Biology subjects

Sanchez, F.

Publications and source records attributed to Sanchez, F..

13 recordsLinked to original sources

bioRxiv2026

Preclinical evaluation of the biodistribution, safety, and hemocompatibility of PEG-coated iron oxide magnetic nanoparticles in a viral oncogenesis mouse model

Previously, we demonstrated the biosafety of polyethylene glycol-coated iron oxide nanoparticles (MAG@PEG) in a cellular model of viral oncogenesis, supporting their further preclinical evaluation. Herein, we evaluated the safety and biodistribution of MAG@PEG in tumor-bearing mice and assessed the influence of an external magnetic field on nanoparticle distribution. Animals were randomly assigned to three groups: G1, control (PBS); G2, MAG@PEG (10 mg/kg); and G3, MAG@PEG (10 mg/kg) with magnetic exposure for 1 h. Doses were administered intraperitoneally weekly for 1 month. Results showed that animal behavior and body weight were unaffected by MAG@PEG, while tumor growth was significantly reduced only in G2. Biodistribution studies based on tissue magnetization revealed higher magnetic iron levels in the stomach followed by the spleen, lungs, and tumors, particularly in G2. Histological analysis detected Prussian blue-positive staining mainly in the spleen and in lymphoid-associated structures in the lung, stomach and intestine, while a fraction of MAG@PEG remained within the peritoneal cavity. Serum biochemistry showed no evidence of nephrotoxicity. Furthermore, hemocompatibility studies using human blood samples demonstrated that MAG@PEG was non-hemolytic according to the ASTM F756 standard. Taken together, the biodistribution, histological, biochemical, and hemocompatibility findings provide a comprehensive preclinical assessment of the biosafety of MAG@PEG and identify the route of administration and magnetic targeting as key determinants of nanoparticle biodistribution.

pharmacology and toxicology↗

bioRxiv2026

A Biophysical Platform for Electromechanical Stimulation of Engineered Cardiac Tissues

Human engineered cardiac tissues (ECTs) provide an in vitro model for studying human cardiac physiology and drug responses, but their performance remains limited by culture systems that do not fully reproduce the heart's electrical and mechanical environment. Electrical stimulation (ES) and mechanical stimulation (MS) have each been used to improve ECT function. Their combination, referred to as electromechanical stimulation (ES+MS), can provide further benefits. However, ES+MS depends not only on the presence of both cues but also on how they are coordinated in time. Here, we developed an incubator-compatible biophysical platform that delivers ES and MS independently or in combination, with programmable control over timing, amplitude, frequency, duration, and waveform. Calibration and dynamic characterization demonstrated tissue-relevant strain delivery, rapid and repeatable motion, and minimal attenuation and timing lag at the designated frequency of 1.5 Hz. We then compared four 6 h conditioning regimens: unstimulated control, ES alone, unsynchronized ES+MS, and synchronized ES+MS. We hypothesized that the synchronized ES+MS group, in which electrical excitation was aligned with peak externally applied strain, would produce the greatest increase in contractile force. Consistent with this hypothesis, synchronized ES+MS increased normalized twitch force by approximately 44% on average, whereas the other groups showed no comparable improvement. Twitch-timing metrics did not exhibit coordinated enhancement after 6 h, suggesting that the force increase reflects an adaptive biomechanical response rather than broad tissue maturation. These findings identify ES-MS timing as an important design parameter for ECT conditioning.

