Biology subjects

Wilson, A.

Publications and source records attributed to Wilson, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Inflammasome Activation and IL-1β Release in Alveolar Macrophages Infected with Pseudomonas aeruginosa is Reduced in Hypoxia

Pseudomonas aeruginosa is an important agent of acute or chronic airway infections. A complex set of genetic and environmental factors determine the outcome of a P. aeruginosa airway infection. P. aeruginosa can undergo genetic adaptation to fine tune the expression of a type III secretion system (T3SS) and other virulence factors in response to selective pressures encountered during infection. Genetic and environmental factors predispose many patient groups for P. aeruginosa infections, including people with cystic fibrosis (pwCF). CF is a genetic disorder resulting in areas of hypoxia and thick mucus that fosters P. aeruginosa airway infection. Resident alveolar macrophages (AMs) help coordinate immune responses to P. aeruginosa in airways by producing proinflammatory cytokines such as IL-1{beta}, which can be important for infection resistance. AMs infected with laboratory strains of P. aeruginosa detect the T3SS and activate the NLRC4 inflammasome, resulting in IL-1{beta} release. Studies of inflammasome responses in AMs to a clinical CF isolate of P. aeruginosa have not been reported. Here, we characterized the CF clinical isolate DH1137 and found that it has a downregulated but functional T3SS, is adapted to grow in hypoxia, and induces significant production of the inflammasome cytokines IL-1{beta} and IL-1 during lung infection in a CF mouse model. Inflammasome gene expression was primed in AMs by LPS stimulation, and upon DH1137 infection these cells released IL-1[beta]. Intriguingly, we found that infection of AMs with DH1137 in hypoxia resulted in significantly dampened inflammasome activation compared to normoxia. These data describe a new mechanism that P. aeruginosa may exploit to evade immune detection by tissue-resident lung macrophages in the context of CF.

immunology↗

bioRxiv2026

Systemic endotoxemia induces integrated sickness physiology in female BALB/c mice

Sickness is an organismal response to inflammation, yet its immune, metabolic, neural, and behavioral components are often studied separately and predominantly in male C57BL/6 mice. In this study, we characterized these responses to systemic lipopolysaccharide (LPS) in female BALB/c mice. Mice received intraperitoneal LPS at moderate concentrations and outcomes were assessed during the acute and resolving phases of endotoxemia. LPS caused rapid disappearance of resident peritoneal macrophages, followed by neutrophil accumulation and increased circulating TNF- and IL-6. In the liver, LPS induced inflammatory, acute-phase, and anti-inflammatory transcripts while suppressing genes involved in lipid, cholesterol, and xenobiotic metabolism. Hepatic glutathione was reduced, whereas total superoxide dismutase activity was unchanged. These peripheral responses were followed by transient hypothermia, reduced food intake, and body weight loss. Regional brain mapping showed increased c-Fos labeling in the area postrema, nucleus of the solitary tract, external lateral parabrachial nucleus, paraventricular nucleus of the hypothalamus, and arcuate nucleus. In parallel, LPS selectively promoted IBA1-positive area in the median eminence and arcuate nucleus, whereas several other regions showed no changes, indicating that neuronal and microglial responses are regionally distinct. Behaviorally, LPS reduced locomotion and exploration, increased freezing, and increased forced-swim immobility. Changes in spatial exploration were most pronounced during the acute phase, whereas locomotor suppression and passive stress-coping persisted longer and varied in magnitude with the timing of inflammatory challenge. Together, these findings show that systemic LPS produces a coordinated sickness state in female BALB/c mice that links peripheral inflammation and hepatic metabolic and redox changes with region-specific neuronal and microglial responses, altered thermoregulation and feeding, and behavioral suppression.

immunology↗

bioRxiv2026

Host genetics and social relationships jointly shape fitness-associated microbiome variation in a population of feral horses

