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Creators/Authors contains: "Alexander, J"

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  1. Resistance evolution can undermine antiviral treatment. However, targeting antivirals to shared viral proteins could inhibit resistance evolution if susceptible viruses sensitize resistant ones during cellular coinfection. Pocapavir, a poliovirus capsid inhibitor, uses this sociovirological interference strategy. While susceptible viruses substantially suppress pocapavir resistance in cell culture, a pocapavir clinical trial found widespread resistance and limited clearance time improvements in treated participants. Here, to reconcile these findings, we present an intrahost eco-evolutionary model of pocapavir-treated poliovirus, which reproduces both in vitro interference and clinical resistance evolution. In the short term, high densities of susceptible viruses sensitize resistant ones, mirroring cell culture results. However, over multiple replication cycles, pocapavir’s high potency collapses viral density, reducing coinfection and enabling resistance evolution, as observed clinically. Because resistance suppression relies on coinfection, enhancing susceptible virus survival could offer therapeutic advantages. Counterintuitively, we demonstrate that lessening antiviral potency can increase coinfection, limiting resistance while also maintaining low viral load. These findings suggest that antivirals relying on viral intracellular interactions must balance immediate neutralization with preserving future coinfection for sustained inhibition. Explicitly considering the eco-evolutionary feedback encompassing viral density, shared phenotypes and absolute fitness provides new insights for effective therapy design and illuminates viral evolutionary dynamics more broadly. 
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  2. Illumination uniformity is critical for widefield optical microscopy, especially for high-throughput and accurate quantitative imaging of biological specimens. While traditional Köhler illumination improves uniformity, it often fails to deliver homogeneous intensity across large fields of view. Existing optical and computational correction techniques remain inadequate for a broad range of quantitative imaging applications. Here, we implement a novel illumination device that we call the “effective uniform colorlight integration device” (EUCLID), quantifying improvements in two widefield imaging modalities that require uniform illumination. For both imaging modalities, we demonstrate significantly improved precision of quantitative measurements compared to traditional Köhler illumination. The EUCLID device, which can also provide uniform spectral mixing, can be readily adapted to many other widefield imaging modalities to enhance imaging accuracy and reliability, with low cost and ease of implementation. 
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  3. Abstract Diatoms, a major group of microalgae, play a critical role in global carbon cycling and primary production. Despite their ecological significance, comprehensive genomic resources for diatoms are limited. To address this, we have annotated previously unannotated genome assemblies of 49 diatom species. Genome assemblies were obtained from NCBI Datasets and processed for repeat elements using RepeatModeler2 and RepeatMasker. For gene prediction, BRAKER2 was employed in the absence of transcriptomic data, while BRAKER3 was utilised when transcriptome short read data were available from the Sequence Read Archive. The quality of genome assemblies and predicted protein sets was evaluated using BUSCO, ensuring high-quality genomic resources. Functional annotation was performed using EnTAP, providing insights into the biological roles of the predicted proteins. Our study enhances the genomic toolkit available for diatoms, facilitating future research in diatom biology, ecology, and evolution. 
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  4. Abstract The Western Antarctic Peninsula is undergoing rapid environmental change. Regional warming is causing increased glacial meltwater discharge, but the ecological impact of this meltwater over large spatiotemporal scales is not well understood. Here, we leverage 20 years of remote sensing data, reanalysis products, and field observations to assess the effects of sea surface glacial meltwater on phytoplankton biomass and highlight its importance as a key environmental driver for this region’s productive ecosystem. We find a strong correlation between meltwater and phytoplankton chlorophyll-a across multiple time scales and datasets. We attribute this relationship to nutrient fertilization by glacial meltwater, with potential additional contribution from surface ocean stabilization associated with sea-ice presence. While high phytoplankton biomass typically follows prolonged winter sea-ice seasons and depends on the interplay between light and nutrient limitation, our results indicate that the positive effects of increased glacial meltwater on phytoplankton communities likely mitigate the negative impact of sea-ice loss in this region in recent years. Our findings underscore the critical need to consider glacial meltwater as a key ecological driver in polar coastal ecosystems. 
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  5. Abstract We study a skew product transformation associated to an irrational rotation of the circle$$[0,1]/\sim $$. This skew product keeps track of the number of times an orbit of the rotation lands in the two complementary intervals of$$\{0,1/2\}$$in the circle. We show that under certain conditions on the continued fraction expansion of the irrational number defining the rotation, the skew product transformation has certain dense orbits. This is in spite of the presence of numerous non-dense orbits. We use this to construct laminations on infinite type surfaces with exotic properties. In particular, we show that for every infinite type surface with an isolated planar end, there is aninfiniteclique of$$2$$-filling rays based at that end. These$$2$$-filling rays are relevant to Bavard and Walker’sloop graphs. 
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  6. Abstract Biofilms are ubiquitous surface-associated bacterial communities embedded in an extracellular matrix. It is commonly assumed that biofilm cells are glued together by the matrix; however, how the specific biochemistry of matrix components affects the cell-matrix interactions and how these interactions vary during biofilm growth remain unclear. Here, we investigate cell-matrix interactions inVibrio cholerae, the causative agent of cholera. We combine genetics, microscopy, simulations, and biochemical analyses to show thatV. choleraecells are not attracted to the main matrix component (Vibriopolysaccharide, VPS), but can be attached to each other and to the VPS network through surface-associated VPS and crosslinks formed by the protein Bap1. Downregulation of VPS production and surface trimming by the polysaccharide lyase RbmB cause surface remodeling as biofilms age, shifting the nature of cell-matrix interactions from attractive to repulsive and facilitating cell dispersal as aggregated groups. Our results shed light on the dynamics of diverse cell-matrix interactions as drivers of biofilm development. 
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  7. Abstract Small bodies exist in distinct populations within their planetary systems. These reservoir populations hold a range of compositions, which to first order are dependent on formation location relative to their star. We provide a general overview of the nature of the reservoirs that source exocomets, from the influence of the stellar environment through planetesimal formation to comparisons with Solar System populations. Once transitioned from a young protoplanetary disc to a debris disc, a star can expect to be rained with exocomets. While exocomets are predominantly detected to date at A-type stars, planetesimals plausibly exist across a range of stellar masses, based on exoplanet abundance, debris disc occurrence and white dwarf infall. 
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