Biology subjects

Levy, M.

Publications and source records attributed to Levy, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Structural modeling and experimental validation define the MxA-Thogotovirus nucleoprotein interface that drives restriction and escape

The human MxA (myxovirus resistance protein A) host restriction factor inhibits orthomyxoviruses, such as Thogotovirus (THOV) and influenza A virus (IAV), by binding to their nucleoproteins. Despite being discovered over six decades ago, how MxA interacts with viral targets remains unclear. Earlier studies using evolutionary analysis and mutagenesis showed that the MxA L4 loop, especially a hydrophobic aromatic amino acid at residue 561, is crucial for binding THOV nucleoprotein (NP) and restricting THOV. Here, we combined previous insights with structure prediction methods, molecular dynamics simulations, and experimental validation to define the human MxA L4 loop binding interface to THOV NP. We also evaluated the stability of MxA L4-NP binding through classical all-atom molecular dynamics simulations. Our model revealed MxA L4 binding to a surface-exposed site on THOV NP, including residues previously linked to viral escape from MxA restriction, even though this information was not used to guide our modeling efforts. This MxA-THOV NP interface is distinct from NPs RNA-binding or oligomerization surfaces. Our molecular dynamics simulations also agree with earlier data indicating that F561Y enhances MxA binding to THOV NP, whereas F561W reduces it and F561V ablates it entirely. Based on this model, we predicted specific variants in human MxA or THOV NP that could result in increased host restriction or viral escape. We tested these predictions using a viral minireplicon assay to validate our model. Our efforts will guide vital viral surveillance studies and the development of MxA-based antivirals. (240) Significance StatementThe interferon-stimulated MxA protein encodes a critical barrier to zoonotic spillover of orthomyxoviruses, restricting infection by binding viral nucleoprotein (NP). Despite being among the best-studied interferon-stimulated genes (ISGs), the specific host-viral interaction surface involved in binding or restriction is poorly understood. We address this hurdle using structural modeling and molecular dynamics simulations to generate a model of the biochemical interactions between MxA and Thogotovirus NP. Our model is consistent with previous work identifying mutations that strengthen or weaken the binding interaction. We validate this model using in vitro analysis of predicted mutations at the host-virus interface. Our model provides a framework for additional mutational studies, surveillance of viruses poised for zoonosis, and rational antiviral design. (115)

microbiology↗

bioRxiv2026

Deep learning representations of human Immune Health for precision immunology

The human immune system is composed of [~]30-50 distinct cell types, each of which can exist in different states of activation or differentiation. Indeed, the mammalian immune system has evolved to sense and respond to infections, cancers, injuries, and changes in tissue or host homeostasis (1). Moreover, an increasingly large fraction of approved drugs target the immune system directly, and/or cause immune changes (2-4). A key feature of the immune system is to store some of this information, for example as innate or adaptive immune memory (5). In addition, rewiring of immune network architecture induced by disease, environmental exposures, drug treatments, and/or chronological age allows the immune system to store information in the pattern of connections and activity across populations of immune cells. This ensemble information storage, in addition to changes to individual cells, functions as a major way the immune system encodes aspects of immune history and future potential. Genetic information can identify inherited risk alleles, but cannot capture the continual remodeling of the immune system shaped by exposures, infection, inflammation, therapy, and aging (6, 7). To define and use such ensemble immunotypes, we developed a self-supervised deep learning framework that transforms high-dimensional immune profiles into representations of immune health. MAESTRO (MAsked Encoding Set TRansformer with self-distillatiOn) encodes a set of cells from an individual into an embedding that captures immune cell population-level organization. Pretrained on 1,792 peripheral blood samples comprising over 418 million immune cells across 13 clinical diagnoses, MAESTRO learns immune fingerprints that are stable within individuals yet diverse across populations, states of health, disease, and treatment, providing a quantitative basis for comparing immune states across individuals and over time. These fingerprints capture immune architecture beyond coarse cell type proportions, enabling patient-efficient clinical prediction using simple task specific models. MAESTRO model embeddings retain a temporal dimension of immune history and potential, reflecting signatures of past exposures and baseline features that predict future immune responses. Finally, we demonstrate a translational precision immunotherapy application by testing this approach in metastatic Pancreatic Ductal Adenocarcinoma (PDAC), where pretreatment immune landscape circuitry maps enable patient stratification and therapeutic response prediction. Overall, we developed a large, attention-based model that captures deep network architecture of immune states through self- supervised representations of immune cytometry data as a reusable foundation for precision immunology, converting immune complexity into clinically actionable embeddings for diagnosis, monitoring, and therapy selection.

