Biology subjects

Prem, S.

Publications and source records attributed to Prem, S..

3 recordsLinked to original sources

bioRxiv2026

Charting neuroimaging-based head circumference and cranial shape across development

Quantitative assessment of head growth supports early detection of neurological disease, yet current clinical practice relies on manual measurements that are variable, anatomically limited, and difficult to scale. Here we introduce a fully automated imaging-native framework (CranioTrace) that transforms routine neuroimaging into standardized, population-referenced markers of cranial development. By integrating topology-constrained segmentation, contour regularization, and geometry-based quality control for automated slice selection, CranioTrace robustly extracts head circumference and cranial morphology from heterogeneous MRI and CT data without manual intervention. The framework enabled construction of sex-specific population growth models across pediatric development in a dataset comprising 9,685 scans spanning birth to early adulthood across 25 cohorts. Imaging-derived head circumference shows strong agreement with tape measurements across independent datasets, high reproducibility (intraclass correlation up to 0.99), and consistent performance across modalities. Beyond conventional head circumference, CranioTrace quantifies cranial shape and asymmetry, capturing developmental dynamics that are not accessible through conventional measurements. Population modeling reveals rapid early-life expansion followed by nonlinear deceleration and stable sex differences. Application to neurogenetic cohorts identifies disease-consistent shifts in growth trajectories: head circumference was higher in neurofibromatosis type 1 and 16p11.2 deletion and lower in 22q11.2 deletion and 16p11.2 duplication. By converting clinical imaging archives into scalable cranial phenotypes linked to probabilistic reference models, CranioTrace provides a foundation for imaging-based growth charting, integrated skull-brain phenotyping, and precise assessment of neurodevelopment.

neuroscience↗

bioRxiv2022

Dysregulation of mTOR Signaling Mediates Common Neurite and Migration Defects in Both Idiopathic and 16p11.2 Deletion Autism Neural Precursor Cells

Autism spectrum disorder (ASD) is defined by common behavioral characteristics, raising the possibility of shared pathogenic mechanisms. Yet, vast clinical and etiological heterogeneity suggests personalized phenotypes. Surprisingly, our iPSC studies find that six individuals from two distinct ASD-subtypes, idiopathic and 16p11.2 deletion, have common reductions in neural precursor cell (NPC) neurite outgrowth and migration even though whole genome sequencing demonstrates no genetic overlap between the datasets. To identify signaling differences that may contribute to these developmental defects, an unbiased phospho-(p)-proteome screen was performed. Surprisingly despite the genetic heterogeneity, hundreds of shared p-peptides were identified between autism subtypes including the mTOR pathway. mTOR signaling alterations were confirmed in all NPCs across both ASD-subtypes, and mTOR modulation rescued ASD phenotypes and reproduced autism defects in controls. Thus, our studies demonstrate that genetically distinct ASD subtypes have common defects in neurite outgrowth and migration which are driven by the shared pathogenic mechanism of mTOR signaling dysregulation.

neuroscience↗

bioRxiv2022

A role for brassinosteroid signaling in decision-making processes in the Arabidopsis seedling

Plants often adapt to adverse conditions via differential growth, whereby limited resources are discriminately allocated to optimize the growth of one organ at the expense of another. Little is known about the decision-making processes that underly differential growth. In this study, we developed a screen to identify decision making mutants by deploying two tools that have been used in decision theory: a well-defined yet limited budget, as well as conflict-of-interest scenarios. A forward genetic screen that combined light and water withdrawal was carried out. This identified BRASSINOSTEROID INSENSITIVE 2 (BIN2) alleles as decision mutants with "confused" phenotypes. An assessment of organ and cell length suggested that hypocotyl elongation occurred predominantly via cellular elongation. In contrast, root growth appeared to be regulated by a combination of cell division and cell elongation or exit from the meristem. Brassinosteroid signalling mutants were most severely impaired in their ability to adjust cell geometry in the hypocotyl and cell elongation as a function of distance from the quiescent centre in the root tips. This study describes a novel paradigm for root growth under limiting conditions, which depends not only on hypocotyl-versus-root trade-offs in the allocation of limited resources, but also on an ability to deploy different strategies for root growth in response to multiple stress conditions.

plant biology↗