hantavirus pulmonary syndrome. We used cryopreserved lung tissues from a naturally infected long-tailed colilargo; early, intermediate, and late cell-culture passages of an ANDV isolate from that animal; and lung tissues from golden hamsters experimentally exposed to that ANDV isolate. The resulting complete genome sequences were subjected to detailed comparative genomic analysis against American orthohantaviruses. We identified four amino-acid substitutions related to cell-culture adaptation that resulted in attenuation of ANDV in the typically lethal golden hamster animal model of hantavirus pulmonary syndrome. Mutations in the ANDV nucleocapsid protein, glycoprotein, and small nonstructural protein open reading frames correlated with mutations typical for ANDV strains associated with increased pathogenesis in the small animal model. Finally, we identified three amino-acid substitutions, two in the small nonstructural protein and one in the glycoprotein, that were only present in the clade of viruses associated with person-to-person efficient transmission. Our results indicate that there are virulence-associated and transmission-associated single-nucleotide polymorphisms that could be used to predict strain-specific ANDV virulence and/or transmissibility. ImportanceSeveral orthohantaviruses cause the zoonotic disease hantavirus pulmonary syndrome (HPS) in the Americas. Among them, HPS caused by Andes virus (ANDV) is of great public-health concern because it is associated with the highest case-fatality rate (up to 50%). ANDV is also the only orthohantavirus associated with relatively robust evidence of person-to-person transmission. This work reveals nucleotide changes in the ANDV genome that are associated with virulence attenuation in an animal model and increased transmissibility in humans. These findings may pave the way to early severity predictions in future ANDV-caused HPS outbreaks.

microbiology↗

bioRxiv2022

Jaccard dissimilarity in stochastic community models based on the species-independence assumption

A fundamental problem in ecology is understanding the causes of change in species composition among sites (i.e. beta diversity). At present it is unclear how spatial heterogeneity in species occupancy across sites shapes these patterns. To address this question, we develop probabilistic models that consider two spatial or temporal sites, where presence probabilities vary both among species and between the sites. We derive analytical and approximate formulae for the expectation of pairwise beta-diversity. Using a novel graphical tool, Stochastic Incidence Plots (SIPs), which depict the presence probabilities in two sites across species labels, we develop a means to conceptualize the heterogeneity in presence probabilities: the steepness or unevenness of SIPs reflects species-level heterogeneity, while the degree of overlap between SIPs indicates site-level heterogeneity. Utilizing SIPs and a combinatorial approach in a two-species scenario, we demonstrate that beta-diversity is lower when SIPs are parallel compared to when they are anti-parallel. We also find that this prediction is testable with the well-known checkerboard pattern in incidence matrices. Finally, we applied the method to the species distribution models for five woodpecker species in Switzerland, showing that their spatial distributions will change significantly in the future. Overall, this work improves our understanding of how pairwise beta-diversity responds to occupancy heterogeneity.

ecology↗

bioRxiv2022

Mutations in the SmAPRR2 transcription factor suppressing chlorophyll pigmentation in the eggplant fruit peel are key drivers of a diversified colour palette

Understanding the mechanisms by which chlorophylls are synthesized in the eggplant (Solanum melongena) fruit peel is of great relevance for eggplant breeding. A multi-parent advanced generation inter-cross (MAGIC) population and a germplasm collection have been screened for green pigmentation in the fruit peel and used to identify candidate genes for this trait. A genome-wide association study (GWAS) performed with 420 MAGIC individuals revealed a major association on chromosome 8 close to a gene similar to APRR2. Two variants in SmAPRR2, predicted as having a high impact effect, were associated with the absence of fruit chlorophyll pigmentation in the MAGIC population, and a large deletion of 5.27 kb was found in two reference genomes of accessions without chlorophyll in the fruit peel. The validation of the candidate gene SmAPRR2 was performed by its sequencing in a set of MAGIC individuals and through its de novo assembly in 277 accessions from the G2P-SOL eggplant core collection. Two additional mutations in SmAPRR2 associated with the lack of chlorophyll were identified in the core collection set. The phylogenetic analysis of APRR2 reveals orthology within Solanaceae and suggests that specialization of APRR2-like genes occurred independently in Cucurbitaceae and Solanaceae. A strong geographical differentiation was observed in the frequency of predominant mutations in SmAPRR2, resulting in a lack of fruit chlorophyll pigmentation and suggesting that this phenotype may have arisen and been selected independently several times. This study represents the first identification of a major gene for fruit chlorophyll pigmentation in the eggplant fruit.

genetics↗

bioRxiv2022

The implicit assumptions of classic functional responses and their multi-species extensions

Functional responses are central to describe consumer-resource interactions. Defined as the per capita average feeding rate of consumers, since Hollings seminal papers, they have been widely used in ecology. Hollings central observation was that they often saturate as resource density increases. If the interference between consumers is strong, they also decrease with consumer density. Here we emphasize the stochastic nature of the individual feeding processes and the associated probability distributions of the different behavioral types and show how they control population-averaged feeding rates. We do so by revisiting a classic approach based on the formulation of feeding interactions in terms of individual-based reaction schemes. We highlight the common assumptions underlying the different functional forms and discover a new predator-dependent functional response that should be considered the natural extension of the Holling type II functional response when consumers interference is considered. Our work has clear implications, on the one hand, for both model selection and parameter inference from feeding experiments, and, on the other, for the use of multi-species extensions of these functional responses in population-level food-web dynamic models.

