Biology subjects

Murray, S.

Publications and source records attributed to Murray, S..

At least 19 recordsLinked to original sources

bioRxiv2026

EXCON: a scalable, reproducible Nextflow pipeline for CAFE-based gene EXpansion and CONtraction analysis

Gene family expansion and contraction analysis is a commonly used approach in evolutionary comparative genomics to identify lineage-specific evolutionary pressures on gene copy/family number. CAFE is one of the most popular tools to measure changes in gene family size, but requires a high level of bioinformatics expertise, manual parameter tuning and preprocessing. Here we present EXCON, an automated, Eco-Flow community-developed Nextflow pipeline that integrates NCBI genome download, annotation quality and format pre-processing, orthologous gene family identification (Orthofinder), ultrametric tree formatting, birth-death modelling (CAFE), and GO enrichment analysis (eggNOG-mapper/TopGO) into a single, portable workflow. EXCON accepts genome assemblies and annotations, supports local, HPC and cloud-based computing environments, and requires minimal user configuration. The pipeline auto-selects appropriate CAFE lambda and error models, and separates high variance orthogroups for separate treatment. Applied to a 24-species primate dataset spanning Catarrhini, Platyrrhini and Strepsirrhini, the pipeline identified 358 rapidly evolving gene families, including a DUX (double homeobox) gene showing repeated, independent copy-number turnover across multiple lineages, consistent with the known instability of the D4Z4 macrosatellite repeat it resides in. EXCON is freely available at https://github.com/Eco-Flow/excon.

evolutionary biology↗

bioRxiv2026

An in vivo chemical genetic approach for targeted glycoproteome analysis in Drosophila melanogaster

Glycans impact every aspect of physiology. Despite the rapid increase in relevance and translational potential, there remains a lack of tools for studying glycosylation in vivo. Here, we present FlyMOE, a chemical-genetic platform for targeted glycoprotein profiling in Drosophila melanogaster. Transgenic flies are equipped with biosynthetic capabilities to install bioorthogonally-tagged monosaccharides into the cellular glycoproteome. The genetic tractability of Drosophila allows for versatile application based on developmental stages, genetic drivers and glycosyltransferase enzymes. We employ FlyMOE to create an overview of the glycoproteome of Drosophila tissues and embryos based on mass spectrometry glycoproteomics, and investigate the substrates of individual members of the PGANT glycosyltransferase family in vivo. FlyMOE will allow the detailed investigation of the glycoproteome in Drosophila and similarly genetically modifiable in vivo model systems.

bioengineering↗

bioRxiv2025

Na+/H+ Exchanger Isoform 1 Regulates Apoptosis Susceptibility in Pulmonary Arterial Smooth Muscle from the Sugen/Hypoxia model of Pulmonary Hypertension

Pulmonary hypertension (PH) is characterized by vascular remodeling driven in part by apoptosis-resistant pulmonary arterial smooth muscle cells (PASMCs). Na/H exchanger isoform 1 (NHE1) regulates intracellular pH and plasma membrane cytoskeleton anchoring, influencing PASMC migration and proliferation, but the role of NHE1 in apoptosis remains unclear. NHE activity and NHE1 surface expression were increased in PASMCs from the Sugen/Hypoxia (SuHx) rat model compared to controls. Despite increased endoplasmic reticulum (ER) stress at baseline, SuHx PASMCs were resistant to apoptosis following H2O2 challenge. Pharmacological inhibition of NHE activity with ethyl-isopropyl amiloride (EIPA) and silencing with siRNA restored apoptosis in SuHx PASMCs. Conversely, NHE1 overexpression in control PASMCs conferred apoptosis resistance. Expression of mutant NHE1 constructs lacking ion translocation or binding to the adaptor protein, ezrin, also reduced H2O2-induced apoptosis. Mechanistically, apoptotic stimulation with H2O2 increased p38 phosphorylation in PASMCs from control, but not SuHx, rats, indicating impaired activation of this pro-apoptotic pathway. NHE1 suppression via EIPA or siRNA restored p38 phosphorylation in SuHx PASMCs, while overexpression of NHE1 (wild-type or mutants) suppressed p38 activation following apoptotic stimulation. Inhibition of p38 with SB203580 prevented the pro-apoptotic effect of EIPA, validating a role for p38 signaling in NHE1-mediated apoptosis resistance in SuHx PASMCs. These findings identify NHE1 as necessary and sufficient for PASMC apoptosis resistance in PH, by a mechanism independent of ion transport or ezrin-binding functions but involving suppression of p38 phosphorylation. Targeting NHE1-dependent pathways may restore PASMC apoptosis and offer a novel therapeutic strategy to reverse pulmonary vascular remodeling in PH.

