Biology subjects

Hyde, J.

Publications and source records attributed to Hyde, J..

11 recordsLinked to original sources

bioRxiv2025

Pulmonary Vascular Endothelial Dysfunction is Induced by Non-Pulsatile Pulmonary Blood Flow in an Ovine Classic Glenn Model

Structured AbstractO_ST_ABSBackgroundC_ST_ABSPulmonary vascular disease (PVD) in patients with single ventricular heart disease following the partial cavalpulmonary connection (Glenn) is a significant source of morbidity. However, the etiology of pulmonary vascular endothelial cell (EC) dysfunction, an established precursor to PVD, is incompletely understood but may involve abnormal blood flow patterns, hypoxemia, and polycythemia. HypothesisUtilizing an ovine Glenn model, we hypothesized that non-pulsatile pulmonary blood flow (PBF) induces pulmonary vascular EC dysfunction, independent of hypoxemia or polycythemia. MethodsSeven lambs (6-8 weeks old) underwent a Glenn procedure. Eight weeks later, Glenn and age-matched controls were studied. The response to the endothelium-dependent vasodilator acetylcholine (Ach) was determined in isolated pulmonary arteries (PA). Nitric oxide (NO) and endothelin-1 (ET-1) signaling was determined in right lung tissues. Indices of cell proliferation, angiogenesis, and apoptosis were determined in PA endothelial cells (PAECs). Comparisons were made by unpaired t-test and ANOVA. ResultsThere were no differences in age, hemoglobin, or oxygen saturation between groups. Mean PA pressure and left PA flow were higher, and right lung blood flow was lower in Glenn lambs compared to controls (p<0.05). All other baseline hemodynamics were similar. Glenn PAs had impaired relaxation to Ach. Glenn lung NO metabolite levels (NOx) and eNOS protein were lower, and ET-1 levels and prepro-ET-1 protein were higher than controls (p<0.05). Glenn PAECs had higher rates of proliferation and angiogenesis, and decreased apoptosis (p < 0.05). ConclusionsThe initiation of non-pulsatile PBF following the Glenn induces early EC dysfunction independent of hypoxemia and polycythemia.

physiology↗

bioRxiv2025

Globally unified analysis of riverine eDNA reveals common associations of fish biodiversity with drainage characteristics

Freshwater biodiversity is declining at a pace that outstrips the capacity of existing monitoring approaches both in temporal and spatial dimensions, highlighting the urgent need for rapid and scalable assessment and attribution of biodiversity states and changes. Here, we present one of the first global assessments and unified analyses of riverine fish biodiversity using environmental DNA (eDNA) collected from 1818 sites across 113 river systems. We quantified species richness, functional redundancy, phylogenetic diversity, and genetic sequence diversity, and related them to drainage characteristics. Our results showed that eDNA effectively captured global patterns of multi-faceted riverine fish biodiversity and disentangled the roles of climate and human activities in shaping biodiversity-area relationships. Catchments in warmer climates consistently enhanced biodiversity accumulation with area, while higher human activity intensity weakened this scaling. Species richness, functional, and genetic sequence diversity exhibited stronger negative responses to human activities in larger catchments. In contrast, phylogenetic diversity showed the strongest negative effects in smaller catchments with these impacts diminishing as catchment area increased, highlighting the facet-dependent nature of biodiversity responses to environmental gradients. Our findings demonstrate the power of eDNA-based datasets for harmonized, multi-faceted biodiversity assessments, offering a scalable approach for detecting and attributing biodiversity change and informing conservation strategies under accelerating global change.

ecology↗

bioRxiv2025

Integrated reanalysis of global riverine fish eDNA datasets shows robustness and congruence of biodiversity conclusions

