Biology subjects

Varma, G.

Publications and source records attributed to Varma, G..

5 recordsLinked to original sources

bioRxiv2026

The Canadian Pediatric Imaging Platform (C-PIP) Reference Sample: Neuroimaging Protocol and Cross-site Validation for Harmonized Multimodal Pediatric Imaging

Understanding how the human brain matures from infancy through adolescence is essential for identifying factors that influence health outcomes. Magnetic resonance imaging (MRI) provides powerful tools for characterizing structural, microstructural, functional, and metabolic aspects of brain development; however, many pediatric imaging studies are constrained by small sample sizes, limited geographic diversity, lack of longitudinal measurement, restricted age ranges, and heterogeneous acquisition protocols. While recent large-scale neuroimaging consortia have begun to address these challenges, such resources remain limited in the Canadian context, creating a critical gap. The Canadian Pediatric Imaging Platform (C-PIP) has developed a multisite neuroimaging framework across three of Canada's largest pediatric hospitals: Alberta Children's Hospital (Calgary), Centre Hospitalier Universitaire Sainte-Justine (Montreal), and the Hospital for Sick Children (Toronto). These three sites were united through a national initiative, leveraging high-performance MRI systems to accelerate Canadian neurodevelopmental research. In addition, C-PIP has implemented a centralized data sharing infrastructure to facilitate open science and collaborative research across institutions. Here, we describe the development and implementation of a multimodal MRI acquisition protocol designed to support multimodal longitudinal studies of typical and atypical brain development spanning infancy through adolescence. Within-site stability and cross-site stability of C-PIP core MRI sequences were evaluated using a travelling-participant study. The C-PIP MRI protocol establishes a harmonized, multisite imaging framework that supports large-scale investigations of pediatric brain development and disorders.

neuroscience↗

bioRxiv2025

Standardization of postmortem human brainstem along the rostrocaudal axis to accommodate for heterogeneity in samples

Human postmortem brain tissues provide an indispensable resource that is crucial for the understanding of neurological conditions, whether related to pathology subtype, burden, distribution or cell-type specificity. Pathology staging protocols provide guidelines for standardized sampling of brain tissues, but cover only a subset of regions affected by pathologies. Thus, to study how various neuropathologies and cell types in highly specialized circuit nodes correlate with functions specifically served by these nodes, additional protocols are necessary. This especially applies to brainstem tissues due to the small dimension of regions of interest and interindividual variability of specimens, whether due to procurement or intrinsic differences. Here we systematically assessed factors contributing to heterogeneity in the length of whole brainstem samples and then presented a standardized approach to reproducibly assign rostrocaudal levels, with standardization relying upon readily identifiable internal landmarks. We validated this approach using postmortem MRI imaging. Standardized brainstem length correlated positively with subject height and negatively with subject age of death. By providing a reference series, reproducible levels can be assigned to individual histological sections or MRI images, i.e. when full brainstem specimens are not available and irrespective of platform, promoting reproducibility.

neuroscience↗

bioRxiv2025

Single-nuclear transcriptomics of lymphedema-associated adipose reveals a pro-lymphangiogenic stromal cell population

Chronic lymphedema is a progressive, disfiguring disease that results from dysfunction of the lymphatic vasculature, causing distal accumulation of interstitial fluid, localized development of tissue edema, and expansion of subcutaneous adipose tissue (SAT). As the molecular mechanisms governing SAT remodeling in this disease are unclear, we performed single-nucleus RNA sequencing on paired control and affected SAT biopsies from patients with unilateral lymphedema. Lymphedema samples were characterized by expansion of SAA+ adipocytes, pro-adipogenic stem cells, and proliferation of lymphatic capillaries. A GRIA1+ lymphedema-enriched stromal cell population expressing VEGFC, ADAMTS3, and CCBE1 was identified, suggesting an enhanced axis of communication between adipose stem and progenitor cells (ASPCs) and lymphatic endothelial cells. Furthermore, lymphedema ASPC-conditioned media promoted lymphatic endothelial tube elongation and proliferation in vitro. These findings indicate a critical role for ASPCs in regulating adipocyte differentiation and lymphatic vascular remodeling in lymphedema, and provide a valuable resource for better understanding this disease.

cell biology↗

bioRxiv2020

A Motion Correction Strategy for Multi-Contrast based 3D parametric imaging: Application to Inhomogeneous Magnetization Transfer (ihMT)

PurposeTo propose an efficient retrospective image-based method for motion correction of multi-contrast acquisitions with a low number of available images (MC-MoCo) and evaluate its use in 3D inhomogeneous Magnetization Transfer (ihMT) experiments in the human brain. MethodsA framework for motion correction, including image pre-processing enhancement and rigid registration to an iteratively improved target image, was developed. The proposed method was compared to Motion Correction with FMRIBs Linear Image Registration Tool (MCFLIRT) function in FSL over 13 subjects. Native (pre-correction) and residual (post-correction) motions were evaluated by means of markers positioned at well-defined anatomical regions over each image. ResultsBoth motion correction strategies significantly reduced inter-image misalignment, and the MC-MoCo method yielded significantly better results than MCFLIRT. ConclusionMC-MoCo is a high-performance method for motion correction of multi-contrast volumes as in 3D ihMT imaging.

neuroscience↗

bioRxiv2017

Independence Between Pre-mRNA Splicing And De Novo DNA Methylation In An Isogenic Minigene Resource

Actively transcribed genes adopt a unique chromatin environment with characteristic patterns of enrichment. Within gene bodies, H3K36me3 and cytosine DNA methylation are elevated at exons of spliced genes and have been implicated in the regulation of pre-mRNA splicing. H3K36me3 is further responsive to splicing, wherein splicing inhibition led to a redistribution and general reduction over gene bodies. In contrast, little is known of the mechanisms supporting elevated DNA methylation at actively spliced genic locations. Recent evidence associating the de novo DNA methyltransferase Dnmt3b with H3K36me3-rich chromatin raises the possibility that genic DNA methylation is influenced by splicing-associated H3K36me3. Here, we report the generation of an isogenic resource to test the direct impact of splicing on chromatin. A panel of minigenes of varying splicing potential were integrated into a single FRT site for inducible expression. Profiling of H3K36me3 confirmed the established relationship to splicing, wherein levels were directly correlated with splicing efficiency. In contrast, DNA methylation was equivalently detected across the minigene panel, irrespective of splicing and H3K36me3 status. In addition to revealing a degree of independence between genic H3K36me3 and DNA methylation, these findings highlight the generated minigene panel as a flexible platform for the query of splicing-dependent chromatin modifications.

molecular biology↗