Biology subjects

Welsh, J.

Publications and source records attributed to Welsh, J..

3 recordsLinked to original sources

bioRxiv2025

Physiological Arousal as a Predominant Source of Individual Differences in Functional Brain Networks

Individual differences in brain network function and organization are promising targets for fMRI-based biomarkers in precision psychiatry, yet the sources of individual variability remain poorly understood. We show that arousal, assessed by systemic low-frequency oscillation (sLFO) amplitude in the fMRI signal, accounts for a substantial portion of variance in brain network properties (e.g.: R= 0.70 for default mode network (DMN)-dorsal attention connectivity; R= -0.63 for DMN dynamics). These relationships replicated across sessions, across independent samples, and when assessed with traditional arousal indices. Critically, associations persisted after sLFO denoising, indicating a genuine brain-physiology relationship rather than hemodynamic artifact. Pharmacological manipulation showed that drug-induced sLFO-assessed arousal changes were accompanied by corresponding shifts in network connectivity and dynamics. This work identifies arousal as a prominent determinant of variability in functional brain networks, providing a new perspective on brain-based individual differences while offering an approach to measure arousal directly from fMRI data.

neuroscience↗

bioRxiv2025

Nicotinamide reverses the Warburg effect in Chinese hamster ovary cell culture

The Warburg effect, the preferential conversion of glucose-derived pyruvate to lactate despite available oxygen, is a key feature of Chinese hamster ovary (CHO) cell culture. Lactate accumulation in recombinant protein-producing cell culture is an inefficient usage of glucose, as well as being deleterious to cells. Lactate accumulation lowers culture pH, requiring base addition to maintain bioreactor pH setpoint, which subsequently leads to hyperosmolarity, adversely impacting cell growth, productivity and product quality. A key driver for the Warburg effect, and hence lactate accumulation, is the need to regenerate NAD+ consumed during glycolysis. Since oxidative phosphorylation (OXPHOS) has limited capacity to recycle NADH back to NAD+ at high glycolytic fluxes, cells rely on lactate dehydrogenase (LDH) to convert pyruvate to lactate, simultaneously regenerating NAD+ and sustaining glycolysis. Thus, providing the cells capacity to generate more NAD+ would decrease the reliance on the Warburg effect. In this study, feeding the NAD+ precursor nicotinamide (NAM) leads to reversal of the Warburg effect, inducing the "lactate shift" three days earlier in cell culture and reducing peak lactate concentration by 40%. Transcriptomic analysis further confirms this metabolic shift, with an upregulation of key mitochondrial electron transport chain genes. These results identify NAD+/NADH balance as a key regulator of the Warburg effect and demonstrate NAM supplementation as a simple, cost-effective strategy to mitigate lactate accumulation and improve metabolic efficiency in CHO cell cultures.

bioengineering↗

bioRxiv2023

High resolution longitudinal molecular and morphological tracking of planktonic threats to salmon aquaculture.

Marine-phase salmonid aquaculture is a major component of the coastal economies of Northern Europe, North America and Chile and is under threat from numerous challenges to gill health, many of which originate from the phyto- and zooplankton. Associated losses are growing as a proportion of production year on year. A first step towards mitigating losses is to characterize the biological drivers of poor gill health. Numerous planktonic species have been implicated, including toxic and siliceous microalgae, hydrozoans and scyphozoans; however, rigorous longitudinal surveys of planktonic diversity and gill health have been lacking. In the current study, we present and assess an exhaustive identification approach combining both morphological and molecular methods (environmental DNA metabarcoding) approaches in combination with robust statistical models to identify the planktonic drivers of complex gill disease (CGD) and fish mortality. We undertook longitudinal molecular and microscopic evaluation at two marine aquaculture facilities on the west coast of Scotland using daily data collected during the 2021 growing season (March-October). Examining these two different sites, one sheltered and one exposed to the open sea, we identified new, important, and unexpected planktonic drivers (e.g. doliolids and appendicularians) of CGD and mortality and confirmed the significance of some established threats (e.g. hydrozoans and diatoms). We also explored delayed or lagged effects of planktonic abundances on gill health and undertook a comparison of environmental DNA metabarcoding and microscopy in their ability to identify and quantify planktonic species. Our data highlight the diversity of planktonic threats to salmonid aquaculture as well as the importance of using both molecular and morphological approaches to detect those. Despite our study relying on two farm sites only, our results evidence the role of the different planktonic players on salmon gill disease; there is now an urgent need to expand systematic longitudinal molecular and morphological approach across multiple sites and over multiple years. The resultant catalogue of main biological drivers will enable early warning systems, new treatments and, ultimately, a sustainable platform for future salmonid aquaculture in the marine environment.

zoology↗