Biology subjects

Edwards, G.

Publications and source records attributed to Edwards, G..

16 recordsLinked to original sources

bioRxiv2025

Ancient metagenomics reveals subglacial microbiomes driven by oxygen availability

Beneath Earths glaciers and ice sheets lies an aquatic realm where ice, water, rock, and microbial life interact, driving chemical reactions that can collectively influence the global carbon cycle, polar oceans, and climate. Efforts to describe subglacial microbiomes have been limited by the challenge of cleanly drilling through hundreds of meters of ice, such that only a few sites have ever been directly sampled. Here we use ancient metagenomics to present the first spatiotemporal characterization of subglacial bacteria and archaea. We extracted DNA from 25 subglacial precipitate samples, sedimentary accumulations of minerals that form in subglacial waters prior to exposure on the surface. The precipitates studied here formed between 16,000 and 570,000 years ago beneath the Antarctic and Laurentide Ice Sheets. We show that postmortem DNA damage patterns can reliably distinguish between ancient subglacial and modern surface taxa, and that this approach can enable reconstruction of subglacial microbiomes across poles and ice ages. Our analysis suggests that subglacial microbiomes are dominated by chemolithoautotrophs, ultra-small microbes, and taxa closely related to those found in deep subsurface or extreme cold and hypersaline environments. These microbiomes split into two distinct clusters distinguished by oxygen availability and redox conditions, irrespective of geography or age. Geochemical measurements of subglacial redox state, measured either indirectly via precipitate calcite Fe and Mn concentrations or directly via water reduction potential, reproduce these same two clusters exactly. Our findings describe how subglacial water redox states are held in balance by microbes, hydrology, and oxygen input from fresh subglacial meltwater, that we interpret to be controlled by the ice sheet response to past climate variations.

genomics↗

bioRxiv2025

Hemispheric Dissociation Revealed by Attentional Isolation and tRNS

Prolonged sensory imbalance, induced by directing attention to one visual field, can paradoxically enhance performance in the opposite, non-attended visual field. This effect is likely driven by the brains homeostatic mechanisms that regulate excitation and inhibition between hemispheres in homotopic attention processing regions. Here, we employed transcranial random noise stimulation (tRNS) to modulate cortical excitability and probe its role in interhemispheric dynamics controlling visual attention. Specifically, we used a procedure called attentional isolation, where neurotypical participants covertly focused their visual attention in one hemifield (the attended visual field) for 30 minutes. Performance changes in both the unattended (opposite) visual field and the attended visual field were measured following this manipulation. We applied transcranial random noise stimulation (tRNS) over the right or left frontoparietal cortex to modulate the excitability of one hemisphere relative to the other during attention isolation, probing the neural mechanisms underlying the observed contralateral performance shift. Our results showed improved performance in the previously unattended visual field following the attentional isolation period after sham stimulation. However, tRNS revealed a functional dissociation between the hemispheres: right hemisphere active stimulation abolished the performance improvement, while left hemisphere stimulation preserved it. These findings suggest distinct roles for the left and right hemispheres in modulating paradoxical visual performance shifts and may inform the development of novel neurorehabilitation strategies for clinical populations.

neuroscience↗

bioRxiv2025

Replicating the facilitatory effects of transcranial random noise stimulation on motion processing: A registered report

Non-invasive brain stimulation (NIBS) techniques have the potential to demonstrate the causal impact of targeted brain regions on specific behaviors, and to regulate or facilitate behavior in clinical applications. Transcranial random noise stimulation (tRNS) is one form of transcranial electric stimulation (tES) in which an alternating current is passed between electrodes at random frequencies. High-frequency tRNS (hf-tRNS) is thought to enhance excitability and has been reported to have facilitatory effects on behavior in healthy and clinical populations. Due to the potential application of tRNS, clear demonstrations of the efficacy and replicability of stimulation are critical. Here, we focused on replicating the facilitatory effect of hf-tRNS over the human middle temporal complex (hMT+) on contralateral motion processing, initially demonstrated by Ghin et al. (2018). In this prior study, the improvement in performance was specific to global motion processing in the visual field contralateral to stimulation. The motivation to replicate this effect was reinforced by the well-supported hypothesis that hMT+ is critical for contralateral global motion processing. However, our results indicated that hf-tRNS does not improve motion discrimination. Specifically, we were unable to replicate a contralateral global motion processing facilitation following hf-tRNS to hMT+. In our within-subject controls, we also found no difference between hf-tRNS to hMT+ on contralateral global motion processing in comparison to sham stimulation, or in comparison to hf-tRNS to the forehead. While it remains possible that our lack of replication could be due to minor changes in the protocol from the original Ghin et al., study, for hf-tRNS to become a widely applied method, the modulatory effect of hf-tRNS should be robust to slight adjustments to the procedure.