physiology↗

bioRxiv2025

A catastrophic marine mortality event caused by a complex algal bloom including the novel brevetoxin producer, Karenia cristata (Dinophyceae)

Harmful algal blooms of Karenia brevis (Dinophyceae) are a global anomaly, occurring in one location worldwide, causing severe marine and acute human impacts via brevetoxins (BTX). During 2025 an unprecedented, currently ongoing, mass marine mortality occurred in South Australia, across an area of [~]20,000 km2, persisting for >6 months, resulting in the deaths of [~]106 marine animals of >550 taxa, with human health impacts. Using custom metabarcoding, long-read sequencing and targeted quantitative PCR, we characterized the microalgal assemblage. Karenia cristata dominated over the sampling area, in an assemblage with four other Karenia species with varied abundances spatially and temporally. High abundances of K. cristata appeared in the austral autumn, and hydrodynamic processes appear to have entrained cells coastward in the semi-enclosed seas. We isolated the species and characterized it using light and electron microscopy, liquid chromatography mass spectrometry and toxicity assays. We show for the first time that the rare and little known K. cristata produces significant BTX with a profile (BTX-2, -3, -B5), differing from K. brevis, with toxicological effects. These findings reveal a novel, significant BTX-producing Karenia, which considering its substantial detrimental marine ecosystem impacts, is an emerging international threat with unknown consequences in changing ocean conditions.

ecology↗

bioRxiv2025

An atlas of TF driven gene programs across human cells

Combinations of transcription factors (TFs) regulate gene expression and determine cell fate. Much effort has been devoted to understanding TF activity in different tissues and how tissue-specificity is achieved. However, ultimately gene regulation occurs at the single cell level and the recent explosion in the availability of single cell gene expression data now makes it possible to understand TF activity at this granular level of resolution. Here, we leverage a large collection of Human Cell Atlas (HCA) single cell data to explore TF activity by examining cell-type and tissue-specific sets of target genes, or regulons. We compile a regulon atlas, CellRegulon, and map the activity of TFs in an extensive set of healthy adult and foetal tissues spanning hundreds of cell types. Using CellRegulon, we describe dynamic patterns of co-regulation, associate TF-modules with different cellular functions and characterise the distribution of active TFs and TF families across cell types. We show that CellRegulon can link disease gene expression signatures to cell types and TFs relevant to the disease. Finally, using a newly generated multiome dataset of the adult lung, we show how CellRegulon can be extended into an enhancer-gene regulatory network (eGRN) to improve cell-type associations with genetic risk loci for diseases, such as childhood onset asthma, COPD and IPF, and to identify high risk gene modules. Our database for easy download and interactive exploration allows researchers to understand key gene modules activated at cell type transitions and will therefore be valuable for tasks such as cell type engineering (https://www.cellregulondb.org).

genetics↗

bioRxiv2024

Spatiotemporal map of the developing human reproductive tract at single-cell resolution