The analysis of environmental DNA (eDNA) has revolutionized biodiversity assessments in aquatic ecosystems, enabling non-invasive monitoring of fish communities across diverse regions. However, the global comparability of these eDNA datasets remains ambiguous due heterogeneous sampling protocols and bioinformatic workflows across studies, particularly regarding the robustness of their conclusions on biodiversity assessments. Here, we conducted a meta-analysis of 58 riverine fish eDNA metabarcoding datasets, covering 1,818 sampling sites worldwide, to evaluate the robustness of eDNA-derived biodiversity patterns. We found that species richness estimates and metrics of community structure derived under a common bioinformatic workflow were overall consistent with those of original analyses, despite the relatively high variability in bioinformatic analyses in the respective original studies. Contrastingly, congruence of species identity varied more extensively across datasets, mostly reflecting different completeness and regional relevance of reference databases. Restricting taxonomic assignment to basin-specific species pools improved species identification accuracy, while datasets lacking publicly accessible or well-curated reference data were more prone to mismatches. Year of sampling had a positive effect on taxonomic congruence, such that more recent studies showed increased robustness, also reflecting improved reference database coverage and enhanced species-level identification over time and overall method congruence in more recent years. Overall, the suitability and potential of eDNA for global biodiversity monitoring is corroborating overall robust biodiversity estimates, irrespective of the bioinformatic approaches. Our study underlines the effectiveness and need of further harmonization of bioinformatic workflows and strengthened region-specific reference databases for improved taxonomic resolution and comparability across studies.

ecology↗

bioRxiv2024

Direct measurement of the mutation rate and its evolutionary consequences in a critically endangered mollusk

The rate at which mutations arise is a fundamental parameter of biology. Despite recent progress in measuring germline mutation rates across diverse taxa, such estimates are missing for much of Earths biodiversity. We present the first estimate of a germline mutation rate from the phylum Mollusca, which is diverged by more than 1200 Ma years from the closest relative for which a mutation rate estimate exists. We sequenced three pedigreed families of the white abalone Haliotis sorenseni, a long-lived, large-bodied, and critically endangered mollusk, and estimated a de novo mutation rate of 8.60e-09 single nucleotide mutations per site per generation. This mutation rate is similar to rates measured in vertebrates with similar generation times and longevity to abalone, and higher than mutation rates measured in faster-reproducing invertebrates. We use our estimated rate to infer baseline effective population sizes (Ne) across multiple Pacific abalone and find that abalone persisted over most of their evolutionary history as large and stable populations, in contrast to extreme fluctuations over recent history and small census sizes in the present day. We then use our mutation rate to infer the timing and pattern of evolution of the abalone genus Haliotis, which was previously unknown due to few fossil calibrations. Our results are an important step toward understanding mutation rate evolution and establish a key parameter for conservation and evolutionary genomics research in mollusks.

evolutionary biology↗

bioRxiv2024

{-}{-}{-}{-}{-}{-}{-}{-}RNA structures within Venezuelan equine encephalitis virus E1 alter macrophage replication fitness and contribute to viral emergence

Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne +ssRNA virus belonging to the Togaviridae. VEEV is found throughout Central and South America and is responsible for periodic epidemic/epizootic outbreaks of febrile and encephalitic disease in equines and humans. Endemic/enzootic VEEV is transmitted between Culex mosquitoes and sylvatic rodents, whereas epidemic/epizootic VEEV is transmitted between mosquitoes and equids, which serve as amplification hosts during outbreaks. Epizootic VEEV emergence has been shown to arise from mutation of enzootic VEEV strains. Specifically, epizootic VEEV has been shown to acquire amino acid mutations in the E2 viral glycoprotein that facilitate viral entry and equine amplification. However, the abundance of synonymous mutations which accumulate across the epizootic VEEV genome suggests that other viral determinants such as RNA secondary structure may also play a role in VEEV emergence. In this study we identify novel RNA structures in the E1 gene which specifically alter replication fitness of epizootic VEEV in macrophages but not other cell types. We show that SNPs are conserved within epizootic lineages and that RNA structures are conserved across different lineages. We also identified several novel RNA-binding proteins that are necessary for altered macrophage replication. These results suggest that emergence of VEEV in nature requires multiple mutations across the viral genome, some of which alter cell-type specific replication fitness in an RNA structure-dependent manner. AUTHOR SUMMARYUnderstanding how viral pathogens emerge is critical for ongoing surveillance and outbreak preparedness. However, our understanding of the molecular mechanisms that drive viral emergence are still not completely understood. Emergence of the mosquito-borne virus Venezuelan equine encephalitis virus (VEEV) is known to require mutations in the viral attachment protein (E2), which drive viremia and transmission. We have observed that emergent strains (epizootic VEEV) also accumulate many silent mutations, suggesting that other determinants independent of protein sequence also contributes to emergence. In this study we identify novel RNA secondary structures associated with epizootic VEEV that alters viral replication in a cell-type dependent manner. We show that these RNA structures are conserved across epizootic viruses and identify host proteins that specifically bind these RNAs. These findings imply that viral emergence requires multiple mutations, a number of which likely alter viral structure in a manner that benefits viral replication and transmission.

