Biology subjects

Angelini, R.

Publications and source records attributed to Angelini, R..

5 recordsLinked to original sources

bioRxiv2026

Peroxisome dynamics during HSV-1 life cycle in human neurons

HSV-1 is increasingly implicated in Alzheimers disease, yet the mechanisms by which it reshapes neuronal metabolism remain incompletely understood. Here, we demonstrate that HSV-1 co-opts peroxisomal biogenesis and lipid metabolic pathways to promote its replication across human neuronal models. In SH-SY5Y cells, infection triggers a marked expansion of the peroxisomal compartment and alters organelle morphology through upregulation of PGC-1 and PEX13/14/19. Pharmacological stimulation of peroxisome proliferation enhances viral production, whereas inhibition of PEX3-PEX19-dependent biogenesis almost completely suppresses infection. Lipidomic profiling reveals a selective increase in peroxisome-derived plasmalogens and sphingolipids, supporting a role for peroxisomes as a metabolic hub for viral envelopment. This remodeling is recapitulated in hiPSC-derived neurons and human brain organoids, where it is strictly dependent on productive replication and re-emerges upon viral reactivation, but not during latency. Collectively, these findings identify peroxisomes as essential replication-permissive organelles exploited by HSV-1 and suggest that recurrent virus-driven peroxisomal and ether-lipid reprogramming may contribute to neuronal vulnerability in neurodegenerative disease.

microbiology↗

bioRxiv2025

Aqueous two-phase bioinks for discrete packing and compartmentalisation of 3D bioprinted cells

The unparalleled ability of aqueous two-phase systems (ATPS) to reproduce microscale cellular and biomaterial compartmentalisation to selectively modulate cell behaviour and functionality is ideal for tissue engineering and regenerative medicine (TERM) purposes. Herein, we introduce new ATPS biomaterial inks for 3D bioprinting of water-in-water (W/W) emulsions, enabling precise cellular crowding for tissue regeneration in vitro and ex vivo. Gelatin methacryloyl (GelMA) was hierarchically dispersed in an alginic acid phase depending on sodium chloride (NaCl) concentration (0-36 g/L). Emulsion droplet size (12.8{+/-}2.6 {micro}m to 52.4{+/-}11.4 {micro}m) influenced degradation and spatial cell localisation (A549, C2C12, MG63). A microfluidic-assisted 3D bioprinting approach allowed fine-tuning of fibre structure adjusting ATPS deposition by modulating flow rates and printing speed. Rheological properties supported the findings of the two-phase partitioning, aiding the selection of the ATPS ink formulation for functional cell-laden construct fabrication. Encapsulation of C2C12 cells revealed enhanced cytoskeletal remodelling at higher salt concentrations. Increased GelMA phase promoted human bone marrow stromal cells (HBMSCs) crowding, mineral deposition and skeletal differentiation. In ovo studies demonstrated degradation control and vascular infiltration via salt modulation. Altogether, ATPS bioinks offer a versatile platform for the assembling of complex, hierarchical tissues with microscale precision, expanding biofabrication strategies for TERM applications.

bioengineering↗

bioRxiv2025

What determines trophic niche breadth? A global analysis of freshwater fishes using isospaces

