Biology subjects

Vargas, P.

Publications and source records attributed to Vargas, P..

16 recordsLinked to original sources

bioRxiv2025

Torque-based immune cell chemotaxis in complex environments

Directed migration in chemical gradients is crucial to the immune response, yet how immune cells navigate complex tissues remains incompletely understood. Using in vitro migration assays and theoretical modeling, we uncover distinct chemotactic strategies in two key immune cell types: neutrophils and dendritic cells (DCs). DCs actively steer toward chemokine gradients via a deterministic torque-like reorientation, while neutrophils bias movement by modulating angular noise and speed. A quantitative Fokker-Planck framework decomposes these behaviors into deterministic and stochastic components. Cytoskeletal perturbations show that microtubules enable torque-based navigation in DCs in collagen gels, whereas actomyosin contractility is required for noise modulation employed by neutrophils and DCs in 2D confined migration assays. Despite both achieving directed migration, the two strategies result in opposing macroscopic outcomes: torque-driven cells minimize dispersion, while noise-biased migration enhances population spread. These results reveal distinct navigation aligned with immune function and demonstrate that immune cell chemotaxis is tuned by cytoskeletal architecture and environmental context.

biophysics↗

bioRxiv2025

Trait-dependent diversification and spatio-ecological limits drive angiosperm diversity unevenness across the Canary Islands archipelago

Island biotas often show highly uneven species richness among lineages, influenced by clade age, diversification rates, and/or spatio-ecological limits. However, disentangling these drivers has been challenging due to the lack of comprehensive datasets across multiple lineages in the same geographical arena. The flora of the Canary Islands includes hundreds of plant lineages with contrasting species richness and harbours the highest number of species that evolved their woodiness in-situ ("insular woodiness"). Here, we present a phylogenomic reconstruction for Canary Island angiosperms and show that diversity unevenness in the flora is not driven by lineage age but by trait-dependent diversification and spatio-ecological limits. Our phylogenomic dataset, based on 1,244 newly generated and 501 published DNA sequences for 669 Canary Island species and 771 closely related mainland taxa, allows us to simultaneously study 435 plant lineages ([~]50% of total). Applying dynamic stochastic modelling, we find the flora is shaped by high extinction and colonisation rates, maintaining a macroevolutionary equilibrium. Additionally, insular woody lineages exhibit higher diversification rates than the remaining flora. Our results suggest the uneven diversity of a highly dynamic insular region can be explained by the interaction of trait evolution and ecological constraints, providing insights into island biodiversity dynamics.

evolutionary biology↗

bioRxiv2025

Super-resolved live imaging of thick biological samples with 3D Random Illumination Microscopy (3D-RIM)

Super-resolved volume imaging of thick, live specimens is greatly hampered by sample induced aberrations and out-of-focus fluorescence. In this work, using a combination of speckled illuminations, remote focusing, three-dimensional photon reassignement and variance processing, we obtained volume images with super-resolution (110 nm transverse, 270 nm axial) on thin samples and maintained a high contrast and high resolution level throughout tens of microns of highly aberrant tissues and up to hundreds of microns in collagen scaffolds.

bioengineering↗

bioRxiv2024

Genomic stability in the Galapagos Scalesia adaptive radiation: Consistent transposable element accumulation despite hybridization and ecological niche shifts

Transposable elements (TEs) have been hypothesized to play a pivotal role in driving diversification by facilitating the emergence of novel phenotypes and the accumulation of divergence between species. Hybridization and adaptation to novel niches are hypothesized to influence TE accumulation in genomes by disrupting genomic regulation, including the suppression of TE replication. The rapid speciation and ecological diversification characteristic of adaptive radiations offer a unique opportunity to examine the link between TE accumulation and speciation, diversification, hybridization and adaptation. Here, focusing on all 15 species of the genus Scalesia (Asteraceae), a radiation endemic to the Galapagos Islands, we test whether hybridization or shifts in ecological niche are associated with changes in TE accumulation in genomes. Our analyses reveal little to no variation in TE accumulation among Scalesia species nor its hybrid populations. Shifts in ecological niches, linked to climatic variation, did not result in discernible changes in TE accumulation, a surprising finding given the anticipated selective pressure imposed by aridity, a factor often linked to genome size reduction. We found no distinct patterns in the temporal accumulation of TEs, and no effects at the class or superfamily level. Our findings challenge the assertion that TEs have directly driven diversification, speciation and local adaptation. Instead, we suggest that TEs may simply be along for the ride, rather than actively contributing to plant diversification.

