Biology subjects

Mohammadi, H.

Publications and source records attributed to Mohammadi, H..

7 recordsLinked to original sources

bioRxiv2026

A nonlinear time-domain finite-element model of the human middle ear subjected to intense sound waves

Computational models of the middle ear are typically developed within the linear range of the middle ear's response, which corresponds to typical sounds in daily life. Understanding middle-ear biomechanics under high-intensity sounds is also important for assessing potential auditory damage under adverse conditions. In this study, a finite-element (FE) model of the human middle ear plus the external ear canal is presented, employing a first-order Ogden hyperelastic material formulation and time-domain nonlinear analysis to capture nonlinear deformation of soft tissues and the resulting middle-ear response. The model was analyzed using pure-tone pressure excitations applied at the ear canal entrance over the 80 Hz to 8 kHz frequency range and 110 to 180 dB sound pressure levels (SPL). The ear canal pressure near the tympanic membrane (TM) and full-field three-dimensional response of the middle ear structures were examined. Across the investigated frequency range, the simulated middle-ear motion exhibited a transition from predominantly piston-like behavior at low frequencies, up to 1 kHz, to increasingly intricate multi-modal and multi-directional vibration patterns at higher frequencies. Nonlinear behaviors became increasingly significant at high frequencies and high stimulus levels, including compressive/expansive pressure-displacement relationships, waveform distortions, and the emergence of non-harmonic spectral components. The model developed in this study provides a computational framework for studying nonlinear sound transmission through the middle ear and its implications for high-intensity acoustic exposure. The findings contribute to a better understanding of middle-ear mechanics under adverse conditions and support future investigations of acoustic trauma and hearing protection strategies.

bioengineering↗

bioRxiv2025

React-to-Me: A Conversational Interface for Interactive Exploration of the Reactome Pathway Knowledgebase.

The Reactome Pathway Knowledgebase (www.reactome.org) provides expert-curated information on human biological pathways, molecular interactions, and disease mechanisms. However, its complex data model and keyword-based search interface present accessibility barriers for non-expert users. In contrast, general-purpose conversational AI systems offer intuitive natural language interfaces but lack the domain-specificity, transparent sourcing, and factual reliability required for scientific applications. To address this gap, we developed React-to-Me (https://reactome.org/chat), a domain-specific conversational assistant that enables users to query Reactome using natural language while maintaining scientific rigor and source traceability. React-to-Me integrates hybrid retrieval-augmented generation (RAG) with constrained language model generation to ensure that all responses are grounded in curated Reactome content and directly linked to corresponding knowledgebase entries. When internal coverage is insufficient, the system defers to trusted external biomedical sources rather than generating speculative or unverified content. Computational benchmarking confirmed that combining semantic vector search with keyword-based matching substantially improved contextual grounding and factual precision relative to dense-only retrieval baselines. In blinded expert evaluations, grounded responses were more likely to receive higher quality ratings than ungrounded counterparts, with significant gains in factual accuracy, biological specificity, and mechanistic depth. User surveys further indicated strong satisfaction with ease of use, citation reliability, and factual accuracy. These findings demonstrate that domain-specific grounding can markedly improve the reliability and usability of conversational AI for biological knowledge exploration. React-to-Me provides a transparent and scientifically robust interface for accessing and exploring Reactome content and is freely available at https://reactome.org/chat. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=130 SRC="FIGDIR/small/693752v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@1ef0d73org.highwire.dtl.DTLVardef@15c2d4dorg.highwire.dtl.DTLVardef@a2338corg.highwire.dtl.DTLVardef@e639fd_HPS_FORMAT_FIGEXP M_FIG C_FIG

scientific communication and education↗

bioRxiv2025

Multicellular Calcium Waves in Cancer-Associated Fibroblasts Regulate Neuronal Mimicry and Anisotropy Leading to Immune Exclusion

Stromal barriers exclude CD8+ T cells from accessing cancer cells and hamper immune-mediated tumour control. Through multi-pronged analysis of tumours that transition from immune inflamed to immune excluded, we reveal that the formation of stromal barriers is associated with the acquisition of neuronal gene expression programmes in cancer-associated fibroblasts (CAFs), including TUBB3 expression. This leads to neuronal mimicry, with stromal barrier formation underpinned by coordinated transient bursts of intracellular calcium release, similar to those observed in neuronal tissue. Blockade of calcium release through either pharmacological or molecular interventions, such as STC2 depletion, prevents CAF alignment and the build-up of CD8+ T cells at stromal boundaries. Nintedanib treatment prevents neuronal mimicry and restores immune-mediated tumour control. Thus, we uncover unexpected mimicry of neuronal behaviour in CAFs, document the mechanism by which it leads to immune exclusion, and identify ways to prevent the induction of neuronal mimicry and restore immune-mediated tumour control. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=95 SRC="FIGDIR/small/684281v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@938ee5org.highwire.dtl.DTLVardef@18a9c48org.highwire.dtl.DTLVardef@11a5982org.highwire.dtl.DTLVardef@ea6a79_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2025

Cell migration sculpts evolutionary dynamics favouring therapy resistance in lung cancer

