Biology subjects

Murray, M.

Publications and source records attributed to Murray, M..

At least 19 recordsLinked to original sources

bioRxiv2026

An open imaging and AI resource enabling unbiased quantification of extrachromosomal DNA at scale

Quantitative imaging of extrachromosomal DNA (ecDNA) is increasingly important for studying cancer heterogeneity and adaptation, yet automated analysis has been limited by the absence of accessible imaging data, gold standard annotations and adaptable computational tools. Here we establish an open resource for computational ecDNA imaging, integrating 2,986 native-resolution metaphase FISH image sets with manual annotations, standardized benchmarks and open-source quantification frameworks. We use this resource to systematically compare existing and newly developed approaches spanning rule-based computer vision, deep-learning-based segmentation and probabilistic localization. This comparison reveals count-dependent underestimation that distorts ecDNA copy-number distributions and motivates ecCount, a probabilistic localization method developed here to preserve individual ecDNA signals and quantitative burden. ecCount achieves an object-level F1 score of 0.939 on held-out images with minimal count bias. Together, the images, annotations, retrainable models, evaluation tools and guided workflows provide community infrastructure for applying, adapting and improving automated ecDNA quantification across experimental systems.

genetics↗

bioRxiv2026

CD1b-specific T cells are transcriptionally closer to conventional CD4 T cells than to innate-like NKT and MAIT cells

Unconventional T cells recognize non-peptide antigens presented by molecules other than the major histocompatibility complex (MHC) proteins. Among unconventional T cells, natural killer T (NKT) cells, which recognize CD1d-lipid complexes, mucosal-associated invariant T (MAIT) cells, which recognize MR1-metabolite complexes, and {gamma}{delta} T cells, are thoroughly studied. CD1b presents self- and mycobacterial lipids to relatively understudied T cell subsets. Like MAIT cells and type I NKT cells, CD1b-specific cells include subpopulations with conserved TCRs. Consequent to their recognition of a nearly monomorphic antigen-presenting molecule, CD1b-specific T cells might share innate-like features with MAIT, type I NKT, and {gamma}{delta} T cells. Due to their low frequency in the peripheral blood, CD1a-, CD1b-, and CD1c-specific T cells have been studied predominantly as in vitro-expanded clones, so even basic information about their native ex vivo immunophenotypes is lacking. Here, we sort and transcriptionally profile ex vivo two T cell populations that recognize CD1b presenting mycobacterial mycolipids and compare them with conventional CD4 and CD8 T cells, {gamma}{delta} T cells, NK cells, MAIT cells, and NKT cells. We show that both the invariant TCR-expressing CD4+, CD1b-GMM-specific germline encoded mycolyl-reactive (GEM) T cells, as well as the diverse TCR-expressing CD1b-GMM-specific T cells, are transcriptionally closer to conventional T cells than to the innate-like T cell populations {gamma}{delta}, MAIT and type I NKT cells. Thus, despite their recognition of non-polymorphic antigen presenting molecules, CD1b-specific T cells show adaptive rather than innate-like transcriptional features.

immunology↗

bioRxiv2026

Dissecting Complex Interactions Between Ferroptosis and the Proteasome

The proteasome is an essential multiprotein complex whose inhibition can lead to apoptosis. Ferroptosis is a non-apoptotic cell death mechanism whose fundamental regulation continues to be elucidated. How proteasome function regulates ferroptosis sensitivity is poorly understood and difficult to study given the essential nature of the proteasome. Here, we isolated the effects of proteasome inhibition on ferroptosis by combining direct cell death imaging, cell death pathway-specific inhibitors, and mathematical modeling. We find that proteasome inhibition enhances sensitivity to ferroptosis induced by glutathione peroxidase 4 (GPX4) inhibition while simultaneously promoting resistance to ferroptosis induced by system x - inhibition. Sensitization to GPX4 inhibition requires protein synthesis but not the apoptosis execution machinery and is opposed by the activating transcription factor 4 (ATF4) stress response pathway. This work demonstrates a complex role for proteasome function in ferroptosis regulation and establishes new methods to dissect cross-talk between ferroptosis and essential cellular processes.

