Latest Publications

Matthew J Padgett , Nela Fucelova , Johannes Boltze, Timothy J England , Tuuli Hietamies , Karen Horsburgh , Terence J Quinn , Emily S Sena , Lorraine M Work, Marietta Zille, Rebecca C Trueman, Tracy D Farr

Hypoperfusion via bilateral carotid artery stenosis is the most common mouse model of vascular cognitive impairment, but the literature varies surrounding which behavioural tests are most appropriate to detect cognitive deficits in this model. We aimed to address this via a systematic review and meta-analysis. We also aimed to provide a recommendation that also considers how the tests cover the different cognitive domains. We identified 1714 publications and extracted data from 56. Interestingly, only six cognitive behavioural tests were employed across the literature with the most common being the Morris water and radial arm mazes, followed by the Y maze, novel object recognition, open field, and the Barnes maze. While all examined tests were able to detect cognitive impairments in hypoperfused mice, there was a high degree of heterogeneity across the publications, highlighting that not all research groups consistently observed cognitive deficits in the model. There was also evidence of publication bias, and occasionally some publications with extremely high effect sizes were influential. We recommend all tests, but ideally experiments should be complemented with additional approaches that examine a greater range of cognitive functions.

Journal of Cerebral Blood Flow & Metabolism, January 2026

Agnieszka Mierek-Adamska, Jose Gutierrez-Marcos, Claudia A. Blindauer

Zinc and cadmium share similar chemical properties; however, while zinc is an indispensable microelement involved in several physiological processes, cadmium is highly toxic. Cadmium toxicity results at least to some extent from replacing zinc (and other metals) from their active sites in enzymes and other proteins. This highlights why the correct population of metalloproteins with metals is crucial for proper cellular metabolism. In the face of growing demand for food, both in terms of quantity and quality, a rapid development of crop cultivars containing a higher amount of bioavailable zinc in the edible parts of plants, crucially without the simultaneous accumulation of cadmium, is imperative. Type 4 plant metallothioneins (pMT4s) are seed-specific proteins for which a potential role as a zinc specificity filter has been proposed. It was suggested that two conserved histidine residues are key for discrimination between zinc and cadmium. In this study, we analysed the metal-binding properties of Sorghum bicolor pMT4 (SbMT4) wild-type and mutant proteins with histidine/s replaced by tyrosine/s (H32Y, H40Y, and H32Y/H40Y) using mass spectrometry, elemental analysis, and NMR spectroscopy. SbMT4 is a Zn-thionein, but unexpectedly, it was also fully folded in the presence of cadmium – owing to a zinc ion remaining in the mononuclear Cys₂His₂ site in domain II. All three mutant proteins were misfolded in the presence of either zinc or cadmium, but increased Cd-to-protein stoichiometry was observed. The presence of histidines impacted SbMT4 metal selectivity when expressed in bacterial cells, but did not affect Zn/Cd accumulation in transgenic Arabidopsis thaliana plants.

Journal of Inorganic Biochemistry, January 2026

Gbeminiyi J. Oyedele, Ankit Shanker, Michael J. Tildesley, Ivo Vlaev

Adherence to self-isolation was a central measure for controlling the spread of COVID-19; however, compliance varied widely. Understanding the behavioural determinants that drive adherence is critical for informing future public health intervention. This study applied the COM-B model to examine the associations between capability, opportunity, motivation, and self-isolation behaviour during the COVID-19 pandemic in the United Kingdom. A retrospective analysis was conducted using secondary data from the UK Office for National Statistics 2019 Opinions and Lifestyle Survey, which was not originally designed to measure COM-B constructs. Structural equation modelling (SEM) was used to examine the relationships between capability, opportunity, motivation, and self-isolation behaviour. Opportunity and motivation were significantly associated with self-isolation, while capability was linked to behaviour indirectly through its association with motivation, reflecting a possible pathway suggested by the structural model. Although some measurement indicators demonstrated lower reliability owing to the use of secondary data, the overall model fit was good (RMSEA = 0.049, CFI = 0.966, TLI = 0.944, SRMR = 0.040). These findings highlight the dominant influence of social and motivational factors in shaping adherence. This study demonstrates the utility of the COM-B model for understanding self-isolation behaviour despite the constraints of secondary data. The findings highlight opportunity and motivation as key levers for promoting adherence and offer actionable insights for policymakers to design interventions that enhance motivation, strengthen social support, and sustain compliance during future public health emergencies.