evolutionary biology↗

bioRxiv2023

Phylogenetics and phylogeography of Euphorbia canariensis reveal an extreme Canarian-Asian disjunction and limited inter-island colonization

Euphorbia canariensis is an iconic endemic species of the Canary Islands and one of the most characteristic species of lowland xerophytic communities known, in Spanish, as cardonal-tabaibal. This species is widely distributed in the archipelago, which contrasts with the theoretically low dispersal abilities suggested by its unspecialized diasporas. Furthermore, the phylogenetic relationships of this species are unclear, although it is thought to be related to the Indian E. epiphylloides and not to other cactus-like Euphorbia of the Canary Islands (E. handiensis) and Africa. Here we aimed to reconstruct the evolutionary history of E. canariensis at two levels: (i) a phylogenetic approach aimed at unravelling relationships of this species and large-scale biogeographic patterns, and (ii) a phylogeographic approach focused on the history of colonization between islands of the Canarian archipelago in relation to habitat availability for this species through time. Based on previous phylogenetic studies of Euphorbia, we sequenced the ITS region for E. canariensis and several potentially related species to build a phylogenetic framework. We also sequenced two cpDNA regions for 92 individuals from 29 populations of E. canariensis representing its distribution range. We estimated the number of inter-island colonization events using PAICE, a recently developed method that includes a sampling effort correction. Additionally, we used species distribution modelling (SDM) to project current habitat availability for E. canariensis to past periods. Phylogenetic results supported the Canarian E. canariensis as closely related to the Southeast Asian E. epiphylloides and E. sessiliflora. In the Canarian archipelago, E. canariensis displayed a surprising west-to-east colonization pattern. The estimated number of inter-island colonization events was c. 20 - 50, and SDM suggested an increase in habitat availability in recent times. In summary, in this study we confirmed an extreme biogeographic disjunction between Macaronesia and Southeast Asia, described only for a small number of plant species, and estimated relatively low dispersal capabilities for E. canariensis, with a west-to-east colonization pattern in the Canary Islands. HighlightsO_LIThe Canarian Euphorbia canariensis is sister to Southeast Asian species. C_LIO_LIThis lineage shows one of the widest disjunctions affecting Macaronesian plants. C_LIO_LIThe lack of intermediate relatives could be the result of extinction events. C_LIO_LIE. canariensis displays low colonization ability in the Canarian archipelago. C_LI

evolutionary biology↗

bioRxiv2022

The genomic basis of the plant island syndrome in Darwin's giant daisies

Oceanic archipelagos comprise multiple disparate environments over small geographic areas and are isolated from other biotas. These conditions have led to some of the most spectacular adaptive radiations, which have been key to our understanding of evolution, and offer a unique chance to characterise the genomic basis underlying rapid and pronounced phenotypic changes. Repeated patterns of evolutionary change in plants on oceanic archipelagos, i.e. the plant island syndrome, include changes in leaf morphology, acquisition of perennial life-style, and change of ploidy. Here, we describe the genome of the critically endangered and Galapagos endemic Scalesia atractyloides Arnot., obtaining a chromosome-resolved 3.2-Gbp assembly with 43,093 candidate gene models. Using a combination of fossil transposable elements, k-mer spectra analyses and orthologue assignment, we identify the two ancestral subgenomes and date their divergence and the polyploidization event, concluding that the ancestor of all Scalesia species on the Galapagos was an allotetraploid. There are a comparable number of genes and transposable elements across the two subgenomes, and while their synteny has been mostly conserved, we find multiple inversions that may have facilitated adaptation. We identify clear signatures of selection across genes associated with vascular development, life-growth, adaptation to salinity and changes in flowering time, thus finding compelling evidence for a genomic basis of island syndrome in Darwins giant daisy radiation. This work advances understanding of factors influencing subgenome divergence in polyploid genomes, and characterizes the quick and pronounced genomic changes in a specular and diverse radiation of an iconic island plant radiation.

