Biology subjects

James, C. E.

Publications and source records attributed to James, C. E..

7 recordsLinked to original sources

bioRxiv2026

Frontoparietal effective connectivity supports working memory in early childhood

Working memory (WM), a core executive function that supports learning and reasoning, undergoes rapid development during early childhood years. Neural activation patterns underlying WM have been extensively studied in both adults and children, revealing increasing involvement of the frontoparietal network (FPN) with age and coordinated interactions with the default mode network (DMN). However, relatively little is known about how these network interactions develop in children, particularly within the visuospatial domain. The present study investigated the influence of age and task performance on effective connectivity within the FPN and its interactions with DMN hubs during a visuospatial WM task in early childhood. Functional MRI data were collected during a visual n-back task with two WM load levels (0-back and 2-back) in 120 typically developing children aged 5-8 years. Dynamic Causal Modeling (DCM) with parametric empirical Bayes was used to estimate effective connectivity among eight regions of interest spanning the FPN and DMN. Behaviorally, age-related gains were steepest under high-load for accuracy, and under low-load for reaction time, suggesting WM capacity is a demand-sensitive marker of development at this age. At the network level, high-load robustly engaged the FPN, whereas low-load was associated with relatively greater engagement of DMN and episodic memory-related regions. Baseline effective connectivity was dominated by parietal-to-frontal drive and strong self-inhibition in the anterior cingulate cortex. Age-related effects on this architecture were sparse, involving asymmetric interhemispheric frontal coupling and reduced parieto-cingulate coupling, whereas accuracy-related effects were larger in magnitude, particularly at self-connections. More accurate children showed greater excitability in frontal and parietal FPN nodes alongside increased self-inhibition in the precuneus, a DMN hub, consistent with a neural efficiency account in which better performance reflects more selective, rather than more global, network engagement. Task load further shaped connectivity in distinct ways: low-load elicited widespread inter-regional modulation, whereas high-load predominantly modulated self-connections, with age and accuracy effects on this modulation dissociating by load. These findings suggest that, in primary school children, current task performance was associated with more pronounced differences in frontoparietal effective connectivity than was age, and that WM-related network engagement becomes increasingly selective and load-dependent across this developmental window.

neuroscience↗

bioRxiv2026

Altered Hippocampal Structure-Function Coupling and Brain-Cognition Aging Profile in Mild Cognitive Impairment

Hippocampal atrophy and altered functional connectivity are prominent features of mild cognitive impairment (MCI), yet their relationships and joint contribution to cognitive impairment remain unclear. We evaluated multidomain cognitive-sensorimotor performance, whole-brain gray matter atrophy patterns, associated functional connectivity, and their coupling in MCI and HC. We conducted this cross-sectional study in 25 clinically diagnosed amnestic and non-amnestic MCI patients and 15 age- and education-matched healthy controls (HC). Participants (57-81 years old) completed a battery assessing general cognition, executive functions, attention, speech-in-noise perception, manual dexterity, and balance, combined with structural and resting-state functional magnetic resonance imaging. Among the 25 MCI patients, 8 (32%) presented with amnestic MCI, 15 (60%) with non-amnestic MCI, and 2 (8%) with subjective cognitive decline. Linear mixed models revealed that semantic fluency (g = 0.74) was the largest discriminator of MCI, followed by attention (g = 0.61), phonemic fluency (g = 0.59), and speech-in-noise perception (g = 0.56). Voxel-based morphometry showed bilateral hippocampal and anteromedial cerebellar gray matter atrophy in MCI. Seed-based functional connectivity analyses indicated that atrophy was not uniformly associated with reduced connectivity. Cortico-subcortical hypoconnectivity emerged only in networks associated with left hippocampal atrophy in MCI compared with HC. Network-based analyses showed disrupted brain-behavior coupling and a stronger detrimental influence of age in MCI than in HC. These findings confirm the critical role of hippocampal structure-function relationships in multidomain MCI symptoms. A decoupled brain-cognition aging profile suggests that multimodal indices integrating hippocampal structure, connectivity, and behavioral performance may strengthen MCI diagnosis.

neuroscience↗

bioRxiv2026

Whole genome sequencing-based characterization of mobile genetic elements in Staphylococcus aureus isolated from patients in Fort Portal Regional Referral Hospital, Western Uganda