microbiology↗

bioRxiv2024

A lack of open data standards for large infrastructure project hampers social-ecological research in the Brazilian Amazon

New infrastructure projects are planned or under construction in several countries, including in the bioculturally diverse Amazon, Mekong, and Congo regions. While infrastructure development can improve human health and living standards, it may also lead to environmental degradation and social change. Accessible, high quality data about infrastructure projects is essential for both monitoring them and studying their social and environmental impacts. We investigated the availability and quality of data on infrastructure projects in the Brazilian Amazon by reviewing the academic literature and surveying researchers from the conservation and development community, then used the results of these surveys to identify critical data attributes for the gathering, organizing, and sharing of infrastructure data by social-ecological researchers and practitioners. Although data on infrastructure in the Brazilian Amazon were generally available, they were often of poor quality and lacked information critical for monitoring and research. Data were often difficult to find and reformat, resulting in loss of time and resources for researchers and other stakeholders. Discrepancies between researchers survey responses on data needs and the types of data used in peer-reviewed articles on infrastructure projects indicate the following information was often missing: geographic extent of the project, construction and operation dates, and project type (e.g., paved vs unpaved road). Including these data in a standardized format, along with making them more readily accessible by hosting them in public repositories and ensuring they are current and comprehensive, would facilitate research and improve planning, decision-making, and monitoring of existing and future infrastructure projects in Brazil and other developing countries. HighlightsO_LIInfrastructure projects across the globe spur economic development but also lead to social- ecological degradation. C_LIO_LIResearchers and practitioners need current and comprehensive data to better mitigate social- ecological changes from infrastructure. C_LIO_LIInfrastructure data are often unavailable, inaccessible, or incomplete. C_LIO_LIFinding and organizing datasets cost researchers hundreds of hours and may lead to abandoned projects. C_LIO_LITo promote better research outcomes, governments and NGOs should ensure datasets on infrastructure are accessible, current, comprehensive, and include such vital information as the projects geographic extent, dates of construction and operation, project type, and essential technical data. C_LI

ecology↗

bioRxiv2023

Three Species of Axenic Mosquito Larvae Recruit a Shared Core of Bacteria in a Common Garden Experiment

