Biology subjects

Jackson, J.

Publications and source records attributed to Jackson, J..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

An artificial nervous system for communication between wearable and implantable therapeutics

Bioelectronics have transformed our capacity to monitor and treat diseases; however, a lack of micrometer-scale, energy efficient communication options limit these devices from forming integrated networks that enable full-body, sensor driven, physiological control. Inspired by our nervous systems ability to transmit information via ionic conduction, we engineered a Smart Wireless Artificial Nervous System (SWANS) that utilizes the bodys own tissue to transmit signals between wearables and implantables. When SWANS emits signals, it generates voltage gradients throughout the body that selectively turn on implanted transistor switches when exceeding their gate threshold voltages. SWANS implantable communication components maintain syringe-injectable footprints and >15x greater power efficiencies than Bluetooth and Near Field Communication. In vivo studies in rats demonstrate SWANS ability to wirelessly regulate dual hind leg motor control by connecting electronic-skin sensors to implantable neural interfaces via ionic signaling as well as coordinate bioelectronics throughout the epidermal, subcutaneous, intraperitoneal, and gastrointestinal spaces.

bioengineering↗

bioRxiv2025

PsiConnect: A Multimodal Neuroimaging Study of Psilocybin-Induced Changes in Brain and Behaviour

PsiConnect is a large-scale neuroimaging study designed to investigate the neural and subjective effects of psilocybin using multimodal neuroimaging. It combines functional, structural, and diffusion-weighted MRI with EEG to examine brain activity in 62 participants before and after a 19 mg dose of psilocybin. The design includes resting-state scans and three naturalistic conditions: guided meditation, music listening, and movie watching. Half of the cohort underwent an 8-week meditation training program, enabling the exploration of interactions among meditation, psilocybin, and brain function. The fMRI data was obtained through multi-echo fMRI, which enhances the signal-to-noise ratio and reduces susceptibility artifacts, thereby improving the reliability of the analyses. A comprehensive battery of behavioural and self-report measures captured both acute and longitudinal cognitive and subjective effects, with follow-ups extending to one year post-administration. The large sample size, multimodal neuroimaging, diversity of contexts, and longitudinal behavioural follow-ups enable the study of psilocybin-induced changes in brain and behaviour with an unprecedented level of detail and reliability. Furthermore, the data is curated according to open science principles to ensure accessibility and interoperability with established neuroimaging processing pipelines. These factors make PsiConnect a valuable and highly reusable resource for researchers in cognitive and computational neuroscience.

neuroscience↗

bioRxiv2025

General Trends in the Calnexin-Dependent Expression and Pharmacological Rescue of Clinical CFTR Variants

Cystic Fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). Though most people with CF have one or two copies of the {Delta}F508 mutation, there are hundreds of other distinct CF mutations that vary in their mechanistic effects and response to therapeutics. Endogenous chaperones are known to have divergent effects on the druggability of CF variants. Nevertheless, it remains unclear how this proteostatic modulation is related to the underlying mechanistic effects of distinct classes of CF mutations. Here, we survey the effects of a previously discovered effector (calnexin, CANX) on the expression and pharmacological rescue of 232 CF variants using deep mutational scanning. We find that CANX is generally required for robust plasma membrane expression of the CFTR protein-particularly for CF variants that perturb its second nucleotide binding domain. CANX also appears to be critical for the pharmacological rescue of CF variants with poor basal expression. Though corrector selectivity is generally dictated by the properties of mutations, we find that CANX enhances the sensitivity of CF variants within a domain swapped region of membranes spanning domain 2 to the type III corrector VX-445. Overall, mutagenic trends suggest CANX modulates the later stages of CFTR assembly and disproportionately affects variants bearing mutations within the C-terminal domains. Interestingly, we find that the loss of CANX results in widespread perturbations of CF variant interactomes and that the proteostatic effects of CANX are generally decoupled from changes in CFTR activity. Together, our findings reveal how the proteostasis machinery may shape the variant-specific effects of corrector molecules.

biochemistry↗

bioRxiv2025

Protective ApoE variants support neuronal function by extracting peroxidated lipids

