Biology subjects

Diaz, F.

Publications and source records attributed to Diaz, F..

At least 19 recordsLinked to original sources

bioRxiv2026

Mechanophenotype of synovial fibroblasts correlates with patients' pathotypes and treatment response in Rheumatoid Arthritis

The mechanical features of synovial fibroblasts may encode clinically relevant information for the management of rheumatoid arthritis. Indeed, it remains poorly understood the links between cellular and microenvironment mechanics with patient stratification and therapeutic response. Here we show that combining organotypic synovial cultures with multimodal mechanophenotyping and transcriptomics identifies distinct ''soft'' and ''stiff'' fibroblast states. Healthy and rheumatoid arthritis fibroblasts were cultured in two or three dimensions (organotypic cell cultures), alone or with endothelial cells, and characterized by high-throughput nanoindentation, picobalance measurements, digital holographic microscopy, Brillouin microscopy and RNA sequencing. Three-dimensional culture reduced single-cell Young's modulus and total mass while increasing dry-mass surface density; endothelial co-culture increased fibroblast stiffness and the longitudinal modulus of intact organotypic cultures. Stiffness-based grouping revealed transcriptional programmes related to extracellular-matrix remodelling, cytoskeletal contractility, and TGF-beta, WNT, and Hippo signalling. Mapping these signatures to publicly available rheumatoid arthritis clinical transcriptomic datasets associated the ''stiff'' state with fibrotic and myeloid-fibrotic pathotypes and treatment-refractory programmes, whereas the ''soft'' state aligned with lymphoid pathotypes and rituximab- or tocilizumab-responsive programmes. These findings support mechanophenotype-associated transcriptional signatures as potential biomarkers for rheumatoid arthritis stratification.

biophysics↗

bioRxiv2025

Taxane-Induced Conformational Changes in the Microtubule Lattice Activate GEF-H1-Dependent RhoA Signaling

Taxanes are widely used chemotherapeutic agents that perturb cell division. They also exert effects during interphase, but the underlying mechanisms are poorly understood. Here, we show that taxanes activate RhoA signaling and induce actin remodeling by displacing the RhoA activator GEF-H1 from microtubules. This taxane-induced release of GEF-H1 occurs rapidly, is independent of tubulin post-translational modifications, and can be recapitulated using purified proteins. In vitro reconstitution assays combined with analyses of microtubule structure revealed that microtubule binding by GEF-H1 is inhibited by microtubule-stabilizing agents that expand the microtubule lattice, such as taxanes and GMPCPP, but not by others, including GTP{gamma}S and discodermolide, which stabilize a compacted microtubule lattice. Our findings demonstrate that alterations in microtubule lattice conformation can activate key signaling pathways, offering new insights into the mode of action of taxanes and the possible origins of their side effects.

cell biology↗

bioRxiv2025

Cigarette Smoke and E-Cigarette Aerosol Extracts Induce Myelopoiesis and Suppress Inflammatory Cytokine Production

Tobacco and nicotine use remain the leading preventable drivers of cancer risk, and both direct and secondhand exposure to combustible cigarettes or electronic nicotine devices perturbs immune function and hematopoiesis. Here, we evaluate the impact of e-cigarette vapor and combustible cigarette smoke on in vitro cell inflammatory responses and in vivo long-term hematopoietic differentiation. In cell-based studies, cigarette smoke extract (CSE) and e-cigarette vapor extract (EVE) consistently suppress LPS-induced TNF- secretion across macrophage/monocyte models, including primary mouse and human cells and complementary cell lines, indicating a reproducible immunosuppressive effect on mature myeloid cells. Brief ex vivo exposure to CSE also alters myeloid subset composition and modifies the proliferative behavior of Tet2-knockout cells, suggesting that smoke-related cues can reshape competitive dynamics among mutant and wild-type myeloid progenitors. To assess consequences of smoking behavior in vivo, we used a custom nose-cone inhalation system to deliver controlled exposures to combustible cigarette smoke or e-cigarette aerosol to mice. Chronic exposure increased myeloid proliferation, consistent with smoking behavior inducing premature aging of the hematopoietic stem cell pool. Thus, these studies support a model in which tobacco exposures blunt innate immune responsiveness while simultaneously driving myeloid expansion conditions that accelerate hematopoietic aging.