BackgroundThe ability of Staphylococcus aureus to evolve through horizontal gene transfer mechanisms aids its success as a versatile pathogen. Mobile genetic elements (MGEs) are linked to potent virulence factors in S. aureus, e.g., the Panton-Valentine leukocidin and toxic shock syndrome toxins, as well as antibiotic resistance genes, e.g., mecA that encodes methicillin resistance. Despite their clinical relevance, molecular surveillance of MGEs in Africa remains limited. Here, we characterize the MGE repertoire of clinically relevant S. aureus isolates from Fort Portal Regional Referral Hospital (FPRRH), western Uganda. MethodsWe assembled a total of 40 genome sequences from previously sequenced S. aureus isolates cultured from patients (skin wounds, urinary tract, and bloodstream infections) at FPRRH during 2017-2019. spaTyper was used to determine the spa genotypes, while the presence of MGEs was screened and annotated for using PlasmidFinder, PHASTEST, Mobile Element Finder, SCCmecFinder, Bakta, MobileOG-db, and IslandViewer tools. ResultsEleven spa types were identified, with spa type t355 predominating. We detected 74 plasmid-derived sequences and 31 insertion sequences. Two SCCmec types, SCCmec type III and SCCmec type IV, were detected, indicating both hospital-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA). Forty-seven intact prophages (all Siphoviridae) were identified, carrying dfrG, sak, and lukPV genes. A total of 191 genomic islands were detected, and these harbored the virulence, immunoevasion, drug, and heavy metal resistance genes, such as nuc, tuf, tst, pvl, tet, blaZ, and mer genes. ConclusionsS. aureus at FPRRH harbors a diverse and functionally rich MGE repertoire, including genomic islands, prophages, insertion sequences, transposons, and plasmids, that contribute to the dissemination of virulence, AMR, and metal resistance determinants. The coexistence of HA-MRSA and CA-MRSA, as seen in other regions of Uganda, underscores the importance of continued genomic surveillance to inform infection control strategies.

genomics↗

bioRxiv2021

Comparative analysis of gene prediction tools for viral genome annotation

The number of newly available viral genomes and metagenomes has increased exponentially since the development of high throughput sequencing platforms and genome analysis tools. Bioinformatic annotation pipelines are largely based on open reading frame (ORF) calling software, which identifies genes independently of the sequence taxonomical background. Although ORF-calling programs provide a rapid genome annotation, they can misidentify ORFs and start codons; errors that might be perpetuated and propagated over time. This study evaluated the performance of multiple ORF-calling programs for viral genome annotation against the complete RefSeq viral database. Programs outputs varied when considering the viral nucleic acid type versus the viral host. According to the number of ORFs, Prodigal and Metaprodigal were the most accurate programs for DNA viruses, while FragGeneScan and Prodigal generated the most accurate outputs for RNA viruses. Similarly, Prodigal outperformed the benchmark for viruses infecting prokaryotes, and GLIMMER and GeneMarkS produced the most accurate annotations for viruses infecting eukaryotes. When the coordinates of the ORFs were considered, Prodigal scored high for all scenarios except for RNA viruses, where GeneMarkS generated the most reliable results. Overall, the quality of the coordinates predicted for RNA viruses was poorer than for DNA viruses, suggesting the need for improved ORF-calling programs to deal with RNA viruses. Moreover, none of the ORF-calling programs reached 90% accuracy for annotation of DNA viruses. Any automatic annotation can still be improved by manual curation, especially when the presence of ORFs is validated with wet-lab experiments. However, our evaluation of the current ORF-calling programs is expected to be useful for the improvement of viral genome annotation pipelines and highlights the need for more expression data to improve the rigor of reference genomes.

bioinformatics↗

bioRxiv2020

Antibiotic resistance profiles and population structure of disease-associated Staphylococcus aureus infecting patients in Fort Portal Regional Referral Hospital, Western Uganda