immunology↗

bioRxiv2026

PolyFold: Evaluation of Open-Use Molecular Structure Prediction Algorithms to Inform Their Utility in Diverse Biological Applications

Withdrawal StatementThe authors have withdrawn this manuscript in order to extend the time of review; the conclusions made in the article were tentative and may not reflect the true nature of the data upon second analysis. Thus, to avoid false conclusions being advanced by other groups, we sought to withdraw the manuscript until the work has undergone further scrutiny and revision. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

bioengineering↗

bioRxiv2026

Spatially resolved, multimodal in vivo Perturb-seq using antibody-based cell hashing

Large-scale perturbation screens have begun to map cell intrinsic gene-function relationships, yet how genes shape tissue architecture remains largely unexplored. To address this gap, we developed PerturbSpace, a novel approach that integrates CRISPR perturbations with spatially hashed single-cell multiomics. This approach enables the first high-throughput, spatially resolved Perturb-seq analysis across complex tissue architecture in vivo. Notably, PerturbSpace enables spatial transcriptome-wide perturbation readouts at organ scale and can be seamlessly integrated with orthogonal modalities. We combine PerturbSpace with surface proteomics and expressed lineage tracing barcodes to demonstrate multimodal compatibility. We use PerturbSpace to study the genetic determinants of tissue architecture. First, we map how 40 transcriptional regulators determine the size and lineage composition of colonies in the spleen during regenerative hematopoiesis. Second, we characterize immune-niche interactions in the liver by dissecting the extrinsic effects mediated by cytokine-secreting immune cells on their neighboring cells. Collectively, our work establishes PerturbSpace as a scalable and cost-effective approach for transcriptome-wide spatial profiling of whole cells while remaining compatible with the single-cell multiomics workflows that the field has already adopted at scale.

genomics↗

bioRxiv2026

Erythroferrone Modulates Osteoblast-Osteoclast Crosstalk During Bone Remodeling

Erythroferrone (ERFE) secretion inhibits hepcidin expression by sequestering several bone morphogenetic protein (BMP) family members to increase iron availability for erythropoiesis. Recent evidence demonstrates that ERFE is also expressed in osteoblasts and osteoclasts and Erfe-/- mice display low-bone-mass arising from increased bone resorption despite a concomitant increase in bone formation. To mechanistically dissect how bone-derived ERFE exerts an osteoprotective effect, we first created Erfefl/fl mice, which were then crossed with Col2.3-Cre mice to generate osteoblast-selective Erfe mutants (or Erfefl/fl;Col2.3-Cre mice). We now demonstrate that ERFE derived from osteoblasts is not responsible for the decreased BMD noted in Erfe-/- mice, revealing enhanced BMD during anabolic stress in Erfefl/fl;Col2.3-Cre mice. Consistently, in contrast to global ERFE loss, osteoblast-selective ERFE loss does not increase osteoclasts in vivo. Furthermore, our results demonstrate that ERFE loss in osteoblasts induces osteoclast Erfe expression in co-culture experiments in vitro. Finally, the osteoclastogenesis gene program is induced in co-culture with osteoblasts only when ERFE is lost in osteoclasts. Taken together, our finding provide strong evidence of osteoclast-derived ERFE as a central osteoprotective regulator of bone mass, its loss resulting in net bone loss in Erfe-/- mice. BRIEF SUMMARYLoss of erythroferrone derived from osteoclasts enhances osteoclastogenesis resulting in accelerated bone loss. SIGNIFICANCE STATEMENTCanonical erythroferrone (ERFE) function includes hepcidin suppression through bone morphogenic proteins (BMPs) sequestration, establishing the rationale for ERFE-mediated regulation of bone homeostasis. We previously showed that global ERFE loss controls bone mass. Here, we report that osteoclast-derived ERFE is a major regulator of osteoclastogenesis. For this, we crossed Erfefl/fl with Col2.3-Cre mice to generate osteoblast-selective Erfe mutants, demonstrating that osteoblast-derived ERFE does not recapitulate bone loss found in global ERFE knockout mice. In contrast, bone mineral density is enhanced during anabolic stress in Erfefl/fl;Col2.3-Cre mice. Finally, we document that osteoclast ERFE loss enhances osteoclastogenesis in co-culture with osteoblasts. Together, the data provide compelling evidence that osteoclast-derived ERFE modulates communication between osteoblasts and osteoclasts.

