Biology subjects

Rodgers, N.

Publications and source records attributed to Rodgers, N..

5 recordsLinked to original sources

bioRxiv2026

Wnt activation prevents epileptogenic hippocampal remodeling in animal models of unilateral and bilateral temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is a heterogeneous disorder with most clinical presentations involving unilateral or bilateral hippocampal seizure onsets. Antiseizure medications are often ineffective for TLE, and epilepsy surgery can have variable outcomes. Risk factors for TLE are readily identifiable and typically precede chronic epilepsy, providing a window of opportunity for preventative treatments. However, there are currently no clinically approved anti-epileptogenic therapies. In this study, we investigate the role of Wnt signaling in epileptogenesis using two mouse TLE models, the intrahippocampal kainate model of unilateral TLE (IHK), and the intraperitoneal kainate model of bilateral TLE (IPK). We specifically examined adult-born immature dentate granule cells as these cells have been heavily implicated in the pathogenesis of TLE and clinical TLE is typically initiated in adulthood. We observed that adult-born immature dentate granule cells undergo pathological morphological changes during epileptogenesis in both the IHK and IPK models of TLE. When compared across epileptogenic zones, however, these changes differed between the two models. Wnt signaling also decreased in these cells in epileptic mice during the epileptogenic period. When mice were treated with SB415286, a highly selective Wnt activator, Wnt signaling in immature dentate granule cells was restored to baseline levels and pathological remodeling changes were reduced in both models. These data therefore suggest that a reduction in Wnt signaling in immature dentate granule cells plays an etiological role in epileptogenesis, and that restoring Wnt signaling using Wnt activating drugs or alternative agents may have therapeutic potential as an anti-epileptogenic strategy in TLE.

neuroscience↗

bioRxiv2026

Clade dynamics support an early origin of crown eukaryotes

The timing of the last eukaryotic common ancestor (LECA) remains a fundamental question in evolutionary biology and palaeontology. Unambiguous eukaryotic-grade fossils appear from 1780 Ma, but no crown-group supergroups are confidently identified before the end of the Mesoproterozoic (ca. 1050 Ma). The late LECA hypothesis suggests that this absence of crown-assignable fossils and biosignatures implies a late Mesoproterozoic origin of the crown. Here we show that this hypothesis is incompatible with the evolutionary dynamics of the eukaryote clade, even under the limited constraints of the fossil record. Studying stem-crown dynamics based on a birth-death model, we show that a late crown age requires diversification rates well below the minimum rate needed to generate observed living eukaryote diversity (~2.5 - 10 million species) for any plausible total group age. Our results suggest that only an early LECA can bridge evolutionary dynamics with the eukaryotic-grade fossil record, the living diversity, and the molecular clock estimates. Based on these constraints, we suggest a feasible minimum age estimate for LECA of ca. 1696 Ma, supported by current fossil evidence and supporting molecular clock estimates. These results also provide a fossil-testable prediction: crown-group eukaryotes likely exist in early Mesoproterozoic assemblages, albeit undetected with current morphology-based approaches.

paleontology↗

bioRxiv2025

Complexity Begets Simplicity: Self-Supervised Learning for Palaeontological Images with Few or No Labels

Palaeontology has seen widespread and growing use of machine learning to classify and analyse large datasets of fossils. However, palaeontology is a challenging field in which to apply machine learning. Datasets may be small or unlabelled, images may be complex and different from standard datasets and palaeontologists may lack specialist training and access to necessary computational resources. We show how these challenges can be addressed by utilising recent developments in self-supervised learning (SSL). Using a frozen DINOv3 feature extractor and a simple linear classifier, with reduced data, we can achieve comparable results to literature benchmarks using Convolutional Neural Networks (CNNs), the previous standard, when classifying fossil tracks, pollen, radiolaria, foraminifera and a dataset of diverse fossil images. Additionally, the rich feature vectors generated by the model can be used for few-shot learning, unsupervised clustering and quantification of disparity. Using state-of-the-art self-supervised methods increases accessibility by reducing code, compute and data required. It also maintains accuracy, while increasing reproducibility by reducing parameters and allowing simple future-proof model agnostic pipelines which may become the new standard approach in palaeontology.

paleontology↗

bioRxiv2023

Relationship of maternal cytomegalovirus-specific antibody responses and viral load to vertical transmission risk following primary maternal infection in a rhesus macaque model

