Biology subjects

Gonzalez, O.

Publications and source records attributed to Gonzalez, O..

12 recordsLinked to original sources

bioRxiv2026

Sequence-dependent conformational and mechanical landscapes of double-stranded nucleic acids

The sequence-dependent mechanical landscapes of double-stranded nucleic acid (dsNA) remain largely unexplored beyond canonical dsDNA. We describe cgNA+, a coarse-grained predictive model of the mechanics of dsRNA, DNA:RNA hybrids, and epigenetically modified dsDNA, all parameterised from 1.26 milliseconds of atomistic simulations. cgNA+ predicts non-local sequence-dependent equilibrium shape and stiffness with errors an order of magnitude smaller than sequence-variability, while enabling exploration of numbers of sequences inaccessible to atomistic simulation. We show that dsNA equilibrium shape is strongly influenced by flanking sequence up to octamer context, with flexible dimer-steps more context-sensitive. CpG-modification alters equilibrium shape comparable to changes caused by single-nucleotide polymorphisms. Groove width analysis across dsNA decamers reveals strong sequence dependence, reflecting the differing characteristic helical geometry of dsDNA and dsRNA, whereas DRHs exhibit mixed behaviour depending on DNA-strand pyrimidine content. CTCF binding sites exhibit a distinct groove width signature. Persistence-length spectra from [~] 9 million sequences indicate that dsRNA is stiffer than dsDNA, whereas DRH exhibit intermediate stiffness modulated by DNA strand pyrimidine content. Persistence length increases upon CpG-modification, but decreases on hypermodification. Overall, the cgNA+ model enables a first, highly accurate, very large-scale, comparative study of sequence-dependent mechanics both within and across dsNA classes, demonstrating previously hidden regulatory layers. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=74 SRC="FIGDIR/small/740023v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@1a430edorg.highwire.dtl.DTLVardef@88469borg.highwire.dtl.DTLVardef@d3a7eforg.highwire.dtl.DTLVardef@1b65a15_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2026

Rusty Blackbirds (Euphagus carolinus) appear to exhibit predator satiation with a resident raptor species

Predator satiation is an understudied topic among vertebrate organisms, especially avian species. In Anderson, South Carolina, a species of migratory black bird, Euphagus carolinus (Rusty Blackbird) was observed roosting seasonally in a patch of Phyllostachys aurea (Golden bamboo) in large numbers. A resident avian predator, Buteo lineatus (Red-shouldered Hawk was seen preying on these roosting blackbirds; however, when this hawk would attack, pin down, and eat a blackbird, the rest of the flock would not react or fly away. Upon initial observation, we questioned if these roosting blackbirds exhibited predator satiation as a protection mechanism against avian predation. When E. carolinus flocked to roost, their numbers were visually counted and compared between at least two members of the research team. After allowing the birds to settle between fifteen seconds and one minute, a B. lineatus call was played with speakers to the flock. Simultaneously, a regulation-sized football was tossed to simulate the hawk attacking a member of the flock. The number of birds that flew away was recorded. Results between roosting numbers and flight numbers upon disturbance were analyzed to see if roosting group size correlates with evasiveness in birds. Results indicated that as blackbird group size increased, the total percentage of escaping birds decreased. Statistical analysis showed the leaving percentage versus the natural logarithm of group size was highly statistically significant (p < 0.001) and had a moderately negative overall correlation (rs = -0.62). Our results suggest that these blackbirds feel safer in large groups instead of small groups during predation events when roosting in dense brush. LAY SUMMARYO_LIThere is little research involving predator satiation tendencies in birds. C_LIO_LIPredator satiation is a strategy developed by prey animals to cope with predators, relying on sheer numbers to avoid predation instead of fight or flight. C_LIO_LIWe observed roosting Rusty Blackbirds in Anderson, SC displaying predator satiation-linked tendencies under avian predation stress when in large groups. C_LIO_LIWe tested the behavior of Rusty Blackbirds by simulating a hawk attack, noting the group size and the number of birds escaping. C_LIO_LIOur results showed that as group size increased, flight percentage decreased under a simulated predator attack. C_LIO_LIRusty Blackbirds seem to use the predator satiation strategy when roosting. C_LI

ecology↗

bioRxiv2026

Greater benefits of assisted gene flow in F2 vs F1 progeny at the cold edge of a species' range

