Biology subjects

Weston, G.

Publications and source records attributed to Weston, G..

3 recordsLinked to original sources

bioRxiv2026

High-Throughput, Multiplex Immunofluorescence for the Computer-automated Immunophenotyping of Mycosis Fungoides

The diagnosis of Mycosis Fungoides (MF) is difficult and often delayed, exacerbated by the constraint of conventional immunohistochemistry (IHC) to analyze only one antigen per tissue section, often necessitating repeat biopsies and extensive workups. We sought to validate a high-throughput Multiplex Immunofluorescence (MIF) method, coupled with computer-automated image analysis, to generate comprehensive immunophenotyping data from a single formalin-fixed, paraffin-embedded (FFPE) biopsy. We applied an 11-biomarker MIF panel across 18 archived skin specimens (9 MF/TCR clonality positive and 9 control/TCR clonality negative). Initial validation confirmed that MIF antigen expression and spatial localization were concordant with sequential IHC-stained sections. Whole slide image stacks were analyzed using both computer-assisted and fully computer-automated pipelines. Both methods successfully delineated immunophenotypic differences. MF specimens showed a significant expansion of hematopoietic cells and proliferative T-lymphocytes compared to controls. Crucially, MF tissues also exhibited a significant increase in the percentage of atypical T-lymphocytes. Our results validate the potential of MIF to obtain comprehensive, high-dimensional diagnostic information from a single tissue section. Integration with computer-automated analysis offers a scalable, high-throughput platform that can significantly aid in the timely and accurate diagnosis of cutaneous lymphomas.

pathology↗

bioRxiv2020

Aberrant structural synaptic dynamics precede disorganization of temporal and spatial coding in the hippocampus upon repeated stress exposure

Stress exposure strongly contributes to the pathophysiology of psychiatric diseases such as depression, schizophrenia, anxiety, and post-traumatic stress disorder. It also affects both function and structure of hippocampal CA1, leading to episodic memory impairment. Here, we used deep-brain optical imaging to elucidate the effects of stress on CA1 pyramidal neuron structural connectivity and activity. We tracked dynamics of dendritic spines during repeated stress and found decrease in spinogenesis followed by decrease in spine stability. In contrast to repeated stress, acute stress led to stabilization of the spines born in temporal proximity to the stressful event. To investigate the link between structural plasticity and activity patterns upon repeated stress, we studied the activity of thousands of CA1 pyramidal neurons in freely-moving. We found an increase in activity and loss of temporal organization followed by a disruption in temporal and spatial coding. Our data suggest that stress-induced sustained increase in activity leads to loss of structural connectivity and subsequent temporal and spatial coding impairments.

neuroscience↗

bioRxiv2019

Stability of excitatory structural connectivity predicts the probability of CA1 pyramidal neurons to become engram neurons

Neurons undergoing activity-dependent plasticity represent experience and are functional for learning and recall thus they are considered cellular engrams of memory. Although increase in excitability and stability of structural synaptic connectivity have been implicated in the formation and persistance of engrams, the mechanisms bringing engrams into existence are still largely unknown. To investigate this issue, we tracked the dynamics of structural excitatory synaptic connectivity of hippocampal CA1 pyramidal neurons over two weeks using deep-brain two-photon imaging in live mice. We found that neurons that will prospectively become part of an engram display higher stability of connectivity than neurons that will not. A novel experience significantly stabilizes the connectivity of non-engram neurons. Finally, the density and survival of dendritic spines negatively correlates to freezing to the context but not to the tone in a trace fear conditioning learning paradigm.

neuroscience↗