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#dynamics

48 posts9 participants1 post today
Public
Rxiv mechanobio

📰 "Longitudinal study of the udder microbiome of Norwegian red dairy cows using metataxonomic and shotgun metagenomic approaches: Insights into pathogen-driven microbial adaptation and succession"
biorxiv.org/content/10.1101/20 #Dynamics #Cell

bioRxiv · Longitudinal study of the udder microbiome of Norwegian red dairy cows using metataxonomic and shotgun metagenomic approaches: Insights into pathogen-driven microbial adaptation and successionBovine mastitis remains the most significant disease affecting dairy herds globally, driven by its multi etiological nature and the complex dynamics of udder immunity and infection. While research addressing the microbial and immunological aspects of the bovine udder is limited, optimizing the udder microbiome has emerged as a promising strategy for preventing mastitis. This longitudinal study aimed to investigate the udder microbiome throughout lactation using both metataxonomic and shotgun metagenomic approaches, including analysis at the metagenome assembled genome (MAG) level. The use of such methodologies provide a deeper understanding of the microbial composition and dynamics within the udder, bridging critical gaps in knowledge and revealing potential interactions between the microbiota and host. Milk samples were collected from 342 individual quarters of 24 Norwegian Red dairy cows. Significant variations in somatic cell count and microbiota composition were observed across lactation stages. Quarters with low somatic cell count (< 100,000 cells/mL) were notably higher during early lactation (80%) and mid-lactation (78.9%) compared to dry-off (53.1%) and late lactation (53%), with high somatic cell count (> 100,000 cells/mL) observed in 20 and 47% of samples. Diversity indices based on Shannon and Simpson metrics indicated significant effects of lactation stage, somatic cell count, and individual animal variability on microbial diversity. PERMANOVA analyses confirmed that individual animal variability (15.73%) and lactation period (5.52%) were the strongest factors influencing microbiota structure, with dysbiosis linked to mastitis-causing pathogens contributing 7.17% of the variance. Key pathogens identified included E. faecalis, S. aureus, S. uberis, and S. chromogenes, with persistent infections observed for S. aureus and S. chromogenes, but not S. uberis. Samples with low somatic cell count were enriched in beneficial genera such as Corynebacterium, Bradyrhizobium, and Lactococcus, while Staphylococcus predominated in milk samples with high somatic cell count. Dimensionality reduction with tSNE and integration with culturomics enhanced milk microbiota classification, providing novel insights into udder microbiota dynamics and their role in bovine mastitis. Metagenomic shotgun sequencing revealed pathogen-specific metabolic signatures in the bovine mammary gland, identifying 289 MetaCyc pathways. Genome-centric analysis reconstructed 142 metagenome-assembled genomes, including 26 from co-assembly and 116 from individual assembly. Multi-locus sequence typing, virulence factors, and antimicrobial resistance gene profiling provided insights into pathogen adaptation and persistence in the bovine mammary gland. Notably, 27 bacteriocin gene clusters and 322 biosynthetic gene clusters were predicted using genome mining tools. Our findings contribute to the establishment of pathogen based therapies and enhance our understanding of the milk microbiome, which remains far from fully characterized. Such insights are vital for developing effective strategies to combat mastitis and improve dairy cattle health. ### Competing Interest Statement The authors have declared no competing interest.
Public
Rxiv mechanobio

📰 "Disease-causing MFN2 mutants impair mitochondrial fission dynamics by distinct DRP1 dysregulation"
biorxiv.org/content/10.1101/20 #Dynamics #Cell

