Biology subjects

Gordon, P.

Publications and source records attributed to Gordon, P..

7 recordsLinked to original sources

bioRxiv2026

High-throughput serial two-photon tomography with BakingTray and BrainSaw

Volumetric imaging is increasingly important in fields such as neuroscience, where quantifying structure and mapping features are inherently three-dimensional problems. Block-face serial two-photon tomography (STPT) has emerged as a powerful approach for high-resolution, whole-organ volumetric imaging. STPT avoids complex sample preparation and balances image quality, speed, and scalability. However, STPT remains niche, in part because of the absence of flexible, general-purpose control software. Here we present BakingTray, an open-source software platform for STPT that extends ScanImage. BakingTrays modular framework accommodates diverse hardware configurations and allows users to build systems customised to their needs. Twelve such systems, which we call BrainSaws, have been constructed worldwide since 2016, with more under construction, and have so far contributed to 35 research papers. The three systems at the Sainsbury Wellcome Centre alone have acquired over 7,000 samples in a busy multi-user facility. We demonstrate the platform across its core neuroscience applications: electrode track localisation, brain-wide cell counting, and bulk projection mapping. Beyond these, we map the cell-type-specific synaptic output of inhibitory neurons in the ventral lateral geniculate nucleus and, with whole-mount staining, amyloid plaques brain-wide in a mouse model of Alzheimers disease. BakingTray is a mature platform for groups or facilities needing a customised volumetric imaging solution, whether built new or converted cheaply from an existing two-photon microscope.

neuroscience↗

bioRxiv2025

Diazepam alters the shape of alpha oscillations recorded from human cortex using EEG

While neural oscillations are conventionally assessed via their frequency, power and phase, developing literature suggests that their shape also provides neurophysiological and functional information. However, the extent to which the shape of oscillations recorded non-invasively in humans index specific brain processes remains unclear. This study implemented a pharmaco-EEG approach to begin addressing this limitation. In 21 healthy adults, resting-state EEG data was collected before and after placebo or diazepam, a positive allosteric modulator of type A {gamma}-aminobutyric acid (GABAA) receptors. The shape of individual cycles in the alpha band was then derived using empirical mode decomposition, followed by extraction of principal components (PCs) describing specific facets of alpha shape. Results of this approach show that all shape features were unchanged following placebo. In contrast, diazepam was associated with complex changes in several shape features, including peak-trough shape and edge speed. While changes in shape were apparent in all cortical lobes, the strongest alterations were specific to sensorimotor and parietal cortices. Taken together, our results support the neurophysiological utility of waveform shape, particularly with respect to non-invasive human recordings. Furthermore, the regional specificity of effects highlights the need for more granular exploration of waveform diversity.

neuroscience↗

bioRxiv2025

Cell layer-specific modification of cell wall is associated with exo-mesocarp split in pistachio (Pistacia vera L.)

Pistachio (Pistacia vera) is a drought and salinity-tolerant perennial whose fruit features a fleshy exo-mesocarp, or "hull," that protects the kernel. Hull development and degradation are key to kernel quality, yet the anatomy and mechanisms driving hull breakdown during late-stage development remain largely unknown. Here, we show that the hull contains anatomically distinct layers of hypodermal parenchyma and filler parenchyma. Using a combination of transcriptome analyses and immunohistochemistry, we show that changes in pectin associated gene expression and modification of this polysaccharide are involved in hull cell size increase, loss of cell-cell adhesion, and softening. Anatomical analysis shows that filler parenchyma expands during late-stage hull development while hypodermal parenchyma remains constant in size. Field data suggest that irrigation and humidity affect pistachio hull split, implicating a role for water status in cell expansion. In summary, the complex interplay between molecular, cellular, and environmental changes suggests that cell layer-specific modifications of the cell wall are linked to exo-mesocarp splitting, forming a model for understanding the mechanism of fruit split during ripening in non-berry fruit crops. HighlightCell-layer specific modifications of the cell wall are associated with cell expansion and loss of cell-cell adhesion, leading to hull split during late-stage pistachio fruit development.

plant biology↗

bioRxiv2020

Lyve-1 expressing perivascular macrophages orchestrate pericyte expansion to sustain angiogenesis in cancer