Gene flow to marginal populations at a species range edge can facilitate rapid adaptation by increasing genetic diversity, reducing inbreeding depression, and introducing novel alleles. In highly inbred populations, hybrid vigor is often observed in the first generation (F1), but hybrid breakdown may diminish fitness in subsequent generations. Thus, benefits of gene flow may be overestimated when only F1 performance is assessed. We tested whether gene flow among populations of the annual plant Erythranthe laciniata (A. Gray) G.L. Nesom, from similar and contrasting environments, confers persistent fitness advantages across F1 and F2 generations at the high-elevation edge of its range in the California Sierra Nevada. Gene flow was experimentally introduced through pollen transfer between cold-edge populations, between cold edge and central populations, and within local cold edge populations, and compared to self-fertilized offspring, the predominant mating strategy of E. laciniata. For F1 progeny, we measured morphological, phenological, and fitness traits in a common garden located near the cold-climate range limit during 2008-2009, a relatively average year, and for F2 progeny in 2009-2010, a relatively wet year. Although F1 crosses showed no initial performance advantage measured in the previous year, F2 progeny from center-to-edge and edge-to-edge crosses significantly outperformed selfed and locally outcrossed lines in fruit mass, total pedicels, biomass, and height. Our findings demonstrate that gene flow can confer long-term fitness benefits, especially among populations adapted to similar selective pressures, and highlight the potential of assisted gene flow to bolster or rescue peripheral populations facing climate change. SIGNIFICANCE STATEMENTSpecies living at the edges of their geographic ranges often have small, isolated populations with limited genetic diversity, which can restrict their ability to adapt to environmental change. Gene flow from other populations may increase adaptive potential, but its long-term consequences remain uncertain because most studies evaluate only first-generation hybrids. Using experimental crosses in the mountain wildflower Erythranthe laciniata, we show that gene flow can produce stronger fitness benefits in second-generation hybrids than in the first generation at a high-elevation range edge. These results suggest that recombination among populations can generate advantageous genetic combinations that emerge over multiple generations. Our findings highlight the potential for assisted gene flow to enhance adaptation and persistence of range-edge populations under climate change.

plant biology↗

bioRxiv2026

Wheat mutants lacking Starch Synthase 1 have altered starch composition and cell wall content

Starch Synthase 1 (SS1) participates in the synthesis of amylopectin. To determine its role in hexaploid bread wheat, we selected and combined TILLING mutations for each homoeologue to create two independent SS1-deficient lines. The lines, which have different combinations of ss1 mutations, both lacked SS1 protein. Both lines exhibited mild but significant changes to starch phenotype, including fewer short amylopectin chains, a slight increase in B-type starch granules and a modest increase in amylose content. Lack of SS1 also led to changes in the thermal properties of starch measured by differential scanning calorimetry including reduced enthalpy, and increased gelatinization temperature. Despite the changes to starch properties, the starch contents of the mutant lines compared to wild types were within the normal range, as were grain weight and protein content. However, the concentration of total- and water-extractable arabinoxylan, and MLG, were increased in white flour compared to wild-type controls. HighlightLack of SS1 led to changes in starch molecular structure and thermal behavior. Starch content and grain weight were normal but cell wall polysaccharides in white flour were increased.

plant biology↗

bioRxiv2025

Age and early life adversity shape heterogeneity of the epigenome across tissues in macaques

Age and early life adversity (ELA) are both key determinants of health, but whether they target similar physiological mechanisms across the body is unknown due to limited multi-tissue datasets from well-characterized cohorts. We generated DNA methylation (DNAm) profiles across 14 tissues in 237 semi-free ranging rhesus macaques, with records of naturally occurring ELA. We show that age-associated DNAm variation is predominantly tissue-dependent, yet tissue-specific epigenetic clocks reveal that the pace of epigenetic aging is relatively consistent within individuals. ELA effects on loci are adversity-dependent, but a given ELA has a coordinated impact across tissues. Finally, ELA targeted many of the same loci as age, but the direction of these effects varied, indicating that ELA does not uniformly contribute to accelerated age in the epigenome. ELA thus imprints a coordinated, tissue-spanning epigenetic signature that is both distinct from and intertwined with age-related change, advancing our understanding of how early environments sculpt the molecular foundations of aging and disease.