bioRxiv · Disease-causing MFN2 mutants impair mitochondrial fission dynamics by distinct DRP1 dysregulationMitochondria undergo fusion and fission. While DRP1 regulates fission, fusion is controlled by OPA1, MFN1, and MFN2. The balance between these processes and the crosstalk between machineries remains poorly understood. MFN2 mutations cause Charcot-Marie-Tooth disease type 2A (CMT2A), affecting mitochondrial fusion and morphology. However, their role in fission is unclear. Using skin fibroblasts from CMT2A patients (L248H and M376V MFN2 mutations) and wild-type mouse embryonic fibroblasts expressing these variants we studied how MFN2 mutations impact mitochondrial dynamics beyond fusion. We analysed mitochondrial morphology and dynamics, by live-cell confocal microscopy, and tested fusion/fission protein levels, oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and oxidative phosphorylation complex subunits. MFN2 mutations impaired mitochondrial fusion and displayed distinct effects on fission and cellular metabolism. L248H-expressing cells showed hyper-elongated mitochondria, impaired fission, and increased OCR, while, M376V cells exhibited fragmentation, enhanced fission, and elevated ECAR. These effects correlated with differential Drp1 phosphorylation. Our findings demonstrate that MFN2 mutants differentially influences fission and metabolism, highlighting the need to consider these effects in therapies aimed at modulating mitochondrial dynamics. ### Competing Interest Statement The authors have declared no competing interest.
Public
Rxiv mechanobio

📰 "LUZP1 Regulates Dendritic Spine Maturation and Synaptic Plasticity in the Hippocampal Dentate Gyrus of Mice"
doi.org/doi:10.1523/JNEUROSCI.
pubmed.ncbi.nlm.nih.gov/401805
#Cytoskeleton #Dynamics

Journal of Neuroscience · LUZP1 Regulates Dendritic Spine Maturation and Synaptic Plasticity in the Hippocampal Dentate Gyrus of MiceLeucine zipper protein 1 (LUZP1) functions in the maintenance and dynamics of the cytoskeleton by interacting with actin and microtubules. Deficiency or mutation of LUZP1 is associated with brain developmental disorders, however, its precise role in brain function remains unclear. We showed that LUZP1 localizes to actin and is highly expressed in CaMKIIα-expressing neurons within the mouse hippocampal dentate gyrus. Depletion of LUZP1 impedes dendritic spine maturation, which is characterized by excess immature filopodia and loss of mature mushroom spines both in vitro and in vivo. LUZP1 knockdown reduces spontaneous electrical activity and synaptic plasticity in hippocampal neurons. Conditional deletion of LUZP1 in CaMKIIα-expressing neurons causes impaired learning and memory behavior in mice of both sexes. Mechanistically, LUZP1 control dendritic maturation by directly interacting with filamin A and modulating the Rac1-PAK1 signaling pathway. These findings shed light on the role of LUZP1 in regulating synaptic plasticity and brain function. Significance Statement Unraveling brain development and function is critical for understanding neurological disorders. The discovery of LUZP1 sheds light on cytoskeletal dynamics, crucial for brain health. LUZP1's interaction with actin and its link to brain disorders highlight its neural importance. LUZP1's presence in specific hippocampal neurons, notably CaMKIIα-expressing ones, provides insights into synaptic function. Depletion of LUZP1 hinders dendritic spine maturation, impacting synaptic activity and plasticity, crucial for neural connectivity. The association of LUZP1 with learning impairments upon deletion in neurons emphasizes its role in cognition. Its involvement in the Rac1-PAK1 pathway offers novel insights into dendritic maturation and synaptic plasticity regulation. These discoveries illuminate LUZP1's significant impact on synaptic plasticity and brain function, hinting at potential interventions for LUZP1-associated neurological disorders.
Public
Rxiv mechanobio

📰 "Investigation of the influence of electrostatic excitation on instabilities and electron transport in ExB plasma configurations"
arxiv.org/abs/2504.02750 #Physics.Plasm-Ph #Dynamics #Cell