neuroscience↗

bioRxiv2024

Modulation of learning-dependent plasticity in the attention network

Non-invasive brain stimulation, such as transcranial random noise stimulation (tRNS), has been shown to enhance cortical excitability and facilitate perceptual learning. However, the neural mechanisms underlying these effects remain poorly understood. Here, we demonstrate that tRNS over the bilateral intraparietal sulcus (IPS) optimizes learning by preventing the decline in neural activity that occurs during short, high-load attentional training, thereby sustaining excitability and enhancing behavioral performance. Using a multi-session tRNS-fMRI paradigm, we investigated how tRNS modulates learning-related plasticity in the attention network during cognitive training. In the sham condition we observed a significant decline in task-evoked BOLD after the training and no behavioral improvement, suggesting crucial neural changes associated with cognitive training that are not evident in the behavioral data. Conversely, in the active tRNS condition, stimulation not only prevented the early decline in task-evoked BOLD activity observed in the sham condition, but it increased it. This change in BOLD activity correlated with improved performance. This suggests that tRNS counteracts early neural adaptation during short training protocols, sustaining activity in task-relevant cortical regions to enable learning that would otherwise fail. By providing the first direct evidence that tRNS mitigates early neural downregulation and preserves functional response dynamics during learning in crucial task-related cortical areas, our study demonstrates that in parietal cortex training-induced plasticity is not accompanied by efficiency-driven reductions in activation, like typically seen in sensory areas. Instead, we propose that sustaining neural excitability through tRNS prolongs plasticity and optimizes cognitive performance in higher order attentional areas. These findings highlight tRNS as a powerful tool for enhancing attentional learning and modulating neuroplasticity in both healthy and clinical populations.

neuroscience↗

bioRxiv2023

A familial missense variant in the AD gene SORL1 impairs its maturation and endosomal sorting.

The SORL1 gene has recently emerged as a strong Alzheimers Disease (AD) risk gene. Over 500 different variants have been identified in the gene and the contribution of individual variants to AD development and progression is still largely unknown. Here, we describe a family consisting of 2 parents and 5 offspring. Both parents were affected with dementia and one had confirmed AD pathology with an age of onset >75 years. All offspring were affected with AD with ages at onset ranging from 53yrs-74yrs. DNA was available from the parent with confirmed AD and 5 offspring. We identified a coding variant, p.(Arg953Cys), in SORL1 in 5 of 6 individuals affected by AD. Notably, variant carriers had severe AD pathology, and the SORL1 variant segregated with TDP-43 pathology (LATE-NC). We further characterized this variant and show that this Arginine substitution occurs at a critical position in the YWTD-domain of the SORL1 translation product, SORL1. Functional studies further show that the p.R953C variant leads to retention of the SORL1 protein in the endoplasmic reticulum which leads to decreased maturation and shedding of the receptor and prevents its normal endosomal trafficking. Together, our analysis suggests that p.R953C is a pathogenic variant of SORL1 and sheds light on mechanisms of how missense SORL1 variants may lead to AD.

neuroscience↗

bioRxiv2022

Improving visual attention following right hemisphere stroke: A preliminary study