Gut microbiome variation is consequential for host fitness, but its contribution to adaptive evolution in host populations remains unclear. Although gut microbiome heritability has been demonstrated in humans, domesticated animals, and wildlife, no study has simultaneously assessed heritability of, and natural selection on, microbiome traits. Moreover, prior studies have not investigated whether non-genetic inheritance mechanisms (e.g., maternal and social transmission) could also contribute to microbiome-mediated adaptation. Using quantitative genetic animal models and shotgun metagenomic data from the long-term, individual-based study of feral Sable Island horses (2394 samples, 794 known-fate individuals), we estimated additive genetic, maternal, and social contributions to fitness-associated dimensions of the microbiome identified using canonical analyses of principal coordinates. Combined, additive genetic, permanent environment, and social effects explained 47% and 38% of the variance in fitness-associated dimensions of microbiota or microbial gene family profiles, respectively, with social effects being 2-4 times stronger than additive genetic effects on average. Contrary to our predictions, we observed no evidence for maternal effects. We provide the first evidence that fitness-associated microbiome traits are heritable, and so, theoretically capable of evolution in response to selection. Strong social effects further indicate the possible concurrent importance of non-genetic inheritance to microbiome-mediated adaptive evolution.

ecology↗

bioRxiv2026

Functional Characterization of Myeloid Neoplasm-associated DDX41 Variants Reveals Pathogenic Interaction with Acquired Hotspot Mutation

Germline variants in DDX41 are the most frequent genetic predisposition to adult hematologic malignancies. The most common variants are truncating, implicating loss of function in the pathogenesis. However, non-truncating variants account for 30-40% of cases, and their impact on essential DDX41 functions remains unknown. We utilized a genetic complementation assay to assess the functionality of 10 recurrent germline non-truncating variants of DDX41. All variants restored viability to Ddx41-deficient hematopoietic progenitor cells at exogenous expression levels. In contrast, the hotspot mutant p.R525H, which is somatically acquired at disease onset in >50% of patients, failed to restore viability. CRISPR-based modeling in cell lines and mice revealed heterogeneity: some variants were non-functional at endogenous expression levels whereas others maintained complete functionality, supporting normal cell proliferation and even lifelong hematopoiesis in a homozygous setting. Notably, co-expression of p.R525H with some variants caused impaired hematopoietic progenitor cell viability, indicating a dominant-negative effect of p.R525H. In contrast, other variants, all classified as variants of unknown significance, were unaffected by the presence of p.R525H. A screen of 100 disease-associated variants confirmed that many non-truncating germline variants are susceptible to p.R525H-mediated dominant-negative effects, whereas wild-type DDX41 is not. These findings indicate that DDX41 variant curation is complicated by variable effects on functionality and variant-specific interactions with somatically-acquired DDX41 mutations. The dominant-negative effect of p.R525H provides a mechanistic basis for the conclusion of recent patient cohort analyses that co-occurrence with a somatic hotspot mutation is a reliable indicator of DDX41-driven disease in carriers of non-truncating variants.

cancer biology↗

bioRxiv2026

Structural basis of the two-photon photoactivation mechanism of orange carotenoid protein

Cyanobacteria have produced Earths oxygen for 2.4 billion years by adapting to fluctuating irradiance. This adaptation relies on orange carotenoid protein (OCP), which mediates light-intensity- dependent photoprotective energy dissipation using a unique two-photon absorption mechanism. Photon absorption by ground-state OCP (OCPO) generates a metastable intermediate (OCP1h{nu}) that either relaxes thermally or, upon absorption of a second photon within [~]1 s, converts to the active photoprotective state (OCPR). By integrating static and time-resolved crystallography, cryo-EM, computation, spectroscopy and biochemistry, we assign the structure of OCP1h{nu}, establish its functional relevance and capture structural snapshots along the OCPO[->]OCP1h{nu} and OCP1h{nu}[->]OCPR photochemical pathways. We elucidate the molecular mechanism of OCP, which serves as a unique biological circuit breaker protecting the photosynthetic machinery from high light flux.

biochemistry↗

bioRxiv2026

Seabird diet and transmission routes mediate the increase in pathogen prevalence with human disturbance