arXiv logo
arXiv.orgInvestigation of the influence of electrostatic excitation on instabilities and electron transport in ExB plasma configurationsPartially magnetized plasmas in ExB configurations - where the electric and magnetic fields are mutually perpendicular - exhibit a cross-field transport behavior, which is widely believed to be dominantly governed by complex instability-driven mechanisms. This phenomenon plays a crucial role in a variety of plasma technologies, including Hall thrusters, where azimuthal instabilities significantly influence electron confinement and, hence, device performance. While the impact of prominent plasma instabilities, such as the electron cyclotron drift instability (ECDI) and the modified two-stream instability (MTSI) on cross-field transport of electron species is well recognized and widely studied, strategies for actively manipulating these dynamics remain underexplored. In this study, we investigate the effect of targeted wave excitation on instability evolution and electron transport using one- and two-dimensional particle-in-cell simulations of representative plasma discharge configurations. A time-varying electric field is applied axially to modulate the spectral energy distribution of the instabilities across a range of forcing frequencies and amplitudes. Our results reveal that the so-called "unsteady forcing" can both suppress and amplify instability modes depending on excitation parameters. In particular, across both 1D and 2D simulation configurations, forcing near 40 MHz effectively reduces ECDI amplitude and decreases axial electron transport by about 30%, while high-frequency excitation near the electron cyclotron frequency induces spectral broadening, inverse energy cascades, and enhanced transport. These findings point to the role of nonlinear frequency locking and energy pathway disruption as mechanisms for modifying instability-driven transport. Our results offer insights into potential pathways to enhance plasma confinement and control in next-generation ExB devices.
Public
Rxiv mechanobio

📰 "From short-sighted to far-sighted: A comparative study of recursive machine learning approaches for open quantum systems"
arxiv.org/abs/2504.02218 #Physics.Chem-Ph #Dynamics #Matrix

arXiv logo
arXiv.orgFrom short-sighted to far-sighted: A comparative study of recursive machine learning approaches for open quantum systemsAccurately modeling open quantum system dynamics is crucial for advancing quantum technologies, yet traditional methods struggle to balance accuracy and efficiency. Machine learning (ML) provides a promising alternative, particularly through recursive models that predict system evolution based on past history. While these models have shown success in predicting single observables, their effectiveness in more complex tasks, such as forecasting the full reduced density matrix (RDM), remains unclear. We extend history-based recursive ML approaches to complex quantum systems, comparing four physics-informed neural network (PINN) architectures: (i) single-RDM-predicting PINN (SR-PINN), (ii) SR-PINN with simulation parameters (PSR-PINN), (iii) multi-RDMs-predicting PINN (MR-PINN), and (iv) MR-PINN with simulation parameters (PMR-PINN). These models are applied to the spin-boson (SB) model and the Fenna-Matthews-Olson (FMO) complex. Our results show that SR-PINN and PSR-PINN, constrained by a narrow history window, fail to capture complex quantum evolution, leading to unstable long-term predictions, especially in nonlinear and highly correlated dynamics. In contrast, MR-PINN and PMR-PINN improve accuracy by extending the forecast horizon, incorporating long-range correlations, and reducing error propagation. Surprisingly, explicitly including simulation parameters such as temperature and reorganization energy in PSR-PINN and PMR-PINN does not consistently enhance accuracy and can even reduce performance, suggesting that these effects are already encoded in the RDM evolution. These findings highlight the limitations of short-sighted recursive forecasting and demonstrate the superior stability and accuracy of far-sighted approaches for long-term predictions.
Public
Rxiv mechanobio

📰 "Identifying potential biomarkers of response to CCR5Δ32 HSCT in HIV infection"
biorxiv.org/content/10.1101/20 #Dynamics #Cell