cancer biology↗

bioRxiv2025

Dissecting structural and functional determinants of microtubule stabilization through guided chemical modulation

Paclitaxel (PTX) is a widely used chemotherapeutic, but its efficacy is limited by peripheral neuropathy, likely due to its structural impact on neuronal microtubules (MTs). To decouple MT stabilization from adverse structural changes, we designed, synthetized and characterized several PTX analogues. Our compound 1b retains PTXs stabilizing activity in vitro and in cells, and the 1b-bound MTs preserve a native-like structure. These facts allowed us to investigate the influence of specific MT structural features on motor proteins behavior and interaction with MT-associated protein Tau. PTX-induced lattice expansion disrupted dynein-mediated retrograde transport and altered kinesin-1 motility. Additionally, PTX reduced Taus initial non-cooperative binding and envelopes growth rate while increasing dwell time and suppressing dynamic binding. In contrast, 1b preserved more physiological Tau dynamics. These findings reveal that MT stabilization and structural modulation can be separated and highlight the functional importance of MT heterogeneity in maintaining neuronal transport and MAP interactions.

molecular biology↗

bioRxiv2023

Can upwelling regions be potential thermal refugia for marine species during climate warming? The case of Mexico

Anthropogenic climate warming will change the thermal habitats of marine species worldwide. Species are expected to migrate to higher latitudes as warming intensifies since behavioral and physiological mechanisms have been adapted to maximize fitness under a specific range of temperatures. However, given the possible intensification of upwelling ecosystems, they may act as potential thermal refugia under climate warming, which could protect the diversity of the marine ecosystems, making them important regions for marine resource management. This research aimed to predict the effects of climate warming on commercial and non-commercial marine species (vertebrate and invertebrates) reported in official Mexican documents (> 300 species) based on a thermal niche characterization with the objective to observe if the upwelling regions can act as potential thermal refugia. For this, we considered Representative Concentration Pathway (6.0 and 8.5) scenarios for the present and the future (2040-2050 and 2090-2100). Current and future patterns of suitability, species distribution, richness, and turnover were calculated via ecological niche models using the minimum volume ellipsoids as an algorithm. The results in this study highlight that beyond migration to higher latitudes, some upwelling regions (not all) could be potentially used as some type of "oasis" by marine species refuging from environmental pressure or zones of higher stability of species. Specifically, the upwelling systems in western Baja California and north of Yucatan may be essential regions for future management in Mexico. Nevertheless, it is important to note that climate change acts on numerous ecosystem features, such as trophic relationships, phenology, and other environmental variables not considered here. Future research could test our hypothesis under more realistic simulations. However, migration toward upwelling regions seems to be the most logical selection from all the available ecosystems as climate refugia for marine species beyond movement to higher latitudes or depths.

ecology↗

bioRxiv2023

Females translate male mRNA transferred during mating

Although RNA is found in the seminal fluid of diverse organisms, it is unknown whether this RNA is functional within females. Here, we develop an experimental proteomic method called VESPA (Variant Enabled SILAC Proteomic Analysis) to test the hypothesis that Drosophila male seminal fluid RNA is translated by females. We find strong evidence for 67 male-derived, female-translated proteins (mdFTPs) in female lower reproductive tracts at six hours postmating, many with predicted functions relevant to reproduction. Gene knockout experiments indicate that genes coding for mdFTPs play diverse roles in postmating interactions, with effects on fertilization efficiency, and the formation and persistence of the insemination reaction mass, a trait hypothesized to be involved in sexual conflict. These findings advance our understanding of reproduction by revealing a novel mechanism of postmating molecular interactions between the sexes that strengthens and extends male influences on reproductive outcomes in previously unrecognized ways. Given the diverse species known to carry RNA in seminal fluid, this discovery has broad significance for understanding molecular mechanisms of cooperation and conflict during reproduction.

evolutionary biology↗

bioRxiv2022

Chromosome-length genome assemblies of cactophilic Drosophila illuminate links between structural and sequence evolution.