Human disturbances can alter patterns of wildlife infection, but their effects are likely to differ between terrestrial and marine environments. Seabirds range across land and sea and are therefore exposed to diverse human pressures such as urbanization, agriculture, and landfills, as well as fisheries, shipping, and marine pollution. However, most literature on wildlife infection has focused on terrestrial hosts or single type of disturbance (e.g., urbanization). Studying seabirds, which exploit diverse diets and habitats, offers a unique opportunity to disentangle how disturbances at sea and on land, as well as diets, and transmission routes, can change pathogen prevalence at a global scale. We conducted a global literature review and extracted datasets on seabird infection status for a range of pathogens, seabirds diets (piscivore, invertivore, generalist), and pathogen transmission routes (contact-based, vector-borne, intermediate host) to link pathogen prevalence to human disturbances at sea and on land. Our results showed that the association between human disturbances and pathogen prevalence was mediated by species diets and differed across transmission routes. Across gradients of human disturbance at sea, pathogen prevalence in piscivorous seabirds increased from near zero to over 0.7, particularly for contact-based pathogens. Land-based disturbance was also associated with higher pathogen prevalence in generalists across transmission routes, whereas invertivores showed a negative association with terrestrial disturbance. These results indicate that piscivores are most vulnerable in heavily disturbed marine environments, while generalists face greater risk on highly disturbed lands, suggesting that effective disease mitigation will require targeted management actions in both environments.

ecology↗

bioRxiv2026

A prelimbic molecular clock of protein synthesis for memory persistence

Emotionally salient associative memories can endure for long periods, yet the mechanisms that determine their long-term stability remain unclear. Here we show that the prelimbic (PL) cortex integrates temporally structured translational programs to control both the consolidation and reconsolidation of cued threat memories. Using Pavlovian threat conditioning with in vivo fiber photometry, we found that PL calcium dynamics tightly track memory strength: discrete threat-predictive cues evoked robust activity during recent and single-timepoint remote retrieval, whereas prior retrieval selectively weakened remote expression, independent of contextual influences. Translational profiling of PL Camk2a cells uncovered a biphasic consolidation program, with an early phase characterized by ER stress-linked translational repression and robust oligodendrocyte plasticity, followed by a delayed phase engaging synaptic growth pathways. Loss- and gain-of-function approaches demonstrated that eIF2-regulated, cap-independent translation is essential for recent consolidation and for the enduring stabilization of remote memory, whereas retrieval-induced destabilization engages a mechanistically distinct, eIF4E-dependent translational pathway required for reconsolidation. These findings identify the PL cortex as a dynamic node in which discrete modes of translational control govern the long-term persistence of emotional memories.

neuroscience↗

bioRxiv2025

UC Irvine Brain Initiative Cell Atlas Network (BICAN) Brain Procurement Program for the Center for Multiomic Human Brain Cell Atlas Project

High-quality neurotypical postmortem human brain tissue is essential but difficult to obtain for constructing comprehensive human brain cell atlases. Here we describe the establishment of UC Irvines Brain Procurement Program, a coordinated initiative to collect and process neurotypical donor brains for multiomic mapping studies within the NIH BRAIN Initiative Cell Atlas Network (BICAN) consortium. Through partnerships with the Orange County Coroners Office, the UC Irvine Willed Body Program, UCI Medical Center, and the Childrens Hospital of Orange County, we have developed standardized workflows encompassing donor identification, postmortem brain recovery and processing, region-of-interest dissection, neurotypical donor selection, and data management. Our experience demonstrates the feasibility of a community-based, multi-institutional procurement framework while highlighting challenges in recruiting neurotypical donors and ensuring demographic representation reflective of Southern California. We further identify opportunities to strengthen outreach and donation pathways. This program provides a scalable model for advancing population-reflective, high-quality human brain cell atlas efforts. HighlightsO_LIEstablish a multi-site pipeline for procuring high-quality neurotypical human brains. C_LIO_LIDemonstrate feasibility of donor collection across childhood to adulthood. C_LIO_LIIdentify barriers and propose strategies to improve broad donor recruitment. C_LI