Cytomegalovirus (CMV) is the most common congenital infection and cause of birth defects worldwide. Primary CMV infection during pregnancy leads to a higher frequency of congenital CMV (cCMV) than maternal re-infection, suggesting that maternal immunity confers partial protection. However, poorly understood immune correlates of protection against placental transmission contributes to the current lack of an approved vaccine to prevent cCMV. In this study, we characterized the kinetics of maternal plasma rhesus CMV (RhCMV) viral load (VL) and RhCMV-specific antibody binding and functional responses in a group of 12 immunocompetent dams with acute, primary RhCMV infection. We defined cCMV transmission as RhCMV detection in amniotic fluid (AF) by qPCR. We then leveraged a large group of past and current primary RhCMV infection studies in late-first/early-second trimester RhCMV-seronegative rhesus macaque dams, including immunocompetent (n=15), CD4+ T cell-depleted with (n=6) and without (n=6) RhCMV-specific polyclonal IgG infusion before infection to evaluate differences between RhCMV AF-positive and AF-negative dams. During the first 3 weeks after infection, the magnitude of RhCMV VL in maternal plasma was higher in AF-positive dams in the combined cohort, while RhCMV glycoprotein B (gB)- and pentamer-specific binding IgG responses were lower magnitude compared to AF-negative dams. However, these observed differences were driven by the CD4+ T cell-depleted dams, as there were no differences in plasma VL or antibody responses between immunocompetent AF-positive vs AF-negative dams. Overall, these results suggest that levels of neither maternal plasma viremia nor humoral responses are associated with cCMV following primary maternal infection in healthy individuals. We speculate that other factors related to innate immunity are more important in this context as antibody responses to acute infection likely develop too late to influence vertical transmission. Yet, pre-existing CMV glycoprotein-specific and neutralizing IgG may provide protection against cCMV following primary maternal CMV infection even in high-risk, immunocompromised settings. Author summaryCytomegalovirus (CMV) is the most common infectious cause of birth defects globally, but we still do not have licensed medical interventions to prevent vertical transmission of CMV. We utilized a non-human primate model of primary CMV infection during pregnancy to study virological and humoral factors that influence congenital infection. Unexpectedly, we found that the levels virus in maternal plasma were not predictive of virus transmission to the amniotic fluid (AF) in immunocompetent dams. In contrast, CD4+ T cell depleted pregnant rhesus macaques with virus detected in AF had higher plasma viral loads than dams not showing placental transmission. Virus-specific antibody binding, neutralizing, and Fc-mediated antibody effector antibody responses were not different in immunocompetent animals with and without virus detectable in AF, but passively infused neutralizing antibodies and antibodies binding to key glycoproteins were higher in CD4+ T cell-depleted dams who did not transmit the virus compared to those that did. Our data suggests that the natural development of virus-specific antibody responses is too slow to prevent congenital transmission following maternal infection, highlighting the need for the development of vaccines that confer levels of pre-existing immunity to CMV-naive mothers that can prevent congenital transmission to their infants during pregnancy.

immunology↗

bioRxiv2017

COREMIC: a web-tool to search for a root-zone associated CORE MICrobiome

Microbial diversity on earth is extraordinary, and soils alone harbor thousands of species per gram of soil. Understanding how this diversity is sorted and selected into habitat niches is a major focus of ecology and biotechnology, but remains only vaguely understood. A systems-biology approach was used to mine information from databases to show how it can be used to answer questions related to the core microbiome of habitat-microbe relationships. By making use of the burgeoning growth of information from databases, our tool \"COREMIC\" meets a great need in the search for understanding niche partitioning and habitat-function relationships. The work is unique, furthermore, because it provides a user-friendly statistically robust web-tool (http://coremic2.appspot.com), developed using Google App Engine, to help in the process of database mining to identify the \"core microbiome\" associated with a given habitat. A case study is presented using data from 31 switchgrass rhizosphere community habitats across a diverse set of soil and sampling environments. The methodology utilizes an outgroup of 28 non-switchgrass (other grasses and forbs) to identify a core switchgrass microbiome. Even across a diverse set of soils (5 environments), and conservative statistical criteria (presence in more than 90% samples and FDR q-val < 0.05% for Fishers exact test) a core set of bacteria associated with switchgrass was observed. These included, among others, closely related taxa from Lysobacter spp., Mesorhizobium spp, and Chitinophagaceae. These bacteria have been shown to have functions related to the production of bacterial and fungal antibiotics and plant growth promotion. COREMIC can be used as a hypothesis generating or confirmatory tool that shows great potential for identifying taxa that may be important to the functioning of a habitat (e.g. host plant). The case study, in conclusion, shows that COREMIC can identify key habitat-specific microbes across diverse samples, using currently available databases and a unique freely available software.

microbiology↗