cell biology↗

bioRxiv2026

Development of a Humanized Mouse Model for Studying adult Spinal Cord myelination, remyelination and Drug Efficacy

Oligodendrocytes are essential for central nervous system (CNS) function through their roles in myelination and neuronal support. Remyelination, the regeneration of myelin after damage, often fails in human demyelinating diseases, leading to progressive neurological dysfunction. While the biology of rodent oligodendroglia has been investigated in depth, species-specific differences have hindered the study of human oligodendrocyte progenitor cells maturation using current animal models. To address this gap, we developed a humanized oligodendroglia chimeric mouse model by transplanting human iPSC-derived O4+ oligodendroglial progenitors (hiOLs) into the developing spinal cord of myelin deficient-immunosuppressed mice followed by demyelination of the adult humanized spinal cord. This paradigm allows in vivo investigation of hiOL fate during their maturation and ageing, and the response of their settled progeny to demyelinating injury. Following transplantation during postnatal development, hiOLs proliferated, migrated, and differentiated into mature oligodendrocytes, initiating axonal myelination. A population of undifferentiated, proliferative adult human oligodendrocyte progenitors presisted, indicating a reservoir of these cells capable of responding to injury. Spinal cord focal demyelination via lysolecithin injection in the adult humanized spinal cord led to transient loss of human-derived mature oligodendrocytes and myelin, followed by myelin recovery together with endogenous cells. Treatment with the histamine receptor H3 antagonist, bavisant, a recently identified promyelinating compound, significantly enhanced hiOL maturation and myelin production, indicating promotion of their differentiation when administered post-demyelination. Electron microscopy showed an increased number of human-derived remyelinated axons together with decreased g-ratios in bavisant treated animals. This humanized spinal cord model of myelination/demyelination-remyelination faithfully recapitulates key aspects of human oligodendrocyte biology and CNS repair, providing a powerful tool to study human-specific myelination and remyelination mechanisms and screen for emerging remyelinating therapies. Its application in disease modeling and preclinical testing holds promise for advancing personalized treatments in demyelinating and neurodegenerative disorders.

neuroscience↗

bioRxiv2026

Dynamic Regulation of CD300b, and CD300f on Myeloid Cells in Oral Immunotherapy

IntroductionOral immunotherapy (OIT) induces desensitization in IgE-mediated food allergy, yet the role of myeloid cells in acquisition of tolerance is unclear. CD300 receptors regulate activation of myeloid cells, with CD300f acting as an inhibitory receptor and CD300b as an activating receptor. Their modulation during OIT may reflect effector cell reprogramming and serve as biomarkers of treatment response. MethodsThirty-five patients undergoing OIT were prospectively enrolled. Peripheral blood was collected at baseline and first 3 months of up-dosing; 19 patients completed sampling upon reaching maintenance. CD300b and CD300f expression in eosinophils, monocytes, and neutrophils was analyzed by flow cytometry. Allergen-specific IgE and IgG4 were measured by ImmunoCAP. Associations with clinical parameters were assessed using logistic regression. Results. Baseline CD300b was higher in patients with lower starting doses (p[≤]0.05). CD300f expression was lower in those with atopic dermatitis or multiple food allergies (p[≤]0.03). A significant downregulation of CD300b expression in the surface of eosinophils, monocytes, and neutrophils, was noted early in treatment (p[≤]0.05). Expression of CD300f was slightly but non-significantly increased. Longitudinally, the expression of CD300f increased on eosinophils, whereas CD300b expression decreased on the surface of monocytes and neutrophils. Specific IgE reduction correlated with downregulation of CD300b expression in monocytes (R=0.51, p=0.02) and higher CD300f expression in eosinophils (R=-0.45, p=0.05). ConclusionsDownregulation of CD300b and upregulation of CD300f during OIT suggests myeloid cell reprogramming toward a less inflammatory phenotype. These dynamic changes in expression and their correlation with serologic markers of desensitization, suggest CD300b and CD300f as candidate biomarkers for understanding and monitoring OIT response. Key MessageO_LIOIT is associated with downregulation of the activating receptor CD300b and upregulation of the inhibitory receptor CD300f on myeloid cells. C_LIO_LIMyeloid cell reprogramming accompanies OIT, extending immune tolerance beyond adaptive regulatory mechanisms. C_LIO_LICD300b and CD300f expression dynamics correlate with clinical dosing and serologic markers of OIT response. C_LI

immunology↗

bioRxiv2025

Epigenomic and transcriptomic analyses reveal cnidocyte specialization in a sea anemone