ecology↗

bioRxiv2022

Wild common crossbills produce redder body feathers when their wings are clipped

The animal signaling theory posits that conspicuous colorations exhibited by many animals have evolved as reliable signals of individual quality. Red carotenoid-based ornaments may depend on enzymatic transformations (oxidation) of dietary yellow carotenoids, which could occur in the inner mitochondrial membrane (IMM). Thus, carotenoid ketolation and cell respiration could share the same biochemical pathways. Accordingly, the level of trait expression (redness) would directly reveal the efficiency of individuals metabolism and hence, the bearer quality in an unfalsifiable way. Different avian studies have described that the flying effort may induce oxidative stress. A redox metabolism modified during the flight could thus influence the carotenoid conversion rate and, ultimately, animal coloration. Here, we aimed to infer the link between red carotenoid-based ornament expression and flight metabolism by increasing flying effort in wild male common crossbills Loxia curvirostra (Linnaeus). In this order, 295 adult males were captured during winter in an Iberian population. Half of the birds were experimentally handicapped through wing feather clipping to increase their flying effort, the other half being used as a control group. The rump feathers were also plucked in all the birds to stimulate plumage regrown of a small surface during a short time-lapse. Thirty-four birds with fully grown rump feathers could be recaptured in the subsequent weeks. Among them, male crossbills with experimentally impaired flying capacity showed redder rump feathers than controls. This result would support the hypothesis that the flying metabolism influences the redox enzymatic reactions required for converting yellow dietary carotenoids to red ketocarotenoids. Summary statementCarotenoid-based colorations may depend on pigment enzymatic transformations linked to mitochondrial function. The flight metabolism could influence this. Here, common crossbills with clipped wings produced redder feathers than controls.

evolutionary biology↗

bioRxiv2021

Emerging Hantaviruses in Central Argentina: first case of Hantavirus Pulmonary Syndrome caused by Alto Paraguay Virus and a novel orthohantavirus in Scapteromys aquaticus rodent.

Orthohantaviruses are emerging rodent-borne pathogens that cause Hantavirus Pulmonary Syndrome in humans. They have a wide range of rodent reservoir hosts and are transmitted to humans through aerosolized viral particles generated by the excretions of infected individuals. Since the first description of HPS in Argentina, new hantaviruses have been reported throughout the country, most of which are pathogenic to humans. We present here the first HPS case infected with Alto Paraguay virus reported in Argentina. Until now, Alto Paraguay virus was considered a non-pathogenic orthohantavirus since it was identified in a rodent, Hollochilus chacarius. In addition to this, with the goal of identifying potential hantavirus host species in the province of Santa Fe, we finally describe a novel orthohantavirus found in the native rodent Scapteromys aquaticus, which differed from other hantaviruses described in the country so far. Our findings implicate an epidemiological warning regarding these new orthohantaviruses circulating in Central Argentina as well as new rodent species that must be considered as hosts from now on.

pathology↗

bioRxiv2020

Competitive dominance in plant communities: Modeling approaches and theoretical predictions

Understanding the main determinants of species coexistence across space and time is a central question in ecology. However, ecologists still know little about the scales and conditions at which biotic interactions matter and how these interact with the environment to structure species assemblages. Here we use recent theory developments to analyze plant distribution and trait data across Europe and find that plant height clustering is related to both evapotranspiration and gross primary productivity. This clustering is a signal of interspecies competition between plants, which is most evident in mid-latitude ecoregions, where conditions for growth (reflected in actual evapotranspiration rates and gross primary productivities) are optimal. Away from this optimum, climate severity likely overrides the effect of competition, or other interactions become increasingly important. Our approach bridges the gap between species-rich competition theories and large-scale species distribution data analysis.

ecology↗

bioRxiv2019

A mitochondria-targeted antioxidant affects the carotenoid-based plumage of red crossbills

The mechanisms involved in the production of red carotenoid-based ornaments in vertebrates are still poorly understood. Those colours generated by red carotenoids often depend on the enzymatic production (ketolation) of these pigments from dietary yellow carotenoids. Recently, it has been proposed that this conversion takes place at the inner mitochondrial membrane (IMM). This implies that carotenoid ketolation and cell respiration could share the same biochemical pathways. Such a link would favour the evolution of red ketocarotenoid-based ornaments as reliable indices of individual quality under a sexual selection scenario. We exposed captive male red crossbills (Loxia curvirostra Linnaeus) to two different synthetic antioxidants designed to penetrate into the IMM: a synthetic ubiquinone (mitoQ) and a superoxide dismutase mimetic (mitoTEMPO). MitoQ decreased the blood levels of substrate yellow carotenoids and tocopherol. This could be attributed to the characteristics of the mitoQ molecule, which can distort the IMM structure, increasing free radical (superoxide) production and, potentially, antioxidant consumption. Contrarily, mitoTEMPO-treated birds increased the plasma levels of the second most abundant red ketocarotenoid of red crossbills (i.e. canthaxanthin). MitoTEMPO also increased plumage redness and total ketocarotenoid concentration in feathers among those birds exhibiting a redder plumage at the beginning of the study, rising the plasma values of the main red pigment (3-hydroxyechinenone) in paler birds. The results as a whole support the involvement of the mitochondrial antioxidant machinery in carotenoid biotransformation. The fact that the initial plumage redness determined the effect of mitoTEMPO suggests that the mitochondrial-based mechanism is intimately linked to individual quality. Summary statementAntioxidants designed to penetrate the mitochondrial membrane increased avian plumage redness but depending on pre-existing colouration. This supports mitochondrial involvement in the evolution of carotenoid-based ornaments as reliable quality signals.

evolutionary biology↗