neuroscience↗

bioRxiv2025

Stimulation of cholesterol efflux inhibits herpesvirus nuclear egress

Cholesterol in herpesvirus envelopes and host membranes supports membrane fusion during virus entry. However, little is known about how cholesterol affects other aspects of the viral replication cycle. Here, using an infection model that begins with reactivation from latency, bypassing the entry step, we demonstrate that depleting intracellular cholesterol inhibits the production of infectious Kaposis sarcoma-associated herpesvirus (KSHV). Treatment of latently infected cells with the liver X receptor (LXR) agonist 22(R)-hydroxycholesterol (22OH) increased expression of sterol response genes, including the cholesterol efflux pump ATP binding cassette subfamily A member 1 (ABCA1), and reduced intracellular cholesterol. 22OH treatment initially enhanced lytic reactivation, but diminished viral protein accumulation during late replication, while altering accumulation of host proteins that regulate the cell cycle and innate immunity. Cholesterol efflux led to an increase in the proportion of capsids lacking viral genomes in the nucleus and a reduction in nucleocapsids accessing the cytoplasm. Next, we used a herpes simplex virus (HSV) infection model to explore if 22OH affected the conserved herpesvirus nuclear egress complex (NEC), comprised of two viral proteins that accumulate at the inner nuclear membrane and facilitate primary envelopment. We found that 22OH inhibited HSV-1 and HSV-2 replication and spread in plaque reduction assays and impaired localization of NEC proteins pUL31 and pUL34 to the nuclear periphery. These findings indicate that cholesterol efflux inhibits herpesvirus replication by interfering with the formation of nucleocapsids competent to complete nuclear egress. IMPORTANCECholesterol plays key roles in regulating the fluidity of cellular membranes and the trafficking and lateral diffusion of transmembrane proteins. Herpesviruses encode a variety of transmembrane proteins that traffic to different cellular compartments, while herpesvirus capsids and tegument proteins interact with nuclear and trans-Golgi network membranes throughout the primary and secondary envelopment process, respectively. This produces viral particles with cholesterol as an envelope component which is required to support membrane fusion during entry. Our discovery that cholesterol efflux inhibits KSHV nuclear egress suggests that cholesterol plays important supportive roles at this stage of lytic replication. Moreover, we observed that cholesterol efflux mediated by oxysterol treatment has widespread effects on host cell protein expression, resulting in a non-classical antiviral state. Cholesterol likely supports the proper trafficking of viral proteins to nuclear sites of virion assembly or is influencing the fluidity of nuclear membranes used for viral primary envelopment and de-envelopment during nuclear egress.

microbiology↗

bioRxiv2025

Microbiome Dynamics During Translocation of the Critically-Endangered Frog Craugastor ranoides

O_LIAmphibian populations are declining and species going extinct due to habitat loss, climate change and emerging infectious disease, prompting the increasing use of translocations as a conservation tool. C_LIO_LISkin-associated microbial communities play a key role in amphibian health, particularly in protecting hosts from pathogenic infection. However, to date we know relatively little about the impact of translocation on the dynamics of skin-associated microbes, or the consequences of translocation-mediated disturbance of the microbiome for amphibian health. C_LIO_LIWe investigated the skin microbiome of the critically endangered frog Craugastor ranoides, now restricted to a fraction of its historical range in Costa Rica. We first conducted a multi-population survey to characterise among-population variation in skin bacterial communities. We then translocated individuals to a new site, using radio tracking to monitor them over time and assess individual-level changes in body mass, microbiome composition, and predicted microbial function. C_LIO_LIWe found limited among-population variation in skin microbiome composition across three different populations of C. ranoides. Response of the microbiome to translocation was highly individual-specific; some frogs demonstrated relatively stable community richness and composition, whilst others exhibited marked turnover in bacterial membership and predicted function. Body mass showed similar dynamics, but several of the recaptured frogs had gained mass after several days in the translocation site. C_LIO_LISynthesis and Applications: Our findings highlight the importance of considering microbiome dynamics in threatened species translocations to optimize individual health. This includes considering whether individuals should be prioritised for translocation based on their initial microbiome composition, and understanding how shifts in microbiome post-translocation may alter overall success of translocation efforts. These insights extend beyond amphibians, offering a broader framework for integrating long-term monitoring of host microbiomes and health into conservation efforts. C_LI

ecology↗

bioRxiv2025

Quantitative genetics of shy-bold behaviour and plastic response to novel predator cues in the cherry shrimp, Neocaridina davidi