The human reproductive tract plays an essential role in species perpetuation. Its development involves complex processes of sex specification, tissue patterning and morphogenesis, which, if disrupted, can cause lifelong health issues, including infertility. Here, we generated an extensive single-cell and spatial multi-omic atlas of the human reproductive tract during prenatal development, which allowed us to answer questions that smaller-scale, organ-focused experiments could not address before. We identified potential regulators of sexual dimorphism in reproductive organs, pinpointing novel genes involved in urethral canalisation of the penis, with relevance to hypospadias. By combining histological features with gene expression data, we defined the transcription factors and cell signalling events required for the regionalisation of the Mullerian and Wolffian ducts. This led to a refinement of how the HOX code is established in the distinct reproductive organs, including increased expression of thoracic HOX genes in the rostral mesenchyme of the fallopian tube and epididymis. Our study further revealed that the epithelial regionalisation of the fallopian tube and epididymis required for sperm maturation in adulthood is established early in development. In contrast, later events in gestation or postnatally are necessary for the regionalisation of the uterocervical canal epithelium. By mapping sex-specific reproductive tract regionalisation and differentiation at the cellular level, our study offers valuable insights into the causes and potential treatments of reproductive disorders.

developmental biology↗

bioRxiv2024

A multiomic atlas of human early skeletal development

Bone and joint formation in the developing skeleton rely on co-ordinated differentiation of progenitors in the nascent developing limbs and joints. The cell states, epigenetic processes and key regulatory factors underlying their lineage commitment to osteogenic and other mesenchymal populations during ossification and joint formation remain poorly understood and are largely unexplored in human studies. Here, we apply paired single-nuclei transcriptional and epigenetic profiling of 336,000 droplets, in addition to spatial transcriptomics, to construct a comprehensive atlas of human bone, cartilage and joint development in the shoulder, hip, knee and cranium from 5 to 11 post-conception weeks. Spatial mapping of cell clusters to our highly multiplexed in situ sequencing (ISS) data using our newly developed tool ISS-Patcher revealed new cellular mechanisms of zonation during bone and joint formation. Combined modelling of chromatin accessibility and RNA expression allowed the identification of the transcriptional and epigenetic regulatory landscapes that drive differentiation of mesenchymal lineages including osteogenic and chondrogenic lineages, and novel chondrocyte cell states. In particular, we define regionally distinct limb and cranial osteoprogenitor populations and trajectories across the fetal skeleton and characterise differential regulatory networks that govern intramembranous and endochondral ossification. We also introduce SNP2Cell, a tool to link cell-type specific regulatory networks to numerous polygenic traits such as osteoarthritis. We also conduct in silico perturbations of genes that cause monogenic craniosynostosis and implicate potential pathogenic cell states and disease mechanisms involved. This work forms a detailed and dynamic regulatory atlas of human fetal skeletal maturation and advances our fundamental understanding of cell fate determination in human skeletal development.

developmental biology↗

bioRxiv2024

A frameshift mutation in the murine Prkra gene causes dystonia and exhibits abnormal cerebellar development and reduced eIF2α phosphorylation.

Mutations in Prkra gene, which encodes PACT/RAX cause early onset primary dystonia DYT-PRKRA, a movement disorder that disrupts coordinated muscle movements. PACT/RAX activates protein kinase R (PKR, aka EIF2AK2) by a direct interaction in response to cellular stressors to mediate phosphorylation of the subunit of the eukaryotic translation initiation factor 2 (eIF2). Mice homozygous for a naturally arisen, recessively inherited frameshift mutation, Prkralear-5J exhibit progressive dystonia. In the present study, we investigate the biochemical and developmental consequences of the Prkralear-5J mutation. Our results indicate that the truncated PACT/RAX protein retains its ability to interact with PKR, however, it inhibits PKR activation. Furthermore, mice homozygous for the mutation have abnormalities in the cerebellar development as well as a severe lack of dendritic arborization of Purkinje neurons. Additionally, reduced eIF2 phosphorylation is noted in the cerebellums and Purkinje neurons of the homozygous Prkralear-5J mice. These results indicate that PACT/RAX mediated regulation of PKR activity and eIF2 phosphorylation plays a role in cerebellar development and contributes to the dystonia phenotype resulting from this mutation. Summary StatementThis study shows, for the first time, a role of reduced eIF2 phosphorylation in DYT-PRKRA and the cerebellum development in a mouse model.