A thorough understanding of adaptation and speciation requires model organisms with both a history of ecological and phenotypic study as well as a robust set of genomic resources. For decades, the cactophilic Drosophila species of the southwestern US and northern Mexico have fit this profile, serving as a crucial model system for understanding ecological adaptation, particularly in xeric environments, as well as the evolution of reproductive incompatibilities and speciation. Here, we take a major step towards gaining a complete molecular description of this system by assembling and annotating seven chromosome-length de novo genomes across the three species D. mojavensis, D. arizonae, and D. navojoa. Using this data, we present the most accurate reconstruction of the phylogenetic history of this clade to date. We further demonstrate a relationship between structural evolution and coding evolution both within and between species in this clade, and use this relationship to generate novel hypotheses for adaptation genes. All of our data are presented in a new public database (cactusflybase.arizona.edu), providing one of the most in-depth resources for the analysis of inter- and intraspecific evolutionary genomic data.

genomics↗

bioRxiv2022

European scenarios for future biological invasions

O_LIInvasive alien species are one of the major threats to global biodiversity, ecosystem integrity, natures contribution to people and human health. While scenarios about potential future developments have been available for other global change drivers for quite some time, we largely lack an understanding of how biological invasions might unfold in the future across spatial scales. C_LIO_LIBased on previous work on global invasion scenarios, we developed a workflow to downscale global scenarios to a regional and policy-relevant context. We applied this workflow at the European scale to create four European scenarios of biological invasions until 2050 that consider different environmental, socio-economic and socio-cultural trajectories, namely the European Alien Species Narratives (Eur-ASNs). C_LIO_LIWe compared the Eur-ASNs with their previously published global counterparts (Global-ASNs), assessing changes in 26 scenario variables. This assessment showed a high consistency between global and European scenarios in the logic and assumptions of the scenario variables. However, several discrepancies in scenario variable trends were detected that could be attributed to scale differences. This suggests that the workflow is able to capture scale-dependent differences across scenarios. C_LIO_LIWe also compared the Global- and Eur-ASNs with the widely used Global and European Shared Socioeconomic Pathways (SSPs), a set of scenarios developed in the context of climate change to capture different future socio-economic trends. Our comparison showed considerable divergences in the scenario space occupied by the different scenarios, with overall larger differences between the ASNs and SSPs than across scales (global vs. European) within the scenario initiatives. C_LIO_LIGiven the differences between the ASNs and SSPs, it seems that the SSPs do not adequately capture the scenario space relevant to understanding the complex future of biological invasions. This underlines the importance of developing independent, but complementary, scenarios focused on biological invasions. The downscaling workflow we presented and implemented here provides a tool to develop such scenarios across different regions and contexts. This is a major step towards an improved understanding of all major drivers of global change including biological invasions. C_LI

ecology↗

bioRxiv2022

A scenario-guided strategy for the future management of biological invasions

Future dynamics of biological invasions are highly uncertain because they depend on multiple environmental, societal and socio-economic drivers. We adopted a qualitative scenario approach to explore the future of invasive alien species (IAS) in Europe and created an overall strategy for their management that considers different plausible future developments. The scenarios and strategy were developed during two online workshops with a multidisciplinary team of experts. First, we downscaled four global scenarios of biological invasions to the European level. Second, we developed a management strategy structured into 19 goals that cover a broad array of IAS-related topics (i.e. policy, research, public awareness and biosecurity), and provided solutions for achieving these goals considering the European scenarios. Third, we identified four interrelated recommendations around which any long-term strategy for managing IAS in Europe can be structured: (i) a European biosecurity regime, (ii) a dedicated communication strategy, (iii) data standardization and management tools, and (iv) a monitoring and assessment system. Finally, we identified the feasibility of the IAS management strategy, finding strong differences among the four scenarios. High levels of technological development, public environmental awareness, and effectiveness of IAS policies facilitated the implementation of the overall management strategy. Together, our results indicate that it is time for a new management of biological invasions in Europe based on a more integrative perspective across sectors and countries to be better prepared for future challenges.

ecology↗

bioRxiv2022

Trans-generational physiological condition of embryos is conditioned by maternal thermal stress in Octopus maya