Scientific Reports, January 2026

Shashank K. Pandey, Tatiana S. Moraes, Aswin Nair, Bibek Aryal, Abdul Azeez, Pal Miskolczi, Guillaume Maucort, Fabrice P. Cordelières, Lysiane Brocard, Gwendolyn V. Davis, Hannah Dromiack, Swanand Khanapurkar, Sara I. Walker, George W. Bassel, Emmanuelle M. Bayer, Rishikesh P. Bhalerao

Dormancy is a key mechanism in perennial plants in boreal and temperate regions, protecting buds from winter damage by repressing precocious bud break before spring onset. How plants robustly time dormancy release under fluctuating environments remains unknown. Here, we show that, rather than simply sensing cold duration, buds leverage warm spikes to sense winter progression and time dormancy release. This timing mechanism is mediated by previously unrecognized regulation of plasmodesmata by warm spikes acting through tree ortholog of FLOWERING LOCUS T (FT1) and the gibberellic acid pathway. Our results reveal FT1 as a previously unrecognized, suppressor of callose levels and show that warm spikes repress cold induction of FT1 and GA pathway to suppress PD opening and dormancy release. Importantly, buds exhibit heterogeneity in bud break. This heterogeneity in bud break crucial for bet hedging is amplified under temperature fluctuations and is associated with the thermal responsiveness of plasmodesmata. Altogether, our work reveals dynamic plasmodesmata regulation as a crucial tissue-level mediator of variable temperature processing by buds, enabling robust adaptation of trees to seasonal changes.

Nature Communications, January 2026

Steven Xingyu Wu, Christopher N. Davis,Mark Arnold, Michael J. Tildesley

Previous research efforts on highly pathogenic H5N1 avian influenza (HPAI) suggest that different avian species exhibit a varied severity of clinical signs after infection. Waterfowl, such as ducks or geese, can be asymptomatic and act as silent carriers of H5N1, making detection harder and increasing the risk of further transmission, potentially leading to significant economic losses. For backyard hobby farmers, passive reporting is a common HPAI detection strategy. We aim to develop a computational, mechanistic model to quantify the effectiveness of this strategy by simulating the spread of H5N1 in a mixed-species, small-population backyard flock. Quantities such as detection time and undetected burden of infection in various scenarios are compared. Our results indicate that the presence of ducks can lead to a higher risk of an outbreak and a higher burden of infection. If most ducks within a flock are resistant to H5N1, detection can be significantly delayed. We find that within-flock infection dynamics can heavily depend on the species composition in backyard farms. Ducks, in particular, can pose a higher risk of transmission within a flock or between flocks. Our findings can help inform surveillance and intervention strategies at the flock and local levels.

PLOS Computational Biology, January 2026

Amol Mohan Bhandare, Adwoa Boaten, Dylan Dunkwu, Jade Hill, Biborka Balazs, Nicholas Dale

Impaired CO₂ responsiveness in epilepsy can result in hypoventilation and hypercapnia and these respiratory disturbances are key contributors to Sudden Unexpected Death in Epilepsy (SUDEP). While mild to moderate inflammation is known to modulate respiratory function, its specific role in regulating respiratory responses in the context of epilepsy remains unclear. We studied the effects of lipopolysaccharide (LPS)-induced inflammation and microglial inhibition via minocycline during the acute and chronic phases of epilepsy on hypercapnic ventilatory responses (HCVR) in the intrahippocampal kainic acid model of temporal lobe epilepsy in male C57BL/6 mice. LPS treatment during acute seizures and minocycline during spontaneous seizures in the chronic phase of epilepsy restored the impaired HCVR in mice. Notably, LPS treatment during acute seizures also reduced the frequency of spontaneous seizures. In contrast, minocycline given during acute seizures and LPS administered during chronic epilepsy further exacerbated HCVR impairment. Immunohistochemical analysis of chemosensitive retrotrapezoid nucleus (RTN) revealed varied effects of different treatments in epileptic mice on microglia density, morphology and their expression of triggering receptor expressed on myeloid cells 2 (TREM2), P2Y12 receptor, and astrocytic adenosine 2A receptor (A2AR). Overall, the inflammation during epileptogenic or acute phase preserves HCVR and reduces spontaneous seizure frequency in chronic epilepsy, whereas in chronic phase it worsens HCVR. Although not yet fully validated, changes in microglial and astrocytic receptor expression could contribute to this HCVR impairment and may represent a mechanistic target for preserving HCVR in epilepsy; a dysfunction that could potentially lead to SUDEP.

Journal of Neuroinflammation, January 2026