Cnidarians, including corals, hydras, jellyfish, and sea anemones, possess specialized stinging cells called cnidocytes that function in prey capture and defense. These cells represent a striking evolutionary innovation and produce distinct types of organelles such as venom injecting nematocysts and mechanically entangling spirocysts. While their biomechanics and transcriptional regulation have been studied extensively, little is known about their epigenetic regulation. Here, we combined epigenetic profiling with RNA sequencing in the sea anemone Nematostella vectensis to explore regulatory programs underlying cnidocyte diversity. We identified cell-type-specific regulatory elements in promoter and enhancer regions and linked them to distinct gene expression programs. This analysis revealed fundamental differences between nematocytes and spirocytes and uncovered a previously unrecognized nematocyte population that expresses the Nep3 toxin but lacks most other toxins. These findings highlight the complexity of cnidocyte regulation and suggest greater cellular diversity within this defining cnidarian cell type than previously appreciated.

evolutionary biology↗

bioRxiv2025

Identification of genetic and non-genetic modifiers of genomic imprinting through whole genome screening in humans

Genomic imprinting is required for normal development, and abnormal methylation of differentially methylated regions (iDMRs) controlling the parent of origin-dependent expression of the imprinted genes has been found in constitutional disorders affecting growth, metabolism, neurobehavior, and in cancer. In most of these cases the cause of the imprinting abnormalities is unknown. Also, these studies have generally been performed on a limited number of CpGs, and a systematic investigation of iDMR methylation in the general population is lacking. By analysing the iDMRs in a large number of peripheral blood DNA methylation array datasets of unaffected individuals and patients with rare disorders, we determined the most common iDMR methylation profiles and identified many genetic and non-genetic factors contributing to their variability. We found that methylation variability is not homogeneous within the iDMRs and that the CpGs closer to the ZFP57 binding sites are less susceptible to methylation changes. We demonstrated the methylation polymorphism of three iDMRs and the atypical behaviour of several others, and reported the association of 25 disease- and 47 non-disease-complex traits, including blood cell type composition, as well as 15 mendelian or chromosomal disorders, with iDMR methylation changes in blood DNA. These findings identify several genetic and non-genetic factors associated with genomic imprinting maintenance in humans, which may have a role in the aetiology of the diseases associated with imprinting abnormalities and have clear implications in molecular diagnostics.

genetics↗

bioRxiv2025

Effect of obesity on the acute response to SARS-CoV-2 infection and development of post-acute sequelae of COVID-19 (PASC) in nonhuman primates

Long-term adverse consequences of SARS-CoV-2 infection, termed "long COVID" or post-acute sequelae of COVID (PASC), are a major component of overall COVID-19 disease burden. Prior obesity and metabolic disease increase the severity of acute disease, but SARS-CoV-2 infection also contributes to the development of new-onset metabolic disease. Since the COVID pandemic occurred in the context of the global obesity epidemic, an important question is the extent to which pre-existing obesity modifies long-term responses to SARS-CoV-2 infection. We utilized a nonhuman primate model to compare the effects of infection with the SARS-CoV-2 delta variant in lean and obese/insulin-resistant adult male rhesus macaques over a 6-month time course. While some longitudinal responses to SARS-CoV-2 infection, including overall viral dynamics, SARS-CoV-2-specific IgG induction, cytokine profiles, and tissue persistence of viral RNA, did not appreciably differ between lean and obese animals, other responses, including neutralizing Ab dynamics, lung pathology, body weight, degree of insulin sensitivity, adipocytokine profiles, body temperature, and nighttime activity levels were significantly different in lean versus obese animals. Furthermore, several parameters in lean animals were altered following SARS-CoV-2 infection to resemble those in obese animals. Notably, persistent changes in multiple parameters were present in most animals, suggesting that PASC may be more prevalent than estimated from self-reported symptoms in human studies.

