Biology subjects

Jones, J. S.

Publications and source records attributed to Jones, J. S..

7 recordsLinked to original sources

bioRxiv2026

Functional connectivity correlates of the hierarchical p-factor model in youth at neurodevelopmental risk

BackgroundEmotional and cognitive difficulties often co-occur in neurodevelopmental conditions. While transdiagnostic, dimensional approaches offer a more precise framework for understanding mental health than diagnostic categories, their neural correlates in youth with learning difficulties remain poorly understood. This study investigates associations between transdiagnostic mental health dimensions and resting-state functional connectivity in struggling learners. MethodsCross-sectional behavioural data from the Centre for Attention, Learning and Memory (CALM) for struggling learners (N = 378) was used to replicate a hierarchical model of mental health from the Conners Parent Rating Short Form, the Revised Childrens Anxiety and Depression Scale and the Strengths and Difficulties Questionnaire. Functional connectomes were derived from resting-state fMRI data (N = 67), and partial least squares regression related mental health dimensions to connectivity within and between large-scale brain networks. ResultsThe replicated model comprised a general p-factor, two broad domains (internalising and externalising), and three specific dimensions (specific internalising, neurodevelopmental and social maladjustment). Symptom severity was associated with two connectivity patterns: greater default mode network coupling to frontoparietal and attention networks, and reduced connectivity between visual and somatomotor systems. These effects were strongest for the neurodevelopmental and social maladjustment dimensions, respectively. ConclusionsThese findings align with population-level evidence linking mental health dimensions to brain network organization, extending it to struggling learners and offering new insight into the neural basis of mental health vulnerability in neurodevelopmentally at-risk youth.

neuroscience↗

bioRxiv2025

Design, Expression, and Purification of a Soluble Form of the Retina-Specific Membrane Transporter, ABCA4

The ATP-binding cassette transporter A-subfamily member, ABCA4, is highly expressed in rod and cone photoreceptors in the retina, where it transports cis- and trans-retinal and is indispensable for vision. Genetic mutations in the ABCA4 gene lead to a wide range of inherited retinal degenerative diseases, including Stargardt disease (STGD1) and autosomal recessive cone-rod dystrophy. It is an integral membrane protein with twelve transmembrane -helices that complicates studies with the full-length ABCA4 transporter. We have engineered the full-length ABCA4 by transforming its membrane helices, creating a soluble homolog (ABCA4s). Most hydrophobic residues in the membrane helices were substituted with structurally compatible but hydrophilic residues. The re-engineered ABCA4s was expressed in insect cells, and it was found in the cytosolic extract, which was purified by immunoaffinity chromatography. Purified ABCA4s was enzymatically active, all-trans-retinal stimulated its ATPase activity, and its activity remained stable. SignificanceABCA4 is a 12-pass transmembrane protein that plays essential roles in the human retina and multiple visual diseases. Historically, the purification of ABCA4 and other large membrane proteins has relied on detergent-based purification, which renders the proteins enzymatic activity highly unstable. We describe here the design of a truly soluble analog of ABCA4 with stable enzymatic activities. Its 12 transmembrane helices were transformed using selective amino acid substitution, and deleterious substitutions were carefully avoided. This soluble form will pave the way for mechanistic studies of the enzyme and its disease-causing genetic variants. The methodology described here should be widely applicable to other complex membrane proteins facilitating their studies without the need for reconstitution in lipids.

biochemistry↗

bioRxiv2022

Exploring Neural Heterogeneity in Inattention and Hyperactivity

Inattention and hyperactivity are cardinal symptoms of Attention Deficit Hyperactivity Disorder (ADHD). These characteristics have also been observed across a range of other neurodevelopmental conditions, such as autism and dyspraxia, suggesting that they might best be studied across diagnostic categories. Here, we evaluated the associations between inattention and hyperactivity behaviours and features of the structural brain network (connectome) in a large transdiagnostic sample of children (Centre for Attention, Learning, and Memory; n = 383). In our sample, we found that a single latent factor explains 77.6% of variance in scores across multiple questionnaires measuring inattention and hyperactivity. Partial Least-Squares (PLS) regression revealed that variability in this latent factor could not be explained by a linear component representing nodewise properties of connectomes. We then investigated the type and extent of neural heterogeneity in a subset of our sample with clinically-elevated levels of inattention and hyperactivity. Multidimensional scaling combined with k-means clustering revealed two neural subtypes in children with elevated levels of inattention and hyperactivity (n = 232), differentiated primarily by nodal communicability--a measure which demarcates the extent to which neural signals propagate through specific brain regions. These different clusters had indistinguishable behavioural profiles, which included high levels of inattention and hyperactivity. However, one of the clusters scored higher on multiple cognitive assessment measures of executive function. We conclude that inattention and hyperactivity are so common in children with neurodevelopmental difficulties because they emerge from multiple different trajectories of brain development. In our own data, we can identify two of these possible trajectories, which are reflected by measures of structural brain network topology and cognition. Research HighlightsO_LIWe investigated variability in structural brain network organisation and its relationship with cognition and behaviour in a sample of 383 children. C_LIO_LIWe did not find linear components of brain structure that explained continuous variations in inattention and hyperactivity across this heterogeneous sample. C_LIO_LIFollowing this, we explored different attributes of brain organisation in children with particularly elevated levels of inattention and hyperactivity (n = 232). C_LIO_LIAmong highly inattentive and hyperactive children, we found two profiles of structural brain organisation ( neurotypes), which were differentiated primarily by the communicability of nodes in frontal and occipital brain areas. C_LIO_LIThese subgroups did not differ on additional measures of behaviour. However, the lower-nodal-communicability group demonstrated weaker performance on cognitive assessments of executive function and visuospatial processing. C_LIO_LIWe discuss the implications that these findings have for our understanding of variability in neurodevelopmental difficulties and related conditions, such as ADHD C_LI

neuroscience↗

bioRxiv2021

The Neural Correlates of Working Memory Training in Typically Developing Children

