Biology subjects

Browne, M.

Publications and source records attributed to Browne, M..

12 recordsLinked to original sources

bioRxiv2026

The PSInet Plant Water Potential Database: advancing new perspectives on plant water status, traits, and hydraulic processes

Water potential gradients drive water flow within and between soils and plants, and the internal plant water potential controls a wide range of physiological processes including photosynthesis, growth, and mortality. Notwithstanding this clear relevance for many critical aspects of ecosystem function, water potential data have historically been relatively inaccessible and unnetworked. The absence of a centralized repository for plant water potential time series limits our ability to integrate a wealth of ecophysiological information from other networks and from remote sensing. Closing this gap is necessary to address unresolved questions about plant responses to drought and heat stress, and to make confident predictions about plant and ecosystem function in a warming world. Here, we introduce the PSInet database -- a global collection of plant water potential time series from 285 datasets representing 523 species. We present the workflow that guided database development and evaluate its key features. Through a series of preliminary analyses, we then highlight the potential of the PSInet database for applications including: a) advancing plant water use strategy frameworks; b) disentangling the impacts of soil versus atmospheric drought stress; c) assessing the long-held assumption of pre-dawn equilibration of ecosystem water potential; d) understanding the risk of drought-driven mortality; and e) benchmarking remote-sensing data products and land-surface models.

plant biology↗

bioRxiv2026

Quantifying visual pathway overlap to identify training-related microstructural change in hemianopia

BackgroundVisual training can improve residual vision in hemianopia, but there is significant variability in patient outcomes which may reflect differences in neural structures preserved after injury. Diffusion MRI tractography offers a means of assessing white-matter microstructure in vivo, however substantial overlap between neighbouring visual pathways complicates attribution of differences to specific tracts. We quantified tract overlap to identify relatively unique pathway segments to assess training-related microstructural change. MethodsDiffusion MRI data was acquired in six participants with homonymous hemianopia before and after 3-6 months of visual training. Tractography was used to reconstruct three pathways implicated in residual vision: lateral geniculate nucleus (LGN)-V1, LGN-V5 and pulvinar-V5, together with secondary superior colliculus-LGN and superior colliculus-pulvinar pathways. Streamline overlap was quantified along neighbouring tracts, and comparison of pre- to post-training fractional anisotropy was restricted to unique or pair-specific non-overlapping segments. Exploratory relationships with visual outcomes were also examined. ResultsFractional anisotropy increased after training in both early and late pair-specific segments of the LGN-V5 pathway in the lesioned hemisphere. In the late segment, this increase was significantly greater than in the corresponding unique LGN-V1 segment, whereas change in the early LGN-V5 segment did not differ significantly from the unique pulvinar-V5 segment. No significant training-related changes were observed in collicular pathways. Brain-behaviour analyses also preferentially implicated LGN-V5: baseline fractional anisotropy was strongly associated with post-training Gabor detection, and training-related fractional anisotropy change showed a positive association with improvement in Gabor detection, although the latter did not survive multiple comparison correction. ConclusionThese findings support a role for the LGN-V5 pathway in visual plasticity after hemianopia and demonstrate the importance of explicitly quantifying tract overlap when attributing microstructural change to small, neighbouring white-matter pathways.

neuroscience↗

bioRxiv2026

Distinct fibroblast and perivascular senotypes define spatial niches that regulate fibrosis

Fibrotic conditions contribute to significant global morbidity and mortality. Yet the underlying processes that orchestrate fibrosis remain poorly understood due to the cellular and spatial complexity of the stromal, immune, and vascular compartments that regulate fibrotic disease progression. Senescent cells (SnCs) have been implicated in fibrosis, but their roles are unclear, as evidence indicates that they serve both pathogenic and reparative functions. Here, we show that fibrosis-associated SnCs contain functionally divergent senotypes that are organized into distinct spatial niches. Using integrated single-cell and spatial transcriptomics analyses and hierarchical factorization in a murine fibrosis model, we identify fibroblast and perivascular SnC subpopulations that upregulate diverse programs related to extracellular matrix (ECM) production, immune signaling, and vascular remodeling. Fibroblast senotypes localize to discrete microenvironments with distinct tissue architectures, including niches associated with fibrotic signaling, immune activity, and cartilage development. Perivascular SnCs occupy interfaces between fibrotic signaling and immune-active niches and upregulate vascular and fibrotic remodeling pathways. Depletion of pericyte-lineage SnCs increases vascular maturation and fibrotic ECM deposition, providing mechanistic validation of the beneficial role these SnCs play in vascular remodeling and fibrosis modulation. In addition, using a new web-based infrastructure to query our senotype gene signatures in public datasets, we demonstrate that these senotypes are conserved across different murine and human fibrotic conditions. These findings establish senescence as a spatially organized regulator of fibrosis and identify perivascular senescence as a link between vascular remodeling and fibrotic outcomes.