evolutionary biology↗

bioRxiv2021

Actin dynamics regulation by TTC7A/PI4KIIIα axis limits DNA damage and cell death during leukocyte migration

The actin cytoskeleton has a crucial role in the maintenance of the immune homeostasis by controlling various cell processes, including cell migration. Mutations in the TTC7A gene have been described as the cause of a primary immunodeficiency associated to different degrees of gut involvement and alterations in the actin cytoskeleton dynamics. Although several cellular functions have been associated with TTC7A, the role of the protein in the maintenance of the immune homeostasis is still poorly understood. Here we leverage microfabricated devices to investigate the impact of TTC7A deficiency in leukocytes migration at the single cell level. We show that TTC7A-deficient leukocytes exhibit an altered cell migration and reduced capacity to deform through narrow gaps. Mechanistically, TTC7A-deficient phenotype resulted from impaired phosphoinositides signaling, leading to the downregulation of the PI3K/AKT/RHOA regulatory axis and imbalanced actin cytoskeleton dynamic. This resulted in impaired cell motility, accumulation of DNA damage and increased cell death during chemotaxis in dense 3D gels. Our results highlight a novel role of TTC7A as a critical regulator of leukocyte migration. Impairment of this cellular function is likely to contribute to pathophysiology underlying progressive immunodeficiency in patients.

immunology↗

bioRxiv2020

Pinching the cortex of live cells reveals thickness instabilities caused by Myosin II motors

The cell cortex is a contractile actin meshwork, which determines cell shape and is essential for cell mechanics, migration and division. Because the cortical thickness is below optical resolution, it has been generally considered as a thin uniform two-dimensional layer. Using two mutually attracted magnetic beads, one inside the cell and the other in the extracellular medium, we pinch the cortex of dendritic cells and provide an accurate and time resolved measure of its thickness. Our observations draw a new picture of the cell cortex as a highly dynamic layer, harboring large fluctuations in its third dimension due to actomyosin contractility. We propose that the cortex dynamics might be responsible for the fast shape changing capacity of highly contractile cells that use amoeboid-like migration.

biophysics↗

bioRxiv2020

HIF2α is a Direct Regulator of Neutrophil Motility

Orchestrated recruitment of neutrophils to inflamed tissue is essential during initiation of inflammation. Inflamed areas are usually hypoxic, and adaptation to reduced oxygen pressure is typically mediated by hypoxia pathway proteins. However, it is still unclear how these factors influence the migration of neutrophils to and at the site of inflammation either during their transmigration through the blood-endothelial cell barrier, or their motility in the interstitial space. Here, we reveal that activation of the Hypoxia Inducible Factor-2 (HIF2) due to deficiency of HIF-prolyl hydroxylase domain protein-2 (PHD2) boosts neutrophil migration specifically through highly confined microenvironments. In vivo, the increased migratory capacity of PHD2-deficient neutrophils resulted in massive tissue accumulation in models of acute local inflammation. Using systematic RNAseq analyses and mechanistic approaches, we identified RhoA, a cytoskeleton organizer, as the central downstream factor that mediates HIF2-dependent neutrophil motility. Thus, we propose that the here identified novel PHD2-HIF2-RhoA axis is vital to the initial stages of inflammation as it promotes neutrophil movement through highly confined tissue landscapes.

immunology↗

bioRxiv2020

Genomic evidence for recurrent genetic admixture during domestication mediterranean olive trees (Olea europaea).

