Biology subjects

Menon, N.

Publications and source records attributed to Menon, N..

4 recordsLinked to original sources

bioRxiv2026

Orientation Dependence of R2' in White Matter: Digital Characterization, Modelling and Implications for Studying Brain Physiology

PurposeR2*, the transverse relaxation rate, reflects local magnetic field inhomogeneities from susceptibility differences with R2, the reversible component sensitive to blood oxygenation. Orientation dependence of R2 and R2* in white matter (WM) are attributed primarily to myelin, with vascular contributions to R2 uncharacterized. This study examined WM R2 orientation dependence, evaluated existing models, and developed an improved model combining myelin and blood. MethodsSimulations used BOLDswimsuite with 2D WM voxels (5,000 fibres). Spin-echo (TE = 70ms) and gradient-echo (TE = 35ms) signals were simulated across 30 fibre orientations (0{degrees}-90{degrees}). R2' was calculated as R2* - R2. Oxygenation, cerebral blood volume (CBV), vessel size, and vessel geometry were varied. Four published models and a novel Myelin-Blood model were fitted to R2' data and compared using R2 and RMSE. ResultsR2 and R2* showed strong orientation dependence. Parallel and mixed vessel geometries produced greater R2' amplitude and orientation dependence than random geometries; decreasing oxygenation and increasing CBV amplified orientation effects. Vessel size altered peak locations. Existing vascular models performed poorly, and the Empirical Myelin Model erred near the magic angle. The Myelin-Blood model provided near-perfect fits (mean R2 = 0.999, RMSE = 0.007 Hz), reducing RMSE by ~74%. DiscussionWM R2' cannot be explained by vascular or myelin effects alone. Myelin is the primary determinant of orientation dependence, but vascular contributions were evident near the magic angle and low oxygenation. The Myelin-Blood model improves WM R2 characterisation and may reduce orientation-dependent bias and improve interpretation of WM BOLD fMRI signals.

neuroscience↗

bioRxiv2026

Hemodynamic Responses in the White Matter (WM): Reduced Blood Flow in Deep WM During Hypercapnia Revealed by Multi-Delay pCASL in Healthy Young Adults

The white matter (WM) cerebrovascular response remains poorly understood compared with grey matter (GM), partly due to technical challenges in perfusion quantification. Previous studies of cerebrovascular reactivity (CVR) have mostly been performed using BOLD MRI, and it is unclear to what extent they reflect changes in cerebral blood flow (CBF). In this work, we used multi-delay pseudo-continuous arterial spin labeling (pCASL) to quantify hypercapnia-induced CBF changes ({Delta}CBF) while accounting for regional variability in arterial transit time. Twenty-five healthy young adults underwent MRI during normocapnia and hypercapnia (inhalation of a 4% CO2 gas mixture). Hypercapnia induced robust positive {Delta}CBF in cortical GM (26.7 {+/-} 13.5%), superficial WM (17.2 {+/-} 12.6%), periventricular regions (13.6 {+/-} 10.6%), and subcortical GM (25.7 {+/-} 14.1%) (all p < 0.0001). In contrast, deep WM exhibited a near-zero group-mean CBF response (1.0 {+/-} 8.9%, p = 0.57), with 10 of 25 participants demonstrating negative {Delta}CBF. Negative CBF responses were consistently localized to the corona radiata, centrum semiovale, and optic radiation. Quality-control analyses showed that deep-WM {Delta}CBF estimates are robust, supporting the reliability of these findings. Moreover, across tissue compartments, higher baseline CBF was associated with reduced hypercapnic responsiveness, and deep-WM responses were strongly coupled with cortical GM responses across individuals. These results demonstrate that hypercapnia-induced cerebrovascular responses are highly heterogeneous across tissue depths and provide evidence that negative CBF responses can occur in healthy deep WM in the presence of vasodilation elsewhere. The findings challenge the assumption of uniformly positive perfusion responses during hypercapnia and support a potential role for flow redistribution arising from regional differences in vascular resistance and reserve capacity.