bioengineering↗

bioRxiv2026

Plasticity of the mutation rate and spectrum in eukaryotic marine phytoplankton

The ability to adapt shapes the future of any species or population. Adaptive potential is primarily determined by the spontaneous mutation rate {micro} and the mutation spectrum, which define the new genetic variation available to selection. Increasing evidence points to the plasticity of the mutation rate and spectrum, which vary according to environment. However, data is lacking for marine phytoplankton, an essential group for marine ecosystems as well as a major player in biogeochemical cycles. Here, we measure the plasticity of mutation rates and spectra in the chlorophyte Ostreococcus tauri by mutation accumulation experiments in 4 different conditions: low salinity, high salinity, low temperature, and high temperature. {micro}SNM is lowest under low salinity, doubles under high salinity and low temperature and quadruples under high temperature. SNM spectra become increasingly biased towards C:G[->]T:A transitions with increasing {micro}SNM. While {micro}ID does not change with the environment, the structural mutation rate {micro}SM is higher at low temperature, likely due to transposon activity. Given the rapid environmental changes associated with global climate change, mutation rates and spectra plasticity may critically influence the adaptive potential of marine primary producers.

evolutionary biology↗

bioRxiv2025

Genomic analysis of Ostreococcus tauri-infecting viruses reveals a hypervariable region associated with host--virus interactions

While the genus Prasinovirus, known to infect prasinophyte green algae (class Mamiellophyceae), is abundant in the oceans, the genetic mechanisms governing the ecology and (co)evolution of these viruses remain poorly understood. In this study, we sequenced the complete genomes of eighteen viruses infecting the cosmopolitan unicellular green alga Ostreococcus tauri (OtVs) and one specific to Micromonas commoda (McV-20T). Of these viruses, twelve were previously isolated from the coastal Mediterranean Sea and seven were newly isolated from two different geographical locations (i.e., the South Pacific Gyre and the North Sea). Phylogenetic analysis classified these viruses as new members of the Prasinovirus genus and defined three distinct OtV clades: designated OtV-type 1, OtV-type 2a and OtV-type 2b. The OtV-type 1 includes three new viruses isolated from the Pacific Ocean and the previously sequenced genome OtV6. The OtV-type 1 form a large cluster within the Micromonas-infecting virus clade, sharing five unique homologous genes with all Micromonas viruses. In addition, genetic features of OtV-type 1, including a higher number of CDSs ([~]260) and lower GC content ([~]41%), were more closely allied to Micromonas viruses than to those of OtVs, suggesting an alternative host or a recent host switch from Micromonas to O. tauri. By analyzing the OtV genomes, we found a faster-evolving central hypervariable region (HVR), where the OtV-type 2b displayed the largest region, i.e., three times longer than other OtVs. This region encodes genes mainly associated with host cell recognition and attachment and under strong selective pressure (positive and negative). Notably, most viruses associated with OtV-type 2b showed the broadest host range. Infection dynamics between the hosts and the viruses appeared highly specific to host-virus pairs, suggesting complex interactions in the Ostreococcus-prasinovirus system. Finally, by observing viral lysates with electron microscopy, we observed novel morphologies never described for these viruses. Overall, this study provides new insights into the genetic diversity of prasinoviruses and describes for the first time a viral plasticity that might be strongly shaped by antagonistic coevolution with their hosts.

microbiology↗

bioRxiv2025

Unlocking Genetic Diversity in Colombian Cassava Landraces for Accelerated Breeding

Cassava (Manihot esculenta Crantz) is a staple food for hundreds of millions across the global south. In this study, we investigated genomic diversity among over 1000 cassava genotypes, with a particular focus on the addition of 387 newly sequenced landrace varieties originating from diverse climates across Colombia. As cassava was domesticated in or near the Amazon basin, these landraces represent untapped genetic diversity that could be used to help improve modern varieties. As theory predicts, we found that landraces retain high genetic diversity, observing variation lacking in breeding lines from Asia and Africa, where introductions likely caused population bottlenecks. Genetic differentiation in landraces reflects both space and climate of origin, suggesting the combined effects of demography and selection. To identify alleles with the potential to inform targets for gene editing, we assessed the diversity of loss-of-function (LoF) mutations across these landraces. We found evidence that deleterious LoF alleles were purged by inbreeding. Notably, genes retaining LoF alleles despite inbreeding were significantly enriched for functions related to the biosynthesis of coumarins and the regulation of plant immunity, suggesting selection on postharvest quality and disease resistance. We further identified specific loci associated with climates of origin, motivating future experiments using targeted knockouts to test hypotheses about the adaptive value of specific LoF alleles. This work supports longstanding hypotheses about landraces as a reservoir of genetic diversity and establishes the foundation to leverage this variation in cassava to discover alleles for accelerated breeding via gene editing. Short summaryThis study explores the genetic diversity of cassava by sequencing 387 landrace varieties and wild relatives from diverse climates in Colombia, aiming to identify potential gene targets for gene editing to enhance climate resilience. The research focuses on loss-of-function mutations, which are expected to have large effects and provide testable targets. Genome-wide association analysis reveals multiple potential targets associated with climate adaptation in cassava.