Current anthropogenic global warming generates profound metabolic alterations in marine ectotherm invertebrates capable of leading a wide range of these species to extinction. The most worrying and devastating consequence may be that the effect of thermal stress overpasses the individual generations. To evaluate the transgenerational effect of thermal stress on the cephalopod Octopus maya, this study experimentally tests morphology, respiratory metabolism, antioxidant mechanisms, and oxidative stress indicators of the embryos incubated at two temperatures (24 and 30{degrees}C) produced by females acclimated at 24 and 30{degrees}C. The results demonstrate that, regardless of their incubation temperature, embryos from females acclimated at 30{degrees}C are smaller, show more accelerated development, and higher respiratory rates than those from females acclimated at 24{degrees}C. These embryos confirmed a greater oxidative stress degree, as well as an increased amount of soluble carbonylated proteins and catalase activity as the main enzyme during the activation development stage (even the highest in the embryos incubated at 30{degrees}C). Finally, a collapse of the antioxidant defense system was observed, measured as lower both CAT activity and GSH concentrations. Additionally, soluble carbonylated proteins reduced and GST activity increased in embryos incubated at 30{degrees}C from females maintained at high temperatures in a clear deleterious and transgenerational effect of thermal stress on this octopus species.

physiology↗

bioRxiv2022

Human anelloviruses produced by recombinant expression of synthetic genomes.

Human anelloviruses are acquired universally in infancy, highly prevalent, abundant in blood, and extremely diverse. Their apparent lack of pathogenicity indicates that they are a major component of the commensal human virome. Despite their being extensively intertwined with human biology, these viruses are poorly understood. A major impediment in studying anelloviruses is the lack of an in vitro system for their production and/ or propagation. Here we show that the T cell-derived human cell line MOLT-4 can be transfected with plasmids comprising tandem anellovirus genomes to produce viral particles visualized by electron microscopy. We found that a previously described human anellovirus of the Betatorquevirus genus (LY2), as well as a second Betatorquevirus detected by sequencing DNA extracted from a human retinal pigmental epithelium (nrVL4619), can be synthesized and produced by these means, enabling further molecular virology studies. Southern blot was used to demonstrate replication, and site-directed mutagenesis of the viral genome was performed to show that the production of anellovirus in this cell line is dependent on the expression of certain viral proteins. Finally, experiments performed in mice using purified nrVL4619 particles produced in MOLT-4 cells demonstrated infectivity in vivo in the tissue of origin. These results indicate that anelloviruses can be produced in vitro and manipulated to improve our understanding of this viral family which is ubiquitous in humans and many other mammals. Applications of this work to gene therapy and other therapeutic modalities are currently under investigation. IMPORTANCEAnelloviruses are a major component of the human virome. However, their biology is not well understood mainly due to the lack of an in vitro system for anellovirus production and/or propagation. In this study, we used multiple orthogonal measures to show that two different anelloviruses belonging to the Betatorquevirus genus can be produced in a T-cell-derived human cell line, MOLT-4, via recombinant expression of synthetic genomes. Additionally, we show that anellovirus particles generated in this in vitro system demonstrate infectivity in vivo. Our findings enable new molecular virology studies of this highly prevalent, non-pathogenic, and weakly immunogenic family of viruses, potentially leading to therapeutic applications.

microbiology↗

bioRxiv2021

Landscape genetics across the Andes Mountains: Environmental variation drives genetic divergence in the leaf-cutting ant Atta cephalotes

Disentangling the mechanisms underlying spatial distribution of genetic variation into those due to environment or physical barriers from mere geographic distance is challenging in complex landscapes. The Andean uplift represents one of the most heterogeneous habitats where these questions remain unexplored as multiple mechanisms might interact, confounding their relative roles. We explore this broad question in the leaf-cutting ant Atta cephalotes, a species distributed across the Andes Mountains using nuclear microsatellite markers and mtCOI gene sequences. We investigate spatial genetic divergence across the Western range of Northern Andes in Colombia by testing the relative role of alternative scenarios of population divergence, including geographic distance (IBD), climatic conditions (IBE), and physical barriers due to the Andes Mountains (IBB). Our results reveal substantial genetic differentiation among A. cephalotes populations for both types of markers, but only nuclear divergence followed a hierarchical pattern with multiple models of genetic divergence imposed by the Western range. Model selection showed that IBD, IBE (temperature and precipitation), and IBB (Andes mountains) models, often proposed as individual drivers of genetic divergence, interact, and explain up to 33% of genetic divergence in A. cephalotes. IBE models remained significant after accounting for IBD, suggesting that environmental factors play a more prominent role when compared to IBB. These factors in combination with idiosyncratic dispersal patterns of ants appear to determine hierarchical patterns of gene flow. This study enriches our understanding of the forces shaping population divergence in complex habitat landscapes.