BackgroundThe olive tree (Olea europaea L. subsp. europaea, Oleaceae) has been the most economic perennial crop for Mediterranean countries since its domestication around 6,000 years ago. Two taxonomic varieties are currently recognized: cultivated (var. europaea) and wild (var. sylvestris) trees. To shed light into the recent evolution and domestication of the olive tree, we sequenced the genomes of twelve individuals: ten var. europaea, one var. sylvestris, and one outgroup taxon (subsp. cuspidata). All of them were analysed together with an improved assembly of var. europaea reference genome and the available assembly of var. sylvestris. ResultsOur analyses show that cultivated olives exhibit slightly lower levels of overall genetic diversity than wild forms, and that this can be partially explained by the occurrence of a mild population bottleneck 5000-7000 years ago during the primary domestication period. We also provide the first phylogenetic analysis of genome-wide sequences, which supports a continuous process of domestication of the olive tree. This, together with population structure and introgression analyses highlights genetic admixture with wild populations across the Mediterranean Basin in the course of domestication. ConclusionsAltogether, our results suggest that a primary domestication area in the eastern Mediterranean basin was followed by numerous secondary events across most countries of southern Europe and northern Africa, often involving genetic admixture with genetically rich wild populations, particularly from the western Mediterranean Basin. Based on selection tests and a search for selective sweeps, we found that genes associated with stress response and developmental processes were positively selected in cultivars. However, we did not find evidence that genes involved in fruit size or oil content were under positive selection.

evolutionary biology↗

bioRxiv2019

Plant budding speciation predominant by ecological and geographical differentiation: an ‘evolutionary snapshot’ in Iberodes (Boraginaceae)

O_LITraditional classification of speciation modes has focused on physical barriers to gene flow. While allopatry has been viewed as the most common mechanism of speciation, parapatry and sympatry, both entail speciation in the face of ongoing gene flow and thus both are far more difficult to detect and demonstrate. Iberodes (Boraginaceae, NW Europe) with a small number of recently derived species (five) and contrasting morphological traits, habitats and distribution patterns constitutes an ideal system in which to study drivers of lineage divergence and differentiation. C_LIO_LITo reconstruct the evolutionary history of the genus, we undertook an integrative study entailing: (i) phylogenomics based on restriction-site associated DNA sequencing (RAD-seq), (ii) morphometrics, and (iii) climatic niche modelling. C_LIO_LIKey results revealed a history of repeated progenitor-derivative speciation, manifesting in paraphyletic pattern within Iberodes. Climatic niche analyses, together with the morphometric data and species distributions, suggest that ecological and geographical differentiation have interacted to shape the diversity of allopatric and parapatric distributions observed in Iberodes. C_LIO_LIOur integrative study has enabled to overcome previous barriers to understanding parapatric speciation by demonstrating the recurrence of progenitor-derivative speciation in plants with gene flow and ecological differentiation, explaining observed parapatry and paraphyly. C_LI

evolutionary biology↗

bioRxiv2019

Profilin and formin constitute a pacemaker system for robust actin filament growth

The actin cytoskeleton drives many essential biological processes, from cell morphogenesis to motility. Assembly of functional actin networks requires control over the speed at which actin filaments grow. How this can be achieved at the high and variable levels of soluble actin subunits found in cells is unclear. Here we reconstitute assembly of mammalian, non-muscle actin filaments from physiological concentrations of profilin-actin. We discover that under these conditions, filament growth is limited by profilin dissociating from the filament end and the speed of elongation becomes insensitive to the concentration of soluble subunits. Profilin release can be directly promoted by formin actin polymerases even at saturating profilin-actin concentrations. We demonstrate that mammalian cells indeed operate at the limit to actin filament growth imposed by profilin and formins. Our results reveal how synergy between profilin and formins generates robust filament growth rates that are resilient to changes in the soluble subunit concentration.

biochemistry↗

bioRxiv2018

Glioma cell migration in confined microchannels via a motor-clutch mechanism

Glioma tumor dispersion involves invading cells escaping the tumor bulk and migrating into the healthy brain parenchyma. Here, they encounter linearly aligned track-like tissue structures such as axon bundles and the perivascular space. These environments also contain micrometer-scale pores that impose mechanical confinement on invading cells. To study glioma cell migration in an in vitro system that reproduces some of these features, we used microfluidic devices with 60 m2 cross-sectional area channels that confine cells into one-dimensional (1D) tracks. Individual cell tracking revealed strongly persistent migration at a mean rate of 8.5 {+/-} 0.33 nm s-1. Notably, a 1D computational cell migration simulator predicts migration behaviors of glioma cells without significant adjustment of parameters estimated from previous experiments on two-dimensional (2D) substrates. Pharmacological inhibitors of integrin-mediated adhesions, myosin II activation, or drugs targeting F-actin assembly or microtubule dynamics influence migration consistent with simulations where relevant parameters are changed. These results suggest that cell parameters calibrated to a motor-clutch model on 2D substrates effectively predict 1D confined migration behaviors a priori. Our results outline a method for testing biophysical mechanisms of tumor cell migration in confined spaces and predicting the effects of anti-motility therapy.