cell biology↗

bioRxiv2026

Leptospirosis in Southern Sea Otters from Central California: Detection of Fatal Infections and Pathologic Findings

Leptospira interrogans serovar Pomona infections cause periodic outbreaks among California sea lions (CSL; Zalophus californianus) and sporadic deaths in phocids; however, frequency of infection and associated health impacts are uncharacterized among sympatric threatened southern sea otters (SSO; Enhydra lutris nereis), which are important sentinels of coastal health. Given the broad impacts of L. interrogans on other marine mammals, our objective was to screen selected SSO for infection, determine whether leptospirosis contributes to SSO mortality, and describe leptospiral-associated lesions. A retrospective review (2005-2025) yielded 19 candidates that underwent case review, including Leptospira immunohistochemistry (IHC), serology, and polymerase chain reaction (PCR), with a special focus on renal and hepatic lesions. Kidney was PCR-positive for 74% (14/19) of suspected cases and for eight of these, DNA sequence-based serogroup typing detected L. interrogans serogroup Pomona. Seven of the 14 PCR-positive leptospirosis cases were classed as fatal based on positive renal IHC and moderate to severe tubulointerstitial nephritis. All fatal cases had anti-L. interrogans serovar Pomona antibody titers [≥]1:25,600. All remaining (n=7) PCR-positive cases were considered nonfatal leptospirosis cases due to minimal and/or unrelated renal lesions, and negative IHC. Nonfatal Leptospira-infected cases ranged from seronegative to low positive (1:400) for serovar Pomona. Antibody titers for Leptospira PCR-negative cases were negative. For fatal cases, gross renal changes were often inapparent or characterized by miliary white cortical foci. Renal histologic lesions included tubulointerstitial nephritis, acute tubular necrosis and suppurative tubulitis with intratubular bacteria in fatal cases, and positive IHC staining for leptospiral antigen in lesions. Gross hepatic changes were also inapparent in fatal cases and histologic lesions were rare, characterized in one animal by hepatocellular disassociation and in two sea otters by limited leptospiral antigen detection by IHC. Most Leptospira-infected sea otters (71%, 10/14) stranded during higher rainfall months in California, suggesting possible land-to-sea transmission from terrestrial hosts. Given these findings, and because L. interrogans serovar Pomona infections have been confirmed in sympatric CSLs and terrestrial mammals from adjacent watersheds, focused investigation of potential marine and terrestrial disease transmission dynamics could provide new information to reduce mortalities of SSO.

pathology↗

bioRxiv2025

A Dynamical Density Functional Theory Framework for Non-Equilibrium Phase Dynamics in Biomolecular Condensates

Biomolecular condensates, membrane-less organelles that arise from liquid-liquid phase separation (LLPS) of proteins and nucleic acids, play vital roles in cellular organization and regulation. Computational modeling is crucial for uncovering the molecular mechanisms behind LLPS; however, the fluctuations across a wide range of spatial scales and the inherently non-equilibrium nature of these systems make capturing their long-timescale dynamics particularly challenging. Here, we present a continuum dynamical density functional theory (DDFT) framework that captures the non-equilibrium dynamics of LLPS by integrating a physics-based statistical mechanical theory with key experimentally-derived parameters. Our model couples DDFT with a continuum free energy functional, incorporating two-body correlations between monomers and surface tension effects to determine binodal densities under phase coexistence. By solving the DDFT equations, we describe the time evolution of phase-separated domains, capturing key long-timescale processes such as droplet maturation, coalescence, and interface relaxation, phenomena that are difficult to probe using atomistic or mesoscale coarse-grained simulations. This implementation integrates experimental phase equilibrium data with molecular-scale descriptors, such as amino acid properties, to construct a quantitative link between molecular interactions and macroscopic phase behavior. However, the approach is generalizable, providing a foundation for self-contained molecular-to-continuum modeling bridge platforms.