bioengineering↗

bioRxiv2026

3D, multi-omic imaging reveals molecular biomarkers of the pre-metastatic niche in lung cancer

The recurrence rate following complete surgical resection of primary non-small cell lung cancer is as high as 55%, yet no approach currently exists to evaluate the risk of local recurrence. The premetastatic paradigm is the recognition that metastasis is preceded by reprogramming naive tissues to prime a microenvironment for tumor cell survival and subsequent reactivation. Identification of biomarkers of the pre-metastatic niche would allow us to evaluate a patients risk of local relapse in the normal lung parenchyma surrounding the resected tumor. We designed a workflow incorporating in vivo modelling, radiology, and deep learning-guided three-dimensional (3D) imaging, spatial proteomics, and transcriptomics to identify previously unreported signals associated with the early transformation of the lung parenchyma announcing regional metastasis. We curated biorepository spanning timepoints before and after resection of primary Lewis Lung Carcinoma (LLC) tumors. Using radiology and cellular resolution 3D histology, we calculated the number and distribution of metastases in mouse lungs and developed an algorithm to guide placement of spatial proteomics and transcriptomics to regions containing early micro-metastases and the pre-metastatic microenvironment. Molecular and tissue features associated with presence, size, and location of metastases guided the identification of both myeloid (F4/80) and senescent (p16/p21) cell signatures in the premetastatic and metastatic environments. Finally, multiparametric flow cytometry of metastatic lungs in a senescence reporter GEMM (tdTomato-p16 INKA mice) resolved senescent cells including alveolar macrophages as the cellular phenotypes associated with these early premetastatic signatures. Altogether, this work highlights a novel AI-assisted approach for detection of biomarkers of tissue remodeling during lung cancer invasion.

bioengineering↗

bioRxiv2026

Immune checkpoint inhibitors amplify type 2 immune mediated repair bypro-regenerative scaffolds

Extracellular matrix (ECM) scaffolds induce type 2 immunity to promote repair. Here, we show that immune cells recruited to ECM-treated murine muscle injuries and clinical soft tissue defects express immune checkpoints. Specifically, TH2 cells and regulatory T cells (Tregs) increase LAG3 expression, while macrophages express PDL2. TCR analysis and a triple-reporter strain for interleukin (IL)-13 and Treg fate-mapping suggest that Tregs in ECM-treated wounds transition into TH2-like exTregs that express LAG3. Immune checkpoint inhibition (ICI) significantly stimulated type 2 immunity in ECM-treated wounds, including increased TH2 cells, Treg transition to TH2-like exTregs, and pro-regenerative macrophages. Moreover, ICI enhanced muscle repair and reduced fibrosis in ECM-treated wounds. Collectively, these findings show Treg/TH2 plasticity in wound healing and introduce a novel ICI application to enhance immune-mediated regeneration.

bioengineering↗

bioRxiv2026

Regulatory T cells clonally expand and contribute to stromal cell function in fibrotic response to synthetic implants

Fibrosis plays a key role in both chronic disease progression and failure of synthetic biomaterial implants. However, the contribution of adaptive immunity to fibrotic development remains incompletely understood, particularly for regulatory T cells (Tregs). Here, we used single-cell multiomic profiling, integrating transcriptomics with T cell receptor (TCR) sequencing, to map Treg heterogeneity and clonal dynamics in a synthetic material-induced model of fibrosis. We uncovered progressive Treg clonal expansion accompanied by TCR activation signatures and an increasingly immunosuppressive phenotype along a continuous transcriptional trajectory. These Tregs suppressed immune responses and influenced extracellular matrix and vascular gene expression. Cell-cell communication inference predicted Treg-driven activation of pro-fibrotic and vasculogenic transcriptional programs in fibroblasts and endothelial cells, including Sox-family transcription factors. Functional Treg depletion increased inflammation and significantly reduced neovascularization. Together, these findings identify Treg functions in the fibro-vascular niche through stromal cell modulation, highlighting immune-stromal interactions as an important axis in fibrosis.

