Biology subjects

Hernandez, P.

Publications and source records attributed to Hernandez, P..

7 recordsLinked to original sources

bioRxiv2025

Genetic structure of mesophotic and shallow Acropora aculeus on isolated atolls of Eastern Australia

Acropora is the most diverse and widespread coral genus in the world. Although known for its critical ecological role in shallow-water habitats, its abundance and diversity at upper mesophotic depths have only recently been uncovered. Consequently, little is known about the genetic structuring of mesophotic Acropora populations and their potential ecological and evolutionary relationships with shallow populations. Here, we present the first population genomic evaluation of the depth-generalist coral Acropora aculeus to assess genetic structuring across depths (10 and 40 m) and regions (the Great Barrier Reef (GBR) and the Western Coral Sea (WCS)). We observed strong geographic differentiation between regions, indicating the relative isolation of WCS atolls, with some gene flow occurring from WCS to the GBR, but rarely in the opposite direction. Conversely, we observed no geographic or depth-related genetic structuring within regions, although sample sizes limited the evaluation of local allelic patterns of depth structuring. Our results indicate that widespread connectivity within regions characterizes the broadcast spawning A. aculeus. The lack of depth differentiation should be explored to see whether the wide depth range of some species may be safeguarded against a rapidly changing climate.

genomics↗

bioRxiv2023

A non-invasive photoactivatable split-Cre recombinase system for genome engineering in zebrafish.

The cyclic recombinase (Cre)/loxP recombination system is a powerful technique for in vivo cell labeling and tracking. However, achieving high spatiotemporal precision in cell tracking using this system is challenging due to the requirement for reliable tissue-specific promoters. In contrast, light-inducible systems offer superior regional confinement, tunability and non-invasiveness compared to conventional lineage tracing methods. Here, we took advantage of the unique strengths of the zebrafish to develop an easy-to-use highly efficient, genetically encoded, Magnets-based, light-inducible transgenic Cre/loxP system. Our system relies on the reassembly of split Cre fragments driven by the affinity of the Magnets and is controlled by the zebrafish ubiquitin promoter. We demonstrate that our system does not exhibit phototoxicity or leakiness in the dark, and it enables efficient and robust Cre/loxP recombination in various tissues and cell types at different developmental stages through noninvasive illumination with blue light. Our newly developed tool is expected to open novel opportunities for light-controlled tracking of cell fate and migration in vivo. HighlightsO_LIzPA-Cre is a novel zebrafish transgenic optogenetic split-Cre tool C_LIO_LIzPA-Cre allows loxP-mediated DNA recombination in various tissues and cell types C_LIO_LIIt enables light-induced DNA recombination at different developmental stages. C_LIO_LIIt allows spatio-temporal DNA recombination in a specific tissue region with high resolution C_LI

developmental biology↗

bioRxiv2022

The unique structure and replication mode of the replication system of Klebsiella pneumoniae plasmid pIGMS31

Due to their relatively small size and the lack of housekeeping genes, bacterial plasmids are very convenient models for studying DNA replication. So, for a long time, they had been intensively studied in this regard. Unfortunately, only a limited number of model plasmid replication systems were analyzed in detail. In the era of high-throughput DNA sequencing, we are faced with an increasing gap in our knowledge of bacterial plasmid replication and a rapidly growing number of deposited new plasmid genome sequences. For this reason, we decided to investigate the replication system of the pIGMS31 plasmid, a representative of the newly described pHW126-like plasmids family. They are small replicons isolated from different clinical and environmental strains of Gamma proteobacteria. Whole shares unique replication modules with no significant similarities to known model plasmid replication systems. In this study, we identified and characterized the basic elements of the pIGMS31 replication module. Studies on regulatory mechanisms of replication initiation of this plasmid as well as on pIGMS31 replication mode were also performed. We revealed that the pIGMS31 replication module is composed of elements typical for both theta and rolling circle replicons. This mosaic structure is reflected in the unique course of replication of this plasmid, with both modes of replication. What is more, our results led us to conclude that pHW126-like plasmids, despite DNA sequence similarity, are a highly diverse group of replicons.

molecular biology↗

bioRxiv2021

Antibodies to the SARS-CoV-2 receptor-binding domain that maximize breadth and resistance to viral escape

An ideal anti-SARS-CoV-2 antibody would resist viral escape1-3, have activity against diverse SARS-related coronaviruses4-7, and be highly protective through viral neutralization8-11 and effector functions12,13. Understanding how these properties relate to each other and vary across epitopes would aid development of antibody therapeutics and guide vaccine design. Here, we comprehensively characterize escape, breadth, and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD), including S3094, the parental antibody of the late-stage clinical antibody VIR-7831. We observe a tradeoff between SARS-CoV-2 in vitro neutralization potency and breadth of binding across SARS-related coronaviruses. Nevertheless, we identify several neutralizing antibodies with exceptional breadth and resistance to escape, including a new antibody (S2H97) that binds with high affinity to all SARS-related coronavirus clades via a unique RBD epitope centered on residue E516. S2H97 and other escape-resistant antibodies have high binding affinity and target functionally constrained RBD residues. We find that antibodies targeting the ACE2 receptor binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency, but we identify one potent RBM antibody (S2E12) with breadth across sarbecoviruses closely related to SARS-CoV-2 and with a high barrier to viral escape. These data highlight functional diversity among antibodies targeting the RBD and identify epitopes and features to prioritize for antibody and vaccine development against the current and potential future pandemics.