Understanding the genetic basis of behavioural variation among-individuals is vital for predicting if, when, and how quickly behaviour can evolve under selection. However, in heterogeneous environments, behavioural plasticity (a source of within-individual variation) may also contribute to the phenotypic variance that can be selected on. If so, a complete picture of evolutionary potential, requires estimation of genotype-by-environment interactions (GxE). Here we investigate the quantitative genetics of shy-bold behavioural variation in the red cherry shrimp, Neocaridina davidi, an emerging decapod model for behavioural, genetic, and ecotoxicological research. Using a suite of behaviours associated with shy-bold personality variation we demonstrate moderate to high behavioural repeatabilities and show how a multivariate approach allows characterising the shape, not just the amount, of variation. Using a half-sib full sib breeding design in which shrimp from known families were tested under either control conditions or with predator (fish) cues present, we jointly estimate the plastic response to elevated risk, and the contribution of genetic factors to phenotypic variance. We find that genetic variance does underpin among-individual differences in behaviour. We also find evidence of plasticity, with individual shrimp shifting towards a shyer, or more risk averse, average phenotype in the presence of fish cues. However, we found no variation in plasticity either among-individuals (IxE) or among-genotypes (GxE). This implies that average behaviour can evolve under predator-mediated selection, but further adaptive evolution of behavioural plasticity may be constrained by a lack of GxE.

evolutionary biology↗

bioRxiv2025

Herpes simplex virus-1 fluidizes the nucleus enabling condensate formation

Molecular processes are profoundly influenced by the biophysical properties of the cell interior. However, the mechanisms that control these physical properties, and the processes they impact remain poorly understood, especially in the nucleus. We hypothesized that some viruses might change the biophysical properties of the nucleus to favor virus survival and replication and found that herpes simplex virus 1 (HSV-1) increases the mesoscale fluidity of the nucleus. The HSV-1 protein ICP4 caused fluidization and enabled growth of synthetic nuclear condensates. Conversely, conditions that decreased nuclear fluidity inhibited the growth of viral replication compartment condensates and reduced infectious virus production. Together, our data suggest that ICP4 increases nuclear fluidity to promote the formation of condensates that drive the progression of the HSV-1 life cycle. We speculate that a key function of ICP4 is to overcome the crowding and elastic confinement within cell nuclei that are a fundamental barrier to virus replication.

cell biology↗

bioRxiv2025

Targeting SCD in SCD-amplified prostate cancer inhibits growth in bone by modulating cellular stress, mTOR, and DNA damage pathways

The bone microenvironment is abundant in adipocytes and fosters metastatic progression, but the underlying mechanisms are not fully understood. We hypothesize that Stearoyl-Coenzyme A Desaturase (SCD) acts as a tumor-promoting enzyme by modulating cellular stress to support the growth and survival of prostate cancer (PCa) in bone. We observe that SCD-amplified PCa cells are highly sensitive to SCD loss and show reduced PCa spheroid size, diminished mTOR signaling, and increased ER stress. Notably, SCD expression is further increased by adipocytes in SCD-amplified cell lines, and its loss increases DNA damage and activates repair pathways in PCa cells only when exposed to adipocytes. Furthermore, we observe PCa cell lines utilize SCD to regulate adipocyte-induced lipid peroxidation. Aligned with these results, pharmacological SCD inhibition in mice bearing SCD-amplified bone tumors reduces tumor size and reveals histochemical evidence of increased ER stress and DNA damage. Collectively, our data highlight the impact of SCD loss on SCD-amplified tumors and suggest germline characteristics of tumors may dictate their response to redox insult and the possibility of targeting DNA repair pathways in combination with SCD inhibition.

cancer biology↗

bioRxiv2025

Reinforced CRISPR interference enables reliable multiplex gene repression in phylogenetically distant bacteria