The evolution of cancer undermines the long-term efficacy of therapy. In this study, we combine experimental, computational, and clinical data analysis to investigate factors influencing the competition of subclones in lung cancer. Lineage tracing reveals unexpected variation in the long-term fate of neutral subclones, with subclones arising near the edge of tumours being favoured. Low levels of cell migration and cell mixing lead to high cell densities in the interior of the tumour that suppress proliferation. Using agent-based modelling and in silico analysis we inferred the extent of cell mixing in human tumours from the TRACERx lung cancer study. This reveals correlations between Epithelial to Mesenchymal Transition (EMT), stromal fibroblasts and levels of cell mixing. Experimental analysis confirms that both TGF{beta}-driven EMT and stromal fibroblasts reduce the variability in subclone fate and promote subclone mixing. Moreover, mixing favours clonal sweeps by subclones resistant to therapy-induced cell killing. Together, these analyses demonstrate that EMT and stromal fibroblasts sculpt tumour evolution by promoting cell mixing and thereby favour the rapid dominance of therapy resistant subclones.

cancer biology↗

bioRxiv2024

Sex-specific effects of intensity and dose of physical activity on BOLD-fMRI cerebrovascular reactivity and cerebral pulsatility

Cerebrovascular reactivity (CVR) and cerebral pulsatility (CP) are important indicators of cerebrovascular health and have been shown to be associated with physical activity (PA). Sex differences have been shown to influence the impact of PA on cerebrovascular health. However, the sex-specific effects of PA on CP and CVR, particularly in relation to intensity and dosage of PA, remains unknown. Thus, this cross-sectional study aimed to evaluate the sex-specific effects of different intensities and doses of PA on CVR and CP. The Human Connectome - Aging dataset was used, including 626 participants (350 females, 276 males) aged 36-85 (mean age: 58.8 {+/-} 14.1 years). Females were stratified into premenopausal and postmenopausal groups to assess the potential influence of menopausal status. Novel tools based solely on resting state fMRI data were used to estimate both CVR and CP. The International Physical Activity Questionnaire was used to quantify weekly self-reported PA as metabolic equivalent of task. Results indicated that both sexes and menopausal subgroups revealed negative linear relationships between relative CVR and PA. Furthermore, females presented a unique non-linear relationship between relative CVR and total PA in the cerebral cortex. In females, there were also relationships with total and walking PA in occipital and cingulate regions. In males, we observed relationships between total or vigorous PA and CVR in parietal and cingulate regions. Sex-specific effects were also observed with CP, whereby females benefited across a greater number of regions and intensities than males, especially in the postmenopause group. Overall, males and females appear to benefit from different amounts and intensities of PA, with menopause status significantly influencing the effect of PA on cerebrovascular outcomes, underscoring the need for sex-specific recommendations in promoting cerebrovascular health.

neuroscience↗

bioRxiv2020

Magnesium Sulfate Attenuates Lethality and Oxidative Damage Induced by Different Models of Hypoxia in Mice

Mg2+ is an important cation in our body. It is an essential co-factor for many enzymes. Despite many works, nothing is known about the protective effects of MgSO4 against hypoxia-induced lethality and oxidative damage in brain mitochondria. In this study, antihypoxic and antioxidative activities of MgSO4 were evaluated by three experimental models of induced-hypoxia (asphyctic, haemic, and circulatory) in mice. Mitochondria protective effects of MgSO4 were evaluated in mice brain after induction of different models of hypoxia. Antihypoxic activity was especially pronounced in asphyctic hypoxia where MgSO4 at dose 600 mg/kg showed the same activity as phenytoin which used as a positive control (P< 0.001). In the haemic model, MgSO4 at all used doses significantly prolonged latency of death. In circulatory hypoxia, MgSO4 (600 mg/kg) doubles the survival time. MgSO4 significantly decreased Lipid peroxidation, protein carbonyl, and improved mitochondrial function and glutathione content in brain mitochondria compared to control groups. The results obtained in this study showed that MgSO4 administration has protective effects against lethality induced by different models of hypoxia and improves brain mitochondria oxidative damage.Competing Interest StatementThe authors have declared no competing interest.View Full Text

pharmacology and toxicology↗

bioRxiv2017

Modelling of the cardiopulmonary responses to maximal aerobic exercise in patients with cystic fibrosis

Cystic fibrosis (CF) is a debilitating chronic condition, which requires complex and expensive disease management. Exercise has now been recognised as a critical factor in improving health and quality of life in patients with CF. Hence, cardiopulmonary exercise testing (CPET) is used to determine aerobic fitness of young patients as part of the clinical management of CF. However, at present there is a lack of conclusive evidence for one limiting system of aerobic fitness for CF patients at an individual patient level.\n\nHere, we perform detailed data analysis that allows us to identify important systems-level factors that affect aerobic fitness. We use patients data and principal component analysis to confirm the dependence of CPET performance on variables associated with ventilation and metabolic rates of oxygen consumption. We find that the time at which participants cross the anaerobic threshold (AT) is well correlated with their overall performance. Furthermore, we propose a predictive modelling framework that captures the relationship between ventilatory dynamics, lung capacity and function and performance in CPET within a group of children and adolescents with CF. Specifically, we show that using Gaussian processes (GP) we can predict AT at the individual patient level with reasonable accuracy given the small sample size of the available group of patients. We conclude by presenting future perspectives for improving and extending the proposed framework.\n\nOur modelling and analysis have the potential to pave the way to designing personalised exercise programmes that are tailored to specific individual needs relative to patients treatment therapies.

physiology↗