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Potter, S.

Publications and source records attributed to Potter, S..

14 recordsLinked to original sources

Asymmetric migration shapes genetic structure of the invasive avian vampire fly (Philornis downsi) across the Galapagos Islands.

Biological invasions on islands provide a natural framework to study how dispersal and connectivity influence evolutionary and ecological processes. The avian nest parasitic fly, Philornis downsi - first recorded in Darwins finch nests in 1997 - causes high mortality in endemic land birds, yet its inter-island and sex-specific patterns of dispersal and genetic structure remain poorly understood. We use low-coverage whole genome sequencing to investigate genome-wide patterns of genetic diversity, directional migration and effective population size in P. downsi across five major Galapagos Islands and its native range in mainland Ecuador. We find evidence for a genetic bottleneck in the Galapagos, isolation by distance, and evidence that the island closest to the Ecuadorian mainland, San Cristobal, is genetically divergent from the other four islands sampled, despite retaining the highest genetic diversity. No evidence was found for sex-biased dispersal; however, sex-biased genetic structure was detected using only markers from inferred autosomal scaffolds. We found asymmetric gene flow with higher migration rates from San Cristobal westward to the other islands, matching the direction of both southeast trade winds and major cargo shipping routes. Our results suggest both natural and human-mediated colonisation of P. downsi from the mainland through San Cristobal to the other islands, followed by high inter-island dispersal among closely situated sink islands. Our findings are critical for prioritising islands for control strategies that will reduce P. downsi impacts on vulnerable endemic birds and underscore the value of understanding directional migration patterns for managing invasive species in metapopulations.

evolutionary biology↗

Bathymetric Resolution-Dependent Biases in Antarctic Benthic Biodiversity Models: Hotspots Hold, Counts Shift

Antarctic benthic organisms are highly diverse and play a critical role in the Southern Ocean ecosystem. Despite decades of sampling, vast areas of the Antarctic continental shelf remain biologically unsurveyed due to logistical and financial constraints, limiting baseline knowledge essential for effective conservation planning. Species distribution models (SDMs) allow biodiversity to be inferred in the absence of biological data by linking benthic community patterns to environmental predictors. However, the resolution of the environmental predictors, particularly bathymetry, varies significantly between regions, casting doubt about how reliably SDMs can be used to predict into regions where only coarse-resolution data are available. Here, we show that SDMs trained on high-resolution data underestimate Antarctic benthic morphospecies richness by up to 18% when applied to aggregated coarse-resolution environmental data (and up to 50% when using satellite-derived ETOPO bathymetry). Using six systematically degraded versions of high-resolution multibeam bathymetry and annotated seafloor imagery across three Antarctic regions, we evaluate SDM performance both with and without additional environmental variables. High-resolution bathymetry captures terrain complexity most effectively, but we find that the spatial distribution of richness hotspots and the median richness per cell remain consistent, provided models are applied at the same resolution at which they were trained. Our results suggest that while high-resolution bathymetry may enhance local predictions, coarse-resolution data may be more robust for regional-scale predictions, such as those used for Antarctic shelf-wide spatial planning.

ecology↗

Adult Marine Annelid Platynereis dumerilii Chemically Stunt the Growth of Juveniles

Within species, individuals of the same age can differ in size. Previously, parental genetics, nutrition, space, and social interactions have been suggested to explain different growth rates. However, direct effects of larger individuals on the physiology and growth of smaller individuals are poorly understood. In this study, we investigated how larger individuals of the marine worm Platynereis dumerilii can impact the growth of smaller conspecifics. Comparing growth distributions in communally and individually reared worms, we show that larger worms suppress the growth of smaller ones. Furthermore, we were able to demonstrate that this suppression is chemically mediated. The chemical cue does not originate from faeces but is water soluble, stable for several days and smaller than 3 kDa. Our findings highlight the importance of non-reproduction related chemical signalling, showing evidence that dominant individuals can chemically suppress the growth of their conspecifics. This study provides new insights into how hierarchy can be established and maintained in a population and is particularly relevant for the growing community studying this model species.