pathology↗

bioRxiv2025

Make it grow, Pseudozyma aphidis extract promotes plant growth

Increasing global population demands higher agricultural yield while avoiding the use of harmful products in agriculture. The use of beneficial micro-organisms is an Eco-friendly approach to reduce the use of fertilizers and plant growth promoting (PGP) products. This study is focused on the fungus Pseudozyma aphidis (P. aphidis), a yeast like dimorphic fungus beneficial to plants and related to the phytopathogenic fungus Ustilago maydis that causes corn smut disease. Our lab isolated a unique P. aphidis strain (PA12) that has shown significant plant protection and plant growth activity. We extracted and screened the active PGP fraction from PA12, calibrated treatment dosage and application method. Tomato, corn and melon plants treated with PA12 extract exhibited; increased germination, shoot length, biomass and higher yield. Our results demonstrate the potential of P. aphidis extract application as an eco-friendly PGP agent that can contribute to reduction of harmful agricultural products usage.

plant biology↗

bioRxiv2025

Pseudozyma aphidis bio-active extract inhibit plant pathogens and activate induce resistance in tomato plants

The constant growth in the world population demands a constant increase in agricultural yields. One of the main ways to increase agricultural yields is by improving the control of pests and pathogens. Human health and environmental concerns regarding the traditional synthetic pesticides challenge the scientific community to discover new and less harmful ways to control pests, such as the development of biocontrol agents and natural-based pesticides. Previous studies have established that application of live P. aphidis can be used for biocontrol of diverse fungal and bacterial phytopathogens. Here demonstrate activity of two semi-purified fractions from P. aphidis, one containing the antimicrobial metabolites and the other containing the resistance inducing metabolites. Our results from the in vitro experiments with the antimicrobial extract show that P. aphidis metabolites strongly inhibit important fungal and bacterial phytopathogens. In planta experiments demonstrated a significant, dose-dependent reduction in disease infection when a spore suspension of B. cinerea was treated or exposed to the extracted metabolites. From the other hand, our results showed that the application a semi-purified aqueous fraction from P. aphidis on tomato plants rapidly up-regulated the expression of defense-related genes, which are associated with both the induced systemic resistance and the systemic acquired resistance pathways. In conclusion, this study further enhances our understanding of the biochemical mechanisms behind P. aphidis main modes of action: antibiosis and induced resistance. It also demonstrates the great potential of this unique biocontrol agent as a source for new natural-based pesticides and/or enhanced resistance substances.

microbiology↗

bioRxiv2023

Evidence for kilometer-scale biophysical features at the Gulf Stream front

Understanding the interplay of ocean physics and biology, particularly at the submesoscale and below (<30km), is an ongoing challenge in oceanography. While poorly constrained, these scales may be of critical importance for understanding how changing ocean dynamics will impact marine ecosystems. Fronts in the ocean, regions where two disparate water masses meet and isopycnals become tilted towards vertical, are considered hotspots for biophysical interaction, but there is limited observational evidence at the appropriate scales to assess their importance. Western boundary currents like the Gulf Stream are of particular interest as these dynamic physical regions are thought to influence both productivity and composition of primary producers; however, how exactly this plays out, and at what scales, is not well known. Using satellite data and two years of detailed in situ observations across the Gulf Stream front near Cape Hatteras, North Carolina, U.S.A., we investigate how submesoscale frontal dynamics could affect biological communities associated with frontal regions and generate hotspots of productivity and export. In this analysis we assess the seasonality and phenology of the region, generalize the kilometer-scale structure of the front, and analyze 69 transects to assess two physical processes of potential biogeochemical importance: cold shelf filament subduction and high salinity Sargasso Sea obduction. We link these processes observationally to the meander phase of the Gulf Stream and discuss how cold filament subduction could be exporting carbon and how obduction of high salinity water from depth often leads to high chlorophyll-a. Finally, we report on phytoplankton community composition in each of these features and integrate these new observations into our understanding of frontal submesoscale dynamics. Plain Language SummaryPhytoplankton move with large currents and are stirred by eddies with diameters ranging from 100s of kilometers down to the meter scale. Their growth is impacted by physical factors like light and temperature and also chemical and biological factors like nutrient availability, and their accumulation is also impacted by top down controls (zooplankton grazing, viral lysis) and competition with other phytoplankton. This interplay of physics and biology in determining the biomass and composition of phytoplankton communities is poorly understood and is key to understanding marine ecosystem resilience and structure in a changing ocean. In this work we investigated the impact of physics and biology on phytoplankton across scales focusing on the Gulf Stream front. Fronts in the ocean are where lines of equal density go from being horizontal to having a vertical tile, and because of this can enable nutrients and plankton to move from depth to the surface and vice versa. The objective of this work is to understand how physics might drive important changes in phytoplankton biomass and composition in the Gulf Stream front, which is amongst the sharpest gradients in temperature, density, and current speed in the global ocean. We find two frequent processes at the front, the apparent subduction of cold filaments down along the edge of the Gulf Stream, associated with meander troughs, and obduction of high salinity Sargasso Sea water into the front linked to meander crests. While ephemeral, these processes are frequent and could have a large impact on local phytoplankton biomass, phytoplankton composition, and the export of organic matter to depth. Key PointsO_LIThe frontal zone between the Gulf Stream and the shelf has an interface water mass which appears to have different origins with a range of biogeochemical impacts. C_LIO_LIMeanders appear to largely control the frontal interface: troughs lead to subduction of shelf filaments and crests lead to obduction of high salinity water. C_LIO_LIThese two processes are common at the front and could lead to ephemeral kilometer- scale export and productivity. C_LI