Working memory training improves childrens cognitive performance on untrained tasks; however, little is known about the underlying neural mechanisms. We investigated this in 32 typically developing children aged 10-14 years (19 girls and 13 boys; Devon, UK) using a randomized controlled design and multi-modal MRI. Training improved working memory performance and increased intrinsic functional connectivity between the bilateral intraparietal sulci. Furthermore, improvements in working memory were associated with greater recruitment of the left middle frontal gyrus on a complex span task. The repeated engagement of fronto-parietal regions during training may increase their activity and functional connectivity over time, affording greater working memory performance. We discuss the plausibility of generalizable cognitive benefits from a neurobiological perspective and implications for neurodevelopmental theory. This is not the version of record.

neuroscience↗

bioRxiv2021

Segregation and integration of the functional connectome in neurodevelopmentally 'at risk' children

Functional connectivity within and between Intrinsic Connectivity Networks (ICNs) transforms over development and supports high order cognitive functions. But how variable is this process, and does it diverge with altered cognitive developmental trajectories? We investigated age-related changes in integration and segregation within and between ICNs in neurodevelopmentally at-risk children, identified by practitioners as experiencing cognitive difficulties in attention, learning, language, or memory. In our analysis we used performance on a battery of 10 cognitive tasks, alongside resting-state functional Magnetic Resonance Imaging in 175 at-risk children and 62 comparison children aged 5-16. We observed significant age-by-group interactions in functional connectivity between two network pairs. Integration between the ventral attention and visual networks and segregation of the limbic and fronto-parietal networks increased with age in our comparison sample, relative to at-risk children. Furthermore, functional connectivity between the ventral attention and visual networks in comparison children significantly mediated age-related improvements in executive function, compared to at-risk children. We conclude that integration between ICNs show divergent neurodevelopmental trends in the broad population of children experiencing cognitive difficulties, and that these differences in functional brain organisation may partly explain the pervasive cognitive difficulties within this group over childhood and adolescence. Research HighlightsO_LIWe investigated functional brain organisation and its development in 175 children who experience neurodevelopmental difficulties in cognition and behaviour, relative to a comparison sample (n=62) C_LIO_LIWe replicated common neurodevelopmental trends across the samples: functional connectivity increased within Intrinsic Connectivity Networks and the default-mode network increasingly segregated with age C_LIO_LINeurodevelopmentally at-risk children also showed different age-related changes in functional connectivity between the ventral attention and visual networks and between the fronto-parietal and limbic networks C_LIO_LIFurthermore, the integration between the ventral attention and visual networks in comparison children mediated age-related changes in cognition, relative to at-risk children C_LI

neuroscience↗

bioRxiv2021

Genetically Engineered Strains for Combinatorial Cardiovascular Optobiology

Optogenetic effectors and sensors provide a novel real-time window into complex physiological processes, enabling determination of molecular signaling processes within functioning cellular networks. However, the combination of these optical tools in mice is made practical by construction of genetic lines that are optically compatible and genetically tractable. We present a new toolbox of 21 mouse lines with lineage -specific expression of optogenetic effectors and sensors for direct biallelic combination, avoiding the multiallelic requirement of Cre recombinase -mediated DNA recombination, focusing on models relevant for cardiovascular biology. Optogenetic effectors (11 lines) or Ca2+ sensors (10 lines) were selectively expressed in cardiac pacemaker cells, cardiomyocytes, vascular endothelial and smooth muscle cells, alveolar epithelial cells, lymphocytes, glia, and other cell types. Optogenetic effector and sensor function was demonstrated in numerous tissues. Arterial/arteriolar tone was modulated by optical activation of the second messengers InsP3 (opto1AR) and cAMP (opto{beta}2AR), or Ca2+- permeant membrane channels (CatCh2) in smooth muscle (Acta2) and endothelium (Cdh5). Cardiac activation was separately controlled through activation of nodal/conducting cells or cardiac myocytes. We demonstrate combined effector and sensor function in biallelic mouse crosses: optical cardiac pacing and simultaneous cardiomyocyte Ca2+ imaging in HCN4BAC-CatCh2/MHC-GCaMP8 crosses. These experiments highlight the potential of these mice to explore cellular signaling in vivo, in complex tissue networks.

physiology↗

bioRxiv2018

In vivo multiphoton microscopy of cardiomyocyte calcium dynamics in the beating mouse heart

We demonstrated intravital multiphoton microscopy in the beating heart in an intact mouse and optically measured action potentials with GCaMP6f, a genetically-encoded calcium indicator. Images were acquired at 30 fps with spontaneous heart beat and continuously running ventilated breathing. The data were reconstructed into three-dimensional volumes showing tissue structure, displacement, and GCaMP activity in cardiomyocytes as a function of both the cardiac and respiratory cycle.

physiology↗