microbiology↗

bioRxiv2021

Rotavirus susceptibility of antibiotic-treated mice ascribed to diminished expression of interleukin-22

The commensal microbiota regulates susceptibility to enteric pathogens by fine-tuning mucosal innate immune responses, but how susceptibility to enteric viruses is shaped by the microbiota remains incompletely understood. Past reports have indicated that commensal bacteria may either promote or repress rotavirus replication in the small intestine of mice. We now report that rotavirus replicated more efficiently in the intestines of germ-free and antibiotic-treated mice compared to animals with an unmodified microbiota. Antibiotic treatment also facilitated rotavirus replication in type I and type III interferon (IFN) receptor-deficient mice, revealing IFN-independent proviral effects. Expression of interleukin-22 (IL-22) was strongly diminished in the intestine of antibiotic-treated mice. Treatment with exogenous IL-22 blocked rotavirus replication in microbiota-depleted wild-type and Stat1-/- mice, demonstrating that the antiviral effect of IL-22 in animals with altered microbiome is not dependent on IFN signaling. In antibiotic-treated animals, IL-22-induced a specific set of genes including Fut2, encoding fucosyl-transferase 2 that participates in the biosynthesis of fucosylated glycans which can mediate rotavirus binding. Interestingly, IL-22 also blocked rotavirus replication in antibiotic-treated Fut2-/- mice. Furthermore, IL-22 inhibited rotavirus replication in antibiotic-treated mice lacking key molecules of the necroptosis or pyroptosis pathways of programmed cell death. Taken together, our results demonstrate that IL-22 determines rotavirus susceptibility of antibiotic-treated mice, yet the IL-22-induced effector molecules conferring rotavirus resistance remain elusive.

immunology↗

bioRxiv2017

Capture-based DNA methylation sequencing facilitates diagnosis and reveals potential pathogenic mechanisms in teratogenic diabetes exposure

Diabetic embryopathy (DE) describes a spectrum of birth defects associated with a teratogenic exposure to maternal diabetes in utero. These defects strongly overlap the phenotypes of known genetic syndromes; however, the pathogenic mechanisms underlying DE remain uncertain and there are no definitive tests that distinguish the diagnosis. Here, we explore the potential of DNA methylation as both a diagnostic biomarker and a means of informing disease pathogenesis in DE. Capture-based bisulfite sequencing was used to compare patterns of DNA methylation at 2,800,516 sites genome-wide in seven DE neonates and 11 healthy neonates, including five with in utero diabetes exposure. DE infants had significantly lower global DNA methylation (ANOVA, Tukey HSD p=0.045) than diabetes-unexposed, healthy controls (UH), with multiple sites showing large (mean methylation difference = 16.6%) and significant (p<0.001) differential methylation between the two groups. We found that a subset of 237 highly differentially methylated loci could accurately distinguish DE infants from both UH and diabetes-exposed healthy infants (sensitivity 80% -100%). Differentially methylated sites were enriched in intergenic (p<3.52x10-15) and intronic (p<0.001) regions found proximal to genes either associated with Mendelian syndromes that overlap the DE phenotype (e.g. TRIO, ANKRD11), or known to influence early organ development (e.g. BRAX1, RASA3). Further, by integrating information on cis-sequence variation, we found that 39.3% of loci with evidence for allele-specific methylation also showed differential methylation between DE and controls. Our study suggests a role for aberrant DNA methylation and cis-sequence variation in the pathogenesis of DE, and highlights the diagnostic potential of DNA methylation for teratogenic birth defects.

genetics↗

bioRxiv2017

Novel Chemolithotrophic And Anoxygenic Phototrophic Genomes Extracted From Ice-Covered Boreal Lakes

Although an important fraction of the worlds lakes remains ice-covered during a large proportion of the year, little is known about the microorganisms that govern the biogeochemical processes occurring under-ice along the stratigraphic redox gradients. Reconstructed genomes provide evidence for anoxygenic photosynthesis involving fixation of carbon using reduced sulphur and iron as an electron donor in the anoxic zone of the sampled lake systems. In addition to anoxygenic photosynthesis, our molecular data reveals novel chemolithoautotrophic organisms and supports the existence of methanotrophs in bottom anoxic waters. Reconstructed genomes matched methanotrophs related to Methylobacter tundripaludum, phototrophic Chloroflexi and Chlorobia, as well as lithoautotrophic genomes affiliated to the Betaproteobacteria class and Planctomycetes phylum. Based on our in-depth characterization, complex metabolic interactomes emerge unique to each lakes redox tower and with sulfur, iron and carbon cycling tightly intertwined through chemolithotrophy and anoxygenic photosynthesis.

ecology↗