Tackling antimicrobial resistance (AMR) is particularly challenging in low-resource settings such as Fort Portal Regional Referral Hospital (FPRRH) in Western Uganda. Specific knowledge of local AMR epidemiology is required to inform evidence-based improvement of antibiotic stewardship measures in the hospital. To address this, we combined existing antimicrobial susceptibility testing (AST) from FPRRH, with whole genome sequencing (WGS) of 41 Staphylococcus aureus isolates (2017-2019). AST revealed 73% (30/41) of isolates were resistant to one or more antibiotics and 29% (12/41) were multi-drug resistant (MDR). Resistance phenotypes were largely explained by the presence of antibiotic resistance genes in WGS data. Five isolates were methicillin-resistant S. aureus (MRSA) and MDR. Although all isolates were susceptible to clindamycin, a 24% carriage of erm genes suggests potential for rapid development of resistance. We inferred a population structure for the S. aureus isolates by comparing their core genomes. Twenty isolates formed a tight cluster corresponding to multilocus sequence typing clonal complex (CC) 152, a CC found to be particularly prevalent in northern Africa. The frequency of genes associated with methicillin, chloramphenicol and ciprofloxacin resistance were significantly lower among CC152 strains than non-CC152 strains; thus, in keeping with previous work, we find that CC152 is almost exclusively methicillin-sensitive S. aureus (MSSA). Also, in agreement with other studies, we observed that the occurrence of Panton-Valentine leukocidin toxin-encoding genes was significantly higher among CC152 strains than non-CC152 strains. However, we also observed that the coagulase gene was over-represented in this CC, further defining the virulence strategy of this important pathogen. By generating detailed information about the epidemiology of circulating S. aureus and their antibiotic susceptibility, our study has provided, for the first time, data on which evidence-based infection and AMR interventions at FPRRH can be based.

microbiology↗

bioRxiv2019

Formal string instrument training in a class setting enhances cognitive and sensorimotor development of primary school children

This randomized controlled trial shows for the first time that focused musical instrumental practice as compared to traditional sensitization to music provokes robust cognitive and sensorimotor transfer effects. Over the last two years of primary school (10-12-year-old children), sixty-nine children received biweekly musical instruction by professional musicians within the regular school curriculum. The intervention group learned to play string instruments, whereas the control group, peers in parallel classes, was sensitized to music via listening, theory, and some practice. Broad benefits manifested in the intervention group as compared to the control group for working memory, attention, processing speed, cognitive flexibility, matrix reasoning, sensorimotor hand function and bimanual coordination Apparently, learning to play a complex instrument in a dynamic group setting impacts development much stronger than classical sensitization to music. Our results therefore highlight the added value of intensive musical instrumental training in a group setting, encouraging general implementation in public primary schools, better preparing children for secondary school and for daily living activities.\n\nHighlights- Music practice produces multiple cognitive transfer effects in school children\n- Making music causes stronger cognitive benefits than sensitization to music\n- Music practice in a class setting improves executive functions and abstract thinking\n- Playing string instruments enhances fine manual dexterity and bimanual coordination

neuroscience↗

bioRxiv2017

Campylobacter jejuni transcriptome changes during loss of culturability in water

BackgroundThe natural environment serves as a potential reservoir for Campylobacter, the leading cause of bacterial gastroenteritis in humans. However, little is understood about the mechanisms underlying variations in survival characteristics between different strains of C. jejuni in natural environments, including water.\n\nResultsWe identified three Campylobacter jejuni strains that exhibited variability in their ability to retain culturability after suspension in water at two different temperatures (4{degrees}C and 25{degrees}C). Of the three, strains C. jejuni M1 exhibited the most rapid loss of culturability whilst retaining viability. Using RNAseq transcriptomics, we characterised C. jejuni M1 gene expression in response to suspension in water by analyzing bacterial suspensions recovered immediately after introduction into water (Time 0), and from two sampling time/temperature combinations where considerable loss of culturability was evident, namely (i) after 24 h at 25{degrees}C, and (ii) after 72 h at 4{degrees}C. Transcript data were compared with a culture-grown control. Some gene expression characteristics were shared amongst the three populations recovered from water, with more genes being up-regulated than down. Many of the up-regulated genes were identified in the Time 0 sample, whereas the majority of down-regulated genes occurred in the 25{degrees}C (24 h) sample.\n\nConclusionsVariations in expression were found amongst genes associated with oxygen tolerance, starvation and osmotic stress. However, we also found upregulation of flagellar assembly genes, accompanied by down-regulation of genes involved in chemotaxis. Our data also suggested a switch from secretion via the sec system to via the tat system, and that the quorum sensing gene luxS may be implicated in the survival of strain M1 in water. Variations in gene expression also occurred in accessory genome regions. Our data suggest that despite the loss of culturability, C. jejuni M1 remains viable and adapts via specific changes in gene expression.

microbiology↗