biophysics↗

bioRxiv2025

Immunometabolic Reprogramming of Monocytes in Tuberculosis Infection and Disease

RationaleMonocytes are central to host defence against Mycobacterium tuberculosis (Mtb), yet their functional and metabolic profiles during latent TB infection (TBI) and active TB disease (TBD) remain poorly defined. Immunometabolic dysfunction may underlie ineffective responses in TB, but cell-specific mechanisms are unclear. ObjectivesTo compare the phenotypic, functional, and metabolic profiles of circulating monocytes from individuals with TBI, TBD, and healthy controls (HC), and assess the impact of treatment. MeasurementsPeripheral blood monocytes were profiled using high-dimensional flow cytometry, Luminex cytokine/chemokine assays, and SCENITH, a flow-based metabolic assay. Unstimulated and Mtb-stimulated monocytes from treatment-naive and treated individuals were analysed. Main ResultsMonocytes from TBI and TBD showed distinct phenotypes from HC, marked by elevated CD14 and CD45RA. HLA-DR was reduced in TBI versus HC and further decreased in TBD. TNF receptors were downregulated in TBI but unchanged in TBD. Baseline cytokine and chemokine profiles in TBI and TBD were similar (yet distinct from HC), but Mtb stimulation elicited a stronger cytokine response in TBI. Metabolically, TBI and TBD monocytes exhibited increased glycolysis and reduced mitochondrial dependence versus HC. Treatment partially restored mitochondrial function. Upon Mtb challenge, TBI monocytes had higher glycolytic capacity than TBD. ConclusionsMonocyte metabolic plasticity and cytokine production distinguish latent from active TB and are partially reversible with treatment. Circulating monocyte metabolism reflects TB immune status and may serve as a biomarker or therapeutic target. Reprogrammed glycolytic profiles in TBI contrast with impaired adaptability in TBD, suggesting dysfunctional myeloid activation during disease.

immunology↗

bioRxiv2025

Accessory subunits of PRC2 mimic H3K27me3 to restrict the spread of Polycomb domains

The Polycomb repressive complex 2 (PRC2) is essential for normal development by maintaining developmental gene repression. PRC2 deposits the repressive chromatin mark H3 lysine 27 tri-methyl (H3K27me3) through a read-write loop that involves direct interactions between PRC2 and H3K27me3. According to current models, the PRC2-H3K27me3 read-write loop is initiated by the PRC2 subunits JARID2 and PALI1 that mimic H3K27me3. However, it is unknown what restricts the PRC2-H3K27me3 read-write loop from spreading H3K27me3 indefinitely. To answer this question, we generated mutant mice where PRC2 subunits cannot mimic H3K27me3. Unexpectedly, the mutations led to delayed Hox genes activation and a homeotic transformation characteristic of a Polycomb gain-of-function in vivo and the spread of H3K27me3 beyond Polycomb domains in stem cells. Collectively, we show that H3K27me3 mimicry evolved to compete against the PRC2-H3K27me3 read-write loop in a process that restrains PRC2 and restricts the spread of Polycomb domains. HighlightsO_LIH3K27me3 mimicry antagonises Polycomb function in vivo. C_LIO_LIJARID2 and PALI1 synergise to allosterically regulate PRC2 during development. C_LIO_LIH3K27me3 mimicry by JARID2 and PALI1 antagonises PRC2 in stem cells. C_LIO_LIJARID2 and PALI1 mimic H3K27me3 to restrict the spread of Polycomb domains. C_LI