animal behavior and cognition↗

Memory T cell rapid recall is driven by memory-specific AP-1 recruitment determined by epigenome and co-factor interactions

CD4 T cell memory is essential for long-lasting protective immunity to repeat infections. Unlike naive T cells, memory cells possess rapid recall ability to quickly produce effector molecules in response to antigen re-exposure. This ability was shown to be associated with epigenetic gene poising. Here, we examine how the activation-inducible transcription factors, AP{square}1 and NF{square}{kappa}B, regulate rapid recall gene expression. We found that AP-1 is required for their induction and that the enhanced induction of rapid recall genes in memory cells is associated with memory-specific binding of AP{square}1. Memory-specific AP{square}1 binding, in turn, is enabled by enhanced chromatin accessibility and reduced DNA methylation at regulatory elements. As the AP-1 DNA-binding motif itself does not contain methylatable CpGs, methylation likely affects the binding of AP-1 co-factors, such as ETS proteins, or accessibility of the region in general. Finally, both common and memory-specific AP{square}1/NF{square}{kappa}B binding sites show strong overlap with autoimmune and inflammatory disease risk variants, highlighting the clinical relevance of memory T cell epigenetic regulation.

immunology↗

Sizing up phylogenetic testing in geometric morphometrics: A case study of allometry

AbstractAccounting for phylogenetic relatedness in the analysis of shape has become a common practice, deemed necessary to factor in the non-independence between species because of common ancestry. However, when adjusting error distributions to account for relatedness, the phylogenetic-generalised-least-squares (PGLS) test can obscure an important component of variation called conservative trait correlation (CTC). This is the amount of variation in a response variable that is both attributable to a predictor variable and phylogenetically structured. If CTC represents a large amount of correlated variation, true biological associations with strong phylogenetic signal (from unrepeated evolutionary events for example) might not be supported using a PGLS. We demonstrate this effect using geometric morphometric shape analysis on 370 crania from the speciose Australian rock- wallabies (genus Petrogale). In this clade, well-recognised allometric patterns such as scaling of the braincase (Hallers rule) and snout length (craniofacial evolutionary allometry) are supported using ordinary least squares (OLS) regression, but not PGLS, indicating that important between-species shape variation is lost. We then apply two methods capable of quantifying aspects of the missing variation: variation partitioning (VARPART), which estimates the proportion of variation shared between the predictor and phylogeny, and multi- response phylogenetic mixed models (MR-PMM), which identify the strength of correlation within the phylogenetic component of trait variance. Both methods show that CTC dominates the allometric shape variation in our sample, highlighting its importance in assessing phylogenetically informed models. We suggest approaches that can consider CTC become more widely used to better understand morphology and its predictors.

evolutionary biology↗

Transitions in human gut viral communities from ancient to industrialized societies

The composition and function of the human gut microbial community (the microbiome) have changed substantially over millennia, with implications for human health. While microbiome research has focused primarily on bacterial dynamics, the long-term history of gut viral communities (the virome) remains largely unexplored, despite their crucial role in shaping bacterial populations. We analyzed gut viromes from 14 pre-modern human coprolites (1301 BCE-1400s CE), as well as 502 non-industrialized and 492 industrialized contemporary human fecal samples. We found that, from pre-modern to contemporary and industrialized populations, human gut viral communities have become more similar in gene content, increasingly dominated by temperate lifestyles, and more supportive of bacterial pathogenicity. These synergistic ecological shifts suggest that long-term changes, especially with industrialization, have fundamentally altered the gut virome, likely affecting human health. These insights into historical shifts in gut viral community and function open potential avenues for ecologically grounded therapeutics to enhance gut microbiome resilience.

microbiology↗

Real-Time Viability Assessment of Ex Vivo Mouse Kidneys for Transplant Applications Using Dynamic Optical Coherence Tomography

