Biology subjects

Moss, D.

Publications and source records attributed to Moss, D..

3 recordsLinked to original sources

bioRxiv2025

Cognitive and autonomic physiological responses to daily transcutaneous auricular vagus nerve stimulation in healthy adults

IntroductionThe vagus nerve regulates autonomic processes central to cognition. Transcutaneous auricular vagus nerve stimulation (taVNS) can acutely modulate executive function in healthy adults, but the effects of repeated dosing, roles of executive subdomains, and importance of sex as a biological variable require clarification. MethodIn a randomized, single-blind, sham-controlled, parallel group study, 12 healthy adults (six women) received 10 consecutive days of left monoaural taVNS (VNS) or sham (CON), with a two-week follow-up rechallenge. Stimulation (100Hz; 200{micro}s pulse width) was delivered continuously (online) at rest and during the Eriksen Flanker (inhibition), Wisconsin Card Sorting (shifting), and Sternberg (working memory) tasks. Resting autonomic measures included pupil diameter, skin conductance (SCL), mean R-R interval (mRR), respiration, and blood pressure. Primary outcomes were analyzed with linear mixed models and [S]idak-corrected contrasts. ResultsTen days of taVNS produced immediate and cumulative changes in multiple executive function subdomains that remained evident at rechallenge, with the strongest effects on accuracy. Across tasks, benefits were most pronounced in women; men displayed initial performance costs, but with greater longitudinal improvements. Cognitive effects were most evident on higher-difficulty trials. Autonomically, taVNS increased SCL during and after stimulation, amplified stimulus- and task-evoked pupil responses, and transiently lengthened mRR. Stimulation was well tolerated and blinding was acceptable. ConclusionsResolution of taVNS effects to higher-difficulty trials supports adaptive-gain modulation within executive function networks. The combination of larger evoked pupil/SCR, transient mRR lengthening, and increased SCL indicates that taVNS increased autonomic flexibility and arousal. Our findings identify biological sex and stimulation intensity as potentially important considerations for taVNS efficacy and provide longitudinal estimates to guide dosing, biomarker selection, and trial design. Collectively, the results support continued development of taVNS as a safe tool for the modulation of executive function and autonomic activity in healthy adults.

neuroscience↗

bioRxiv2024

Epac activation reduces trans-endothelial migration of undifferentiated neuroblastoma cells and cellular differentiation with a CDK inhibitor further enhances Epac effect.

AbstractNeuroblastoma (NB) is the most common solid extracranial neoplasm found in children and is derived from primitive sympathoadrenal neural precursor. The disease accounts for 15% of all cancer deaths in children. The mortality rate is high in patients presenting with a metastatic tumour even with extensive treatments. This signifies the need for further research towards the development of new additional therapies that can combat not only tumour growth but metastasis, especially amongst the high-risk groups. During metastasis, primary tumour cells become migratory and travel towards a capillary within the tumour. They then degrade the matrix surrounding the pericytes and endothelial cells traversing the endothelial barrier twice to establish a secondary. This led to the hypothesis that modulation of the endothelial cell junctional stability could have an influence on tumour metastasis. To test this hypothesis, agents that modulate endothelial permeability on NB cell line migration and invasion were assessed in vitro in a tissue culture model. The cAMP agonist and its antagonists were found to have no obvious effect on both SK-N-BE2C and SK-N-AS migration, invasion and proliferation. Next, NB cells were cocultured with HDMEC cells and live cell imaging was used to assess the effect of an Epac agonist on trans-endothelial cell migration of NB cells. Epac1 agonist remarkably reduced the trans-endothelial migration of both SK-N-BE2C and SK-N-AS cells. These results demonstrate that an Epac1 agonist may perhaps serve as an adjuvant to currently existing therapies for the high-risk NB patients.

cancer biology↗

bioRxiv2018

CDK inhibitors reduce cell proliferation and reverse hypoxia-induced metastasis of neuroblastoma tumours in a chick embryo model

Neuroblastoma is a paediatric cancer with a poor prognosis. This is in part due to the widespread metastasis at time of presentation, which is refractory to current treatment modalities. New therapeutic agents that can control not only tumour growth but also metastasis are urgently needed.\n\nOne current therapeutic option used in the clinic is differentiation therapy with retinoic acid, where the terminal differentiation of the neuroblastoma cells reduces tumour growth in the primary tumour as well as at metastatic sites. However, retinoic acid only works in a subset of patients.\n\nWe investigated the potential of CDK inhibitors on neuroblastoma cell differentiation, tumour progression and metastasis by utilising a 3R compliant cost effective preclinical chick embryo model. In both SK-N-AS and BE(2)C cell lines, when engrafted on the chorioallantoic membrane of chick embryos, we observed a reduction of tumour cell proliferation as well as a reduction in hypoxia preconditioning-driven metastasis by 60%. In addition, the expression of a panel of genes with known roles in metastasis, which increased upon hypoxia-preconditioning, was largely reduced by a CDK1 inhibitor. These results provide a promising alternative to currently existing therapies and might aid the development of new treatment protocols for retinoic acid-resistant patients.

cancer biology↗