molecular biology↗

bioRxiv2025

Tissue-dependent mechanosensing by cells derived from human tumors

Alterations of the extracellular matrix (ECM), including both mechanical (such as stiffening of the ECM) and chemical (such as variation of adhesion proteins and deposition of hyaluronic acid (HA)) changes, in malignant tissues have been shown to mediate tumor progression. To survey how cells from different tissue types respond to various changes in ECM mechanics and composition, we measured physical characteristics (adherent area, shape, cell stiffness, and cell speed) of 25 cancer and 5 non-tumorigenic cell lines on 7 different substrate conditions. Our results indicate substantial heterogeneity in how cell mechanics changes within and across tissue types in response to mechanosensitive and chemosensitive changes in ECM. The analysis also underscores the role of HA in ECM with some cell lines showing changes in cell mechanics in response to presence of HA in soft substrate that are similar to those observed on stiff substrate. This pan-cancer investigation also highlights the importance of tissue-type and cell line specificity for inferences made based on comparison between physical properties of cancer and normal cells. Lastly, using unsupervised machine learning, we identify phenotypic classes that characterize the physical plasticity, i.e. the distribution of physical feature values attainable, of a particular cell type in response to different ECM-based conditions.

biophysics↗

bioRxiv2024

Fluorescence lifetime-based FRET biosensors for monitoring N-terminal domain interactions of TDP-43 in living cells: A novel resource for ALS and FTD drug discovery

TAR DNA-binding protein 43 (TDP-43) pathological aggregates are widely implicated in Alzheimers disease, frontotemporal dementia and amyotrophic lateral sclerosis. While therapeutic platforms targeting TDP-43 have predominantly targeted its aggregation, recent findings suggest that loss of functional TDP-43 dimers and multimers -- essential for RNA processing -- occur upstream of aggregation and is driven through disruption of N-terminal domain (NTD) interactions. Here, we demonstrate that these interactions are targetable via cellular fluorescence lifetime-based FRET biosensors which we used to screen the FDA-approved Selleck library. Our NTD-specific hit ketoconazole rescues sorbitol-induced TDP-43 mislocalization and aggregation, and ameliorates TDP-43 induced downregulation of SREBP2, a TDP-43 mRNA binding target with known implication in ALS. In addition, ketoconazole improves neurite outgrowth in a TDP-43 overexpressing neuron model and motor dysfunction in TDP-43 overexpressing C. elegans. Taken together, our platform represents a novel approach for targeting NTD-dependent TDP-43 interactions, and the identification of ketoconazole validates an exciting translational premise for TDP-43 drug discovery.

neuroscience↗

bioRxiv2024

Long-read transcriptomic identification of synaptic adaptation to amyloid pathology in the App(NL-G-F) knock-in mouse model of the earliest phase of Alzheimer's disease

Genome-wide association studies (GWAS) have identified a transcriptional network of Alzheimers disease (AD) risk genes that are primarily expressed in microglia and are associated with AD pathology. However, traditional short-read sequencers have limited our ability to fully characterize how GWAS variants exert their effects on gene expression regulation or alternative splicing in response to the pathology, particularly resulting in inaccurate detection of splicing. To address this gap, we utilized long-read RNA-sequencing (RNA-seq) in the AppNL-G-F knock-in mouse model to identify changes in splicing and novel transcript isoforms in response to amyloid-{beta}. We show that long-read RNA-seq can recapitulate the expected induction of microglial expressed risk genes such as Trem2 in response to amyloid-{beta} at 9 months of age associated with ageing-dependent deficiencies in spatial short-term memory in the AppNL-G-F knock-in mice. Our results not only identified novel splicing events and transcript isoform abundance in genes associated with AD, but also revealed the complex regulation of gene expression through splicing in response to amyloid plaques. Surprisingly, the regulation of alternative splicing in response to amyloid was seen in genes previously not identified as AD risk genes, expressed in microglia, neurons and oligodendrocytes, and included genes such as Syngr1 that modulate synaptic physiology. We saw alternative splicing in genes such as Ctsa, Clta, Dennd2a, Irf9 and Smad4 in mice in response to amyloid, and the orthologues of these genes also showed transcript usage changes in human AD brains. Our data suggests a model whereby induction of AD risk gene expression associated with microglial proliferation and activation is concomitant with alternative splicing in a different class of genes expressed by microglia and neurons, which act to adapt or preserve synaptic activity in response to amyloid-{beta} during early stages of the disease. Our study provides new insights into the mechanisms and effects of the regulation of genes associated with amyloid pathology, which may ultimately enable better disease diagnosis, and improved tracking of disease progression. Additionally, our findings identify new therapeutic avenues for treatment of AD.