Trophic niche is one of the most tractable dimensions of a species niche. Several hypotheses have been proposed to explain global variation in species trophic niches, but empirical tests are limited. Stable isotope analysis (SIA) of {delta}{superscript 1}3C (a proxy for basal sources) and {delta}{superscript 1} N (a proxy for vertical trophic position) has increasingly been used to estimate trophic niche variation. We performed SIA on a dataset of over 33,000 stable isotope samples from freshwater fishes across six ecoregions. For 541 populations (358 species), we estimated the size of {delta}{superscript 1}3C x {delta}{superscript 1} N isospace--a bivariate representation of trophic niche breadth. We evaluated isospace variation in relation to environmental factors, species traits, and sampling scale, testing both novel and long-standing hypotheses about the drivers of trophic niche variation. A Boosted Regression Tree Model best predicted isospace, with environmental and trait-based variables among the strongest predictors. Fish isospaces were broader in regions with warmer temperatures, higher humidity, and precipitation variability, suggesting that more productive, diverse, and seasonal ecosystems are associated with broader trophic niches. Conversely, isospace size declined with increasing basin fish richness, which may reflect heightened interspecific competition or historical competitive exclusion. Isospace size was slightly smaller in large lakes compared to rivers, streams, and small lakes. Within-population variation in body size was strongly and positively associated with isospace size, highlighting the role of ontogenetic dietary shifts. Fish with truncate-rounded fins had broader isospaces than those with forked-lunate fins, likely due to the former having more limited movement and greater spatial isolation that resulted in greater between-individual niche variation. Primary consumers had larger isospaces than intermediate and top consumers. Predators showed relationships consistent those observed from analysis encompassing all trophic guilds, but non-predators deviated with regards to four variables--solar radiation, basin richness, average body size, and caudal fin aspect ratio. Isospace size increased with the number of sampled individuals, habitats and years surveyed. Although isospace patterns have well-documented limitations as trophic ecology metrics, our findings nonetheless conform with several longstanding hypotheses for trophic niche variation and stimulate new ideas about environmental and biological drivers of niche breadth.

ecology↗

bioRxiv2020

Visualising Cholesterol in Brain by On-Tissue Derivatisation and Quantitative Mass Spectrometry Imaging

Despite being a critical molecule for neurobiology and brain health, mass spectrometry imaging (MSI) of cholesterol has been under reported compared to other lipids, due to the difficulty in ionising the sterol molecule. In the present work we have employed an on-tissue enzyme-assisted derivatisation strategy to improve detection of cholesterol in brain tissue sections. We report distribution and levels of cholesterol across specific brain structures of the mouse brain, in a model of Niemann-Pick type C1 (NPC1) disease, and during brain development. MSI revealed how cholesterol changes during development and that in the adult is highest in pons and medulla of the brain stem. Cholesterol was significantly reduced in the corpus callosum and other brain regions in the Npc1 null mouse, confirming hypomyelination at the molecular level. Our study demonstrates the potential of MSI to the study of sterols in neuroscience.

biochemistry↗

bioRxiv2018

Imaging Oxysterols in Mouse Brain by On-Tissue Derivatisation-Robotic Liquid Micro-Extraction Surface Analysis-Liquid Chromatography Mass Spectrometry

Dysregulated cholesterol metabolism is implicated in a number of neurological disorders. Many sterols, including cholesterol and its precursors and metabolites, are biologically active and important for proper brain function. However, spatial cholesterol metabolism in brain and the resulting sterol distributions are poorly defined. To better understand cholesterol metabolism in situ across the complex functional regions of brain, we have developed on-tissue enzyme-assisted derivatisation in combination with micro-liquid-extraction for surface analysis and liquid chromatography - mass spectrometry to image sterols in tissue slices (10 {micro}m) of mouse brain. The method provides sterolomic analysis at 400 {micro}m spot diameter with a limit of quantification of 0.01 ng/mm2. It overcomes the limitations of previous mass spectrometry imaging techniques in analysis of low abundance and difficult to ionise sterol molecules, allowing isomer differentiation and structure identification. Here we demonstrate the spatial distribution and quantification of multiple sterols involved in cholesterol metabolic pathways in wild type and cholesterol 24S-hydroxylase knock-out mouse brain. The technology described provides a powerful tool for future studies of spatial cholesterol metabolism in healthy and diseased tissues.\n\nSignificanceThe brain is a remarkably complex organ and cholesterol homeostasis underpins brain function. It is known that cholesterol is not evenly distributed across different brain regions, however, the precise map of cholesterol metabolism in the brain remains unclear. If cholesterol metabolism is to be correlated with brain function it is essential to generate such a map. Here we describe an advanced mass spectrometry imaging platform to reveal spatial cholesterol metabolism in situ at 400 {micro}m resolution on 10 {micro}m tissue slices from mouse brain. We mapped, not only cholesterol, but also other biologically active sterols arising from cholesterol turnover in both wild type and mice lacking cholesterol 24-hydroxylase (Cyp46a1), the major cholesterol metabolising enzyme.

neuroscience↗