In this study we describe the generation of two new species of axenic mosquito, Aedes albopictus and Aedes triseriatus. Along with Aedes aegypti, axenic larvae of these three species were exposed to an environmental water source to document the assembly of the microbiome in a common garden experiment. Additionally, the larvae were reared either individually or combinatorially with the other species to characterize the effects of co-rearing on the composition of the microbiome. We found that the microbiome of the larvae was composed of a relatively low diversity collection of bacteria from the colonizing water. The abundance of bacteria in the water was a poor predictor for their abundance in the larvae, suggesting the larval microbiome is made up of a subset of relatively rare aquatic bacteria. We found eleven bacterial 16S rRNA gene amplicon sequence variants (ASVs) that were conserved amongst >90% of the mosquitoes sampled, including two found in 100% of the larvae, pointing to a conserved core of bacteria capable of colonizing all three species of mosquito. Yet, the abundance of these ASVs varied widely between larvae suggesting individuals harbored largely unique microbiome structures, even if they overlapped in membership. Finally, larvae reared in a tripartite mix of the host species consistently showed a convergence in the structure of their microbiome, indicating that multi-species interactions between hosts potentially lead to shifts in the composition of their respective microbiomes. IMPORTANCEThis study is the first report of the axenic (free of external microbes) rearing of two species of mosquito, Aedes albopictus and Aedes triseriatus. With our previous report of axenic Aedes aegypti, brings the number of axenic species to three. We designed a method to perform a common garden experiment to characterize the bacteria the three species of axenic larvae assemble from their surroundings. Furthermore, species could be reared in isolation or in multi-species combinations to assess how host species interactions influence the composition of the microbiome. We found all three species recruited a common core of bacteria from their rearing water, with a large contingent of rare and sporadically detected bacteria. Finally, we also show that co-rearing of mosquito larvae leads to a coalescence in the composition of their microbiome, indicating that host species interactions potentially influence the composition of the microbiome.

microbiology↗

bioRxiv2022

Speciation genomics and the role of depth in the divergence of rockfishes (Sebastes) revealed through Pool-seq analysis of enriched sequences

Speciation in the marine environment is challenged by the wide geographic distribution of many taxa and potential for high rates of gene flow through larval dispersal mechanisms. Depth has recently been proposed as a potential driver of ecological divergence in fishes and yet it is unclear how adaptation along these gradients shapes genomic divergence. The genus Sebastes contains numerous species pairs that are depth segregated and can provide a better understanding of the mode and tempo of genomic diversification. Here we present exome data on two species pairs of rockfishes that are depth segregated and have different degrees of divergence: S. chlorostictus-S. rosenblatti and S. crocotulus-S. miniatus. We were able to reliably identify islands of divergence in the species pair with more recent divergence (S. chlorostictus-S. rosenblatti) and discovered a number of genes associated with neurosensory function, suggesting a role for this pathway in the early speciation process. We also reconstructed demographic histories of divergence and found the best supported model was isolation followed by asymmetric secondary contact for both species pairs. These results suggest past ecological/geographic isolation followed by asymmetric secondary contact of deep to shallow species. Our results provide another example of using rockfish as a model for studying speciation and support the role of depth as an important mechanism for diversification in the marine environment.

evolutionary biology↗

bioRxiv2022

Hyperactivity of indirect pathway-projecting spiny projection neurons drives compulsive behavior

Compulsive behaviors are a hallmark symptom of obsessive compulsive disorder (OCD). Striatal hyperactivity has been linked to compulsive behavior generation in correlative studies in humans and causal studies in rodents. However, the contribution of the two distinct striatal output populations to the generation and treatment of compulsive behavior is unknown. These populations of direct and indirect pathway-projecting spiny projection neurons (SPNs) have classically been thought to promote or suppress actions, respectively, leading to a long-held hypothesis that increased output of direct relative to indirect pathway promotes compulsive behavior. Contrary to this hypothesis, here we find that indirect pathway hyperactivity drives compulsive grooming in the Sapap3-knockout mouse model of OCD-relevant behavior. Furthermore, we show that suppression of indirect pathway activity using optogenetics or treatment with the first-line OCD pharmacotherapy fluoxetine is associated with reduced compulsive behavior. Together, these findings highlight the striatal indirect pathway as a potential new treatment target for compulsive behavior.

neuroscience↗

bioRxiv2020

The Intergenic Small Non-Coding RNA ittA is Required for Optimal Infectivity and Tissue Tropism in Borrelia burgdorferi

