Biology subjects

Pugh, K.

Publications and source records attributed to Pugh, K..

5 recordsLinked to original sources

bioRxiv2024

Simulations probe the role of space in the interplay between drug-sensitive and drug-resistant cancer cells

The interplay between drug-sensitive and drug-resistant cancer cells has been observed to impact cell-to-cell interactions in experimental settings. However, the role that space plays in these interactions remains unclear. In this study, we develop mathematical models to investigate how spatial factors affect cell-to-cell competition between drug-sensitive and drug-resistant cancer cells in silico. We develop two baseline models to study cells from the epithelial FaDu cell line subjected to two drugs, specifically the ATR inhibitor ceralasertib and the PARP inhibitor olaparib, that target DNA damage response pathways. Our baseline models are: (1) a temporally resolved ordinary differential equation (ODE) model, and (2) a spatio-temporally resolved agent-based model (ABM). The models simulate cells in well-mixed and spatially structured cell systems, respectively. The ODE model is calibrated against in vitro data and is thereafter mapped onto the baseline ABM which, in turn, is extended to enable a simulation-based investigation on how spatial factors impact cell-to-cell competition. Simulation results from the extended ABMs demonstrate that the in silico treatment responses are simultaneously affected by: (i) the initial spatial cell configurations, (ii) the initial fraction of drug-resistant cells, (iii) the drugs to which cells express resistance, (iv) drug combinations, (v) drug doses, and (vi) the doubling time of drug-resistant cells compared to the doubling time of drug-sensitive cells. These results reveal that spatial structures of the simulated cancer cells affect both cell-to-cell interactions, and the impact that these interactions have on the ensuing population dynamics. This leads us to suggest that the role that space plays in cell-to-cell interactions should be further investigated and quantified in experimental settings.

cancer biology↗

bioRxiv2020

The impact of second language immersion: Evidence from a bi-directional longitudinal cross-linguistic study

Brice et al. (2019) presented data from the first epoch of a longitudinal study of the neurobiological underpinnings of first-language (L1) and second-language (L2) processing. Results showed a similar network of activation for reading across L1 and L2, as well as significant convergence of print and speech processing across a network of left-hemisphere regions in both L1 and L2 with greater activation and convergence for L2 in anterior regions, and greater activation and convergence for L1 in posterior regions of the reading network. Here, we present the first look at longitudinal changes in these effects. L2 showed relatively few changes in activation, with some shifts in the weighting between ventral and dorsal processing. L1, however, showed more widespread differences in processing, suggesting that the neurobiological footprint of reading is dynamic, with both L1 and L2 impacting each other. Print/speech convergence showed very little longitudinal change, suggesting that it is a stable marker of the differences in L1 and L2 processing.

neuroscience↗

bioRxiv2020

Thalamus is a common locus of reading, arithmetic, and IQ: Analysis of local intrinsic functional properties

Neuroimaging studies of basic achievement skills, reading and arithmetic, often control for the effect of IQ to identify unique neural correlates of each skill. This may underestimate possible effects of common factors between achievement and IQ measures on neuroimaging results. Here, we simultaneously examined achievement (reading and arithmetic) and IQ measures in young adults, aiming to identify MRI correlates of their common factors. Resting-state fMRI (rs-fMRI) data were analyzed using two metrics assessing local intrinsic functional properties; regional homogeneity (ReHo) and fractional amplitude low frequency fluctuation (fALFF), measuring local intrinsic functional connectivity and intrinsic functional activity, respectively. ReHo highlighted the thalamus/pulvinar (a subcortical region implied for selective attention) as a common locus for both achievement skills and IQ. More specifically, the higher the ReHo values, the lower the achievement and IQ scores. For fALFF, the left superior parietal lobule, part of the dorsal attention network, was positively associated with reading and IQ. Collectively, our results highlight attention-related regions, particularly the thalamus/pulvinar as a key region related to individual differences in performance on all the three measures. ReHo in the thalamus/pulvinar may serve as a tool to examine brain mechanisms underlying a comorbidity of reading and arithmetic difficulties, which could co-occur with weakness in general intellectual abilities. HighlightsO_LIAchievement (reading; arithmetic) and IQ measures are simultaneously examined; not controlling for IQ. C_LIO_LIReHo and fALFF are used to examine local intrinsic functional connectivity and activity, respectively. C_LIO_LIHigher ReHo in thalamus/pulvinar is associated with lower performance on all the three measures. C_LIO_LIHigher fALFF in the left superior parietal lobule is associated with higher word reading and IQ. C_LI

neuroscience↗

bioRxiv2019

Universal brain signature of emerging reading in two contrasting languages

Despite dissimilarities among scripts, a universal hallmark of literacy in adults is the convergent brain activity for print and speech. Little is known, however, how early it emerges. Here we compare speech and orthographic processing systems in two contrasting languages, Polish and English, in 100 7-year-old children performing identical fMRI tasks. Results show limited language variation, with speech-print convergence evident mostly in left fronto-temporal perisylvian regions. Correlational and intersect analyses revealed subtle differences in the strength of this coupling in several regions of interest. Specifically, speech-print convergence was higher for transparent Polish than opaque English in right temporal area, associated with phonological processing. Conversely, speech-print convergence was higher for English than Polish in left fusiform, associated with visual reading. We conclude that speech-print convergence is a universal marker of reading even at the beginning of reading acquisition while minor variations can be explained by the differences in the orthographic transparency.

neuroscience↗

bioRxiv2019

Associations between Processing Speed and Psychopathology in a Transdiagnostic, Pediatric Sample

ObjectiveThe present study sought to examine the relationships between processing speed (PS), mental health disorders, and learning disorders. Prior work has tended to explore relationships between PS deficits and individual diagnoses (i.e., anxiety, autism, ADHD, depressive) in isolation of one another, often relying on relatively modest sample sizes. In contrast, the present work simultaneously investigated associations between PS deficits and these diagnoses, along with specific learning disabilities (i.e., reading, math), in a large-scale, transdiagnostic, community self-referred sample.\n\nMethodA total of 843 children, ages 8-16 were included from the Healthy Brain Network (HBN) Biobank. Given the presence of four PS tasks in HBN, principal component analysis (PCA) was employed to create a composite measure that represented the shared variance of the four PS tasks, referred to as PC1. Intraclass correlation coefficient (ICC) between the four PS measures, as well as PC1, were calculated to assess reliability. We then used multiple linear regression models to assess specific relationships between PS deficits and psychiatric diagnoses.\n\nResultsICCs were moderate between WISC-V tasks (0.663), and relatively modest between NIH Toolbox Pattern Comparison and other PS scales (0.14-0.27). Regression analyses revealed specific significant relationships between PS and reading and math disabilities, ADHD-inattentive type (ADHD-I), and ADHD-combined type (ADHD-C). Secondary analyses accounting for inattention dimensionally diminished associations with ADHD-C, but not ADHD-I or specific learning disability subtypes. The present study did not find a significant relationship with Autism Spectrum Disorder after accounting for inattentive symptoms. Consistent with prior work, demographic variables, including sex, socioeconomic status, and motor control exhibited independent relationships with PC1 as well.\n\nDiscussionThis study provided a comprehensive examination of PS, mental health disorders, and learning disabilities through a transdiagnostic approach. Implications for understanding how PS interacts with a highly heterogeneous childhood sample, as well as the need for increased focus on detection of affected populations are discussed.

developmental biology↗