ApoE mediates the transport of lipids from neurons to glial lipid droplets. ApoE4, a major risk factor for Alzheimer's disease, impairs this transport pathway, increasing risk for neurodegeneration. ApoE2 and ApoE3 Christchurch (ApoE3Ch) variants confer resistance to developing the disease, yet little is known regarding how these protective variants affect lipid transport. Here, we explored how lipoprotein particles containing different ApoE isoforms affect neuronal health in vitro and in intact rodent hippocampi. We demonstrate that ApoE2 and ApoE3Ch particles protect neurons from ferroptosis by preferentially extracting peroxidated unsaturated lipids through the neuronal ABCA7 transporter. ApoE4 particles, on the other hand, exacerbate the effects of these toxic lipids leading to endolysosomal dysfunction. By reducing the peroxidated lipid burden in ApoE4 neurons, ApoE2 and ApoE3Ch particles rescue endolysosomal function and restore defects in neuronal activity. Our findings reveal a new mechanism by which ApoE2 and ApoE3Ch isoforms protect neurons from neurodegenerative disease.

neuroscience↗

bioRxiv2025

Glucosylceramide induced ectosomes propagate pathogenic α-synuclein in Parkinson's disease

Intercellular transmission of -synuclein contributes to Parkinsons disease pathology. Yet, the mechanisms of -synuclein spread are not fully understood. Here, we used live-cell microscopy to examine the impact of Parkinsons disease associated lipid alterations on -synuclein release. We discovered that increased glucosylceramides induce ectosome shedding from primary neurons, and from dopaminergic neurons derived from Parkinsons disease patient iPSCs harboring mutations in GBA1 (N370S, L444P and W378G) and LRRK2 (G2019S and R1441H) compared to their isogenic control. We show that elevated glucosylceramide similarly increases vesicle release and uptake by other neurons in living mouse brains using 2-photon microscopy. Finally, we show that ectosomes are loaded with pathogenic -synuclein and lead to the transmission of -synuclein pathology to neighbouring neurons. These data reveal ectosomes as the predominant route for -synuclein transmission that can only be appreciated by live-cell imaging technologies.

cell biology↗

bioRxiv2025

Testing a general theory for flowering time shift as a function of growing season length

Understanding the effects of climate change on the evolution of phenological timing, such as start of flowering, is of major interest because phenology is critical for fitness of populations, and underpins many ecological dynamics. Much recent research has focused on the correlation between phenological timing and the arrival of spring. However, the evolutionarily optimal seasonal timing should depend also on the duration of the growing season, within which entire annual life cycles must unfold. Optimal energy allocation theory can explicitly address life-history scheduling in a seasonal environment, and be used to predict how scheduling should adaptively respond to seasonality shifts. Here we extend a seminal theoretical framework for perennial plant scheduling by Iwasa & Cohen (1989), and predict a specific nonlinear relationship between growing season length and optimal flowering time expressed as number of days after the start of the growing season. We tested and found strong support for this a priori prediction in two independent common-garden experiments with purple loosestrife (Lythrum salicaria) and European goldenrod (Solidago virgaurea) populations sampled along latitudinal gradients in Sweden. Climate warming is commonly associated with changes in both the start and the duration of the growing season. Considering both effects, our findings suggest that as springs start earlier and growing seasons lengthen, shifts in optimal flowering time expressed as calendar date may initially stall before accelerating, potentially explaining observed variation in phenological shifts across systems. More broadly, we show how mechanistic life history theory can advance understanding of phenological change beyond correlative conclusions. SIGNIFICANCE STATEMENTThe optimal timing for a plant to flower depends both on when spring begins and on the total length of the growing season--both shifting with climate change. However, the adaptation of flowering time to changes in growing season length is much less explored than to an advancing spring. Building on existing theory, we predict a nonlinear relationship between growing season length and optimal flowering time. Data on two species (purple loosestrife and European goldenrod) grown in common gardens strongly support this prediction. Our results demonstrate why species can vary in their observed phenological responses to climate change. More broadly, we highlight the power of mechanistic life history theory for explaining and predicting phenological shifts.