Genetic screens are essential for uncovering novel molecular mechanisms and identifying the functions of hypothetical proteins. CRISPR interference (CRISPRi) is a powerful, programmable, and sequence-specific gene repression technology that can be used for high-throughput screening and targeted gene repression. Despite its ease of use, the initial development of CRISPRi systems is labor-intensive in many non-model organisms. Our goal is to simplify this by establishing a host-agnostic CRISPRi platform that utilizes the serine recombinase-assisted genome engineering (SAGE) system. This system integrates CRISPRi machinery directly into the bacterial chromosome, overcoming the limitations of plasmid-based systems and enabling wide sharing across diverse bacteria. We demonstrate the design and optimization of multiplexed CRISPRi to repress multiple genes simultaneously in phylogenetically distant bacteria. We use a Francisella novicida-derived Cas12a system that processes multiple distinct CRISPR RNAs, each targeting a unique gene sequence, from a single transcript. This allows easy multi-gene repression. By reinforcing gene repression with multiple guides targeting a single gene, we achieve robust genetic perturbations without the need to pre-screen the efficacy of guide RNAs. Using this toolkit, we perturb multiple combinations of growth and visual phenotypes in Pseudomonas fluorescens and demonstrate simultaneous repression of multiple fluorescent proteins to near background levels in bacteria from various other genera. While the tools are directly portable to all SAGE-compatible microbes, we illustrate the utility of SAGE by optimizing CRISPRi performance in Rhodococcus jostii through a combinatorial screen of Cas protein and CRISPR array expression variants. The efficient integration of CRISPRi machinery via the SAGE system paves the way for versatile genetic screening, enabling profound insights into gene functions both in laboratory conditions and relevant naturalistic scenarios.

microbiology↗

bioRxiv2025

Efficient genetic code expansion tools enable in vivo study of lysine acetylation in non-model bacteria

Recent proteomic advancements have revealed widespread N{varepsilon}-lysine acetylation in pathways governing pathogenicity, metabolism, and antibiotic resistance in bacteria. The spontaneous, non-specific nature of this modification in prokaryotes obscures its biological role, necessitating prokaryotic specific in vivo interrogation systems. Genetic Code Expansion (GCE) offers a powerful method to investigate the roles and regulation dynamics of acetyl-lysine in vivo with the precise incorporation of a suite of non-canonical amino acids, including acetyl-lysine analogs. However, its use has been largely restricted to E. coli strains due to challenges associated with implementation and optimization of the technology in more diverse bacterial strains. Here, we present a bacterial host-agnostic, readily optimizable GCE platform designed to site-specifically incorporate non-canonical amino acids into target proteins within living bacteria. We further demonstrate the versatility of this technology by showcasing, for the first time, the successful incorporation of acetyl-lysine in a non-E. coli bacterium.

synthetic biology↗

bioRxiv2025

Primary envelopment of Kaposi's sarcoma-associated herpesvirus at the nucleoplasmic reticulum

