Biology subjects

Bright, M.

Publications and source records attributed to Bright, M..

6 recordsLinked to original sources

bioRxiv2026

Neuro-Metabolic and Vascular Dysregulation are Functional Biomarkers of Acquired Brain Injury

Emerging clinical and neuropathological evidence suggests a direct link between traumatic brain injury (TBI) and neurodegenerative diseases (ND), but the mechanisms by which TBI contributes to ND onset and progression remain unclear. To bridge this gap, the NINDS TBI-ADRD consortium developed a diagnostic framework to guide the design and evaluation of TBI-ADRD experiments using translational neuroimaging (DCE-MRI, 18F-FDG-PET) and advanced image-processing pipelines. Neuro-metabolic and vascular dysregulation (MVD) and metabolic functional connectomics (MFC) were evaluated in 8-month C57BL/6J mice at 30- and 60-days post-injury (DPI). Both MVD and MFC revealed significant changes at 30- and 60-DPI that were sex- and injury side-dependent. Female mice showed greater regional MVD alterations, while MFC identified sex-dependent changes at 30-DPI that diminished by 60-DPI. These findings suggest that a single mid-life closed-head injury induces sexually dimorphic MVD and brain network remodeling, supporting the potential of MVD as a sensitive biomarker for improved clinical monitoring post-TBI.

neuroscience↗

bioRxiv2026

AQuA2-Cloud: a web platform for fluorescence bioimaging activity analysis

BackgroundAdvanced biological imaging analysis platforms such as Activity Quantification and Analysis (AQuA2) enable accurate spatiotemporal activity analysis across diverse cell populations within many species. These tools are increasingly important for investigating cellular signaling dynamics and behavior. However, despite advances in the accuracy and species capability of AQuA2, it remains computationally demanding for analysis of long time-series datasets and requires all users to maintain a MATLAB license, which may limit accessibility and large-scale deployment. ResultsTo address these limitations, we have designed and made available AQuA2-Cloud, a portable software stack and web platform developed as an improvement and further evolution of AQuA2. This container-deployable system permits multi-user cloud-based high accuracy activity quantification with intuitive workflows, export of analysis data and project files, and comparable processing times. The platform offers integrated features such as in-browser analysis control interfaces, asynchronous program state control, multiple users and user management, support for unreliable connections, file uploading and downloading via web browsers and File Transfer Protocol, and centralized organization of analysis output. ConclusionAQuA2-Cloud constitutes a cloud-native solution for laboratories or research groups seeking to centralize analysis of spatiotemporal biological imaging datasets while reducing software installation and licensing barriers for end users. The platform enables researchers with minimal technical expertise to perform advanced bioimaging analysis through standard web browsers while maintaining the analytical capabilities of AQuA2. AQuA2-Cloud source code, deployment procedures, and documentation are freely available at (https://github.com/yu-lab-vt/AQuA2-Cloud).

bioinformatics↗

bioRxiv2025

Complement biosynthesis in human brain: Insights from single-nucleus transcriptomics of hippocampus.

Complement is a key contributor to neuroinflammation, driving pathology in neurodegenerative diseases (NDDs); however, little is known about the source of complement in brain. Effective targeting of complement in NDDs requires understanding of its source; in particular, which brain cells express complement genes, how expression is regulated and how expression changes in disease. To address this knowledge gap, we identified and integrated single-nucleus RNA sequencing (snRNA-seq) datasets from 398,097 nuclei across 48 hippocampal samples from non-demented brains to create a comprehensive transcriptomic atlas of complement gene expression ("complementome") in healthy brain. Expression levels of genes encoding complement components, receptors, and regulators were analysed across different brain cell types and the impact of sex and age on complement gene expression tested. To test impact of disease, we generated a further atlas from datasets comprising 11 non-demented and 12 Alzheimers disease (AD) patient hippocampi to assess changes in complement gene expression in AD. All glial cells in the non-demented hippocampus expressed complement genes. C1Q A/B/C genes were exclusively expressed in microglia, while C3 was highly expressed in microglia and astrocytes. Notably, C3 expression defined a subset of pro-inflammatory microglia. Complement receptor encoding genes (C3AR1, C5AR2, ITGAM, ITGAX, ITGB2, VSIG4) were predominantly expressed in microglia, while neurons expressed a set of brain-specific putative receptors (NPTX 1/2, NPTXR, NRP1). Endothelial cells abundantly expressed key regulators (CD46, CD55, CD59, CFH), while neurons and OPCs expressed a set of putative regulators (CSMD 1/2/3, and SUSD4). Astrocytes abundantly expressed CLU. Cell type-specific gender differences included higher expression of C1Q A/B/C, C1R, C1S in female microglia and higher expression of ITGAM and ITGAX in male microglia. Generally higher complement gene expression was seen in older donors. Compared to controls, AD microglia showed higher expression of C1QB and C3, and AD astrocytes showed higher C1S and C3 expression. Expression of ITGAX was elevated in AD microglia compared to controls, while many AD cell types demonstrated reduced expression of brain-specific putative receptors. Defining the complementome in non-demented hippocampus provides a baseline for exploration of brain complement expression. Complement expression is upregulated in AD, likely contributing to neuroinflammation and highlighting its potential as a therapeutic target. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=183 SRC="FIGDIR/small/652374v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@100fbc1org.highwire.dtl.DTLVardef@1905402org.highwire.dtl.DTLVardef@7b8573org.highwire.dtl.DTLVardef@176424a_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