Left inattention is common in individuals following right cerebrovascular accident (RCVA). In neurotypical adults, we have previously found prolonged rightward visual attention resulted in a subsequent increase in leftward attention. Here we applied the same method in neurological patients with RCVA and found improved post-intervention attention both to the left and right of visual fixation in participants with mild to no leftward inattention in comparison to a control. No such benefit was detected in participants with more pronounced leftward inattention. Given the feasibility of the intervention which leverages performance in the right unaffected visual space, future studies should examine the longevity and generalizability of such an intervention to other attention demanding tasks.

neuroscience↗

bioRxiv2021

Biological Insights Knowledge Graph: an integrated knowledge graph to support drug development

The use of knowledge graphs as a data source for machine learning methods to solve complex problems in life sciences has rapidly become popular in recent years. Our Biological Insights Knowledge Graph (BIKG) combines relevant data for drug development from public as well as internal data sources to provide insights for a range of tasks: from identifying new targets to repurposing existing drugs. Besides the common requirements to organisational knowledge graphs such as being able to capture the domain precisely and give the users the ability to search and query the data, the focus on handling multiple use cases and supporting use case-specific machine learning models presents additional challenges: the data models must also be streamlined for the performance of downstream tasks; graph content must be easily customisable for different use cases; different projections of the graph content are required to support a wider range of different consumption modes. In this paper we describe our main design choices in implementation of the BIKG graph and discuss different aspects of its life cycle: from graph construction to exploitation.

systems biology↗

bioRxiv2021

On the hybrid origin of the C2 Salsola divaricata agg. (Amaranthaceae) from C3 and C4 parental lineages

O_LIC2 photosynthesis is characterized by recapturing photorespiratory CO2 by RuBisCO in Kranz-like cells and is therefore physiologically intermediate between C3 and C4 photosynthesis. C2 can be interpreted as an evolutionary precursor of C4 and/or as the result of hybridization between a C3 and C4 lineage. C_LIO_LIWe compared the expression of photosynthetic traits among populations of the Salsola divaricata agg. (C2) from humid subtropical to arid habitats on the coasts of the Canary Islands and Morocco and subjected them to salt and drought treatments. We screened for enhanced C4-like expression of traits related to habitat or treatment. We estimated species trees with a transcriptome dataset of Salsoleae and explored patterns of gene tree discordance. With phylogenetic networks and hybridization analyses we tested for hybrid origin of the Salsola divaricata agg. C_LIO_LIWe observed distinct independent variation of photosynthetic traits within and among populations and no clear evidence for selection towards C4-like trait expression in more stressful habitats or treatments. We found reticulation and gene tree incongruence in Salsoleae supporting a putative hybrid origin of the Salsola divaricata agg. C_LIO_LIC2 photosynthesis in the Salsola divaricata agg. combines traits inherited from its C3 and C4 parental lineages and seems evolutionarily stable, possibly well adapted to a wide climatic amplitude. C_LI

evolutionary biology↗

bioRxiv2021

CENP-N promotes the compaction of centromeric chromatin

The histone variant CENP-A is the epigenetic determinant for the centromere, where it is interspersed with canonical H3 to form a specialized chromatin structure that nucleates the kinetochore. The arrangement of nucleosomes at the centromere into higher order structure is unknown. Here we demonstrate that the CENP-A interacting protein CENP-N promotes the stacking of CENP-A containing mono-nucleosomes and nucleosomal arrays through a previously undefined interaction between the 6 helix of CENP-N with the DNA of a neighboring nucleosome. We describe the cryoEM structures and biophysical characterization of such CENP-N mediated nucleosome stacks and nucleosomal arrays and demonstrate that this interaction is responsible for the formation of densely packed chromatin at the centromere in the cell. Our results provide first evidence that CENP-A, together with CENP-N, promotes specific chromatin higher order structure at the centromere. One-Sentence SummaryThe centromere-associated protein CENP-N promotes centromere-specific nucleosome stacking and higher order structures in vitro and in the cell.

molecular biology↗

bioRxiv2021

Melbournevirus-encoded histone doublets are recruited to virus particles and form destabilized nucleosome-like structures