Kidney transplantation remains the preferred treatment for patients with end-stage kidney disease. However, the ongoing shortage of donor organs continues to limit the availability of transplant treatments. Existing evaluation methods, such as the kidney donor profile index (KDPI) and pre-transplant donor biopsy (PTDB), have various limitations, including low discriminative power, invasiveness, and sampling errors, which reduce their effectiveness in organ quality assessment and contribute to the risk of unnecessary organ discard. In this study, we explored the dynamic optical coherence tomography (DOCT) as a real-time, non-invasive approach to monitor the viability of ex vivo mouse kidneys during static cold storage over 48 hours. The dynamic metrics logarithmic intensity variance (LIV), early OCT correlation decay speed (OCDSe), and late OCT correlation decay speed (OCDSl) were extracted from OCT signal fluctuations to quantify temporal and spatial tissue activity and deterioration. Our results demonstrate that DOCT provides complementary functional information to morphological assessment offered by conventional OCT imaging, showing potential to improve pre-transplant organ evaluation and clinic decision-making.

bioengineering↗

Inter-cellular mRNA Transfer Alters Human Pluripotent Stem Cell State

Inter-cellular transmission of mRNA is being explored in mammalian species using immortal cell lines (1-3). Here, we uncover an inter-cellular mRNA transfer phenomenon that allows for the adaptation and reprogramming of human primed pluripotent stem cells (hPSCs). This process is induced by the direct cell contact-mediated coculture with mouse embryonic stem cells (mESCs) under the condition impermissible for human primed PSC culture. Mouse-derived mRNA contents are transmitted into adapted hPSCs only in the coculture. Transfer-specific mRNA analysis show the enrichment for divergent biological pathways involving transcription/translational machinery and stress-coping mechanisms, wherein such transfer is diminished when direct cell contacts are lost. After 5 days of mESC culture, surface marker analysis, and global gene profiling confirmed that mRNA transfer-prone hPSC efficiently gains a naive-like state. Furthermore, transfer-specific knockdown experiments targeting mouse-specific transcription factor-coding mRNAs in hPSC show that mouse-derived Tfcp2l1, Tfap2c, and Klf4 are indispensable for human naive-like conversion. Thus, inter-species mRNA transfer triggers cellular reprogramming in mammalian cells. Our results support that episodic mRNA transfer can occur in cell cooperative and competitive processes(4), which provides a fresh perspective on understanding the roles of mRNA mobility for intra- and inter-species cellular communications.

cell biology↗

The N-terminal extension of Arabidopsis ARGONAUTE 1 is essential for microRNA activities

microRNAs (miRNAs) regulate target gene expression through their ARGONAUTE (AGO) effector protein, mainly AGO1 in Arabidopsis thaliana. In addition to the highly conserved N, PAZ, MID and PIWI domains with known roles in RNA silencing, AGO1 contains a long, unstructured N-terminal extension (NTE) of little-known function. Here, we show that the NTE is indispensable for the functions of Arabidopsis AGO1, as a lack of the NTE leads to seedling lethality. Within the NTE, the region containing amino acids (a.a.) 91 to 189 is essential for rescuing an ago1 null mutant. Through global analyses of small RNAs, AGO1-associated small RNAs, and miRNA target gene expression, we show that the region containing a.a. 91-189 is required for the loading of miRNAs into AGO1. Moreover, we show that reduced nuclear partitioning of AGO1 did not affect its profiles of miRNA and ta-siRNA association. Furthermore, we show that the 1-to-90a.a. and 91-to-189a.a. regions of the NTE redundantly promote the activities of AGO1 in the biogenesis of trans-acting siRNAs. Together, we report novel roles of the NTE of Arabidopsis AGO1.

plant biology↗

Mechanics of lung cancer: A finite element model shows strain amplification during early tumorigenesis