bioRxiv · Identifying potential biomarkers of response to CCR5Δ32 HSCT in HIV infectionWhile HIV can be effectively suppressed to a chronic, mostly asymptomatic infection with combination antiretroviral therapy (cART), a cure is still needed. Hematopoietic stem cell transplantation (HSCT) from HIV-resistant donors has shown promise and has resulted in HIV remission in five patients. However, this treatment strategy does not guarantee HIV remission; six other patients who received a similar transplant had poor outcomes and died within a year of treatment. These different outcomes may be due to inter-individual differences in HIV infection dynamics that result in heterogeneity of therapeutic responses to HSCT. Using a previously published mechanistic model of HIV infection and virtual populations calibrated from patient data, we performed simulations to understand how different parameters in the model can influence the observed heterogeneity in therapeutic outcomes across virtual patient populations. Our simulations confirmed that discontinuation of cART, without HSCT, always leads to viral rebound, and that time to rebound differs across patients due to the interindividual variability (IIV) in underlying infection dynamics. Extending the duration of cART only slightly increased the predicted median time to rebound and its variance. By contrast, HSCT followed by cART cessation led to HIV remission, but only for a subset of the virtual patients. The proportion of patients predicted to go into remission depends directly on the ratio of donor to host cell immune cells in the post-HSCT chimeric immune system. Of the mechanistic model parameters, no single parameter determined whether a patient was a responder or a non-responder; rather, the interactions between multiple model parameters were crucial in driving treatment responses. In contrast, virtual equivalents of clinically accessible observations, e.g. viral load and cell populations at specific times, were shown to be better predictors than mechanistic model parameters in separating patients into non-responding (viral rebound) and responding (no rebound) clusters. ### Competing Interest Statement The authors have declared no competing interest.
Public
Rxiv mechanobio

📰 "Vitronectin binding affinity and cell viability effect of novel mechanotherapy drugs for neuroblastoma"
biorxiv.org/content/10.1101/20 #Dynamics #Cell

bioRxiv · Vitronectin binding affinity and cell viability effect of novel mechanotherapy drugs for neuroblastomaHigh-risk neuroblastoma (HR-NB) is an aggressive form of childhood cancer with a five-year survival rate of under 50%, underscoring the need for more efficacious and less toxic treatments. The glycoprotein Vitronectin (VN) has been linked to poor prognosis in patients with HR-NB, and thus inhibitors of its function represent a promising avenue for molecular mechanotherapy. The present study sought to investigate the binding affinity between the somatomedin B (SMB) domain of VN and natural compounds derived from medicinal plants. The therapeutic potential of α-amyrin (AMY), lupeol (LUP), and Olax chalcone A (Olax CHA) was tested in combination with an integrin antagonist of VN, cilengitide (CLG), using the SK-N-BE(2) HR-NB cell line as a model. Molecular docking studies indicated a potential for protein-ligand interactions for all selected compounds, of which CLG demonstrated the most favorable binding free energy (kcal/mol), followed by LUP, AMY and Olax CHA. Molecular dynamics simulations demonstrated that the SMB domain of VN initially exhibited flexibility, with alpha carbon-root mean square deviation (RMSD) stabilizing at approximately 1.8-2.1 A. While all compounds demonstrated a dose-dependent decrease in SK-N-BE(2) cell viability, CLG exhibited higher IC50 values. Although the combination of AMY and LUP with CLG did not result in enhanced efficacy, Olax CHA exhibited a superior antiproliferative effect with higher IC50 values than AMY and LUP, and additionally showed potential synergism with CLG, suggesting a more effective therapeutic approach. This work provides valuable insights into the potential use of mechanotherapy drugs and natural products to enhance HR-NB treatment that can be expanded in future studies centered on Olax CHA. ### Competing Interest Statement The authors have declared no competing interest.
Public
Rxiv mechanobio

📰 "Identity-Based Language Shift Modeling"
arxiv.org/abs/2504.01552 #Physics.Soc-Ph #Dynamics #Math.Na #Cs.Na #Cell

arXiv logo
arXiv.orgIdentity-Based Language Shift ModelingThe preservation of endangered languages is a widely discussed issue nowadays. Languages represent essential cultural heritage and can provide valuable botanical, biological, and geographical information. Therefore, it is necessary to develop efficient measures to preserve and revitalize endangered languages. However, the language shift process is complex and requires an interdisciplinary approach, including mathematical modeling techniques. This paper develops a new mathematical model that extends previous works on this topic. We introduce the factor of ethnic identity, which is a proxy for a more complex nexus of variables involved in an individual's self-identity and/or a group's identity. This proxy is socially constructed rather than solely inherited, shaped by community-determined factors, with language both indexing and creating the identity. In our model, we divide speakers into groups depending on with which language they identify themselves with. Moreover, every group includes monolinguals and bilinguals. The proposed model naturally allows us to consider cases of language coexistence and describe a broader class of linguistic situations. For example, the simulation results show that our model can result in cyclic language dynamics, drawing a parallel to cell population models. In this way, the proposed mathematical model can serve as a useful tool for developing efficient measures for language preservation and revitalization.
Public
Rxiv mechanobio