ecology↗

bioRxiv2025

A synaptic-astrocytic proteomic signature associated with synaptopathy in Alzheimer's Disease

Synapse loss is the greatest correlate of cognitive impairment in Alzheimers Disease (AD) and offers a therapeutic avenue alongside disease-modifying therapies. However, the events preceding synapse loss in the human condition have not been well characterised. In this study, we describe a pseudotemporal profile of alterations in the synaptic proteome prior to excitatory synapse loss in human post-mortem brain AD tissue using synapse proteomics and synaptome mapping techniques. In a region with early-stage disease pathology, the most predominant changes were pre-synaptic and featured changes in metabolism and exocytosis. In a mid-stage disease state, alongside initial synapse loss, there was a dominance of inhibitory synaptic changes. In a region with late-stage disease pathology and profound synapse loss, post-synaptic changes were most prevalent with a range of canonical synaptic transmission pathways reduced and differential excitatory synapse subtype pathology. Synapse loss was associated with changes in astrocytic proteins which were enriched for those at peri-synaptic astrocytic processes, including an upregulation of complement activation and endocytosis; a signature that differed from the astrocyte cytosolic proteome. Taken together, this provides evidence of a cascade of events leading to synapse loss with multiple points for therapeutic intervention to alleviate cognitive decline in AD. Data are available via ProteomeXchange with identifier PXD056052.

neuroscience↗

bioRxiv2024

Claustrum projections to the anterior cingulate modulate nociceptive and pain-associated behaviour

The anterior cingulate cortex (ACC) processes nociceptive information and pain unpleasantness. The claustrum is a subcortical region that provides robust feed-forward inhibition onto the ACC, suggesting this circuit could play a role in modulating pathological states such as pain. However, the function of this circuit in the context of acute and chronic inflammatory pain is unclear. Here, we show that claustrocingulate neurons exhibit a bimodal pattern of activation following acute pain but are suppressed during states of chronic inflammatory pain. Molecular lesion and chemogenetic suppression of claustrocingulate neurons increased acute nociception but interfered with pain learning. Activation of this pathway rescued mechanical allodynia associated with chronic pain. Together, these results suggest claustrocingulate neurons are a critical component of the pain neuromatrix, and dysregulation of this connection may contribute to chronic pain.

neuroscience↗

bioRxiv2023

Bidirectional chemogenetic modulation of claustral activity causes altered cortical dynamics

In recent years, there has been a growing interest in understanding the function of the claustrum. The claustrum is a thin, long, subcortical structure with dense connections to the cortex. Despite these extensive connections, the manner in which the claustrum influences broader cortical activity remains unclear. We used mesoscale calcium fluorescence imaging to examine resting state cortical activity (1-5Hz) and sensory-evoked responses in lightly anesthetized mice, before and after bi-directional chemogenetic modulation of claustrum-prefrontal neurons. Claustrum inhibition resulted in increased activity in anterior-medial cortical areas, whereas claustrum excitation resulted in decreased activity in anterior-medial cortical regions. Claustrum inhibition also led to an increased local coupling between areas of frontal cortex, a decreased correlation between anterior medial regions-of-interest (ROIs) and lateral and posterior ROIs, and an increased sensory evoked response in the visual cortex. These results are consistent with the finding that the claustrum has a large feed-forward inhibitory effect on the PFC, and the concept that specific claustrocortical pathways may modulate recruit and synchronize activity in topographically distinct cortical modules. Together these results show that neural activity in the claustrum modulates the excitability of prefrontal cortical networks, suggesting a potential target for prefrontal-dependent behaviors such as learning, attention, and stress regulation.

