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Garner, K.

Publications and source records attributed to Garner, K..

4 recordsLinked to original sources

Cytoplasmic localization of 5hmC reveals RNA hydroxymethylation in breast cancer

DNA methylation (5-methylcytosine, 5mC) is a major repressive epigenetic mark that can be iteratively oxidized by ten-eleven-translocation (TET) enzymes to 5-hydroxymethylcytosine (5hmC); beyond DNA, modifications of RNA can also affect transcript stability and processing, yet RNA hydroxymethylation remains unexplored in breast cancer (BC). Here, we identify a quantifiable cytoplasmic 5hmC signal in BC cell lines and, more prominently, in human BC tissue, using immunoassays and digital pathology, and confirm with an adapted, RNase-sensitive, RNA-specific ELISA that this signal reflects hydroxymethylation of total RNA and mRNA. Cytoplasmic 5hmC was significantly enriched in triple-negative (ER-/PR-/HER2-) and grade 3 tumors, and correlated with increased cytoplasmic TET2/TET3 in tissue and TET3 upregulation in TCGA. As a leading candidate mechanism, TET3 expression was associated with RNA-processing/spliceosomal transcripts, and TET3 knockdown in three TNBC cell lines reduced a subset of these targets, independently supported across 70 DepMap breast cancer lines.

cancer biology↗

Hemispheric laterality of the putamen predicts pseudoneglect

Healthy individuals tend to exhibit a subtle leftward attentional bias, a phenomenon termed pseudoneglect. While this bias is thought to reflect a right-hemisphere dominance when allocating spatial attention, the contribution of subcortical structures remains poorly understood. Although lesion and neuroimaging studies in clinical populations have implicated asymmetries in the basal ganglia and thalamus to dysfunction in spatial attention, it remains unclear whether naturally occurring subcortical asymmetries in healthy individuals predict behavioural biases in spatial attention. In this study, we investigated whether volumetric asymmetries in subcortical structures are associated with biases in spatial attention in a non-clinical population. This was achieved by using the landmark task to assess spatial biases, alongside acquiring T1-weighted MRI data from 44 healthy participants. The subcortical regions were segmented using the FIRST algorithm to estimate the volumetric asymmetry of specific regions. We found that variability in pseudoneglect was predicted by the degree of leftward lateralisation of putamen volume, indicating that the putamen contributes to the magnitude of spatial attention biases. This also suggests that the left putamen may support right-hemisphere neocortical dominance through the indirect pathway. These findings bridge anatomical and behavioural measures, highlighting the functional relevance of subcortical asymmetry in shaping attentional processes in the healthy brain. Our findings pave the way for early diagnosis of neurological disorders associated with subcortical atrophies including Parkinsons Disease and dementia. Significance StatementHemispheric dominance in cortical networks shape attentional biases, but the role of subcortical structures remains poorly understood. Here we show that natural variability in the lateralisation of the putamen predicts individual differences in pseudoneglect--a subtle leftward bias in spatial attention observed in healthy adults. Using MRI and psychophysics, we demonstrate that greater leftward putamen asymmetry is associated with stronger leftward bias, independent of eye dominance and microsaccadic behaviour, and moderated by handedness. These findings reveal a structural subcortical basis for attentional asymmetries and suggest that simple behavioural measures could serve as non-invasive markers of early subcortical changes relevant to disorders such as Parkinsons disease, Alzheimers disease, and ADHD.

neuroscience↗

Modulation of alpha oscillations by attention is predicted by hemispheric asymmetries of subcortical regions.

Evidence suggests that subcortical structures play a role in high-level cognitive functions such as the allocation of spatial attention. While there is abundant evidence in humans for posterior alpha band oscillations being modulated by spatial attention, little is known about how subcortical regions contribute to these oscillatory modulations, particularly under varying conditions of cognitive challenge. In this study, we combined MEG and structural MRI data to investigate the role of subcortical structures in controlling the allocation of attentional resources by employing a cued spatial attention paradigm with varying levels of perceptual load. We asked whether hemispheric lateralization of volumetric measures of the thalamus and basal ganglia predicted the hemispheric modulation of alpha-band power. Lateral asymmetry of the globus pallidus, caudate nucleus, and thalamus predicted attention-related modulations of posterior alpha oscillations. When the perceptual load was applied to the target and the distractor was salient caudate nucleus asymmetry predicted alpha-band modulations. Globus Pallidus was predictive of alpha-band modulations when either the target had a high load, or the distractor was salient, but not both. Finally, the asymmetry of the thalamus predicted alpha band modulation when neither component of the task was perceptually demanding. In addition to delivering new insight into the subcortical circuity controlling alpha oscillations with spatial attention, our finding might also have clinical applications. We provide a framework that could be followed for detecting how structural changes in subcortical regions that are associated with neurological disorders can be reflected in the modulation of oscillatory brain activity.

neuroscience↗

Cognitive capacity limits are remediated by practice-induced plasticity in a striatal-cortical network

Humans show striking limitations in information processing when multitasking, yet can modify these limits with practice. Such limitations have been linked to a frontal-parietal network, but recent models of decision-making implicate a striatal-cortical network. We adjudicated these accounts by investigating the circuitry underpinning multitasking in 100 individuals and the plasticity caused by practice. We observed that multitasking costs, and their practice induced remediation, are best explained by modulations in information transfer between the striatum and the cortical areas that represent stimulus-response mappings. Specifically, our results support the view that multitasking stems at least in part from taxation in information sharing between the putamen and pre-supplementary motor area (pre-SMA). Moreover, we propose that modulations to information transfer between these two regions leads to practice-induced improvements in multitasking. Significance statementHumans show striking limitations in information processing when multitasking, yet can modify these limits with practice. Such limitations have been linked to a frontal-parietal network, but recent models of decision-making implicate a striatal-cortical network. We adjudicated these accounts by investigating the circuitry underpinning multitasking in 100 individuals and the plasticity caused by practice. Our results support the view that multitasking stems at least in part from taxation in information sharing between the putamen and pre-supplementary motor area (pre-SMA). We therefore show that models of cognitive capacity limits must consider how subcortical and cortical structures interface to produce cognitive behaviours, and we propose a novel neurophysiological substrate of multitasking limitations.

neuroscience↗