📰 "A kinetic model of jet-corona coupling in accreting black holes"
arxiv.org/abs/2504.01062 #Physics.Plasm-Ph #Astro-Ph.He #Dynamics #Cell

arXiv logo
arXiv.orgA kinetic model of jet-corona coupling in accreting black holesBlack hole (BH) accretion disks are often coupled to ultramagnetized and tenuous plasma coronae close to their central BHs. The coronal magnetic field can exchange energy between the disk and the BH, power X-ray emission, and lead to jetted outflows. Up until now, the coronal physics of BH accretion has only been studied using fluid modeling. We construct the first model of a BH feeding on a zero-net-flux accretion disk corona based on kinetic plasma physics. This allows us to self-consistently capture how collisionless relativistic magnetic reconnection regulates the coronal dynamics. We present global, axisymmetric, general relativistic particle-in-cell simulation of a BH coupled, via a series of magnetic loops, to a razor-thin accretion disk. We target the jet-launching regime where the loops are much larger than the BH. We ray-trace high-energy synchrotron lightcurves and track the flow of Poynting flux through the system, including along specific field-line bundles. Reconnection on field lines coupling the BH to the disk dominates the synchrotron output, regulates the flux threading the BH, and ultimately untethers magnetic loops from the disk, ejecting them via a magnetically striped Blandford-Znajek jet. The jet is initially Poynting-dominated, but reconnection operates at all radii, depleting the Poynting power logarithmically in radius. Coronal emission and jet launch are linked through reconnection in our model. This link might explain coincident X-ray flaring and radio-jet ejections observed during hard-to-soft X-ray binary state transitions. It also suggests that striped jet launch could be heralded by a bright coronal counterpart. Our synchrotron signatures resemble variability observed from the peculiar changing-look AGN, 1ES 1927+654, and from Sagittarius A*, hinting that processes similar to our model may be at work in these contexts.
Public
Rxiv mechanobio

📰 "AquIRE reveals multiple mechanisms of clinically induced RNA damage and the conservation and dynamics of glycoRNAs"
biorxiv.org/content/10.1101/20 #Dynamics #Cell

bioRxiv · AquIRE reveals multiple mechanisms of clinically induced RNA damage and the conservation and dynamics of glycoRNAsRNA is subject to many modifications, from small chemical changes such as methylation through to conjugation of biomolecules such as glycans. As well as these endogenously written modifications, RNA is also exposed to damage induced by its environment. Certain clinical compounds are known to drive covalent modifications of RNA with a growing appreciation for how these affect function. To understand the regulation of these modifications we need a reliable, sensitive and rapid methodology for their quantification. Thus, we developed AquIRE and applied it to the analysis of drug-induced RNA damage, showing this to be widespread with intricate temporal dynamics. Using the same methodology we identify RNA:protein crosslinking and the rewriting of the epitranscriptome as a consequence of clinical RNA damage. We also demonstrate how liquid-liquid phase separation increases RNA damage and expand the horizons of the glycoRNA world across the kingdoms of life and into cell-free glycoRNA. ### Competing Interest Statement The authors have declared no competing interest.
Public
Rxiv mechanobio