Early lung cancer lesions develop within a unique microenvironment that undergoes constant cyclic stretch from respiration. While tumor stiffening is an established driver of tumor progression, the contribution of stress and strain to lung cancer is unknown. We developed tissue scale finite element models of lung tissue to test how early lesions alter respiration-induced strain. We found that an early tumor, represented as alveolar filling, amplified the strain experienced in the adjacent alveolar walls. Tumor stiffening further increased the amplitude of the strain in the adjacent alveolar walls and extended the strain amplification deeper into the normal lung. In contrast, the strain experienced in the tumor proper was less than the applied strain, although regions of amplification appeared at the tumor edge. Measurements of the alveolar wall thickness in clinical and mouse model samples of lung adenocarcinoma (LUAD) showed wall thickening adjacent to the tumors, consistent with cellular response to strain. Modeling alveolar wall thickening by encircling the tumor with thickened walls moved the strain amplification radially outward, to the next adjacent alveolus. Simulating iterative thickening in response to amplified strain produced tracks of thickened walls. We observed such tracks in early-stage clinical samples. The tracks were populated with invading tumor cells, suggesting that strain amplification in very early lung lesions could guide pro-invasive remodeling of the tumor microenvironment. The simulation results and tumor measurements suggest that cells at the edge of a lung tumor and in surrounding alveolar walls experience increased strain during respiration that could promote tumor progression. Author SummaryLung cancer is the leading cause of cancer-related death in the world. Efforts to identify and treat patients early are hampered by an incomplete understanding of the factors that drive early lesion progression to invasive cancer. We aimed to understand the role of mechanical strain in early lesion progression. The lung is unique in that it undergoes cyclic stretch, which creates strain across the alveolar walls. Computational models have provided fundamental insights into the stretch-strain relationship in the lung. In order to map the strain experienced in the alveolar walls near a tumor, we incorporated a tumor into a tissue scale model of the lung under stretch. We used finite element modeling to apply physiological material behavior to the lung and tumor tissue. Based on reported findings and our measurements, tumor progression was modeled as stiffening of the tumor and thickening of the tumor-adjacent alveolar walls. We found that early tumors amplified the strain in the tumor-adjacent alveolar walls. Strain amplification also arose at the tumor edges. Simulating strain-mediated wall stiffening generated tracks of thickened walls. We experimentally confirmed the presence of tracks of thickened extracellular matrix in clinical samples of LUAD. Our model is the first to interrogate the alterations in strain in and around a tumor during simulated respiration and suggests that lung mechanics and strain amplification play a role in early lung tumorigenesis.

cancer biology↗

Cornering an Ever-Evolving Coronavirus: TATX-03, a fully human synergistic multi-antibody cocktail targeting the SARS-CoV-2 Spike Protein with in vivo efficacy

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created an ongoing global human health crisis and will likely become endemic, requiring novel sustainable therapeutic strategies. We report on the discovery of a fully human multi-antibody cocktail (TATX-03) targeting diversified non-overlapping epitopes on the SARS-CoV-2 spike protein that suppressed replication-competent viral titers to undetectable levels in the lungs of SARS-CoV-2 challenged hamsters upon both prophylactic and therapeutic administration. While monotherapy with two of the individual cocktail components also showed clear in vivo protection, neither recapitulated the efficacy of TATX-03. This synergistic effect was further supported by examining in vivo efficacy of these individual antibodies and corresponding combination therapy at a lower dose. Furthermore, in vitro screenings using VSV-particles pseudo-typed with spike proteins representing the SARS-CoV-2 variants of concern Alpha, Beta, and Delta showed that TATX-03 maintained its neutralization potency. These results merit further development of TATX-03 as a potential therapy for SARS-CoV-2 infection with resistance to mutagenic escape.

immunology↗

Combinatorial transcriptional profiling of mouse and human enteric neurons identifies shared and disparate subtypes in situ.