biophysics↗

bioRxiv2018

Three-Dimensional Histology of Whole Zebrafish by Sub-Micron Synchrotron X-ray Micro-Tomography

Histological studies providing cellular insights into tissue architecture have been central to biological discovery and remain clinically invaluable today. Extending histology to three dimensions would be transformational for research and diagnostics. However, three-dimensional histology is impractical using current techniques. We have customized sample preparation, synchrotron X-ray tomographic parameters, and three-dimensional image analysis to allow for complete histological phenotyping using whole larval and juvenile zebrafish. The resulting digital zebrafish can be virtually sectioned and visualized in any plane. Whole-animal reconstructions at subcellular resolution also enable computational characterization of the zebrafish nervous system by region-specific detection of cell nuclei and quantitative assessment of individual phenotypic variation. Three-dimensional histological phenotyping has potential use in genetic and chemical screens, and in clinical and toxicological tissue diagnostics.\n\nOne Sentence SummarySynchrotron X-ray micro-tomography can be used to rapidly create 3-dimensional images of fixed and stained specimens without sectioning, enabling computational histological phenotyping at cellular resolution.

pathology↗

bioRxiv2017

Phylogenomics of the olive tree (Olea europaea) disentangles ancient allo- and autopolyploidizations in Lamiales.

BackgroundPolyploidization is one of the major evolutionary processes that shape eukaryotic genomes, being particularly common in plants. Polyploids can arise through direct genome doubling within a species (autopolyploidization) or through the merging of genomes from distinct species after hybridization (allopolyploidization). The relative contribution of either mechanism in plant evolution is debated. Here we used phylogenomics to dissect the tempo and mode of duplications in the genome of the olive tree (Olea europaea), one of the first domesticated Mediterranean fruit trees.\n\nResultsOur results depict a complex scenario involving at least three past polyploidization events, of which two -at the bases of the family Oleaceae and the tribe Oleeae, respectively- are likely to be the result of ancient allopolyploidization. A more recent polyploidization involves specifically the olive tree and relatives.\n\nConclusionOur results show the power of phylogenomics to distinguish between allo- and auto- polyplodization events and clarify the conundrum of past duplications in the olive tree lineage.

evolutionary biology↗

bioRxiv2017

Oral diseases: a 14-year experience of a Chilean institution with a systematic review from eight countries

BACKGROUNDRetrospective studies to assess the distribution of oral diseases (ODs) are helpful in estimating the prevalence of oral diagnoses in the population, and thus help in preventive and curative services. Prevalence and frequency data for ODs are available from many countries, but information from Chile is scarce.\n\nMETHODSThis study investigated the frequency of ODs in a Chilean population. For this, we included all patients treated at the University of Talca (UTALCA, Chile) between 2001 and 2014. Patient characteristics were retrieved from medical files. To contextualize our results, we conducted a systematic review (SystRev) using Publish or Perish software (PoP), Google Scholar and MEDLINE/PubMed.\n\nRESULTSOne hundred sixty-six ODs were diagnosed, and the most prevalent groups were soft tissue tumours, epithelial pathology and salivary gland pathology. Individually, irritation fibroma, oral lichen planus (OLP) and mucocele were the most common diagnoses. ODs frequently affected unspecified parts of the mouth (including cheek, vestibule and retromolar area), gum, lips, tongue and palate. In the SystRev, the more studied diagnoses were leukoplakia, OLP and recurrent aphthous stomatitis; prevalent lesions included Fordyces spots, recurrent aphthous stomatitis and fissured tongue. Chilean patients and SistRev shared almost all ODs.\n\nCONCLUSIONThe results reflect ODs diagnosed in a specialized service of oral pathology and medicine in Chile and will allow the establishment of preventive/curative policies, adequate health services and dentistry curriculum.

pathology↗