Biology subjects

Cooney, L.

Publications and source records attributed to Cooney, L..

4 recordsLinked to original sources

bioRxiv2026

Critical flicker fusion thresholds predict attentional blink magnitude

The critical flicker fusion (CFF) threshold is a psychophysical measure used to quantify the temporal resolution of the visual system and is known to vary across individuals. However, it is unclear if this measure is stimulus-specific, or if it may represent a more fundamental processing rate for visual perception in general. Here, we assess if individual variation in CFF is predictive of two features of visual processing that are dependent on temporal perception: the attentional blink and global motion sensitivity. In a non-clinical sample of 84 individuals, flicker fusion thresholds were predictive of the magnitude of the attentional blink. In contrast, we found no link between flicker fusion and global motion sensitivity in a sample of 79 individuals. Our results suggest that CFF reflects a visual processing rate that impacts other, more complex perceptual tasks.

neuroscience↗

bioRxiv2026

Ocrelizumab Modulates Both B and T Cell Immune Capacities in Multiple Sclerosis

To understand the molecular and cellular mechanisms beyond B-cell depletion with the anti-CD20 monoclonal antibody ocrelizumab, we used comprehensive muti-modal flow cytometry and functional assays in a prospective longitudinal multiple sclerosis (MS) cohort. Ocrelizumab depleted the vast majority of B cells and showed selective effects on different B cells subsets. Analysis of residual/replenished B cells revealed relative enrichment of regulatory B cells like CD27+CD43+ B1 and CD24hiCD38hi transitional B cells, and reduction of CD27+ memory B cell subsets and CD19+IgD+CD27-naive B cells at early time points (1-3 month) and before subsequent infusions at 4-7 months, 11-14 months, and >18 months. CD20+ T cells and peripheral helper T-cells (Tph) were also reduced. RNA sequencing analysis showed B1 cells have significantly higher expression of LGALS1, KCNN4, ITGB1, and IL2RB. Compared to transitional B cells, B1 cells also displayed significantly higher expression of tissue homing molecules ITGAX (CD11c), S100A4, ITGB1, and CXCR3. IL10 signaling pathway is increased in these B cells. Ex vivo B cell functional assays indicated the residual/replenishing B cells were anergic following ocrelizumab, with increased IL10/TNF and IL10/IL6 ratios under BCR stimulation. Ocrelizumab treatment may create a self-reinforcing regulatory circuit: the reduction of Tph cells could alleviate suppression of regulatory B cells, which subsequently expand and further promote regulatory T cell networks via IL2RB, LGALS1, and an increased IL-10 signaling pathway.

immunology↗

bioRxiv2026

Elevated ferritin as a companion biomarker of myeloid-driven inflammation in RNP/Sm co-positive, treatment-resistant SLE endotype