Tumor associated macrophages (TAMs) are a highly plastic stromal cell type which support cancer progression. Using single-cell RNA-sequencing of TAMs from a spontaneous murine model of mammary adenocarcinoma (MMTV-PyMT) we characterize a subset of these cells expressing lymphatic vessel endothelial hyaluronic acid receptor 1 (Lyve-1) which spatially reside proximal to blood vasculature. We demonstrate that Lyve-1+ TAMs support tumor growth and identify a pivotal role for these cells in maintaining a population of perivascular mesenchymal cells which express alpha-smooth muscle actin and phenotypically resemble pericytes. Using photolabeling techniques show that mesenchymal cells maintain their prevalence in the growing tumor through proliferation and uncover a role for Lyve-1+ TAMs in orchestrating a selective platelet-derived growth factor-CC-dependent expansion of the perivascular mesenchymal population, creating a pro-angiogenic niche. This study highlights the inter-reliance of the immune and non-immune stromal network which support cancer progression and provides therapeutic opportunities for tackling the disease.

cancer biology↗

bioRxiv2020

Cytoplasmic pool of spliceosome protein SNRNP70 regulates the axonal transcriptome and development of motor connectivity

Regulation of pre-mRNA splicing and polyadenylation plays a profound role in neurons by diversifying the proteome and modulating gene expression during development and in response to physiological cues. Although most pre-mRNA processing reactions are thought to occur in the nucleus, numerous splicing regulators are also found in neurites. Here, we show that U1-70K/SNRNP70, a major spliceosomal component, localizes in RNA-associated granules in axons. We identify the cytoplasmic pool of SNRNP70 as an important local regulator of motor axonal growth, nerve-dependent acetylcholine receptor (AChR) clustering and neuromuscular synaptogenesis. This cytoplasmic pool has a protective role for a limited number of axonal transcripts preventing them from degradation. Moreover, non-nuclear SNRNP70 is able to locally regulates splice variants of transcripts such as agrin, thereby locally controlling formation of synapses. Our results point to an unexpected, yet essential, function of local SNRNP70 in axonal development and indicate a role of splicing factors in local RNA metabolism during establishment and maintenance of neuronal connectivity.

neuroscience↗

bioRxiv2020

A conserved role for SFPQ in repression of pathogenic cryptic last exons

The RNA-binding protein SFPQ plays an important role in neuronal development and has been associated with several neurodegenerative disorders, including ALS, FTLD, and Alzheimers Disease. Here, we report that loss of sfpq leads to premature termination of multiple transcripts due to widespread activation of previously unannotated cryptic last exons (CLEs). These CLEs appear preferentially in long introns of genes with neuronal functions and dampen gene expression outputs and/or give rise to short peptides interfering with the normal gene functions. We show that one such peptide encoded by the CLE-containing epha4b mRNA isoform is responsible for neurodevelopmental defects in the sfpq mutant. The uncovered CLE-repressive activity of SFPQ is conserved in mouse and human, and SFPQ-inhibited CLEs are found across ALS iPSC-derived neurons. These results greatly expand our understanding of SFPQ function and uncover a new gene regulation mechanism with wide relevance to human pathologies.

neuroscience↗

bioRxiv2020

Hnrnpul1 loss of function affects skeletal and limb development

Mutations in RNA binding proteins can lead to pleiotropic phenotypes including craniofacial, skeletal, limb and neurological symptoms. Heterogeneous Nuclear Ribonucleoproteins (hnRNPs) are involved in nucleic acid binding, transcription and splicing through direct binding to DNA and RNA, or through interaction with other proteins in the spliceosome. We show a developmental role for Hnrnpul1 in zebrafish, resulting in reduced craniofacial tendon length, severe adult-onset scoliosis and reduced fin size. We demonstrate a role of Hnrnpul1 in alternative splicing and transcriptional regulation using RNA sequencing. Given its cross-species conservation and role in splicing it would not be surprising if it had a role in human development but the developmental role of this gene in humans has not been explored. Whole exome sequencing detected a frameshift variant in HNRNPUL1 in two siblings with congenital limb malformations which remain variants of unknown significance. Zebrafish Hnrnpul1 mutants suggest an important developmental role of hnRNPUL1 and provide motivation for exploring potential conservation of ancient regulatory circuits involving hnRNPUL1 in human development.

developmental biology↗