neuroscience↗

bioRxiv2023

A simple and reliable method for claustrum localization across age in mice

1.The anatomical organization of the rodent claustrum remains obscure due to lack of clear borders that distinguish it from neighboring forebrain structures. Defining what constitutes the claustrum is imperative for elucidating its functions. Methods based on gene/protein expression or transgenic mice have been used to spatially outline the claustrum but often report incomplete labeling and/or lack of specificity during certain neurodevelopmental timepoints. To reliably identify claustrum cells in mice, we propose a simple immunolabelling method that juxtaposes the expression pattern of claustrum-enriched and cortical-enriched markers. We determined that claustrum cells immunoreactive for the claustrum-enriched markers Nurr1 and Nr2f2 are devoid of the cortical marker Tle4, which allowed us to differentiate the claustrum from adjoining cortical cells. Using retrograde tracing, we verified that nearly all claustrum projection neurons lack Tle4 but expressed Nurr1/Nr2f2 markers to different degrees. At neonatal stages between 7 and 21 days, claustrum projection neurons were identified by their Nurr1-postive/Tle4-negative expression profile, a time-period when techniques used to localize the claustrum in adult mice are ineffective. Finally, exposure to environmental novelty enhanced the expression of the neuronal activation marker cFos in the claustrum region. Notably, cFos labeling was mainly restricted to Nurr1-positive cells and nearly absent from Tle4-positive cells, thus corroborating previous work reporting novelty-induced claustrum activation. Taken together, this method will aid in studying the claustrum during postnatal development and may improve histological and functional studies where other approaches are not amenable.

neuroscience↗

bioRxiv2023

State dependent constraints on claustrocortical communication and function

Neural activity in the claustrum has been associated with a range of vigilance states, yet the activity patterns and efficacy of synaptic communication of identified claustrum neurons have not been thoroughly determined. Here we show that claustrum neurons projecting to the retrosplenial cortex were most active during synchronized cortical states such as non-rapid-eye-movement (NREM) sleep and were suppressed during increased cortical desynchronization in arousal, movement, and REM sleep. The efficacy of claustrocortical signaling was also increased during NREM and diminished during movement due in part to increased cholinergic tone. Finally, claustrum activation during NREM sleep enhanced memory consolidation through the phase-resetting of cortical delta waves. Therefore, claustrocortical communication is constrained to function most effectively during cognitive processes associated with synchronized cortical states, such as memory consolidation. Key PointsO_LIClaustrum neurons are suppressed/activated during desynchronized/synchronized cortical states C_LIO_LIClaustrocortical connectivity is increased in non-REM and suppressed during movement C_LIO_LIClaustrocortical communication is heightened during low cholinergic tone C_LIO_LIClaustrum - modulated cortical delta waves enhance the consolidation of a labile memory C_LI

neuroscience↗

bioRxiv2023

Omix: A Multi-Omics Integration Pipeline

SummaryThe Omix pipeline offers an integration and analysis framework for multiomics intended to preprocess, analyse, and visualise multimodal data flexibly to address various research questions. From biomarker discovery and patient stratification to the investigation of complex biological processes, Omix empowers researchers to derive valuable insights from omics data. Using Alzheimers Disease (AD) bulk proteomics and transcriptomics datasets generated from two distinct regions derived from post-mortem brains, we demonstrate the utility of Omix in generating an integrated pseudo-temporal multi-omics profile of AD. Availability and ImplementationOmix is implemented as a software package in R. The code for the Omix package is available at https://github.com/eleonoreschneeg/Omix. Reference documentation and online tutorials are available at https://eleonore-schneeg.github.io/Omix. All code is open-source and available under the GNU General Public License v3.0 (GPL-3). Contacteleonore.schneegans17@imperial.ac.uk, johanna.jackson@imperial.ac.uk

bioinformatics↗

bioRxiv2023

Experimental drought reduces the productivity and stability of a recovering calcareous grassland