ecology↗

bioRxiv2023

Hippocampal Ripples linked to Declarative Memory Judgments in Children

Intracranial studies have demonstrated significant roles for hippocampal ripples in human declarative memory. Yet, the developmental trajectory and contribution of ripples to memory processes in children remain unknown. We studied hippocampal ripple activity using intracranial recordings in 14 children (age: 6-14) undergoing epilepsy monitoring. After watching a pink panther cartoon twice, participants engaged in an old/new recognition test, determining whether events portrayed in short (4s) videoclips stemmed from the cartoon they had just viewed. Our results reveal a significant rise in ripple rate during successful recognition of familiar events. An anticipatory decline in ripple rate preceded recognition errors. Interestingly, when participants viewed the cartoon passively during the initial full-length screenings, the overall temporal pattern of ripple activation remained consistent across repetitions, and significantly distinct from explicit recognition. We conclude that hippocampal ripples in children play a key role in declarative memory, supporting the explicit identification of previously encountered events.

neuroscience↗

bioRxiv2023

Investigating a Gulf Stream Frontal Eddy North of Cape Hatteras: Questioning Overall Impacts on Ecology

Ocean physics and biology can interact in myriad and complex ways. Eddies, features found at many scales in the ocean, can drive substantial changes in physical and biogeochemical fields with major implications for marine ecosystems. Mesoscale eddies are challenging to model and difficult to observe synoptically at sea due to their fine-scale variability yet broad extent. In this work we observed a frontal eddy just north of Cape Hatteras via an intensive hydrographic, biogeochemical, and optical sampling campaign. Frontal eddies occur in western boundary currents around the globe and there are major gaps in our understanding of their ecosystem impacts. In the Gulf Stream, frontal eddies have been studied in the South Atlantic Bight, where they are generally assumed to shear apart passing Cape Hatteras. However, we found that the observed frontal eddy had different physical properties and phytoplankton community composition from adjacent water masses, in addition to continued cyclonic rotation. In this work we first synthesize the overall ecological impacts of frontal eddies in a simple conceptual model. This conceptual model led to the hypothesis that frontal eddies could be well timed to supply zooplankton to secondary consumers off Cape Hatteras where there is a notably high concentration and diversity of top predators. Towards testing this hypothesis and our conceptual model we report on the biogeochemical state of this particular eddy connecting physical and biological dynamics, analyze how it differs from Gulf Stream and shelf waters even in "death", and refine our initial model with this new data. Key PointsO_LIIn-depth investigation of a frontal eddy in the Gulf Stream off Cape Hatteras, North Carolina C_LIO_LIContinued physical and biogeochemical differences are observed between the eddy and adjacent water masses even as it begins to shear apart C_LIO_LIWe share a conceptual model of the ecological impact of frontal eddies with a hypothesis that they supply zooplankton to secondary consumers C_LI Plain Language SummaryFrontal eddies are spinning masses of water (~30km in diameter) that move along western boundary currents like the Gulf Stream. When they form they carry productive coastal water into the Gulf Stream and drive upwelling within their cores. Together this leads to an increase in the amount of phytoplankton within them - much higher compared to surrounding nutrient-limited Gulf Stream water. On the east coast of the United States one common area of frontal eddy formation is just off Charleston, SC. Eddies then travel up the coast and dissipate near Cape Hatteras, NC. In this work we measured a wide range of physical and biological properties of a frontal eddy just north of Cape Hatteras. We compared these properties within the eddy to the coastal water on one side and the Gulf Stream water on the other, finding clear differences in phytoplankton community composition and other physical and chemical properties. Using the results of these observations together with previous studies we share a simple model for how frontal eddies may impact phytoplankton, zooplankton, and fish - hypothesizing that they may contribute to the high diversity and density of top predators off Cape Hatteras.