The organization of genomic DNA into defined nucleosomes has long been viewed as a hallmark of eukaryotes. This paradigm has been challenged by the identification of minimalist histones in archaea, and more recently by the discovery of genes that encode fused remote homologs of the four eukaryotic histones in Marseilleviridae, a subfamily of giant viruses that infect amoebae. We demonstrate that viral doublet histones localize to the cytoplasmic viral factories after virus infection, and ultimately to mature virions. CryoEM structures of viral nucleosome-like particles show strong similarities to eukaryotic nucleosomes, despite the limited sequence identify. The unique connectors that link the histone chains contribute to the observed instability of viral nucleosomes, and some histone tails assume structural roles. Our results further expand the range of organisms that have nucleosomes and suggest a specialized function of histones in the biology of these unusual viruses. One Sentence SummarySome large DNA viruses encode fused histone doublets that are targeted to viral factories and assemble into open nucleosome-like structures.

molecular biology↗

bioRxiv2021

FAN1 nuclease activity affects CAG expansion and age at onset of Huntington's disease

The age at onset of motor symptoms in Huntingtons disease (HD) is driven by HTT CAG repeat length but modified by other genes. We used exome sequencing of 683 HD patients with extremes of onset or phenotype relative to CAG length to identify rare variants associated with clinical effect. We identified damaging coding variants in candidate modifier genes from prior genome-wide association studies associated with altered HD onset or severity. Variants in FAN1 clustered in its DNA-binding and nuclease domains and were associated predominantly with earlier onset HD. Nuclease activities of these variants correlated with residual age at motor onset of HD. Mutating endogenous FAN1 to a nuclease-inactive form in an induced pluripotent stem cell model of HD led to rates of CAG expansion comparable to those observed with complete FAN1 knock out. Together, these data implicate FAN1 nuclease activity in slowing somatic repeat expansion and hence onset of HD.

neuroscience↗

bioRxiv2020

Behavioral rebound following isolation of attention

Stable sensory perception is achieved through balanced excitatory-inhibitory interactions of lateralized sensory processing. In real world experience, sensory processing is rarely equal across lateralized processing regions, resulting in continuous rebalancing. Using lateralized attention as a case study, we predicted rebalancing lateralized processing following prolonged spatial attention imbalance could cause a gain in attention the opposite direction. In neurotypical human adults, we isolated covert attention to one visual field with a 30-minute attention-demanding task and found an increase in attention in the opposite visual field after manipulation. We suggest a gain in lateralized attention in the previously unattended visual field is due to an overshoot through attention rebalancing. The offline post-manipulation effect is suggestive of long-term potentiation affecting behavior. Our finding of visual field specific attention rebound could be critical for the development of clinical rehabilitation for patients with a unilateral lesion and lateralized attention deficits. This proof-of-concept study initiates the examination of overshoot following the release of imbalance in other lateralized control and sensory domains, important in our basic understanding of lateralized processing.

neuroscience↗

bioRxiv2020

Attention network modulation via tRNS correlates with attention gain

Transcranial Random Noise Stimulation (tRNS) can enhance vision in the healthy and diseased brain. Yet, the impact of tRNS on large-scale cortical networks is still unknown. We investigated the impact of tRNS coupled with behavioral training on resting-state functional connectivity and attention. We trained human subjects for four consecutive days on two attention tasks, while receiving tRNS over the intraparietal sulci, the middle temporal areas, or sham stimulation. We measured resting state functional connectivity of nodes of the dorsal and ventral attention network (DVAN) before and after training. We found a strong behavioral improvement and increased connectivity within the DVAN after parietal stimulation only. Crucially, behavioral improvement positively correlated with connectivity measures. We conclude changes in connectivity is a marker for the enduring effect of tRNS upon behavior. Our results suggest that tRNS has strong potential to augment cognitive capacity in healthy individuals and promote recovery in the neurological population.

neuroscience↗

bioRxiv2020

Controlling brain state prior to stimulation of parietal cortex prevents deterioration of sustained attention