O_LIGrasslands comprise 40% of terrestrial ecosystems and are globally important for food production, carbon storage, and other ecosystem services. However, grasslands in many areas are becoming increasingly exposed to extreme wet and dry periods resulting from global temperature increases. C_LIO_LITherefore, understanding how grasslands will respond to climate change is a pressing issue for managing changes to biodiversity and ecosystem service provision. C_LIO_LIHere, we use experimental manipulations of precipitation (50% increase and 50% decrease of growing-season precipitation) to investigate the resistance of the diversity and productivity of a calcareous grassland community recovering from historical agricultural conversion. C_LIO_LIWe found that decreasing growing season precipitation led to reductions of mean productivity (25 % decrease in peak above-ground biomass) and its temporal stability (54 % increase in biomass variance across years). However, the grassland community composition was resistant to the precipitation manipulations, with no clear difference in community compositional turnover, dissimilarity, or biodiversity indices. Furthermore, the precipitation manipulations had no effect on the path of ongoing (30 year) recovery of grassland plant diversity from the period of previous agricultural conversion. C_LIO_LIWhile the diversity of this calcareous grassland was resistant to precipitation extremes (at least in the short term), sustained reductions in growing-season precipitation reduced productivity and its temporal stability demonstrating that different properties of grasslands can vary in their responses to changes in precipitation. C_LI

ecology↗

bioRxiv2023

Experimentally induced drought and growing season stage modulate community-level functional traits in a temperate grassland

O_LIExtreme precipitation events are expected to become more intense and frequent with climate change. This climatic shift may impact the structure and dynamics of natural communities and the key ecosystem services they provide. Changes in species abundance under these extreme conditions are thought to be driven by functional traits, morpho-physiological characteristics of an organism that impact its fitness. Future environmental conditions may, therefore, favour different functional traits to those in present-day communities. C_LIO_LIHere, we measure functional traits on 586 vascular plants in a temperate grassland where precipitation has been experimentally manipulated for six years. We calculated community-weighted means of five functional traits (plant height, leaf dry matter content, leaf thickness, specific leaf area, and leaf phosphorus concentration) and compared community-weighted means between three levels of precipitation: drought (-50%), irrigated (+50%), and control. Additionally, we contrasted treatments at two different timings along the growing season: mid-season and late-season. C_LIO_LIWe expected altered community-weighted means for traits associated with a conservative use of water that will result from increased summer stress-induced intraspecific variability in the mid-season and from community composition changes in the late-season, after the field is cut, a common management action across most European grasslands. C_LIO_LIIn the drought treatment, we found significantly lower community-weighted mean plant height and leaf dry matter content. However, we only observed these differences after the mid-season cut. We also observed an increase in leaf phosphorus concentration in the drought treatment before the mid-season cut. A combination of changes in community composition and intraspecific variation contributed to these differences, with community composition being more important after the cut. Species with higher height, leaf dry matter content, and lower leaf thickness showed a more pronounced abundance decline at the drought plots. We observed no changes in functional traits community-weighted means in the irrigated treatment compared to those in control and drought treatments. C_LIO_LISynthesis. Our results suggest how the functional trait composition of grassland communities may shift under climate change-induced drought, stressing the interacting effects with growing season stages. C_LI

ecology↗

bioRxiv2022

A meta-analysis of operational interactions between pinnipeds and fisheries

The global recovery of pinniped populations is a conservation success. However, pinniped population recovery has increased human-wildlife conflict with fisheries, an issue often reported and requiring management, but one that lacks global synthesis. We conduct a meta-analysis to estimate the impacts of operational interactions (specifically, lost catch) between pinnipeds and fisheries. Where quantifiable interactions are reported (n = 36), on average fishers have a 33.7% chance of interacting with pinnipeds on any given fishing day, and 13.8% lost catch. We find a large degree of heterogeneity between studies, with some fisheries experiencing much more negative interactions than others. Specifically, smaller-scale fisheries using nets are up to twice as likely to have negative interactions and lose up to five times more catch compared to large-scale fisheries. We conclude that pinniped-fishery conflict is a substantial global issue, but its impacts are not uniform. To successfully manage long-term coexistence between pinnipeds and humans, explicit data quantifying operational interactions is required. Population recoveries can have unintended consequences for fisheries, and management of ecological, social and economic outcomes is needed for long-term coexistence. TeaserPinniped population recoveries have led to significant impacts on fisheries, but small-scale fisheries lose out most.

zoology↗

bioRxiv2022

Broadly neutralizing SARS-CoV-2 antibodies through epitope-based selection from convalescent patients