plant biology↗

bioRxiv2025

Managing populations after a disease outbreak: exploration of epidemiological consequences of managed host reintroduction following disease-driven host decline

Disease outbreaks in wild populations around the globe can lead to widespread mortality within populations, where recovery of individuals can be rare. An example of this population is the sunflower sea star Pyc-nopodia helianthioides in the Northeastern Pacific coast. The populations of this species, as well as many other sea star populations, have experienced massive mortality events due to an unidentified disease called Sea Star Wasting Disease (SSWD). Pycnopodia play a key role in providing top-down control of kelp grazers in rocky reefs across the Northeastern Pacific coast. This, combined with the massive declines in kelp coverage observed during the 2015-2016 marine heat wave observed in the Northeastern Pacific, has sparked an interest in reintroducing Pycnopodia individuals in the coast to potentially assist in recovery of the populations. However, the epidemiological implications of reintroducing healthy sea stars into the wild populations is an under-explored question. This work explores this question using a dynamical population model of Pycnopodia. We use this model to estimate the impacts of reintroducing healthy individuals into a wild sea star population. This analysis will provide valuable information for managers interested in restoring Pycnopodia populations.

ecology↗

bioRxiv2024

Modeling the impact of optimized airflow and sick pen management on the spread of infectious diseases in swine barns

The airborne spread of infectious livestock diseases plays a crucial role in the propagation of epidemics, particularly in populations confined to densely populated facilities, such as commercial swine barns. Therefore, quantitative assessments for the performance of barn ventilation systems may serve as an alternative biocontainment control strategy to reduce the spread of infectious pathogens. In this study, we present a framework to simulate airborne disease dissemination within swine barns and facilitate the strategic design of control actions, including optimization of ventilation and placement of sick animals (sick pen). This framework is based on a susceptible-infected-recovered (SIR) model that accounts for the between-pen disease spread within swine barns. A pen-to-pen contact network is used to construct a transmission matrix according to the transport of airborne respiratory pathogens across pens in the barns, via our Reynolds-averaged Navier-Stokes computational fluid dynamics (CFD) solver. By employing this CFD-augmented SIR model, we demonstrated that the location of the sick pen and the barn ventilation configuration played crucial roles in modifying disease dissemination dynamics at the barn level. In addition, we examined the effect of natural ventilation through different curtain adjustments. We observed that curtain adjustments either suppress the disease spread by an average of 56.5% or exacerbate the outbreak potential by an average of 5.7%, compared to the scenario where side curtains are not raised. Furthermore, we optimize the ventilation configuration via the selection and placement of ventilation fans through the integration of the CFD-augmented framework with the genetic algorithm to minimize the dissemination of swine disease within barns. Compared to regular barn ventilation settings, our optimized ventilation system significantly reduced disease spread by an average of 43.2%. Our study emphasizes the role of airborne transmission and a strategy for sick pen management in controlling the spread of within-barn disease.

bioengineering↗

bioRxiv2024

Analyzing the intrastate and interstate swine movement network in the United States

