Biology subjects

Loo, S. K.

Publications and source records attributed to Loo, S. K..

3 recordsLinked to original sources

bioRxiv2026

Effects of Instructional Context on Neural Features of Attention during Learning Activities in Children with and without ADHD

Attention is foundational to learning, yet the extent to which features of the instructional environment differentially shape attentional engagement is not well understood. Here we leveraged mobile EEG and video-coded behavioral observation to examine attentional engagement in 6 to 10 years old children with and without a diagnosis of ADHD across instructional conditions varying in delivery modality (video watching, online, in-person) and management of learning (teacher-led versus student-led). EEG measures, including alpha-band (8-12Hz) oscillations, spectral slope and offset, and behavioral measures of active engagement (AE%), passive engagement (PE%), fidgeting, off-task behavior, were examined as a function of instructional context. Attentional engagement, as indicated by higher AE%, lower alpha power, flatter spectral slope and lower offset, was greatest in student-led learning, followed by teacher-led in person learning, synchronous online learning, and asynchronous learning, respectively. Child by instructional context interactions revealed that patterns of attentional engagement were largely consistent regardless of diagnosis, with group effects observed for motor behaviors (PE%, fidgeting) but not for measures of visual attention. Similarly, age showed only main effects, whereby older children showed higher passive engagement, lower fidgeting and off-task behavior, flatter spectral slope, and lower offset. The results underscore: (i) the importance of considering environmental context, such as instructional modality and management of learning, when examining mechanisms of attention and individual differences therein, and (ii) the value of recording multiple behavioral and neural measures, as not all indices commonly assumed to reflect attention capture the same underlying processes.

neuroscience↗

bioRxiv2025

CASTOR1: A Novel Tumor Suppressor Linking mTORC1 and KRAS Pathways in Tumorigenesis and Resistance to KRAS-Targeted Therapies in Non-Small Cell Lung Cancer

Cytosolic arginine sensor for mTORC1 Subunit 1 (CASTOR1) functions as a key regulator of mechanistic target of rapamycin complex 1 (mTORC1) signaling. Despite its frequent dysregulation in cancers via mechanisms such as KSHV microRNA-mediated inhibition or AKT-driven phosphorylation and degradation, the impact of CASTOR1 loss on tumor initiation and progression remains poorly understood. Here, we identify CASTOR1 as a critical tumor suppressor in non-small cell lung cancer (NSCLC) by demonstrating that its genetic ablation amplifies tumorigenesis in a KRAS-driven genetically engineered mouse model (GEMM;LSL-KRASG12D). CASTOR1 deficiency markedly enhances lung tumor incidence, accelerates tumor progression, and increases proliferative indices in KRASG12D-driven tumors (KRASG12D;C1KO) compared to CASTOR1 wild type (WT) tumors (KRASG12D;C1WT). Advanced-stage tumors exhibit elevated phosphorylated CASTOR1 (pCASTOR1) and reduced total CASTOR1 levels, suggesting active degradation during tumorigenesis. Mechanistically, CASTOR1 loss amplifies mTORC1 signaling, as evidenced by heightened phosphorylation of downstream effectors 4EBP1 and S6, while also augmenting AKT and ERK activation, uncovering a crosstalk between the PI3K/AKT/mTORC1 and KRAS/ERK pathways. Furthermore, CASTOR1 ablation induces genome instability, which may contribute to enhanced tumor incidence and progression. Importantly, CASTOR1 deficiency confers resistance to KRASG12D-specific inhibitors, while over half of KRASG12D;C1WT tumors also display resistance. Organoids derived from KRASG12D;C1KO and KRASG12D;C1WT tumors reveal a correlation between KRAS inhibitor resistance and hyperactivation of mTORC1, with mTORC1 and PI3K inhibitors sensitizing resistant tumors to KRASG12D-targeted therapies. These findings position CASTOR1 as a novel tumor suppressor that modulates mTORC1 and KRAS signaling to constrain NSCLC progression. Our study further highlights the therapeutic potential of combining mTORC1 or ERK inhibitors with KRAS-targeted therapies for NSCLC characterized by hyperactive KRAS signaling and impaired CASTOR1 activity. HighlightsO_LICASTOR1 functions as a tumor suppressor in NSCLC by limiting KRAS-driven tumor initiation and progression. C_LIO_LICASTOR1 is frequently lost or inactivated in wild-type tumors during tumor progression, contributing to advanced-stage malignancies. C_LIO_LICASTOR1 deficiency amplifies mTORC1 signaling and enhances PI3K/AKT and KRAS/ERK crosstalk, driving tumorigenesis and resistance to KRAS-specific inhibitors. C_LIO_LICombining mTORC1 or PI3K inhibitors with KRAS-targeted therapies effectively overcomes resistance in KRAS-driven NSCLC. C_LI

cancer biology↗

bioRxiv2017

Atypical functional connectivity in adolescents and adults with persistent and remitted ADHD

We previously provided initial evidence for cognitive and event-related potential markers of persistence/remission of attention-deficit/hyperactivity disorder (ADHD) from childhood to adolescence and adulthood. In this follow-up study, using a novel brain-network connectivity approach, we aimed to examine whether functional connectivity reflects a marker of ADHD remission, or an enduring deficit unrelated to ADHD outcome. High-density EEG was recorded in 110 adolescents and young adults with childhood ADHD (87 persisters, 23 remitters) and 169 typically-developing individuals during an arrow-flanker task, eliciting cognitive control. Functional connectivity was quantified with network-based graph-theory metrics before target onset (pre-stimulus), during target processing (post-stimulus) and in the degree of change between pre-stimulus/post-stimulus. ADHD outcome was examined with parent-reported symptoms and impairment using both a categorical (DSM-IV) and a dimensional approach. Graph-theory measures converged in indicating that, compared to controls, ADHD persisters showed increased connectivity in pre-stimulus theta, alpha and beta and in post-stimulus beta (all p<.01), and reduced pre-stimulus/post-stimulus change in theta connectivity (p<.01). In the majority of indices showing ADHD persister-control differences, ADHD remitters differed from controls (all p<.05), but not from persisters. Similarly, connectivity measures were not associated with continuous outcome measures of ADHD symptoms and impairment in participants with childhood ADHD. These findings indicate that adolescents and young adults with persistent and remitted ADHD share atypical over-connectivity profiles and reduced ability to modulate connectivity patterns with task demands, compared to controls. Brain connectivity impairments may represent enduring deficits in individuals with childhood ADHD irrespective of diagnostic status in adolescence/young adulthood.

neuroscience↗