genetics↗

bioRxiv2021

Patterns of regulatory divergence and gene expression in hybrids are associated with molecular evolution in species undergoing gene flow

The extent to which hybridization disrupts a genes pattern of expression likely governs its propensity for introgression, while its extent of molecular divergence can itself underlie such disruption. Together, these phenomena shape the landscape of sequence and transcriptional divergence across the genome as species diverge. To understand this process, we examine gene expression inheritance, regulatory and molecular divergences in the reproductive transcriptomes of species linked by gene flow. The fruit flies Anastrepha fraterculus and A. obliqua show evidence of gene flow despite clear evolutionary divergence and incomplete reproductive isolation. We find that their transcriptional patterns are a mosaic between those typically observed within and between allopatric species. Genes showing transgressive expression in hybrids or cis-regulatory divergence between species are associated with greater molecular divergence. This may reflect pleiotropic constraints that make them more resistant to gene flow or they may be more likely to experience divergent selection. However, while these highly divergent genes are likely to be important contributors to species differences, they are relatively rare. Instead, most differentially regulated genes, including those linked to reproduction, show high degrees of dominance in hybrids and trans-regulated divergence between species, suggesting widespread genetic compatibility that allowed for the identified introgression. These findings provide insights into how postzygotic isolating mechanisms might evolve in the presence of gene flow: regions showing cis-regulatory divergence or transgressive expression contribute to reproductive isolation, while regions with dominant expression and trans-regulatory divergence act as a buffer of hybrid breakdown, facilitating introgression, and leading to a genomic mosaic of expression and sequence divergence.

evolutionary biology↗

bioRxiv2021

Divergent evolutionary trajectories shape the postmating transcriptional profiles of conspecific and heterospecifically mated females

Postmating-prezygotic (PMPZ) reproductive isolation is hypothesized to result from divergent coevolutionary trajectories of sexual selection and/or sexual conflict in isolated populations (coevolutionary divergence model). However, the genetic basis of PMPZ incompatibilities between species is poorly understood. Here, we use a comparative framework to test predictions of the coevolutionary divergence model using a large transcriptomic dataset generated from con- and heterospecifically mated Drosophila mojavensis and D. arizonae female reproductive tracts. We found striking divergence between the species in the female postmating transcriptional response to conspecific mating, including differences in differential expression (DE), alternative splicing (AS), and intron retention (IR). As predicted, heterospecific matings produced disrupted transcriptional profiles, but the overall patterns of misregulation were different between the reciprocal crosses. Moreover, we found a positive correlation between postmating transcriptional divergence between species and levels of transcriptional disruption in heterospecific crosses, indicating that mating-responsive genes that have diverged more in expression also have more disrupted transcriptional profiles in heterospecifically mated females. Overall, our results are consistent with predictions of the coevolutionary divergence model and lay the foundation for future studies aimed at identifying specific genes involved in PMPZ incompatibilities and the evolutionary forces that have contributed to their divergence in closely related species.

evolutionary biology↗

bioRxiv2021

Effect of the Ecological Location of a Water Source on Entropy and other Spatio-temporal Behavioral Features: An extended and systematic replication

In behavior analysis, the modulation of the effect of time-based schedules by the spatial characteristics of the environment has been scarcely studied. Furthermore, the spatial organization of behavior, despite its ubiquity and ecological relevance, has not been widely addressed. The purpose of the present work was to analyze the effect of water delivery location (peripheral vs. central) on the spatial organization of water-feeding behavior under time-based schedules. One group of rats was exposed to a Fixed Time 30 s-water-delivery schedule and a second group to a Variable Time 30 s schedule. For both groups, in the first phase, the water dispenser was located in the perimetral zone. In the second condition, the water dispenser was located in the central zone. Each location was presented for 20 sessions. Rats trajectories, distance to the dispenser, accumulated time in regions, and entropy measures were analyzed. A differential effect of the location of water delivery in interaction with the time-based schedule was observed on all the analyzed spatial qualities of behavior. The findings are discussed in relation to the ecological proposal of Timberlakes behavioral systems.