Disease prevention and control tactics rely on identifying and restricting animal movement to attenuate the between-premises spread of disease in livestock systems. Therefore, it is essential to uncover between-premises movement dynamics, including shipment distances and network-based control strategies. Here, we analyzed three years of between-premises pig movements, which include 197,022 unique animal shipments, 3,973 premises, and 391,625,374 pigs shipped across 20 U.S. states. We constructed unweighted, directed, temporal networks at 180-day intervals to calculate premises-to-premises movement distances, the size of connected components, network loyalty, and degree distributions, and, based on the out-going contact chains, identified network-based control actions. Our results show that the median distance between premises pig movements was 74.37 km, with median intrastate and interstate movements of 52.71 km and 328.76 km, respectively. On average, 2,842 premises were connected via 6,705 edges, resulting in a weak giant connected component that included 91% of the premises. The premises-level network exhibited loyalty, with a median of 0.65 (IQR: 0.45 - 0.77). Results highlight the effectiveness of node targeting and disease spread; we demonstrated that targeting 25% of farms with the highest degree or betweenness limited spread to 1.23% and 1.7% of premises, respectively. While there is no complete shipment data for the entire U.S., our multi-state movement analysis demonstrated the value and the needs of such data for enhancing the design and implementation of proactive-disease control tactics.

ecology↗

bioRxiv2022

High rates of spontaneous chromosomal duplications are compensated by translational regulation in a photosynthetic unicellular eukaryote

While duplications have long been recognized as a fundamental process driving major evolutionary innovations, direct estimations of spontaneous chromosome duplication rates, leading to aneuploid karyotypes, are scarce. Here, we provide the first estimations of spontaneous chromosome duplication rates in six unicellular eukaryotic species from mutation accumulation (MA) experiments. The spontaneous chromosome duplication rates reach 1x10-4 to 1x10-3 per genome per generation, which is ~4 to ~50 times less frequent than spontaneous point mutations per genome, whereas chromosome duplication events can affect 1 to 7% of the total genome size. Comparative transcriptomics between MA lines with different chromosome duplications reveals a strong positive correlation between RNA expression rate and DNA copy number. However, comparative analyses of the translation rate of mRNAs estimated by polysome profiling unravel a chromosome specific dosage compensation mechanism. In particular, one chromosome with a gene average of 2.1 excess of mRNAs is compensated by an average of ~0.7 decrease in translation rates. Altogether, our results are consistent with previous observations of a chromosome dependent effect of dosage compensation and provide evidence that it may occur during translation. These results support the existence of a yet unknown post-transcriptional mechanism orchestrating the modification of translation of hundreds of transcripts from genes located on duplicated regions in eukaryotes.

evolutionary biology↗

bioRxiv2021

The interplay of spatial scale and landscape transformation moderates the abundance and intraspecific variation in the ecomorphological traits of a phyllostomid bat

Land-use intensification imposes selective pressures that systematically change the frequency of wild population phenotypes. Growing evidence is biased towards the comparison of populations from discrete categories of land uses, ignoring the role of landscape emerging properties on the phenotype selection of wild fauna. Across the largest urban-rural gradient of the Colombian Orinoquia, we measured ecomorphological traits of 216 individuals of the Flat-faced Fruit-eating Bat Artibeus planirostris, to evaluate the scale of effect at which landscape transformation better predicts changes in phenotype and abundance of an urban-tolerant species. Forest percentage at 1.25 km was the main predictor affecting abundance, wing aspect ratio, and body mass of this phyllostomid; but the direction of the effect differed between abundance and ecomorphological traits. Although landscape factors explained changes in the forearm length at all spatial scales, the effect was sex-dependent and the most important predictor was forest percentage at 0.5 km. Our results indicate that landscape elements and spatial scale interact to shape ecomorphological traits and the abundance of A. planirostris. Interestingly, the scale of effect was congruent among all biological responses. A pattern that likely arises since species abundance can reflect the variation on phenotype under different environmental filters across landscape scenarios.