genomics↗

bioRxiv2024

EML4-ALK variant-specific genetic interactions shape lung tumorigenesis

Oncogenic fusions of EML4 and ALK occur in [~]5% of lung adenocarcinomas. More than 15 EML4-ALK variants with distinct breakpoints within EML4 have been identified, but the functional differences between these variants remain poorly understood. Here we use CRISPR/Cas9 somatic genome editing to generate autochthonous mouse models of the two most common EML4-ALK variants, V1 and V3, and show that V3 is more oncogenic than V1. By integrating these models with multiplexed genome editing, we quantify the effects of 29 putative tumor suppressor genes on V1- and V3-driven lung cancer growth in vivo and show that many tumor suppressor genes have dramatically variant-specific effects on tumorigenesis. Analysis of a novel dataset representing the largest human EML4-ALK lung cancer cohort to date identified alterations in the genomic landscape depending on the EML4-ALK variant. These findings demonstrate functional heterogeneity among EML4-ALK variants, suggesting that EML4-ALK variants behave more like distinct oncogenes than a uniform entity. More broadly, these findings highlight the dramatic impact of oncogenic fusions partner proteins on tumor biology.

cancer biology↗

bioRxiv2022

Microbiome network connectivity and composition linked to disease resistance in strawberry plants

Plant recruit diverse microbial communities from the soil biota. Inter-microbial interactions and connectivity in the root microbiome could play essential roles in plant health by promoting resistance to soil-borne pathogens. Yet, understanding these interactions under field conditions is still scarce. Using a strawberry crop model, we characterized the prokaryotic and fungal communities in the rhizosphere and roots of three strawberry cultivars displaying varying resistance degrees to the soil-borne fungal pathogen Macrophomina phaseolina. We tested the hypothesis that resistant cultivars assemble distinct bacterial and fungal communities that foster microbial connectivity and mediate disease resistance. Our results show that the soil-borne pathogen, M. phaseolina, does not perturb the root microbiome of the strawberry cultivars. Microbiome comparative analysis indicated that the highly susceptible cultivar, Sweet Ann, assembles a distinct microbiome that shows reduced network connectivity, whereas more resistant cultivars were enriched in potential beneficial microbes and showed higher network connectivity. Collectively, these results suggest the role of plant genetic traits in the assembly of beneficial microbiome members. Our study reinforces the eminent role of the plant microbiome as trait of selection in breeding programs and stresses further understandings of the genetic and biological mechanisms that mediate microbiome assembly. Uncovering these mechanisms will be key for future plant breeding programs.

microbiology↗

bioRxiv2022

Evolutionary and biomedical implications of sex differences in the primate brain transcriptome

Humans exhibit sex differences in the prevalence of many neurodevelopmental and neurodegenerative conditions. To better understand the translatability of a critical nonhuman primate model, the rhesus macaque, we generated one of the largest multibrain region bulk transcriptional datasets for this species and characterized sex-biased gene expression patterns. We demonstrate that these patterns are similar to those in humans and are associated with overlapping regulatory mechanisms, biological processes, and genes implicated in sex-biased human disorders, including autism. We also show that sex-biased genes exhibit greater genetic variance for expression and more tissue-specific expression patterns, which may facilitate the rapid evolution of sex-biased genes. Our findings provide insights into the biological mechanisms underlying sex-biased disease and validate the rhesus macaque model for the study of these conditions.

neuroscience↗

bioRxiv2020

BNT162b vaccines are immunogenic and protect non-human primates against SARS-CoV-2

A safe and effective vaccine against COVID-19 is urgently needed in quantities sufficient to immunise large populations. We report the preclinical development of two BNT162b vaccine candidates, which contain lipid-nanoparticle (LNP) formulated nucleoside-modified mRNA encoding SARS-CoV-2 spike glycoprotein-derived immunogens. BNT162b1 encodes a soluble, secreted, trimerised receptor-binding domain (RBD-foldon). BNT162b2 encodes the full-length transmembrane spike glycoprotein, locked in its prefusion conformation (P2 S). The flexibly tethered RBDs of the RBD-foldon bind ACE2 with high avidity. Approximately 20% of the P 2S trimers are in the two-RBD down, one-RBD up state. In mice, one intramuscular dose of either candidate elicits a dose-dependent antibody response with high virus-entry inhibition titres and strong TH1 CD4+ and IFN{gamma}+ CD8+ T-cell responses. Prime/boost vaccination of rhesus macaques with BNT162b candidates elicits SARS-CoV-2 neutralising geometric mean titres 8.2 to 18.2 times that of a SARS-CoV-2 convalescent human serum panel. The vaccine candidates protect macaques from SARS-CoV-2 challenge, with BNT162b2 protecting the lower respiratory tract from the presence of viral RNA and with no evidence of disease enhancement. Both candidates are being evaluated in phase 1 trials in Germany and the United States. BNT162b2 is being evaluated in an ongoing global, pivotal Phase 2/3 trial (NCT04380701, NCT04368728).