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBACKGROUND & AIMSC_ST_ABSThe enteric nervous system (ENS) coordinates essential intestinal functions through the concerted action of diverse enteric neurons (EN). However, integrated molecular knowledge of EN subtypes is lacking. To compare human and mouse ENs, we transcriptionally profiled healthy ENS from adult humans and mice. We aimed to identify transcripts marking discrete neuron subtypes and visualize conserved EN subtypes for humans and mice in multiple bowel regions. METHODSHuman myenteric ganglia and adjacent smooth muscle were isolated by laser-capture microdissection for RNA-Seq. Ganglia-specific transcriptional profiles were identified by computationally subtracting muscle gene signatures. Nuclei from mouse myenteric neurons were isolated and subjected to single-nucleus RNA-Seq (snRNA-Seq), totaling over four billion reads and 25,208 neurons. Neuronal subtypes were defined using mouse snRNA-Seq data. Comparative informatics between human and mouse datasets identified shared EN subtype markers, which were visualized in situ using hybridization chain reaction (HCR). RESULTSSeveral EN subtypes in the duodenum, ileum, and colon are conserved between humans and mice based on orthologous gene expression. However, some EN subtype-specific genes from mice are expressed in completely distinct morphologically defined subtypes in humans. In mice, we identified several neuronal subtypes that stably express gene modules across all intestinal segments, with graded, regional expression of one or more marker genes. CONCLUSIONSOur combined transcriptional profiling of human myenteric ganglia and mouse EN provides a rich foundation for developing novel intestinal therapeutics. There is congruency among some EN subtypes, but we note multiple species differences that should be carefully considered when relating findings from mouse ENS research to human GI studies. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=123 SRC="FIGDIR/small/187211v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@1b41277org.highwire.dtl.DTLVardef@12856feorg.highwire.dtl.DTLVardef@1674dadorg.highwire.dtl.DTLVardef@11ca1c8_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG

neuroscience↗

Single cell transcriptomic profiling identifies molecular phenotypes of newborn human lung cells

RationaleWhile animal model studies have extensively defined mechanisms controlling cell diversity in the developing mammalian lung, the limited data available from late stage human lung development represents a significant knowledge gap. The NHLBI Molecular Atlas of Lung Development Program (LungMAP) seeks to fill this gap by creating a structural, cellular and molecular atlas of the human and mouse lung. MethodsSingle cell RNA sequencing generated transcriptional profiles of 5500 cells obtained from two one-day old human lungs (born at gestational ages of 39 and 31 weeks) from the LungMAP Human Tissue Core Biorepository at the University of Rochester. Frozen single cell isolates were captured, and library preparation was completed on the Chromium 10X system. Data was analyzed in Seurat, and cellular annotation was performed using the ToppGene functional analysis tool. Single cell sequence data from 32000 postnatal day 1, 3, 7 and 10 mouse lung (n = 2 at each time point) cells generated by the LungMAP Research Center at Cincinnati Childrens Hospital and Medical Center, using Dropseq platform, was integrated with the human data. In situ hybridization was used to confirm the spatial location of cellular phenotypes. ResultsTranscriptional interrogation of donor newborn human lung cells identified distinct clusters representing multiple populations of epithelial, endothelial, fibroblasts, pericytes, smooth muscle, and immune cells and signature genes for each of these populations were identified. Computational integration of newborn human and postnatal mouse lung development cellular transcriptomes facilitated the identification of distinct cellular lineages among all the major cell types. Integration of the human and mouse cellular transcriptomes also demonstrated cell type-specific differences in developmental states of the newborn human lung cells. In particular, matrix fibroblasts could be separated into those representative of younger cells (n=393), or older cells (n=158). This is the first comprehensive molecular map of the cellular landscape of neonatal human lung, including biomarkers for cells at distinct states of development. Our results indicate that integrated single cell RNA profiling of human and mouse lung will help identify common and species-specific mechanisms of lung development and respiratory disease.

genomics↗

Temperate grass allergy season defined by spatio-temporal shifts in airborne pollen communities

Grass pollen is the worlds most harmful outdoor aeroallergen and sensitivity varies between species. Different species of grass flower at different times, but it is not known how airborne communities of grass pollen change in time and space. Persistence and high mobility of grass pollen could result in increasingly diverse seasonal pollen communities. Conversely, if grass pollen does not persist for an extended time in the air, shifting pollen communities would be predicted throughout the summer months. Here, using targeted high throughput sequencing, we tracked the seasonal progression of airborne Poaceae pollen biodiversity across Britain, throughout the grass allergy season. All grass genera displayed discrete, temporally restricted peaks of pollen incidence which varied with latitude, revealing that the taxonomic composition of grass pollen exposure changes substantially across the allergy season. By developing more refined aeroallergen profiling, we predict that our findings will facilitate the exploration of links between taxon-specific exposure of harmful grass pollen and disease, with concomitant socio-economic benefits.

ecology↗