genetics↗

bioRxiv2024

Ancient genomics reveals a genetic continuum with dual structure in the Classic Copan

Copan was a major capital at the southeasternmost of the Maya civilization, serving as a crossroads connecting Central and South America. In 426/427 CE, the city witnessed the establishment of a royal dynasty, which endured for approximately 400 years. Despite extensive historical and archaeological records, there remains limited information regarding the genetic origins of people who resided in Copan. Here, we present seven Classic Copan genomes including an enigmatic dynastic ruler and his sacrificed companion. Our analysis identifies a high genetic affinity of the Classic Copan with present-day Maya. Both groups exhibit an admixture of Mesoamerican and South American Farmer (SAF) ancestry, with a shift in a dominant component from SAF to Mesoamerican. At the individual level, commoners show a more prominent SAF ancestry, while the royal individual demonstrates nearly equal contributions from two ancestors. These results highlight a dual ancestral structure in this geographic extreme of the Classic Maya state, uncovering a cline of Mesoamerican ancestry across individuals.

evolutionary biology↗

bioRxiv2024

MU-BRAIN: MUltiethnic Brain Rna-seq for Alzheimer INitiative

Alzheimers Disease (AD) exhibits a complex molecular and phenotypic profile. Investigating gene expression plays a crucial role in unraveling the diseases etiology and progression. Transcriptome data across ethnic groups lack, negatively impacting equity in intervention and research. We employed 565 brains across six U.S. brain banks (n=399 non-Hispanic Whites, n=113 Hispanics, n=12 African Americans) to generated bulk RNA sequencing from prefrontal cortex. We sought to identify cross-ancestry and ancestry-specific differentially expressed genes (DEG) across Braak stages, adjusting for sex, age at death, and RNA quality metrics. We further validated our findings using the Religious Orders Study/Memory Aging Project brains (ROS/MAP; n=1,095) and performed metanalysis (n=1,660). We conducted Gene Set and Variation and Enrichment analysis (GSVA; GSEA). We employed a machine-learning approach for phenotype prediction and gene prioritization to construct a polytranscriptomics risk score (PTRS) splitting our sample into training and testing sub-samples, either randomly or by ethnicity ("ancestry-agnostic" and "ancestry-aware", respectively). Lastly, we validated top DEG using single-nucleus RNA sequencing (snRNAseq) data. We identified several DEG associated with Braak staging: AD-known genes VGF (Padj =3.78E- 07) and ADAMTS2 (Pad j=1.21E-04) were consistently differentially expressed across statistical models, ethnicities, and replicated in ROS/MAP. Genes from the heat shock protein (HSP) family, e.g. HSPB7 (Padj =3.78E-07), were the top differentially expressed genes and replicated in ROS/MAP. Ethnic-stratified analyses prioritized TNFSF14 and SPOCD1 as top Hispanics DEG. GSEA highlighted "Alzheimer disease" (Padj =4.24E-06) and "TYROBP causal network in microglia" (Padj =1.68E-08) pathways. Up- and down-regulated genes were enriched in several pathways (e.g. "Immune response activation signal pathways", "Vesicle-mediated transport in synapse", "cognition"). Ancestry-agnostic and ancestry-aware PTRS effectively classified brains (AUC=0.77 and 0.73 respectively) and replicated in ROS/MAP. snRNAseq validated prioritized genes, including VGF (downregulated in neurons; Padj=1.1 E-07). This is the largest diverse AD transcriptome in post-mortem brain tissue, to our knowledge. We identified perturbated genes, pathways and network expressions in AD brains resulting in cross- ethnic and ethnic-specific findings, ultimately highlighting the diversity within AD pathogenesis. The latter underscores the need for an integrative and personalized approach in AD studies.

genetics↗

bioRxiv2023

Neuroectoderm phenotypes in a human stem cell model of O-GlcNAc transferase intellectual disability