Sustained attention is a limited resource which declines during daily tasks. Such decay is exacerbated in clinical and aging populations. Recent research has demonstrated that inhibition of the intraparietal sulcus (IPS) using low-frequency transcranial magnetic stimulation (LF-rTMS) can lead to an upregulation of functional communication within the attention network. Attributed to functional compensation for the inhibited node, this boost outlasts the stimulation for tens of minutes. Despite the neural change, no behavioral correlate has been found in healthy subjects, a necessary direct evidence of functional compensation. To understand the functional significance of neuromodulatory induced fluctuations on attention, we sought to boost the impact of LF-rTMS through controlling neural excitability prior to LF-rTMS, with the goal to impact behavior. Brain state was controlled using high-frequency transcranial random noise stimulation (HF-tRNS), shown to increase and stabilizes neuronal excitability. Using fMRI-guided stimulation protocols combining HF-tRNS and LF-rTMS, we tested the post-stimulation impact on sustained attention via a multiple object tracking task (MOT). Whilst attention deteriorated across time in the control conditions, HF-tRNS followed by LF-rTMS maintained attention performance up to 94 minutes, doubling the length of successful sustained attention. Multimethod stimulation was also more effective when targeting right IPS, supporting the notion of specialized attention processing in the right hemisphere. Used in a cognitive domain dependent on network-wide neural activity, this tool may be effective in causing lasting neural compensation important for clinical rehabilitation.

neuroscience↗

bioRxiv2019

Loss of AKAP1 triggers Drp1 dephosphorylation-mediated mitochondrial fragmentation and loss in retinal ganglion cells

Impairment of mitochondrial structure and function is strongly linked to glaucoma pathogenesis. Despite the widely appreciated disease relevance of mitochondrial dysfunction and loss, the molecular mechanisms underlying mitochondrial fragmentation and metabolic stress in glaucoma are poorly understood. We demonstrate here that glaucomatous retinal ganglion cells (RGCs) show loss of A-kinase anchoring protein 1 (AKAP1), activation of calcineurin (CaN) and reduction of dynamin-related protein 1 (Drp1) phosphorylation at serine 637 (Ser637). These findings suggest that AKAP1-mediated phosphorylation of Drp1 at Ser637 has a critical role in RGC survival in glaucomatous neurodegeneration. Male mice lacking AKAP1 show increases of CaN and total Drp1 level, as well as a decrease of Drp1 phosphorylation at Ser637 in the retina. Ultrastructural analysis of mitochondria shows that loss of AKAP1 triggers mitochondrial fragmentation and loss, as well as mitophagosome formation in RGCs. Loss of AKAP1 deregulates oxidative phosphorylation (OXPHOS) complexes (Cxs) by increasing CxII and decreasing CxIII-V, leading to metabolic and oxidative stress. Also, loss of AKAP1 decreases Akt phosphorylation at Serine 473 (Ser473) and threonine 308 (Thr308) and activates the Bim/Bax signaling pathway in the retina. These results suggest that loss of AKAP1 has a critical role in RGC dysfunction by decreasing Drp1 phosphorylation at Ser637, deregulating OXPHOS, decreasing Akt phosphorylation at Ser473 and Thr308, and activating the Bim/Bax pathway in glaucomatous neurodegeneration. Thus, we propose that overexpression of AKAP1 or modulation of Drp1 phosphorylation at Ser637 are potential therapeutic strategies for neuroprotective intervention in glaucoma and other mitochondria-related optic neuropathies.

neuroscience↗

bioRxiv2017

Predictive feedback to V1 dynamically updates with sensory input

Predictive coding theories propose that the brain creates internal models of the environment to predict upcoming sensory input. Hierarchical predictive coding models of vision postulate that higher visual areas generate predictions of sensory inputs and feed them back to early visual cortex. In V1, sensory inputs that do not match the predictions lead to amplified brain activation, but does this amplification process dynamically update to new retinotopic locations with eye-movements? We investigated the effect of eye-movements in predictive feedback using functional brain imaging and eye-tracking whilst presenting an apparent motion illusion. Apparent motion induces an internal model of motion, during which sensory predictions of the illusory motion feed back to V1. We observed attenuated BOLD responses to predicted stimuli at the new post-saccadic location in V1. Therefore, pre-saccadic predictions update their retinotopic location in time for post-saccadic input, validating dynamic predictive coding theories in V1.

neuroscience↗