molecular biology↗

bioRxiv2024

Caspase-11 drives macrophage hyperinflammation in models of Polg-related mitochondrial disease

Mitochondrial diseases (MtD) represent a significant public health challenge due to their heterogenous clinical presentation, often severe and progressive symptoms, and lack of effective therapies. Environmental exposures, such bacterial and viral infection, can further compromise mitochondrial function and exacerbate the progression of MtD. Infections in MtD patients more frequently progress to sepsis, pneumonia, and other detrimental inflammatory endpoints. However, the underlying immune alterations that enhance immunopathology in MtD remain unclear, constituting a key gap in knowledge that complicates treatment and increases mortality in this vulnerable population. Here we employ in vitro and in vivo approaches to clarify the molecular and cellular basis for innate immune hyperactivity in models of polymerase gamma (Polg)-related MtD. We reveal that type I interferon (IFN-I)-mediated upregulation of caspase-11 and guanylate-binding proteins (GBPs) increase macrophage sensing of the opportunistic microbe Pseudomonas aeruginosa (PA) in Polg mutant mice. Furthermore, we show that excessive cytokine secretion and activation of pyroptotic cell death pathways contribute to lung inflammation and morbidity after infection with PA. Our work sheds new light on innate immune dysregulation in MtD and reveals potential targets for limiting infection- and inflammation-related complications in Polg-related MtD.

immunology↗

bioRxiv2024

The refinement paradox and cumulative cultural evolution: collective improvement in knowledge favors conformity, blind copying and hyper-credulity

Social learning is common in nature, yet cumulative culture (where knowledge and technology increase in complexity and diversity over time) appears restricted to humans. To understand why, we organized a computer tournament in which programmed entries specified when to learn new knowledge and when to refine (i.e. improve) existing knowledge. The tournament revealed a refinement paradox: refined behavior afforded higher payoffs as individuals converged on a small number of successful behavioral variants, but refining did not generally pay. Paradoxically, entries that refined only in certain conditions did best during behavioral improvement, while simple copying entries thrived when refinement levels were high. Cumulative cultural evolution may be rare in part because sophisticated strategies for improving knowledge and technology are initially advantageous, yet complex culture, once achieved, favors conformity, blind imitation and hyper-credulity.

evolutionary biology↗

bioRxiv2023

LipidSIM: inferring mechanistic lipid biosynthesis perturbations from lipidomics with a flexible, low-parameter, systematic Markov Modeling framework

Lipid metabolism is a complex and dynamic system involving numerous enzymes at the junction of multiple metabolic pathways. Disruption of these pathways leads to systematic dyslipidemia, a hallmark of many pathological developments, such as nonalcoholic steatohepatitis and diabetes. Recent advances in computational tools can provide insights into the dysregulation of lipid biosynthesis, but limitations remain due to the complexity of lipidomic data, limited knowledge of interactions among involved enzymes, and technical challenges in standardizing across different lipid types. In this study, we present a low-parameter, biologically interpretable framework named Lipid Synthesis Investigative Markov model (LipidSIM), which models and predicts the source of perturbations in lipid biosynthesis from lipidomic data. LipidSIM achieves this by accounting for the interdependency between the lipid species via the lipid biosynthesis network and generates testable hypotheses regarding changes in lipid biosynthetic reactions. This feature allows the integration of lipidomics with other omics types, such as transcriptomics, to elucidate the direct driving mechanisms of altered lipidomes due to treatments or disease progression. To demonstrate the value of LipidSIM, we first applied it to hepatic lipidomics following Keap1 knockdown and found changes in mRNA expression of the lipid pathways were consistent with the LipidSIM-predicted fluxes. Second, we used it to study lipidomic changes following intraperitoneal injection of CCl4 to induce fast NAFLD/NASH development and the progression of fibrosis and hepatic cancer. Finally, to show the power of LipidSIM for classifying samples with dyslipidemia, we used a Dgat2-knockdown study dataset. Thus, we show that as it demands no a priori knowledge of enzyme kinetics, LipidSIM is a valuable and intuitive framework for extracting biological insights from complex lipidomic data.

