Biology subjects

Mellor, A.

Publications and source records attributed to Mellor, A..

3 recordsLinked to original sources

bioRxiv2026

Attenuation of climatic signals limits prediction of phytoplankton blooms in a temperate shelf sea

Phytoplankton blooms link climatic conditions to marine food webs and carbon cycling, yet relationships between climate forcing and bloom magnitude remain weak and inconsistent in shelf seas. Using a multi-decadal, high-frequency observational record from the western Irish Sea gyre, we investigated how climate variability influences nutrient dynamics and spring phytoplankton bloom development. Sea surface temperature, marine heatwave intensity and the North Atlantic Oscillation exhibited weak and inconsistent relationships with bloom intensity. However, climatic influences were more evident in nutrient dynamics, particularly the timing of seasonal nutrient drawdown, whereas the magnitude of nutrient utilisation was strongly constrained by winter nutrient inventories. Translation of nutrient drawdown into phytoplankton biomass showed marked attenuation: nitrate consumption explained little variability in bloom intensity, whereas silicate drawdown exhibited a moderate, non-deterministic association consistent with functional constraints on diatom growth and community structure. Our results reveal relationships between climate variability and ecosystem function weaken across successive ecosystem levels. While nutrient inventories provide strong constraints on nutrient use, additional ecological and stoichiometric processes influence how nutrient uptake is translated into phytoplankton biomass. Our findings suggest that weak climate-bloom relationships may arise from hierarchical ecological filtering and highlight the importance of biological constraints when assessing ecosystem responses to climate variability in shelf seas.

ecology↗

bioRxiv2024

Sub-clinical glutamate receptor antagonist combinations prevent progressive demyelination.

Multiple sclerosis (MS) affects almost 3 million people globally who suffer demyelination as a series of relapses and remissions that tend towards progressive deterioration over time. The proximate cause is auto-immune attack by the adaptive immune system; therapies directed against this are effective during the relapsing-remitting phase but are less effective or ineffective during progression where other injury mechanisms may be significant. LPS- and cuprizone-induced experimental demyelination share features of progressive demyelination in MS but the underlying mechanisms are not well understood. We show here that these demyelination models can be reproduced ex vivo using short protocols, revealing that combined antagonism of two types of glutamate receptor, NMDA and AMPA, using clinically approved antagonists at sub-clinical doses, can protect against these forms of demyelination. Combined low dose therapy was subsequently shown to be effective in vivo against dietary cuprizone and experimental autoimmune-encephalomyelitis (EAE) models of demyelination and, in particular, protected the smaller myelinated axons that are the main substrate of the function loss in progressive MS.

neuroscience↗

bioRxiv2021

Neuroimmune-glial cells interactions elevate the kynurenine metabolic pathway to sustain neuropathic pain

Neuropathic pain is triggered by injury to the somatosensory system, and is one of the most important types of chronic pain. Nevertheless, critical pathophysiological mechanisms that maintain neuropathic pain are poorly understood. Here, we show that neuropathic pain is abrogated when the kynurenine metabolic pathway (KYNPATH) initiated by the enzyme indoleamine 2,3-dioxygenase (IDO) is ablated pharmacologically or genetically. Mechanistically, it was found that IDO upregulation in dendritic cells that accumulate in the dorsal root leptomeninges led to increased levels of kynurenine (Kyn) in the spinal cord, where Kyn is metabolized by astrocytes-expressed kynurenine-3-monooxygenase into a pro-nociceptive metabolite 3-hydroxykynurenine. In conclusion, these data reveal a novel role for KYNPATH as an important factor maintaining neuropathic pain during neuroimmune-glia cells interactions. This novel paradigm offers potential new targets for drug development against this type of chronic pain.

neuroscience↗