Biology subjects

Hussan, J. R.

Publications and source records attributed to Hussan, J. R..

4 recordsLinked to original sources

bioRxiv2026

A DNA mass conservation mechanism underpins cellular mtDNA number regulation

The nucleoid, which houses mtDNA within the mitochondrial matrix, is a phase-separation-driven biomolecular condensate capable of carrying out a broad spectrum of complex functions, including DNA replication, transcription, and repair. Here, we show by data-driven computational modelling that the concept of a tightly regulated intranucleoid de-oxynucleoside triphoshate (dNTP) pool explains the observation that the number of mtDNA base pairs per cell is conserved in human hybrid cell lines regardless of the size of the introduced mitochondrial genome. This concept is then used to address the enigmatic observation that the synthesis rate of the short DNA strand called 7S DNA, which is part of the triple-stranded displacement loop (D-loop) found in the main noncoding region of mtDNA, increases dramatically during the cell cycle. Collectively, our quantitative analyses suggest that the mammalian mtDNA replisome uses a strictly controlled intranucleoid dNTP pool based predominantly on the synthesis and degradation of 7S DNA. One potential evolutionary explanation for this mechanism is that it offers an energetic advantage by enabling greater reliance on the salvage pathway for mtDNA replication.

molecular biology↗

bioRxiv2026

Genomic regulation of chemo-mechanical stability in plant-derived extracellular vesicles: a multiscale model of composite reinforcement

Plant-derived extracellular vesicles (PDEVs) have emerged as superior candidates for oral drug delivery, exhibiting a gastrointestinal survivability that significantly exceeds that of mammalian exosomes or synthetic liposomes. However, the biophysical rules governing how plant genomic regulation translates into this exceptional mechanical resilience remain unknown. Here, we present a predictive multiscale model of plant-derived extracellular vesicles, linking a parameterised genetic state space to emergent mesoscale mechanics via supra-molecular coarse-grained molecular dynamics (SCG-MD). We demonstrate that the upregulation of sterol methyltransferases (SMT) during the plants theoretical Defence state drives the formation of a phase-separated composite architecture, where rigid domains occupying approximately 36% of the membrane surface area effectively arrest crack propagation. This state achieves a critical rupture tension of 367.0 {+/-} 0.7 mN m-1 corresponding to a 39% increase over the wild-type Ripening state. Crucially, we find that chemical composition alone is insufficient for this reinforcement; vesicles with actively sorted lipid domains (Seeded topology) outperform randomised mixtures (Spontaneous topology) by 23% at identical concentrations. Furthermore, while fluid vesicles stiffen reactively under gastric acid shock (pH 2.5) due to the steric jamming of thermodynamically neutralised headgroups, the Defence state exhibits mechanical homeostasis. These findings suggest that PDEVs function as genetically tunable composite materials, offering a design blueprint for next-generation bio-inspired drug delivery vectors. Ultimately, these theoretical indices provide a predictive biophysical framework awaiting empirical confirmation via in vitro nanomechanical assays.

plant biology↗

bioRxiv2026

A Computational Functional Tissue Unit of the Human Myometrium for In Silico Study of Gestational Excitability and Pathophysiology

The human myometrium undergoes a dramatic transformation during pregnancy, shifting from quiescence to highly synchronised contractility. Understanding this transition is crucial for addressing pathologies such as preterm labour and dystocia (ineffective labour). We present a multi-scale Functional Tissue Unit (FTU) model allowing us to investigate how tissue-level excitability emerges from single-cell electrophysiology. We propose a heterogeneity-driven selection mechanism, wherein a sub-population of cells with high intrinsic excitability dynamically emerges as pace-makers. This active process complements passive depolarisation by interstitial cells, allowing spontaneous excitation to arise without a fixed anatomical pacemaker. Stochastic simulations produced an average burst frequency of 0.047 Hz ({approx}2.8 bursts per minute), closely consistent with clinical measurements of 2-3 contractions per minute during active labour, and demonstrated that this function is robust to spatial topological changes. Furthermore, implementation of inflammation-induced remodelling simulations successfully linked molecular-level changes to a preterm labour phenotype. This model provides a platform for investigating uterine contractility and serves as a component for future whole-organ Physiome models.

bioengineering↗

bioRxiv2025

High reelin expression can explain why the entorhinal cortex is a cradle for Alzheimer's disease

The entorhinal cortex (EC) plays a crucial role in memory functions. Long before the clinical symptoms of Alzheimers disease (AD) emerge, it has already undergone significant degeneration, making it a primary site for the onset of the disease. The reasons for this remain elusive. It was recently shown that in layer II neurons of the anterolateral entorhinal cortex (alECLII neurons), which are especially prone to display a very early increase in intracellular amounts of amyloid-{beta} peptide (A{beta}) and hyperphosphorylated tau protein (p-tau), the large glycoprotein reelin binds to A{beta}, suggesting that reelin functions as a sink for intracellular A{beta}. The expression of reelin is extraordinarily high in alECLII neurons compared to most other cortical neurons. Here, we show by computational modeling that, in a senescent physiology predisposing to frequent inflammation-driven A{beta}42 production bursts, the intracellular amount of A{beta}42-reelin complexes can accumulate to extraordinarily high levels in alECLII neurons compared to the vast majority of cortical neurons. This explains experimental data showing that intracellular accumulations of A{beta}42 positive material ranged from 20 to 80% of the total cytoplasmic volume in EC neurons from patients with sporadic AD. We also show that this extreme intracellular aggregation can cause the accumulation of detrimental hyperphosphorylated tau fragments. Thus, when exposed to recurrent AD-promoting stress, the exceptionally high expression of reelin in alECLII neurons appears to be instrumental in their early demise relative to other cortical neurons.

neuroscience↗