bioinformatics↗

bioRxiv2023

Estimating individuals' exposure to predation risk in group-living baboons, Papio anubis

In environments with multiple predators, the vulnerabilities attached to the spatial positions of group-living prey are not uniform and depend on the hunting styles of the predators. Coursing predators, mainly canids and hyenas, follow their prey over long distances and attack open areas, making individuals at the edge of the group more dangerous than those at the center (marginal predation). In contrast, ambush predators, mainly cats, approach their prey undetected and appear randomly anywhere in the group; therefore, isolated individuals are at a greater risk of predation. However, identifying individuals at high risk of predation requires the simultaneous recording of predator locations and direct observation of predation events, which are both difficult. Therefore, several theoretical methods have been proposed to assess predation risk (predation risk proxies). In a group of wild anubis baboons exposed to predation by leopards, lions, and hyenas, we calculated predation risk proxies using movement data collected from global positioning system (GPS) collars and found that adult males were on the edge of the group with a higher risk of predation (Hypothesis 1). In addition, adult males were more isolated within this group (Hypothesis 2). None of the predation risks differed among the other age-sex classes. The most dominant male was expected to be in the safety center of the group (Hypothesis 3) but was isolated on the periphery, like the other males. Therefore, we discussed why adult males were more peripheral and isolated.

zoology↗

bioRxiv2023

Defining Mitochondrial Cristae Morphology Changes Induced by Aging in Brown Adipose Tissue

Mitochondria are required for energy production and even give brown adipose tissue (BAT) its characteristic color due to their high iron content and abundance. The physiological function and bioenergetic capacity of mitochondria are connected to the structure, folding, and organization of its inner-membrane cristae. During the aging process, mitochondrial dysfunction is observed, and the regulatory balance of mitochondrial dynamics is often disrupted, leading to increased mitochondrial fragmentation in aging cells. Therefore, we hypothesized that significant morphological changes in BAT mitochondria and cristae would be present with aging. We developed a quantitative three-dimensional (3D) electron microscopy approach to map cristae network organization in mouse BAT to test this hypothesis. Using this methodology, we investigated the 3D morphology of mitochondrial cristae in adult (3-month) and aged (2-year) murine BAT tissue via serial block face-scanning electron microscopy (SBF-SEM) and 3D reconstruction software for manual segmentation, analysis, and quantification. Upon investigation, we found increases in mitochondrial volume, surface area, and complexity and decreased sphericity in aged BAT, alongside significant decreases in cristae volume, area, perimeter, and score. Overall, these data define the nature of the mitochondrial structure in murine BAT across aging. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=144 SRC="FIGDIR/small/540609v2_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@96099borg.highwire.dtl.DTLVardef@50b4f4org.highwire.dtl.DTLVardef@983092org.highwire.dtl.DTLVardef@19ceb9b_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract:C_FLOATNO Overview of serial block facing-scanning electron microscopy (SBF-SEM) workflow, data segmentation, and 3D analysis of mitochondria using Amira software for murine interscapular BAT. C_FIG

biophysics↗

bioRxiv2023

Spatial transcriptome profiling uncovers metabolic regulation of left-right patterning