immunology↗

bioRxiv2020

Plant traits that influence flower visits by birds in a montane forest

In a bird-flowering plant network, birds select plants that present traits attractive to them. I studied plant characteristics that might predict flower visitation rate by the most common bird visitors in a bird-flowering plant network located in an elfin forest of the Andes. The nectarivorous birds which had the highest number of interactions with flowering plants in this network were the Coppery Metaltail (Metallura theresiae), the Great Sapphirewing (Pterophanes cyanopterus), and the Moustached Flowerpiercer (Diglossa mystacalis). I analyzed different flower traits (flower aggregation, nectar volume, nectar energy, color, orientation, and dimensions of the corolla) of the common plants that these birds visited with a principal component analysis. The plants most visited by birds were Brachyotum lutescens and Tristerix longebracteatus. While nectar traits of the plants seemed to be the best predictor for bird visitation, there was no statistical association between visitation and plant traits, except for Metallura theresiae in the dry season. I discuss the possible causes of resource partitioning for these nectarivorous birds.

ecology↗

bioRxiv2020

Lethality of SARS-CoV-2 infection in K18 human angiotensin converting enzyme 2 transgenic mice

ABSTRACTVaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease currently lacks a validated small animal model. Here, we show that transgenic mice expressing human angiotensin converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18 hACE2) represent a susceptible rodent model. K18 hACE2-transgenic mice succumbed to SARS-CoV-2 infection by day 6, with virus detected in lung airway epithelium and brain. K18 ACE2-transgenic mice produced a modest TH1/2/17 cytokine storm in the lung and spleen that peaked by day 2, and an extended chemokine storm that was detected in both lungs and brain. This chemokine storm was also detected in the brain at day 4. K18 hACE2-transgenic mice are, therefore, highly susceptible to SARS-CoV-2 infection and represent a suitable animal model for the study of viral pathogenesis, and for identification and characterization of vaccines (prophylactic) and antivirals (therapeutics) for SARS-CoV-2 infection and associated severe COVID-19 disease.

microbiology↗

bioRxiv2020

SARS-CoV-2 infection leads to acute infection with dynamic cellular and inflammatory flux in the lung that varies across nonhuman primate species

There are no known cures or vaccines for COVID-19, the defining pandemic of this era. Animal models are essential to fast track new interventions and nonhuman primate (NHP) models of other infectious diseases have proven extremely valuable. Here we compare SARS-CoV-2 infection in three species of experimentally infected NHPs (rhesus macaques, baboons, and marmosets). During the first 3 days, macaques developed clinical signatures of viral infection and systemic inflammation, coupled with early evidence of viral replication and mild-to-moderate interstitial and alveolar pneumonitis, as well as extra-pulmonary pathologies. Cone-beam CT scans showed evidence of moderate pneumonia, which progressed over 3 days. Longitudinal studies showed that while both young and old macaques developed early signs of COVID-19, both groups recovered within a two-week period. Recovery was characterized by low-levels of viral persistence in the lung, suggesting mechanisms by which individuals with compromised immune systems may be susceptible to prolonged and progressive COVID-19. The lung compartment contained a complex early inflammatory milieu with an influx of innate and adaptive immune cells, particularly interstitial macrophages, neutrophils and plasmacytoid dendritic cells, and a prominent Type I-interferon response. While macaques developed moderate disease, baboons exhibited prolonged shedding of virus and extensive pathology following infection; and marmosets demonstrated a milder form of infection. These results showcase in critical detail, the robust early cellular immune responses to SARS-CoV-2 infection, which are not sterilizing and likely impact development of antibody responses. Thus, various NHP genera recapitulate heterogeneous progression of COVID-19. Rhesus macaques and baboons develop different, quantifiable disease attributes making them immediately available essential models to test new vaccines and therapies.

immunology↗