immunology↗

bioRxiv2025

Chromosomal instability shapes the tumor microenvironment of esophageal adenocarcinoma via a cGAS-chemokine-myeloid axis

Chromosomal instability (CIN), a characteristic feature of esophageal adenocarcinoma (EAC), drives tumor aggressiveness and therapy resistance, presenting an intractable problem in cancer treatment. CIN leads to constitutive stimulation of the innate immune cGAS-STING pathway, which has been typically linked to anti-tumor immunity. However, despite the high CIN burden in EAC, the cGAS- STING pathway remains largely intact. To address this paradox, we developed novel esophageal cancer models, including a CIN-isogenic model, discovering myeloid-attracting chemokines - with the chemokine CXCL8 (IL-8) as a prominent hit - as conserved CIN-driven targets in EAC. Using high-resolution multiplexed immunofluorescence microscopy, we quantified the extent of ongoing cGAS-activating CIN in human EAC tumors by measuring cGAS-positive micronuclei in tumor cells, validated by orthogonal whole-genome sequencing-based CIN metrics. By coupling in situ CIN assessment with single-nucleus RNA sequencing and multiplex immunophenotypic profiling, we found tumor cell-intrinsic innate immune activation and intratumoral myeloid cell inflammation as phenotypic consequences of CIN in EAC. Additionally, we identified increased tumor cell-intrinsic CXCL8 expression in CINhigh EAC, accounting for the inflammatory tumor microenvironment. Using a novel signature of CIN, termed CINMN, which captures ongoing CIN-associated gene expression, we confirm poor patient outcomes in CINhigh tumors with signs of aberrantly rewired cGAS-STING pathway signaling. Together, our findings help explain the counterintuitive maintenance and expression of cGAS-STING pathway components in aggressive, CINhigh tumors and emphasize the need to understand the contribution of CIN to the shaping of a pro-tumor immune landscape. Therapeutic strategies aimed at disrupting the cGAS-driven inflammation axis may be instrumental in improving patient outcomes in this aggressive cancer.

cancer biology↗

bioRxiv2025

A pangenomic approach reveals the sources of genetic variation fueling the rapid radiation of Capuchino Seedeaters

The search for the genetic basis of phenotypes has primarily focused on single nucleotide polymorphisms, often overlooking structural variants (SVs). SVs can significantly affect gene function, but detecting and characterizing them is challenging, even with long-read sequencing. Moreover, traditional single-reference methods can fail to capture many genetic variants. Using long-reads, we generated a Capuchino Seedeater (Sporophila) pangenome, including 16 individuals from seven species, to investigate how SVs contribute to species and coloration differences. Leveraging this pangenome, we mapped short-read data from 127 individuals to perform FST scans and genome-wide association studies. Species divergence primarily arises from SNPs and indels (< 50 bp) in non-coding regions of melanin-related genes, as larger SVs rarely overlap with divergence peaks. One exception was a 55 bp deletion near the OCA2 and HERC2 genes, associated with feather pheomelanin content. These findings support the hypothesis that the reshuffling of small regulatory alleles, rather than larger species-specific mutations, accelerated plumage evolution leading to prezygotic isolation in Capuchinos. TeaserSNPs and indels primarily shape species differences and plumage diversity in Capuchino Seedeaters.

evolutionary biology↗

bioRxiv2023

Geometric constraint of mechanosensing in bone marrow stromal cell cultures prevents stiffness-induced differentiation

Extracellular matrix (ECM) stiffness is fundamental in cell division, movement and differentiation. The stiffness that cells sense is determined not only by the elastic modulus of the ECM material, but also by ECM geometry and cell density. We hypothesised that these factors would influence cell-traction-induced matrix deformations and cellular differentiation in bone marrow stromal cells (BMSCs). To achieve this, we cultivated BMSCs on polyacrylamide hydrogels that varied in elastic modulus and geometry and measured cell spreading, cell-imparted matrix-deformations and differentiation. At low cell density BMSCs spread to a greater extent on stiff compared to soft hydrogels, or on thin compared to thick hydrogels. Cell-imparted matrix deformations were greater on soft compared to stiff hydrogels or thick compared to thin hydrogels. There were no significant differences in osteogenic differentiation relative to hydrogel elastic modulus and thickness. However, increased cell density and/or prolonged culture significantly reduced matrix deformations on soft hydrogels to levels similar to those on stiff substrates. This suggests that at high cell densities cell traction-induced matrix displacements are reduced by both neighbouring cells and the constraint imposed by an underlying stiff support. This may explain observations of the lack of difference in osteogenic differentiation as a function of stiffness.