Fast, Accurate, and Versatile Data Analysis Platform for the Quantification of Molecular Spatiotemporal Signals

Optical recording of intricate molecular dynamics is becoming an indispensable technique for biological studies, accelerated by the development of new or improved biosensors and microscopy technology. This creates major computational challenges to extract and quantify biologically meaningful spatiotemporal patterns embedded within complex and rich data sources, many of which cannot be captured with existing methods. Here, we introduce Activity Quantification and Analysis (AQuA2), a fast, accurate, and versatile data analysis platform built upon advanced machine learning techniques. It decomposes complex live imaging-based datasets into elementary signaling events, allowing accurate and unbiased quantification of molecular activities and identification of consensus functional units. We demonstrate applications across a wide range of biosensors, cell types, organs, animal models, and imaging modalities. As exemplar findings, we show how AQuA2 identified drug-dependent interactions between neurons and astroglia, and distinct sensorimotor signal propagation patterns in the mouse spinal cord.

neuroscience↗

bioRxiv2021

Novel insights on obligate symbiont lifestyle and adaptation to chemosynthetic environment as revealed by the giant tubeworm genome

The mutualism between the giant tubeworm Riftia pachyptila and its endosymbiont Candidatus Endoriftia persephone has been extensively researched over the past 40 years. However, the lack of the host whole genome information has impeded the full comprehension of the genotype/phenotype interface in Riftia. Here we described the high-quality draft genome of Riftia, its complete mitogenome, and tissue-specific transcriptomic data. The Riftia genome presents signs of reductive evolution, with gene family contractions exceeding expansions. Expanded gene families are related to sulphur metabolism, detoxification, anti-oxidative stress, oxygen transport, immune system, and lysosomal digestion, reflecting evolutionary adaptations to the vent environment and endosymbiosis. Despite the derived body plan, the developmental gene repertoire in the gutless tubeworm is extremely conserved with the presence of a near intact and complete Hox cluster. Gene expression analyses establishes that the trophosome is a multi-functional organ marked by intracellular digestion of endosymbionts, storage of excretory products and haematopoietic functions. Overall, the plume and gonad tissues both in contact to the environment harbour highly expressed genes involved with cell cycle, programmed cell death, and immunity indicating a high cell turnover and defence mechanisms against pathogens. We posit that the innate immune system plays a more prominent role into the establishment of the symbiosis during the infection in the larval stage, rather than maintaining the symbiostasis in the trophosome. This genome bridges four decades of physiological research in Riftia, whilst simultaneously provides new insights into the development, whole organism functions and evolution in the giant tubeworm.

evolutionary biology↗

bioRxiv2021

Host-symbiont stress response to lack-of-sulfide in the giant ciliate mutualism

The thiotrophic mutualism between the sulfur-oxidizing, chemoautotrophic (thiotrophic) bacterial ectosymbiont Candidatus Thiobius zoothamnicola and the giant ciliate Zoothamnium niveum thrives in a variety of shallow-water marine environments with highly fluctuating sulfide emission. To persist over time both partners must reproduce and ensure symbiont transmission prior cessation of sulfide, fueling the symbionts carbon fixation and host nourishment. We experimentally investigated the response of this mutualism to waning of sulfide. We found that colonies followed the r-strategy and released initially present but also newly produced macrozooids until death. A fraction of middle-sized longer-lived colonies were particularly proficient in producing and releasing swarmers. The symbionts on the colonies proliferated less and became larger and more rod-shaped under oxic conditions compared to symbionts from freshly collected colonies exposed to sulfide and oxygen. The symbiont monolayer was highly disturbed with epigrowth of other microbes and loss of symbionts that were subsequently found in the experimental seawater. We conclude that both partners response to cessation of sulfide emission was remarkably fast. The colony experienced death within two days but host reproduction through swarmers carrying the symbiont ensured the continuation of the association.

ecology↗