Left-right patterning disturbance can cause severe birth defects, but it remains least understood of the three body axes. We uncovered an unexpected role for metabolic regulation in left-right patterning. Analysis of the first spatial transcriptome profile of left-right patterning revealed global activation of glycolysis, accompanied by right-sided expression of Bmp7 and genes regulating insulin growth factor signaling. Cardiomyocyte differentiation was left-biased, which may underlie the specification of heart looping orientation. This is consistent with known Bmp7 stimulation of glycolysis and glycolysis suppression of cardiomyocyte differentiation. Liver/lung laterality may be specified via similar metabolic regulation of endoderm differentiation. Myo1d, found to be left-sided, was shown to regulate gut looping in mice, zebrafish, and human. Together these findings indicate metabolic regulation of left-right patterning. This could underlie high incidence of heterotaxy-related birth defects in maternal diabetes, and the association of PFKP, allosteric enzyme regulating glycolysis, with heterotaxy. This transcriptome dataset will be invaluable for interrogating birth defects involving laterality disturbance.

developmental biology↗

bioRxiv2022

Rapid, in-patient adaptations of Legionella pneumophila to the human host

Legionella pneumophila are host-adapted bacteria that infect and reproduce primarily in amoeboid protists. Using similar infection mechanisms, they infect human macrophages, and cause Legionnaires disease, an atypical pneumonia, and the milder Pontiac fever. We hypothesized that, despite these similarities, the hosts are different enough so that there exist high-selective value mutations that would dramatically increase the fitness of Legionella inside the human host. By comparing a large number of isolates from independent infections, we identified two genes, mutated in three unrelated patients, despite the short duration of the incubation period (2-14 days). One is a gene coding for an outer membrane protein (OMP) belonging to the OmpP1/FadL family. The clinical strain, carrying the mutated OMP homolog, grows faster in macrophages than the wild type strain, and thus appears to be better adapted to the human host. The other is a gene coding for a protein involved in cyclic-di-GMP regulation, which in turn modulates flagellar activity. As human-to-human transmission is very rare, fixation of these mutations into the population and spread into the environment is unlikely. Therefore, convergent evolution - here mutations in the same genes observed in independent human infections - could point to adaptations to the accidental human host. These results suggest that despite its ability to infect, replicate, and disperse from amoebae, L. pneumophila is not well adapted to the human host. Impact statementLegionella pneumophila is primarily infecting amoeboid protists, but occasionally infects human lung macrophages, causing Legionnaires disease, an atypical pneumonia. By comparing 171 isolates from patients to their probable environmental source, we identified 119 mutations that presumably occurred in-patient. Among these, several mutations occurred in the gene. In particular, two genes were mutated thrice, significantly more often than expected by chance alone, and are likely to represent adaptations to the human host. We experimentally show that, for one mutation at least, the mutated strain grows faster in human macrophages than in amoebae. By specifically investigating in-patient mutations, we were able to identify two genes that might be involved in human host-specific adaptations of L. pneumophila. This result suggests that L. pneumophila is not particularly well adapted to the human host, as mutations get fixed in-patient, during the short course of an infection (2-14 days), indicating a very high selective value. Data SummaryThe sequencing data generated in this study are available in the NCBI database under the BioProject accession number: PRJEB52976.

microbiology↗

bioRxiv2022

CD8 T Cell Memory Inflation is Driven by Latent CMV Infection of Lymphatic Endothelial Cells

CMV, a ubiquitous herpesvirus, elicits an extraordinarily large T cell response that is sustained or increases over time, a phenomenon termed memory inflation. Remarkably, even latent, non-productive infection can drive memory inflation. Despite intense research on this phenomenon, the infected cell type(s) involved are unknown. To identify the responsible cell type(s), we designed a Cre-lox murine CMV (MCMV) system, where a spread-deficient ({Delta}gL) virus expresses recombinant SIINFEKL only in Cre+ host cells. We found that latent infection of endothelial cells (ECs), but not dendritic cells (DCs) or hepatocytes, was sufficient to drive CD8 T cell memory inflation. Infection of Lyve-1-Cre and Prox1-CreERT2 mice revealed that amongst EC subsets, infection of lymphatic ECs was sufficient. Genetic ablation of {beta}2m on lymphatic ECs did not prevent inflation, suggesting another unidentified cell type can also present antigen to CD8 T cells during latency. This novel system definitively shows that antigen presentation by lymphatic ECs drives robust CD8 T cell memory inflation. SUMMARYActive T cell immunosurveillance during latent CMV infection results in T cell memory inflation. A novel Cre-lox genetic system for cell-specific antigen expression reveals that lymphatic ECs, but not DCs or hepatocytes, can drive CD8 T cell memory inflation.

