Biology subjects

Guthrie, S.

Publications and source records attributed to Guthrie, S..

5 recordsLinked to original sources

bioRxiv2026

Peer-Led Leadership, Mentoring and Promotion: Conversations Among Female Academics from South Africa, Ghana and the United Kingdom

Here, we report a one-day, cross-cultural, peer-led workshop at the University of Stellenbosch, facilitated by academics from South Africa, Ghana and the United Kingdom. The focus was on leadership, mentoring and promotion. Using short, structured activities alongside small-group discussion, the participants were encouraged to reflect on leadership, mentoring and the perceived gap between being "ready" and being "recognised" for promotion. Descriptive survey findings and free-text reflections highlight the demand for structured peer support, reciprocal mentoring opportunities, and clearer, more transparent promotion processes. Following the event, we performed a structured review of the impact. This highlighted that the workshop participants reported that the event allowed for greater self-awareness into their own leadership approaches, a stronger commitment to purposeful mentoring, and greater confidence and renewed motivation to take concrete steps towards promotion.

scientific communication and education↗

bioRxiv2026

Neurometabolic correlates of accelerated aging and neurocognitive late effects in long-term survivors of pediatric hodgkin lymphoma and acute lymphoblastic leukemia

Adult survivors of pediatric cancers are at elevated risk for neurocognitive late effects, but how these effects relate to metabolic perturbations in the brain remains unclear. To address this knowledge gap, the present study explored associations between neurometabolite levels and neurocognitive function in adult survivors of Hodgkin lymphoma (HL) and acute lymphocytic leukemia (ALL). Data were collected from a single-center observational study conducted at St. Jude Childrens Research Hospital (SJCRH) between October 2022 and November 2024. Adult survivors of HL (N=11 [5 females]; [≥]5 years post-diagnosis; mean [SD] current age 34 [9.5] years) and ALL (N=24 [16 females]; [≥]5 years post-diagnosis; current age 40 [12.6] years) and community controls (N=35 [17 females]; current age 40 [11] years) completed standardized neurocognitive tests of memory, attention, executive function, and processing speed. Participants also underwent proton magnetic resonance spectroscopy (1H MRS) to quantify neurometabolite levels in the left dorsolateral prefrontal cortex (dlPFC), left hippocampus, and left cerebellum. Analyses used regression models to examine differences in the slope of the relationship between neurometabolite and neurocognitive function or between neurometabolite and age. When comparing HL survivors vs controls, significant interactions were identified for group x age on the ratio of myo-inositol to N-Acetyl aspartic acid (mI/NAA; p=0.007) and group x Gamma-Aminobutyric Acid (GABA) on processing speed (p=0.04) in the left dlPFC. When comparing ALL survivors vs controls, significant interactions were identified for group x myo-inositol on verbal fluency in the left hippocampus (p=0.01) and group x GABA on cognitive flexibility in the left cerebellum (p=0.01). These preliminary findings suggest that neuroinflammation may be a mechanistic underpinning of age-associated neurocognitive impairment in pediatric cancer survivors.

neuroscience↗

bioRxiv2025

Preclinical characterization of AT-03, a novel Serum Amyloid P fusion protein that demonstrates pan-amyloid binding and removal

The systemic amyloidoses are progressive disorders caused by extracellular deposition of insoluble amyloid fibrils leading to organ dysfunction that often proves fatal. New therapeutics aiming at removing deposited amyloid are urgently needed to improve patient outcomes. MethodsWe developped AT-03 (originally called SAP-scFc), a fusion protein consisting of serum amyloid P-component, which binds all types of amyloid, linked to a single chain human IgG1 Fc domain. AT-03 binding to diverse types of amyloid and phagocytic activity were assessed both in vitro and in vivo. Therapeutic efficacy was evaluated in an AA mouse model. ResultsAT-03 bound with high potency to AL and ATTR human amyloid extracts. In murine models, intravenously administered AT-03 bound to AA, AL and AApoA2 amyloid, including in the heart. Ex vivo AT-03 opsonization induced phagocytosis of human AL extract by activated human THP-1 macrophages and enhanced in vivo phagocytosis in mice. A single intravenous injection of SAP-scFc induced a significant reduction of splenic amyloid in a murine model of AA amyloidosis. ConclusionsAT-03 binds many amyloid types and can promote macrophage-mediated phagocytosis of the deposits. Thus, AT-03 is a promising novel therapeutic agent for the removal of systemic amyloid.

pathology↗

bioRxiv2020

Cadherins regulate nuclear topography and function of developing ocular motor circuitry

In the vertebrate central nervous system, groups of functionally-related neurons, including cranial motor neurons of the brainstem, are frequently organised as nuclei. The molecular mechanisms governing the emergence of nuclear topography and circuit function are poorly understood. Here we investigate the role of cadherin-mediated adhesion in the development of zebrafish ocular motor (sub)nuclei. We find that developing ocular motor (sub)nuclei differentially express classical cadherins. Perturbing cadherin function in these neurons results in distinct defects in neuronal positioning, including scattering of dorsal cells and defective contralateral migration of ventral subnuclei. In addition, we show that cadherin-mediated interactions between adjacent subnuclei are critical for subnucleus position. We also find that disrupting cadherin adhesivity in dorsal oculomotor neurons impairs the larval optokinetic reflex, suggesting that neuronal clustering is important for co-ordinating circuit function. Our findings reveal that cadherins regulate distinct aspects of cranial motor neuron positioning and establish subnuclear topography and motor function.

developmental biology↗

bioRxiv2017

Genome Graphs

There is increasing recognition that a single, monoploid reference genome is a poor universal reference structure for human genetics, because it represents only a tiny fraction of human variation. Adding this missing variation results in a structure that can be described as a mathematical graph: a genome graph. We demonstrate that, in comparison to the existing reference genome (GRCh38), genome graphs can substantially improve the fractions of reads that map uniquely and perfectly. Furthermore, we show that this fundamental simplification of read mapping transforms the variant calling problem from one in which many non-reference variants must be discovered de-novo to one in which the vast majority of variants are simply re-identified within the graph. Using standard benchmarks as well as a novel reference-free evaluation, we show that a simplistic variant calling procedure on a genome graph can already call variants at least as well as, and in many cases better than, a state-of-the-art method on the linear human reference genome. We anticipate that graph-based references will supplant linear references in humans and in other applications where cohorts of sequenced individuals are available.

bioinformatics↗