neuroscience↗

bioRxiv2024

Caught in the act of triplication: TNF superfamily

In humans, the signaling mechanisms of the 19 paralogs of the tumor necrosis factor superfamily (TNFSF) and the 29 receptor paralogs of the tumor necrosis factor receptor superfamily (TNFRSF) are extensively characterized because of their therapeutic relevance. The functional expansion of TNFSF in vertebrates from a single ancestral gene through successive duplication events is also well established. However, apart from the first identification of a TNFSF homolog, Eiger (dmEiger), in Drosophila melanogaster in 2002, together with its receptor homologs Wengen (dmWgn) and Grindelwald (dmGrnd), this signaling system has remained largely unexplored in invertebrates. More recently, the implication of an Eiger homolog in Plasmodium resistance in malaria vectors has further highlighted the need for a systematic investigation of this pathway in lower invertebrates. Structural comparison of the dmEiger-dmGrnd complex with the canonical 3:3 ligand-receptor configuration observed in human TNFSF-TNFRSF signaling suggests either conservation of this signaling modality since before the bilaterian split or convergent evolution of a similar architecture in both branches. The recent explosion in high-quality proteomes spanning diverse phyla, together with advances in protein-complex prediction using AlphaFold-multimer, now enables large-scale exploration of ligand-receptor evolution across invertebrates. Here, we analyzed 148 near-complete proteomes spanning major invertebrate phyla and identified 290 TNFSF, 336 wengen (wgn), and 115 grindelwald (grnd) homologs, including homologs from lower invertebrates. Structural characterization of 140 selected complexes using AlphaFold and AlphaFold-multimer revealed several key findings: (i) TNFSF and TNFRSF homologs are present in majority of the phyla under invertebrates (ii) the canonical 3:3 ligand-receptor signaling configuration is conserved across invertebrates; (iii) orthologs of 25 out of the 26 genes implicated in TNF signaling pathways are present in lower invertebrates; and (iv) signaling through grnd-like receptors containing a single cysteine-rich domain with CXXCXXXC signature is the predominant signaling mode in invertebrates and becomes highly prevalent in Arthropoda. We also elaborate a hypothesize on the evolutionary trajectories toward a genetically parsimonious signaling by this complex system before functional expansion in vertebrates and species diversification in Arthropoda.

bioinformatics↗

bioRxiv2020

Phylotype-Level Characterization of Complex Lactobacilli Communities Using a High-Throughput, High-Resolution Phenylalanyl-tRNA Synthetase (pheS) Gene Amplicon Sequencing Approach

The lactobacilli to date encompass more than 270 closely related species that were recently re-classified into 26 genera. Because of their relevance to industry, there is a need to distinguish between closely related, yet metabolically and regulatory distinct species, e.g., during monitoring of biotechnological processes or screening of samples of unknown composition. Current available methods, such as shotgun metagenomics or rRNA-based amplicon sequencing have significant limitations (high cost, low resolution, etc.). Here, we generated a lactobacilli phylogeny based on phenylalanyl-tRNA synthetase (pheS) genes and, from it, developed a high-resolution taxonomic framework which allows for comprehensive and confident characterization of lactobacilli community diversity and structure at the species-level. This framework is based on a total of 445 pheS gene sequences, including sequences of 277 validly described species and subspecies (out of a total of 283, coverage of 98%). It allows differentiation between 263 lactobacilli species-level clades out of a total of 273 validly described species (including the proposed species L. timonensis) and a further two subspecies. The methodology was validated through next-generation sequencing of mock communities. At a sequencing depth of [~]30,000 sequences, the minimum level of detection was approximately 0.02 pg per l DNA (equalling approximately 10 genome copies per {micro}l template DNA). The pheS approach along with parallel sequencing of partial 16S rRNA genes revealed a considerable lactobacilli diversity and distinct community structures across a broad range of samples from different environmental niches. This novel complementary approach may be applicable to industry and academia alike. IMPORTANCESpecies within the former genera Lactobacillus and Pediococcus have been studied extensively at the genomic level. To accommodate for their exceptional functional diversity, the over 270 species were recently re-classified into 26 distinct genera. Despite their relevance to both academia and industry, methods that allow detailed exploration of their ecology are still limited by low resolution, high cost or copy number variations. The approach described here makes use of a single copy marker gene which outperforms other markers with regards to species-level resolution and availability of reference sequences (98% coverage). The tool was validated against a mock community and used to address lactobacilli diversity and community structure in various environmental matrices. Such analyses can now be performed at broader scale to assess and monitor lactobacilli community assembly, structure and function at the species (in some cases even at sub-species) level across a wide range of academic and commercial applications.

microbiology↗