Emerging variants of concern (VOCs) are threatening to limit the effectiveness of SARS-CoV-2 monoclonal antibodies and vaccines currently used in clinical practice; broadly neutralizing antibodies and strategies for their identification are therefore urgently required. Here we demonstrate that broadly neutralizing antibodies can be isolated from peripheral blood mononuclear cells (PBMCs) of convalescent patients using SARS-CoV-2 receptor binding domains (RBDs) carrying epitope-specific mutations. This is exemplified by two human antibodies, GAR05, binding to epitope class 1, and GAR12, binding to a new epitope class 6 (located between class 3 and class 5). Both antibodies broadly neutralize VOCs, exceeding the potency of the clinical monoclonal sotrovimab (mAb S309) by orders of magnitude. They also provide potent prophylactic and therapeutic in vivo protection of hACE2 mice against viral challenge. Our results indicate that exposure to Wuhan SARS-CoV-2 induces antibodies that maintain potent and broad neutralization against emerging VOCs using two unique strategies: either by targeting the divergent class 1 epitope in a manner resistant to VOCs (ACE2 mimicry, as illustrated by GAR05 and mAbs P2C-1F11/S2K14); or alternatively, by targeting rare and highly conserved epitopes, such as the new class 6 epitope identified here (as illustrated by GAR12). Our results provide guidance for next generation monoclonal antibody development and vaccine design.

immunology↗

bioRxiv2022

Staphylococcus aureus SigS induces expression of a regulatory protein pair that modulate its mRNA stability

SigS is the sole extracytoplasmic function sigma in S. aureus and is necessary for virulence, immune evasion, as well as surviving exposure to toxic chemicals and environmental stressors. Despite the contribution of SigS to a myriad of critical phenotypes, the downstream effectors of the SigS-dependent S. aureus pathogenesis, immune evasion, and stress response remain elusive. To address this knowledge gap, we analyzed the S. aureus transcriptome following transient over-expression of SigS. We identified a bi-cistronic transcript, up-regulated by 1000-fold, containing two mid-sized genes each containing single domains of unknown function (DUF). We renamed these genes sroA (SigS regulated orfA) and sroB (SigS regulated orfB). We demonstrated that the SigS regulation of the sroAB operon is direct using in vitro transcription analysis. Using northern blot analysis, we also demonstrated that SroA and SroB have opposing auto- regulatory functions on the transcriptional architecture of the sigS locus; with SroA stimulated SigS mRNA levels and SroB stimulating s750 (SigS antisense) levels. We hypothesized that these this opposing regulatory effects were due to a direct interaction. We demonstrated an interaction between SroA and SroB using an in-vivo surrogate genetics approach via Bacterial Two Hybrid. We demonstrated that the SroA effect on SigS is at the post-transcriptional level of mRNA stability, highlighting a mechanism likely used by S. aureus to tightly control SigS levels. Finally, we demonstrate that the sroAB locus promotes virulence in a female murine pneumonia model of infection.

microbiology↗

bioRxiv2022

Social isolation produces a brain-region specific expansion of microglia structure and reorganization of neural activity

Social isolation is a profound form of psychological stress that impacts the mental health of a large proportion of society. Other experimental models of stress and injury have demonstrated microglia activation and alterations in neural activity. Microglia and neural activity undergo coordinated changes under physiological and pathological states. However, the effect of social isolation on microglia and neural activity has not been thoroughly investigated. Here we show that the dorsal medial hypothalamus and hippocampal CA2 region of male mice undergo an increased microglia volume and branching following social isolation, whereas females exhibit this increase in the hypothalamus only. The prefrontal cortex, central amygdala, nucleus accumbens shell, and visual cortex did not exhibit changes in microglia structure in either male or female mice. The home cage resting level of neural activity, as measured by the immediate early gene c-fos, was reduced in CA2 and the prefrontal cortex of female but not male mice following isolation. However, the co-variation in neural activity across brain regions was abolished in male but not female isolated mice. These data show that different brain regions undergo independent and dissociable changes in microglia structure and network activity following social isolation which may account for changes in cognition and behavior associated with this form of psychological stress.

neuroscience↗