ecology↗

bioRxiv2020

Gut Phageome Analysis Reveals Disease-Specific Hallmarks in Childhood Obesity

Changes in the composition of the human gut microbiome are recognized to have a significant association with obesity and metabolic syndrome. Mexico leads worldwide childhood-obesity rankings representing an epidemic problem for public health. To this date, it is still unclear how the gut phageome, the bacteriophage component of the virome, influences childhood obesity and obesity with metabolic syndrome. We characterized the gut phageome of 28 school-age children with healthy normal-weight (NW), obese (O), and obese with metabolic syndrome (OMS) profiles, using metagenomic sequencing of virus-like particles (VLPs) from fecal samples. Viromes derived from VLPs were mainly dominated by Caudovirales, and only Inoviridae family was significantly increased in obesity. The three groups showed a similar number of VLPs, while a significant increase in phage richness and diversity was found in obesity groups compared NW. Few phage contigs dominated the phageome composition in NW, being increased in obesity groups. Interestingly, the majority of the phageome was shared among all individuals, establishing a core and common phageome, which abundances correlated with anthropometric and biochemical traits and bacteria previously associated with obesity and metabolic syndrome. We also established a healthy core phageome shared in >80% of NW samples, with a decreased prevalence in the O and OMS groups. Our data support that changes in the gut phageome may contribute to obesity and metabolic syndrome development via bacterial dysbiosis. We consider the phageome characterization provides the basis for novel diagnostic and therapeutic strategies for managing obesity and preventing metabolic syndrome development in obese children through potential phage manipulation. To the best of our knowledge, this study represents the most in-depth sequenced dataset of human bacteriophages, demonstrating for the first time that alterations of the gut phageome characterize obesity.

genomics↗

bioRxiv2020

The impact of non-additive genetic associations on age-related complex diseases.

Genome-wide association studies (GWAS) are not fully comprehensive as current strategies typically test only the additive model, exclude the X chromosome, and use only one reference panel for genotype imputation. We implemented an extensive GWAS strategy, GUIDANCE, which improves genotype imputation by using multiple reference panels, includes the analysis of the X chromosome and non-additive models to test for association. We applied this methodology to 62,281 subjects across 22 age-related diseases and identified 94 genome-wide associated loci, including 26 previously unreported. We observed that 27.6% of the 94 loci would be missed if we only used standard imputation strategies and only tested the additive model. Among the new findings, we identified three novel low-frequency recessive variants with odds ratios larger than 4, which would need at least a three-fold larger sample size to be detected under the additive model. This study highlights the benefits of applying innovative strategies to better uncover the genetic architecture of complex diseases.

genomics↗

bioRxiv2017

A Comprehensive Reanalysis Of Publicly Available GWAS Datasets Reveals An X Chromosome Rare Regulatory Variant Associated With High Risk For Type 2 Diabetes.

The reanalysis of publicly available GWAS data represents a powerful and cost-effective opportunity to gain insights into the genetics and pathophysiology of complex diseases. We demonstrate this by gathering and reanalyzing public type 2 diabetes (T2D) GWAS data for 70,127 subjects, using an innovative imputation and association strategy based on multiple reference panels (1000G and UK10K). This approach led us replicate and fine map 50 known T2D loci, and identify seven novel associated regions: five driven by common variants in or near LYPLAL1, NEUROG3, CAMKK2, ABO and GIP genes; one by a low frequency variant near EHMT2; and one driven by a rare variant in chromosome Xq23, associated with a 2.7-fold increased risk for T2D in males, and located within an active enhancer associated with the expression of Angiotensin II Receptor type 2 gene (AGTR2), a known modulator of insulin sensitivity. We further show that the risk T allele reduces binding of a nuclear protein, resulting in increased enhancer activity in muscle cells. Beyond providing novel insights into the genetics and pathophysiology of T2D, these results also underscore the value of reanalyzing publicly available data using novel analytical approaches.

genetics↗