animal behavior and cognition↗

bioRxiv2021

The role of the Andean uplift as an asymmetrical barrier to gene flow in the Neotropical leaf-cutting ant Atta cephalotes

Neotropical diversification by the Andean uplift is typically addressed on a large evolutionary scale (e.g. speciation), even though many species are still distributed in both sides of the mountains. The three parallel mountain ranges in the northern Andes (Colombia) impose a major geographical barrier to species migration from South to Central America. How important these barriers are for conspecific diversification of cross-Andean species such as the leaf-cutting ants remains largely unknown. To answer this question, we studied the mtCOI gene of Atta cephalotes, the most widely distributed leaf-cutting ant species. Our hierarchical analyzes evidenced substantial genetic structure among regions and populations, suggesting a more complex biogeographical history of Andean populations than previously thought. These mountains seem to isolate Central American and Western Colombian populations from the rest of A. cephalotes in South America. Population and migration modelling are consistent with the origin of this species in South America and a major role of the Eastern cordillera as a geographical barrier to historical gene flow, restricting dispersion from north to south. These findings provide insights into the role of the Andean uplift as barrier to gene flow and, eventually, implications for monitoring and designing management strategies for leaf-cutting ants.

genetics↗

bioRxiv2021

Microtubule lattice defects promote catastrophes.

Microtubules are dynamic cytoskeletal polymers that spontaneously switch between phases of growth and shrinkage. The probability of transitioning from growth to shrinkage, termed catastrophe, increases with microtubule age, but the underlying mechanisms are poorly understood. Here, we set out to test whether microtubule lattice defects formed during polymerization can affect growth at the plus end. To generate microtubules with lattice defects, we used microtubule-stabilizing agents that promote formation of polymers with different protofilament numbers. By employing different agents during nucleation of stable microtubule seeds and subsequent polymerization phase, we could reproducibly induce switches in protofilament number and induce stable lattice defects. Such drug-induced defects led to frequent catastrophes, which were not observed when microtubules were grown in the same conditions but without a protofilament number mismatch. Microtubule severing at the site of the defect was sufficient to suppress catastrophes. We conclude that structural defects within microtubule lattice can exert effects that can propagate over long distances and affect the dynamic state of the microtubule end.

cell biology↗

bioRxiv2020

Individual-based simulations of genome evolution with ancestry: the GENOMEADMIXR R package

O_LIHybridization between populations or species results in a mosaic of the two parental genomes. This and other types of genome admixture have received increasing attention for their implications in speciation, human evolution, Evolve and Resequence (E&R) and genetic mapping. However, a thorough understanding of how local ancestry changes after admixture, and how selection affects patterns of local ancestry remains elusive. The complexity of these questions limits analytical treatment, but these scenarios are specifically suitable for simulation. C_LIO_LIHere, we present the R package GO_SCPLOWENOMEC_SCPLOWAO_SCPLOWDMIXC_SCPLOWR, which uses an individual-based model to simulate genomic patterns following admixture forward in time. GO_SCPLOWENOMEC_SCPLOWAO_SCPLOWDMIXC_SCPLOWR provides user-friendly functions to set up and analyze simulations under evolutionary scenarios with selection, linkage and migration. C_LIO_LIWe show the flexible functionality of the GO_SCPLOWENOMEC_SCPLOWAO_SCPLOWDMIXC_SCPLOWR workflow by demonstrating 1) how to design an E&R simulation using GO_SCPLOWENOMEC_SCPLOWAO_SCPLOWDMIXC_SCPLOWR and 2) how to use GO_SCPLOWENOMEC_SCPLOWAO_SCPLOWDMIXC_SCPLOWR to verify analytical expectations following from the theory of junctions. C_LIO_LIGO_SCPLOWENOMEC_SCPLOWAO_SCPLOWDMIXC_SCPLOWR provides a mechanistic approach to explore expected genome responses to realistic admixture scenarios. With this package, we aim to aid researchers in testing specific hypotheses based on empirical findings involving admixing populations. C_LI

bioinformatics↗