Most intellectual disabilities are caused by monogenic variation. Mutations in the O-GlcNAc transferase (OGT) gene have recently been linked to a novel congenital disorder of glycosylation (OGT-CDG), involving symptoms of possible neuroectodermal origin. To test the hypothesis that pathology is linked to defects in differentiation during early embryogenesis, we developed an OGT-CDG induced pluripotent stem cell lines together with isogenic controls generated by CRISPR/Cas9 gene-editing. Although the OGT-CDG variant leads to a significant decrease in OGT and O-GlcNAcase protein levels, there were no changes in differentiation potential or stemness. However, differentiation into ectoderm resulted in significant differences in O-GlcNAc homeostasis. Further differentiation to neuronal stem cells revealed differences in morphology between patient and control lines, accompanied by disruption of the O-GlcNAc pathway. This suggests a critical role for O-GlcNAcylation in early neuroectoderm architecture, with robust compensatory mechanisms in the earliest stages of stem cell differentiation.

developmental biology↗

bioRxiv2023

An O-GlcNAc transferase pathogenic variant that affects pluripotent stem cell self-renewal

O-linked {beta}-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential enzyme that modifies proteins with O-GlcNAc. Inborn OGT genetic variants were recently shown to mediate a novel type of Congenital Disorder of Glycosylation (OGT-CDG) which is characterized by X-linked intellectual disability (XLID) and developmental delay. Here, we report an OGTC921Y variant which co-segregates with XLID and epileptic seizures, and results in loss of catalytic activity. Colonies formed by mouse embryonic stem cells carrying OGTC921Y show decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4, Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. These data establish a link between OGT-CDG and embryonic stem cell self-renewal, providing a foundation for examining the developmental aetiology of this syndrome. Summary statementWe show that the C921Y O-GlcNAc transferase variant found in patients with intellectual disability leads to a defect in pluripotent stem cell self-renewal and decreased levels of stem cell markers.

molecular biology↗

bioRxiv2022

A ten-year community reporting database reveals rising coyote boldness and associated human concern in Edmonton, Canada

In cities throughout North America, sightings of coyotes (Canis latrans) have become common. Reports of human-coyote conflict are also rising, as is the public demand for proactive management to prevent negative human-coyote interactions. Effective and proactive management can be informed by the direct observations of community members, who can report their interactions with coyotes and describe the location, time, and context that led to their interactions. To assess the predictors of human-coyote conflict, we used a web-based reporting system to collect 9,134 community-supplied reports of coyotes in Edmonton, Canada, between January 2012 and December 2021. We used a standardized ordinal ranking system to score each report on two indicators of human-coyote conflict: coyote boldness, based on the reported coyote behaviour, and human perceptions about coyotes, determined from the emotions expressed by reporters. We assigned greater conflict scores to behaviours where coyotes followed, approached, charged or contacted pets or people, and to perceptions where reporters expressed fear, worry, concern, discomfort or alarm. Using ordered logistic regression and chi-square tests, we compared conflict scores for each response variable to spatial, temporal and contextual covariates. Our analysis showed that coyotes were bolder in less developed open areas and during the pup rearing season, but human perceptions were most negative in residential areas and during the dispersal season. Reports that mentioned dogs or cats were more likely to describe bolder coyote behaviour, and those that mentioned pets or children had more negative perceptions about coyotes. Coyote boldness and human perceptions both indicated rising human-coyote conflict in Edmonton over the 10 years of reporting.