📰 "Nanopore direct RNA sequencing (DRS) of MS2 bacteriophages in E.coli throughout its life cycle reveals a complex transcriptional activity to control and maintain its growth"
biorxiv.org/content/10.1101/20 #Dynamics #Cell

bioRxiv · Nanopore direct RNA sequencing (DRS) of MS2 bacteriophages in E.coli throughout its life cycle reveals a complex transcriptional activity to control and maintain its growthThe RNA bacteriophage MS2 is a positive single stranded RNA phage that infects the bacterium E. coli and is one of the most crucial and representative model organisms in molecular biology and virology mimicking eukaryotic viruses. Previous research revealed translational control and feedback inhibitions in the MS2 life cycle. However, the dynamics of its transcriptional activity and replication during the life cycle within the bacteria is still relatively unknown. Here, we employed Nanopore Direct RNA sequencing (DRS) to investigate the transcriptome and epitranscriptome landscape of the MS2 in infected E. coli throughout its life cycle and detailed the dynamics of MS2 replication in real-time. We discovered that MS2 phages sustain a high level of transcriptional activity within the bacterial cell. We found large amounts of subgenomic small RNA transcripts containing the coat−encoding region. We found hybrid reads and mutations due to the error−prone activity of the MS2 replicase complex. We evidenced that RNA modification is conserved throughout the entire life cycle in full−length transcripts without the acquisition of new modifications whereas small transcripts did acquire and remove modified sites. The conserved sequence (5″−ΨU−3″) and secondary structure (stem-loops) of Ψ installation sites were the most amenable to RNA modification. Our investigation reveals a more complex transcriptional dynamics of MS2 phages within E. coli to maintain its growth and replicate under host pressure. ### Competing Interest Statement The authors have declared no competing interest.
Public
Rxiv mechanobio

📰 "KIF20A cooperates with Myosin II to drive endosomal carriers fission and protein trafficking"
biorxiv.org/content/10.1101/20 #Cytoskeleton #Dynamics #Myosin

bioRxiv · KIF20A cooperates with Myosin II to drive endosomal carriers fission and protein traffickingFormation of membrane transport carrier relies on cytoskeleton coordination, however how microtubules and actin dynamics cooperate is still poorly understood. In this study, we reveal a novel mechanism by which a kinesin, KIF20A, regulates actomyosin and branched actin dynamics in coordination with Myosin II, facilitating the fission of transport intermediates at early endosomes. We demonstrate that KIF20A is required for maintaining endosomal homeostasis as its inhibition results in the enlargement of both early and late endosomes. Moreover, our findings demonstrate that KIF20A is required for the proper trafficking of Transferrin (Tf), and for ensuring the correct plasma membrane localization of β1 Integrin, a key protein that is critical for cell adhesion and migration. Collectively, these results highlight a new pivotal role of KIF20A as a key regulator of endosomal dynamics and function, contributing to metastatic potential. ### Competing Interest Statement The authors have declared no competing interest.
Public
Rxiv mechanobio

📰 "Substrate stiffness regulates triple-negative breast cancer signaling through CXCR4 receptor dynamics"
biorxiv.org/content/10.1101/20 #Extracellular #Mechanical #Dynamics

bioRxiv · Substrate stiffness regulates triple-negative breast cancer signaling through CXCR4 receptor dynamicsBiophysical properties of the extracellular matrix (ECM), such as mechanical stiffness, directly regulate behaviors of cancer cells linked to cancer initiation and progression. Cells sense and respond to ECM stiffness in the context of dynamic changes in biochemical inputs, such as growth factors and chemokines. While commonly studied as isolated inputs, mechanisms by which combined effects of mechanical stiffness and biochemical factors affect functions of cancer cells remain poorly defined. Using a combination of elastically supportive surface (ESS) culture dishes with defined stiffnesses and single-cell imaging, we report here that culturing cells on a stiff (28 kPa) versus soft (1.5 kPa) substrate increases CXCR4 and EGFR expression and promotes greater ligand-dependent internalization of CXCR4. In addition to increased CXCR4 expression, a stiff ECM also increases basal activation of Akt and ERK as well as signaling through these kinases in response to CXCL12-α and EGF and promotes migration of triple negative breast cancer (TNBC) cells. These data implicate receptor dynamics as a key mediator of Akt and ERK signaling as a mechanism for adverse effects of enhanced ECM stiffness on disease progression in TNBC. ### Competing Interest Statement The authors have declared no competing interest.
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