Herpesvirus egress begins with primary envelopment of newly assembled capsids at the inner nuclear membrane (INM) facilitated by a viral nuclear egress complex (NEC). Primary envelopment has been observed at the peripheral INM as well as at structures known as nuclear infoldings. Nuclear infoldings resulting from invaginations of the INM are known as Type-I nucleoplasmic reticulum (NR), whereas infoldings of both INM and outer nuclear membrane (ONM) are known as Type-II NR. Here, we report that Kaposis sarcoma-associated herpesvirus (KSHV) reactivation from latency and lytic cycle progression correlates with increases in both types of NR invaginations, but primary envelopment was restricted to Type-I NR and the peripheral INM. Over a time-course of infection, DNA-containing KSHV C-capsids were frequently observed budding into nuclear infoldings contiguous with the INM and sparsely decorated with nuclear lamina, characteristic of Type-I NR. These Type-I NR structures co-localized with puncta containing CTP:phosphocholine cytidylyltransferase (CCT), the enzyme that catalyzes the rate-limiting step in phosphatidylcholine (PtdCho) synthesis, and drives de novo membrane biogenesis and membrane curvature required for NR expansion; this may provide sufficient Type-I NR to match requirements for KSHV nuclear egress. The selective utilization of the Type-I NR for primary envelopment despite the concurrent expansion of the Type-II NR suggests a mechanism to target C-capsids into the Type-I NR. We also observed accumulation of de-enveloped KSHV C-capsids in 2nd order nuclear infoldings, suggesting that primary envelopment and de-envelopment can occur not only at the nuclear periphery, but also at the Type-I NR. ImportanceHerpesvirus capsids assemble in the cell nucleus but are too large to exit via nuclear pores. Instead, they invade the inner nuclear membrane and acquire a provisional lipid envelope that is quickly shed through fusion with the outer nuclear membrane, a neat trick that delivers the capsid to the cytoplasm for subsequent steps in assembly and egress. Dynamic rearrangements of the nuclear membrane include invaginations that plumb the depths of the nucleus to facilitate cargo trafficking. Here, we demonstrate that during Kaposis sarcoma-associated herpesvirus (KSHV) replication, nuclear membrane infolding and expansion events increase, coinciding with recruitment of a host enzyme required for phosphatidyl choline synthesis to these sites. We observed an abundance of KSHV capsids at infoldings of the inner nuclear membrane, as well as free capsids in the interior of second order infoldings suggestive of de-envelopment events occurring prior to infold retraction. This complements a more well-established mechanism of KSHV egress at the nuclear periphery, and indeed, we observed concomitant egress of KSHV capsids via both mechanisms from the same nucleus. Similar observations for other herpesviruses by other groups suggests that this versatility in nuclear egress mechanisms is conserved.

microbiology↗

bioRxiv2024

The role of resource defensibility in facilitating sexually-selected weapon evolution: An experimental evolution test

Animal weapons have evolved multiple times primarily for battling for access to mates. Despite intra-sexual selection being common, weapon evolution has evolved relatively rarely. So why do weapons not evolve more commonly? It has been hypothesized that three precursors are necessary for the initiation of weapon evolution: high variance in reproductive success, patchy high-value resources, and spatial environments conducive to one-on-one competition. Here, we test this hypothesis by performing experimental evolution in Drosophila melanogaster, utilizing heterogeneous environments where conditions facilitating territorial defense and opportunities for competitive interactions vary. We examine changes in sexually dimorphic morphology and male aggression that are predicted to occur, based on this model. We also examine whether condition dependence for sexual dimorphism has evolved after 35 and 75 generations of experimental evolution. Aggression did increase, albeit modestly, in environments that facilitate resource defense. Morphological changes are modest although with some trait specific changes to allometry, generally in the opposite direction of our predictions. Condition dependence trends in the opposite direction from those predicted by our hypothesis as well. We discuss our results in the context of the necessary conditions for the evolution of weapons, and if, and when condition dependence of trait exaggeration may evolve.

evolutionary biology↗

bioRxiv2024

Two-photon driven photoprotection mechanism in echinenone-functionalized Orange Carotenoid Protein

Orange carotenoid protein (OCP) is a photoactive protein that mediates photoprotection in cyanobacteria. OCP binds different ketocarotenoid chromophores such as echinenone (ECN), 3- hydroxyechinenone (hECN) and canthaxanthin (CAN). In the dark, OCP is in an inactive orange form known as OCPO; upon illumination, a red active state is formed, referred to as OCPR, that can interact with the phycobilisome. Large gaps still exist in the mechanistic understanding of the events between photon absorption and formation of the OCPR state. Recent studies suggested that more than one photon may be absorbed during the photocycle. Using a two-pulse excitation setup with variable time delays we demonstrate that canthaxanthin-functionalized OCPO forms the OCPR signature after absorption of a single photon. By contrast, OCPO complexed with hECN or ECN does not photoconvert to OCPR upon single photon absorption. Instead, OCPR is formed only upon absorption of a second photon, arriving roughly one second after the first one, implying the existence of a metastable light-sensitive OCP1hv intermediate. To the best of our knowledge, a sequential 2-photon absorption mechanism in a single biological photoreceptor chromophore is unique. It results in a non-linear response function with respect to light intensity, effectively generating a threshold switch. In the case of OCP, this prevents down regulation of photosynthesis at low light irradiance.

biophysics↗