ecology↗

bioRxiv2023

Phytoplankton adaptive resilience to climate change collapses in case of extreme events; A modeling study

As climate change unravels, ecosystems are facing a warming of the climate and an increase in extreme heat events that are unprecedented in recent geological history. We know very little of the ability of oceanic phytoplankton communities, key players in the regulation of Earths climate by the oceans, to adapt to these changes. Quantifying the resilience of phytoplankton communities to environmental stressors by means of adaptive evolution is however crucial to accurately predict the response of marine ecosystems to climate change. In this work, we use an eco-evolutionary model to simulate the adaptive response of marine phytoplankton to temperature changes in an initially temperate oligotrophic water-column. By exploring a wide range of scenarios of phytoplankton adaptive capacity, we find that phytoplankton can adapt to temperature increases -even very large ones- as long as they occur over the time scale of a century. However, when rapid and extreme events of temperature change are considered, the phytoplankton adaptive capacity breaks down in a number of our scenarios in which primary productivity plummets as a result. This suggests that current Earth System Models implicitly assuming perfect and instantaneous phytoplankton adaptation to temperature might be overestimating the phytoplanktons resilience to climate change.

ecology↗

bioRxiv2022

Iron Chelation Improves Ineffective Erythropoiesis and Iron Overload in Myelodysplastic Syndrome Mice

Myelodysplastic syndrome (MDS) is a heterogeneous group of bone marrow stem cell disorders characterized by ineffective hematopoiesis and cytopenias, most commonly anemia. Red cell transfusion therapy for anemia in MDS results in iron overload, correlating with reduced overall survival. Whether treatment of iron overload benefits MDS patients remains controversial. We evaluate underlying iron-related pathophysiology and the effect of iron chelation using deferiprone on erythropoiesis in NUP98-HOXD13 transgenic mice, a highly penetrant well-established MDS mouse model. Our results characterize an iron overload phenotype with aberrant erythropoiesis in these mice which was reversed by deferiprone-treatment. Serum erythropoietin level decreased while erythroblast erythropoietin receptor expression increased in deferiprone-treated MDS mice. We demonstrate, for the first time, normalized expression of the iron chaperones Pcbp1 and Nco4 and increased ferritin stores in late stage erythroblasts from deferiprone-treated MDS mice, evidence of aberrant iron trafficking in MDS erythroblasts. Importantly, erythroblast ferritin is increased in response to deferiprone, correlating with decreased erythroblast ROS. Finally, we confirmed increased expression of genes involved in iron uptake, sensing, and trafficking in stem and progenitor cells from MDS patients. Taken together, our findings provide evidence that erythroblast-specific iron metabolism is a novel potential therapeutic target to reverse ineffective erythropoiesis in MDS. BRIEF SUMMARYIneffective erythropoiesis in MDS mice correlates with aberrant iron trafficking within bone marrow erythroblasts, consistent with findings in MDS patient progenitors, reversed after iron chelation.

pathology↗

bioRxiv2022

Cost-efficient whole genome-sequencing using novel mostly natural sequencing-by-synthesis chemistry and open fluidics platform

We introduce a massively parallel novel sequencing platform that combines an open flow cell design on a circular wafer with a large surface area and mostly natural nucleotides that allow optical end-point detection without reversible terminators. This platform enables sequencing billions of reads with longer read length ([~]300bp) and fast runs times (<20hrs) with high base accuracy (Q30 > 85%), at a low cost of $1/Gb. We establish system performance by whole-genome sequencing of the Genome-In-A-Bottle reference samples HG001-7, demonstrating high accuracy for SNPs (99.6%) and Indels in homopolymers up to length 10 (96.4%) across the vast majority (>98%) of the defined high-confidence regions of these samples. We demonstrate scalability of the whole-genome sequencing workflow by sequencing an additional 224 selected samples from the 1000 Genomes project achieving high concordance with reference data.

genomics↗