Biology subjects

Paterson, T.

Publications and source records attributed to Paterson, T..

6 recordsLinked to original sources

bioRxiv2026

β-Blockers for ED Presentations with Recent Cocaine Use: A Systematic Review

BackgroundCocaine produces cardiovascular toxicity through intense sympathetic stimulation and direct myocardial injury, generating presentations ranging from hypertension and tachycardia to coronary vasospasm, arrhythmia, and myocardial depression. {beta}-blockers are foundational therapies in acute coronary syndromes, yet their use after cocaine exposure remains controversial due to concerns about unopposed -adrenergic stimulation. MethodsA systematic review was conducted in accordance with PRISMA guidelines. PubMed and Google Scholar (2000-2026) were searched for observational studies of adults ([≥]18 years) presenting to acute care with recent cocaine use that compared outcomes between {beta}-blocker recipients and non-recipients. Eligible studies reported in-hospital mortality, myocardial infarction/troponin rise, clinically significant arrhythmia, or haemodynamic instability. Risk of bias was assessed using the Newcastle-Ottawa Scale, and certainty of evidence using GRADE. ResultsFour retrospective ED cohorts (n = 1,140) met inclusion criteria; 503 patients received at least one {beta}-blocker dose. Across studies, {beta}-blocker use was not associated with increased in-hospital mortality or malignant arrhythmias. Myocardial infarction was heterogeneous and sensitive to definition and timing. Haemodynamic data showed no hypertensive surge and modest systolic blood pressure reductions. Risk of bias was moderate, and certainty of evidence very low to low. ConclusionsIn typical ED presentations of recent cocaine use, {beta}-blocker administration does not appear to increase mortality, myocardial infarction, or malignant arrhythmias, and available haemodynamic data do not support a reproducible unopposed- response. However, mechanistic and preclinical evidence suggests potential harm in severe intoxication or myocardial depression. A selective, phenotype-guided approach is warranted, and prospective mechanistic studies are needed. Key PointsO_LIBeta-blockers did not increase deaths, heart attacks, or dangerous heart rhythms in adults who came to the emergency department after recent cocaine use. C_LIO_LIBlood pressure generally decreased after beta-blocker treatment, and no consistent "unopposed alpha" reaction was seen in typical presentations. C_LIO_LICaution is still needed in severe intoxication or cases with heart muscle weakness, but for most emergency presentations, beta-blockers appear safe when used appropriately. C_LI

pharmacology and toxicology↗

bioRxiv2025

Sexual dimorphism in the complete connectome of the Drosophila male central nervous system

Sex differences in behaviour exist across all animals, typically under strong genetic regulation. In Drosophila, fruitless/doublesex transcription factors can identify dimorphic neurons but their organisation into functional circuits remains unclear. We present the connectome of the entire Drosophila male central nervous system. This contains 166,691 neurons spanning the brain and nerve cord, fully proofread and annotated including fruitless/doublesex expression and 11,691 types. We provide the first comprehensive comparison between male and female brain connectomes to synaptic resolution, finding 7,205 isomorphic, 114 dimorphic, 262 male-specific and 69 female-specific types. This resource enables analysis of full sensory-to-motor circuits underlying complex behaviours and the impact of dimorphic elements. Sex-specific/dimorphic neurons are concentrated in higher brain centres while the sensory and motor periphery are largely isomorphic. Within higher centres, male-specific connections are organised into hotspots defined by male-specific neurons or arbours. Numerous circuit switches reroute sensory information to form antagonistic circuits controlling opposing behaviours.

neuroscience↗

bioRxiv2024

Markers, Mechanisms and Metrics of Biological Aging: A Scoping Review

Biological aging is a rapidly growing area of research, which entails characterizing the rate of aging independent of an individuals chronological age. In this review, we analyze the results of biological aging research in 435 papers published in a twelve year window, revealing changing patterns of molecular markers of biological aging use over time, and the development of novel metrics of biological aging. We further identify consistent and discordant research findings, as well as areas of potential future research focusing on questions of measurement with methylation or biomarker-based assessment and other variables relevant to the study of biological age.

molecular biology↗

bioRxiv2024

Multi-omic ADNI CSF and plasma data integration identifies distinct metabolic transitions in disease progression in Alzheimer's Disease

Age and APOE genotype are the strongest known risk factors for late-onset Alzheimers disease (AD), but the mechanisms linking them to neuronal loss remain incompletely defined. Using multiomic data from the Alzheimers Disease Neuroimaging Initiative (ADNI), we propose a unified hypothesis in which two interdependent failure modes--saturation of microglial lipid flux capacity and disruption of the astrocyte-neuron lactate shuttle (ANLS) due to excess astrocytic membrane cholesterol--drive disease progression upstream of amyloid and tau pathology. Stratifying participants by cognitive score quartiles, we find consistent associations linking impaired lipid clearance, metabolic stress, and genetic variants regulating cholesterol handling. These processes appear to reinforce each other, resulting in accelerating neurodegeneration. Our hypothesis reframes AD as a systems-level collapse in metabolic coordination, rather than a purely linear pathological cascade. These insights emerged during the development of digital twin models for personalized interventions, highlighting the power of systems approaches to reveal hidden drivers of neurodegeneration.

neuroscience↗

bioRxiv2024

Connectome-driven neural inventory of a complete visual system

Vision provides animals with detailed information about their surroundings, conveying diverse features such as color, form, and movement across the visual scene. Computing these parallel spatial features requires a large and diverse network of neurons, such that in animals as distant as flies and humans, visual regions comprise half the brains volume. These visual brain regions often reveal remarkable structure-function relationships, with neurons organized along spatial maps with shapes that directly relate to their roles in visual processing. To unravel the stunning diversity of a complex visual system, a careful mapping of the neural architecture matched to tools for targeted exploration of that circuitry is essential. Here, we report a new connectome of the right optic lobe from a male Drosophila central nervous system FIB-SEM volume and a comprehensive inventory of the flys visual neurons. We developed a computational framework to quantify the anatomy of visual neurons, establishing a basis for interpreting how their shapes relate to spatial vision. By integrating this analysis with connectivity information, neurotransmitter identity, and expert curation, we classified the [~]53,000 neurons into 727 types, about half of which are systematically described and named for the first time. Finally, we share an extensive collection of split-GAL4 lines matched to our neuron type catalog. Together, this comprehensive set of tools and data unlock new possibilities for systematic investigations of vision in Drosophila, a foundation for a deeper understanding of sensory processing.

neuroscience↗

bioRxiv2019

The neuroanatomical ultrastructure and function of a biological ring attractor

Neural representations of head direction have been discovered in many species. A large body of theoretical work has proposed that the dynamics associated with these representations is generated, maintained, and updated by recurrent network structures called ring attractors. We performed electron microscopy-based circuit reconstruction and RNA profiling of identified cell types in the heading direction system of Drosophila melanogaster to directly determine the underlying neural network. We identified network motifs that have been hypothesized to maintain the heading representation in darkness, update it when the animal turns, and tether it to visual cues. Functional studies provided additional support for the proposed roles of individual circuit elements. We also discovered recurrent connections between neuronal arbors with mixed pre- and post-synaptic specializations. Overall, our results confirm that the Drosophila heading direction network contains the core components of a ring attractor while also revealing unpredicted structural features that might enhance the networks computational power.

neuroscience↗