ecology↗

bioRxiv2022

ROCK2 Knockout Improves Proliferation Rate in a Cellular Model of Down Syndrome

In a cellular model of Down Syndrome, hTERT immortalized RPE-1 (human retinal pigment epithelial-1) cells carrying an extra copy of chromosome 21 exhibit reduced fitness, in part, as an increase in doubling time (or a reduction in cell proliferation rate) in culture. ROCK2 (Rho associated coiled-coil containing kinase 2) was identified in a whole genome CRISPR knockout (KO) screen designed to identify genes and pathways that could be therapeutically targeted to improve cell proliferation (Replogle JM, et al. manuscript in preparation). ROCK2 KO cell lines of both RPE-1 euploid and trisomy 21 aneuploid cells were created using CRISPR. Trisomy 21 ROCK2 KO cell lines showed a modest increase in cell proliferation rate compared to the parental aneuploid cells, similar to the relative effect that ROCK2 knockout had in the whole genome CRISPR screen. Euploid ROCK2 KO cell lines showed no difference in growth rate vs their ROCK2 expressing counterparts. Changes in doubling time in response to two pharmaceutical ROCK inhibitors, Fasudil and Y27632, also showed the same modest increase in cell proliferation rate in the trisomy 21 cells. The actin cytoskeleton, a target of ROCK2 regulation, exhibited long stress fibers that aligned across multiple contiguous cells in confluent trisomy 21 ROCK2 KO cells compared to the disorganized stress fibers of the parental trisomy 21 cells with normal ROCK2 expression.

cell biology↗

bioRxiv2022

The mesoglea buffers the physico-chemical microenvironment of photosymbionts in the upside-down jellyfish Cassiopea sp.

The jellyfish Cassiopea has a conspicuous lifestyle, positioning itself upside-down on sediments in shallow waters thereby exposing its photosynthetic endosymbionts (Symbiodiniaceae) to light. Several studies have shown how the photosymbionts benefit the jellyfish host in terms of nutrition and O2 availability, but little is known about the internal physico-chemical microenvironment of Cassiopea during light-dark periods. Here, we used fiber-optic sensors to investigate how light is modulated at the water-tissue interface of Cassiopea sp. and how light is scattered inside host tissue. We additionally used electrochemical and fiber-optic microsensors to investigate the dynamics of O2 and pH in response to changes in the light availability in intact living specimens of Cassiopea sp. Mapping of photon scalar irradiance revealed a distinct spatial heterogeneity over different anatomical structures of the host, where oral arms and the manubrium had overall higher light availability, while shaded parts underneath the oral arms and the bell had less light available. White host pigmentation, especially in the bell tissue, showed higher light availability relative to similar bell tissue without white pigmentation. Microprofiles of scalar irradiance into white pigmented bell tissue showed intense light scattering and enhanced light penetration, while light was rapidly attenuated over the upper 0.5 mm in tissue with symbionts only. Depth profiles of O2 concentration into bell tissue of intact, healthy/living jellyfish showed increasing concentration with depth into the mesoglea, with no apparent saturation point during light periods. O2 was slowly depleted in the mesoglea in darkness, and O2 concentration remained higher than ambient water in large (> 6 cm diameter) individuals, even after 50 min in darkness. Light-dark shifts in large medusae showed that the mesoglea slowly turns from a net sink during photoperiods into a net source of O2 during darkness. In contrast, small medusae showed a more dramatic change in O2 concentration, with rapid O2 buildup/consumption in response to light-dark shifts; in a manner similar to corals. These effects on O2 production/consumption were also reflected in moderate pH fluctuations within the mesoglea. The mesoglea thus buffers O2 and pH dynamics during dark-periods.

ecology↗

bioRxiv2022

Outbreak of Highly Pathogenic Avian Influenza H5N1 in New England Seals

The recent incursion of Highly Pathogenic Avian Influenza A (H5N1) virus into North America and subsequent dissemination of virus across the continent, has had significant adverse impacts on domestic poultry, and has led to widespread mortality in many wild bird species. Here we report the recent spillover of H5N1 into marine mammals in the northeastern United States, with associated mortality on a regional scale. This spillover is coincident with a second wave of H5N1 in sympatric wild birds also experiencing regional mortality events. Viral sequences derived from both seal and avian hosts reveal distinct viral genetic differences between the two waves of infection. Spillover into seals was closely related to virus from the second wave, and one of eight seal-derived sequences had the mammalian adaptation PB2 E627K. One-Sentence SummaryAn outbreak of H5N1 in New England seals is the first known population-scale mammalian mortality event associated with the emerging highly pathogenic avian influenza clade 2.3.4.4b.

molecular biology↗