biophysics↗

bioRxiv2022

Do we perform as well as we think we do? A systematic scoping review of self-evaluation of upper-extremity motor performance

The ability to self-evaluate motor performance or estimate performance errors is beneficial for motor learning or relearning in the context of neurologic injury. Some evidence suggests those with injury like stroke may be unable to accurately self-evaluate their performance; however, it is unclear if individuals who are absent of injury are accurate in this domain. We aimed to investigate the accuracy of self-evaluation and potential influencing factors by conducting a systematic search to identify literature involving the self- and objective-evaluation of upper-extremity motor tasks. Twenty-three studies satisfied inclusion criteria. Data revealed a moderate positive correlation between self- and objective evaluations across a variety of tasks, from trivial button pressing to specialized surgical suturing. Both under- and overestimation of performance was found across the papers. Key factors identified to influence the accuracy of self-evaluation were the task purpose, familiarity, difficulty, and whether an individual received a demonstration. This review identified some limitations in this field of research. Most notably, we found that very few studies have investigated the accuracy of self-evaluation of motor performance with the primary goal of comparison to objective performance. Many studies reported the data but did not make direct statistical comparisons. Moreover, due to inconsistencies between how self and objective-evaluations were conducted, we argue that in this area of investigation self-evaluation tools need to replicate the objective evaluation method, or at minimum the self-evaluation tool should ask questions specific to the construct of performance that is being measured objectively.

neuroscience↗

bioRxiv2022

LARP1 regulates metabolism and mTORC1 activity in cancer

The protein mammalian target of rapamycin (mTOR) is a master regulator of cell homeostasis. Although mTOR is aberrantly overactivated in 70% ovarian cancers, mTOR cascade inhibitors (such as those blocking the kinase activity of mTOR itself or upstream kinases PI3K/AKT) have demonstrated disappointing activity in ovarian cancer clinical trials. These findings indicate that, despite its pivotal role in normal cells, hyperactivated mTOR does not act as a master regulator of metabolism in this cancer context. Surprisingly, we have identified that the RNA binding protein LARP1, a known phospho-target of mTORC1 and activator of ribosomal biogenesis, is responsible for metabolic reprogramming in mTOR-dysregulated cancers. LARP1 post-transcriptionally regulates the expression of several hundred rate-limiting enzymes involved in multiple aspects of metabolism, including glycolysis and oxidative phosphorylation. Through this mechanism LARP1 sustains ATP production and mTORC1 localisation on the lysosome, thereby activating cell proliferation despite the scarcity of extracellular nutrients. Our findings show that, by sustaining global cellular metabolism in response to growth factor signalling, LARP1 has a central post-transcriptional role in controlling mTORC1 localisation and driving cancer progression, a key cancer hallmark.

cancer biology↗

bioRxiv2019

Investigating risk factors that predict a dogs fear during veterinary visits

Attending the veterinary clinic is an integral part of the physical welfare of every companion dog. However, some dogs experience their veterinary visits negatively, which poses a risk of injury to the veterinary staff, their guardian (owner) and themselves during veterinary examinations. It may also influence the regularity of non-urgent veterinary appointments. To date there has been conflicting data on the proportion of dogs that are fearful during their veterinary visits. In this study, we explored the risk factors associated with fear during veterinary examination and in novel situations (including first time at the veterinary clinic) from 26,555 responses in the Canine Behavioral Assessment and Research Questionnaire database. According to their guardians, over half (55%) of companion dogs displayed some form of fearful behaviour (mild-extreme) when examined by a veterinarian, while 14% of dogs exhibited severe or extreme fear. A similar trend was observed with dogs responding fearfully in unfamiliar situations, including the dogs first time at the veterinary clinic. Chi-squared tests showed every bivariate relationship was significant (p < 0.05). The most important predictors of fear in a veterinary examination were, in order: the dogs breed group (27.1%), their history of roles or activities (16.7%), where they were sourced (15.2%), their weight (12%), the age of other dogs in the household (9.5%) and dog owner experience (6.3%). However, these risk factors accumulate to explain a total of 7% of variance of fear observed during veterinary examination. Results demonstrate that fear of veterinary visits is common in dogs, but that other factors (including the environment or human-animal interactions) are likely to contribute more to prevalence and severity of this problem than the demographic factors measured here. Finally, we highlight opportunities for future research aimed at facilitating less stressful veterinary visits for dogs and their guardians.

animal behavior and cognition↗