immunology↗

bioRxiv2021

The Importance of Mentors and How to Handle More Than One Mentor

IntroductionWorking with multiple mentors is a critical way for students to expand their network, gain opportunities, and better prepare for future scholastic or professional ventures. However, students from underrepresented groups (UR) are less likely to be mentored or have access to mentors, particularly in science, technology, engineering, and mathematics (STEM) fields. We developed and implemented a workshop, to provide the necessary foundation for students to be better prepared for establishing future mentorships throughout graduate and professional school. MethodsFaculty well-versed in the area of effective mentorship from multiple universities developed and delivered a 1.5-hour workshop to address the roles of a mentor, especially when it comes to UR students, and how students may effectively work with multiple mentors. This workshop was delivered to a group of students from the HBCU Winston Salem State University, and a pre/post-Likert scale-based survey was administered. ResultsWe analyzed the raw data with nonparametric tests for comparison within paired samples. Wilcoxon matched-pairs and signed-rank tests showed statistically significant growth in student self-ratings related to the workshop learning objectives. ConclusionsThe "How to Handle More than One Mentor to Achieve Excellence" workshop was well received as a component of pre-graduate and pre-professional training. Incorporating workshops like this may increase student preparedness around developing and cultivating healthy mentorship relationships throughout STEM training. EDUCATIONAL OBJECTIVESBy the end of this workshop, learners will be able to: O_LIDescribe the role of mentors in developing the next generation of trainees. C_LIO_LIDescribe current research on mentorship among underrepresented populations. C_LIO_LIApply skills on effective communication needed in the development of successful mentorship relationships. C_LIO_LIWork with multiple mentors at one time while maintaining solid professional and personal relationships. C_LI

scientific communication and education↗

bioRxiv2021

Aberrant Functional Connectivity between Reward and Inhibitory Control Networks in Pre-Adolescent Binge Eating Disorder

BackgroundBehavioral features of binge eating disorder (BED) suggest abnormalities in reward and inhibitory control. Studies of adult populations suggest functional abnormalities in reward and inhibitory control networks. Despite behavioral markers often developing in children, the neurobiology of pediatric BED remains unstudied. Methods58 pre-adolescent children (aged 9-10-years) with BED and 66 age, BMI and developmentally-matched control children were extracted from the 3.0 baseline (Year 0) release of the Adolescent Brain Cognitive Development (ABCD) Study. We investigated group differences in resting-state functional MRI (rs-fMRI) functional connectivity (FC) within and between reward and inhibitory control networks. A seed-based approach was employed to assess nodes in the reward (orbitofrontal cortex, nucleus accumbens, amygdala) and inhibitory control (dorsolateral prefrontal cortex, anterior cingulate cortex) networks via hypothesis-driven seed-to- seed analyses, and secondary seed-to-voxel analyses. ResultsOur findings revealed reduced FC between the dlPFC and amygdala, and between the anterior cingulate cortex and orbitofrontal cortex in pre-adolescent children with BED, relative to age, gender, BMI and developmentally matched controls. These findings indicating aberrant connectivity between nodes of inhibitory control and reward networks were corroborated by the whole-brain FC analyses. ConclusionsEarly-onset BED may be characterized by diffuse abnormalities in the functional synergy between reward and cognitive control networks, without perturbations within reward and inhibitory control networks, respectively. The decreased capacity to regulate a reward-driven pursuit of hedonic foods, which is characteristic of BED, may in part, rest on this dysconnectivity between reward and inhibitory control networks.

neuroscience↗