Post-transcriptional regulation via small regulatory RNAs (sRNAs) has been implicated in diverse regulatory processes in bacteria, including virulence. One class of sRNAs, termed trans-acting sRNAs, can affect the stability and/or the translational efficiency of regulated transcripts. In this study, we utilized a collaborative approach that employed data from infection with the Borrelia burgdorferi Tn library, coupled with Tn-seq, together with borrelial sRNA and total RNA transcriptomes, to identify an intergenic trans-acting sRNA, which we designate here as ittA for infectivity-associated and tissue-tropic sRNA locus A. The genetic inactivation of ittA resulted in a significant attenuation in infectivity, with decreased spirochetal load in ear, heart, skin and joint tissues. In addition, the ittA mutant did not disseminate to peripheral skin sites or heart tissue, suggesting a role for ittA in regulating a tissue-tropic response. RNA-Seq analysis determined that 19 transcripts were differentially expressed in the ittA mutant relative to its genetic parent, including vraA, bba66, ospD and oms28 (bba74). Subsequent proteomic analyses also showed a significant decrease of OspD and Oms28 (BBA74) proteins. To our knowledge this is the first documented intergenic sRNA that alters the infectivity potential of B. burgdorferi. AUTHOR SUMMARYLyme disease is a tick-borne infection mediated by the spirochetal bacterium, Borrelia burgdorferi, that is responsible for greater than 300,000 infections in the United States per year. As such, additional knowledge regarding how this pathogen modulates its regulatory armamentarium is needed to understand how B. burgdorferi establishes and maintains infection. The identification and characterization of small, non-coding RNA molecules in living systems, designated as sRNAs, has recalibrated how we view post-transcriptional regulation. Recently, over 1,000 sRNAs were identified in B. burgdorferi. Despite the identification of these sRNAs, we do not understand how they affect infectivity or B. burgdorferi pathogenesis related outcomes. Here, we characterize the ittA B. burgdorferi sRNA and show that it is essential for optimal infection using murine experimental infection as our readout. We also track the effect of this sRNA on the transcriptional and proteomic profile as the first step in providing mechanistic insight into how this important sRNA mediates its regulatory effect.

microbiology↗

bioRxiv2019

Antibiotic resistant bacteria and commensal fungi are common and conserved in the mosquito microbiome

The emerging and increasing prevalence of bacterial antibiotic resistance is a significant public health challenge. To begin to tackle this problem, it will be critical to not only understand the origins of this resistance but also document environmental reservoirs of antibiotic resistance. In this study we investigated the possibility that both colony and field caught mosquitoes could harbor antibiotic resistant bacteria. Specifically, we characterized the antibiotic resistant bacterial populations from colony-reared Aedes aegypti larvae and adults and two field caught mosquito species Coquillettidia perturbans and Ochlerotatus canadensis. The cultured bacterial populations were dominated by isolates belonging to the class Gammaproteobacteria. Among the antibiotic resistant populations, we found bacteria resistant to carbenicillin, kanamycin, and tetracycline, including bacteria resistant to a cocktail of all three antibiotics in combination. The antibiotic resistant bacteria were numerically rare, at most 5% of total cell counts. Isolates were characterized by 16S rRNA gene sequencing, and clustering into Operational Taxonomic Units (OTUs; 99% sequence identity). 27 antibiotic resistant OTUs were identified, although members of an OTU did not always share the same resistance profile. This suggests the clustering was either not sensitive enough to distinguish different bacteria taxa or different antibiotic resistant sub-populations exist within an OTU. Finally, the antibiotic selection opened up a niche to culture mosquito-associated fungi, and 10 fungal OTUs (28S rRNA gene sequencing) were identified. Two fungal OTUs both classified to the class Microbotryomycetes were commonly identified in the field-caught mosquitoes. Thus, in this study we demonstrate that antibiotic resistant bacteria and certain fungi are common and conserved mosquito microbiome members. These observations highlight the potential of invertebrates to serve as vehicles for the spread of antibiotic resistance throughout the environment.

microbiology↗