BackgroundThe profound molecular heterogeneity of SLE remains a fundamental barrier to therapeutic progress. MethodsWe integrated clinical and multi-omic profiling, including transcriptomics, autoantigen microarrays, proteomics, and flow cytometry, across three randomised trials (BEAT-Lupus, CALIBRATE, ACCESS) and two observational cohorts to identify distinct lupus endotypes. FindingsUsing multivariate distance-based matching of autoantibody profiles to integrate molecular heterogeneity, we identified anti-RNP/anti-Sm co-positivity (RNP+Sm+) as a distinct myeloid-dominant inflammatory endotype. Enriched in patients of Black ancestry (approx. 50%), RNP+Sm+ SLE is characterised by expanded intermediate monocytes showing enhanced TLR4-driven inflammation during flares, elevated pro-inflammatory cytokines (TNF-alpha, IL-6, IL-12, IFN-gamma, CCL2), IFNA10-biased interferon signalling, and systemic metabolic activation. IgG autoantibody profiling confirmed epitope spreading to spliceosomes and novel autoreactivity against circadian-metabolic regulators (SIRT1, NCOA1, SREBF1). Clinically, this endotype manifests as high-grade disease activity (2.5-fold flare risk), nephritis, vasculitis, and enteritis. Hyperferritinaemia correlates with flares exclusively in RNP+Sm+ SLE (r=0.81), reflecting underlying macrophage activation. RNP+Sm+ patients exhibit profound therapeutic resistance: 44% failed first-line immunosuppression (rising to 61% in Black patients), while also showing substantially reduced efficacy (60% lower response) with second-line B-cell-depleting therapies (rituximab, obinutuzumab). Resistance to rituximab therapy was driven by rapid B-cell repopulation, rising BAFF levels, and sustained cytokines despite peripheral depletion. Consequently, they remain heavily steroid-dependent and accrued greater organ damage. ConclusionThe RNP+Sm+ signature defines a high-risk, refractory, myeloid-driven lupus endotype characterised by activity linked hyperferritinemia that likely requires therapies directed at the underlying interferon and myeloid-centred pathways. FundingBEAT-Lupus: Arthritis UK and GSK. ACCESS and CALIBRATE: National Institute of Allergy and Infectious Diseases of the NIH. Context and SignificanceSystemic lupus erythematosus (SLE) is immunologically heterogeneous, yet conventional classifications fail to predict therapeutic outcomes. While autoantibodies are central to diagnosis, whether specific combinations define mechanistically distinct subsets remains unresolved. Here, we demonstrate that anti-RNP/anti-Sm co-positivity (RNPSm) identifies a clinically aggressive, myeloid-dominant endotype disproportionately affecting Black patients. Multi-omics integration revealed expansion of intermediate monocytes with enhanced TLR4 expression, IFNA10-biased interferon signalling, and metabolic reprogramming. Clinically, RNPSm patients exhibit nephritis, vasculitis, higher flare rates, and profound first-line therapeutic resistance. Subsequently, this endotype shows poor response to B-cell-depleting therapies, necessitating prolonged glucocorticoid dependence and accelerated organ damage. Establishing RNPSm as a lupus endotype and ferritin as a companion disease activity biomarker enables precision stratification and highlights an underserved, high-risk population requiring urgent development of alternative strategies like myeloid-targeted and interferon-directed therapies. HighlightsO_LIAnti-RNP/Sm co-positivity defines a high-risk, flare-prone, myeloid-dominant SLE endotype C_LIO_LIRNPSm patients, especially Black patients, show profound refractoriness to first-line and B-cell depletion therapies C_LIO_LIExpanded intermediate monocytes with TLR4 upregulation and IFNA10-biased interferon signalling C_LIO_LIHyperferritinaemia correlates with disease activity exclusively in RNPSm patients C_LI

immunology↗

bioRxiv2021

Transcriptomic Insights into the Responses in Leaves Storing Lipid Organelles under Different Irradiances

To increase the nutritional value of forage, transgenic ryegrass known as High Metabolizable Energy (HME) were previously generated that co-express cysteine-oleosin and diacylglycerol O-acyltransferase. HME not only accumulate lipids in the leaf but also has elevated CO2 assimilation and increased biomass. Shading is one of the most influencing factors for ryegrass growth environments particularly in swards. The aim of this study, therefore, was to determine the influence of irradiance levels on photosynthesis and gene expression in the HME leaves when compared with their corresponding non-transformant (NT). Under low light (150-250 {micro}mol m-2 s-1) and standard light (600-1000 {micro}mol m-2 s-1), the HME accumulated more lipid than NT. The previously reported elevated photosynthesis and increased biomass was observed when the HME were grown under standard light but not under low light. Under both light conditions, compared to NT, the HME had upregulated a number of transcripts involved in lipid metabolism, light capturing, photosynthesis, and sugar signalling network while downregulated genes participated in sugar and fructan biosynthesis. We further discuss how the HME differentially manipulated several genes other metabolic pathways including maintenance of redox homeostasis. Combined, the data suggests that the increased photosynthesis capacity in the HME likely corresponds to an increase of micro-lipid sink strength; these are influenced by available light energy and may be related to diffusional and biochemical activities of stomata. Overall, this work provides a clearly understanding of the changes in molecular and biochemical mechanisms underlying the carbon storing as leaf lipid sink of the HME ryegrass. One sentence summaryShading led to increase leaf lipid accumulation but limit the greater photosynthesis trait of high lipid ryegrass which may be related to limitation of biochemical activities of stomata.

molecular biology↗