"Static magnetic field inhibits epithelial mesenchymal transition and metastasis of glioma"
https://doi.org/doi:10.1038/s41598-025-96047-x
https://pubmed.ncbi.nlm.nih.gov/40216876/
#CellMigration #Cell
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"Secreted LysM proteins are required for niche competition and full virulence in Pseudomonas savastanoi during host plant infection"
https://www.biorxiv.org/content/10.1101/2025.04.11.648327v1?rss=1 #CellDivision #Cell
bioRxiv · Secreted LysM proteins are required for niche competition and full virulence in Pseudomonas savastanoi during host plant infectionPhytopathogenic bacteria secrete diverse virulence factors to manipulate host defenses and establish infection. Characterization of the type III secretion system (T3SS)- and HrpL-independent secretome (T3-IS) in Pseudomonas savastanoi pv. savastanoi (Psv), the causal agent of olive knot disease, identified five secreted LysM-containing proteins (LysM1–LysM5) associated with distinct physiological processes critical for infection. Functional predictions from network analyses suggest that LysM1, LysM2, and LysM4 may participate in type IV pilus-related functions, while LysM3 and LysM5 are likely to possess peptidoglycan hydrolase domains critical for cell division. Supporting these predictions, loss of LysM1 function resulted in impaired twitching and swimming motility, highlighting a role in pilus-mediated movement and early host colonization. In contrast, mutants lacking LysM3 or LysM5 exhibited pronounced filamentation and defective bacterial division, underscoring their essential role in septation, a process crucial for both in planta fitness and tumor formation. Structural modeling and protein stability assays demonstrate that LysM3 interacts with peptidoglycan fragments such as tetra-N-acetylglucosamine and meso-diaminopimelic acid, as well as with zinc ions, through conserved LysM and M23 domains. LysM3 also displayed selective bacteriostatic activity against co-inhabiting Gram-negative bacterial competitors, such as Pantoea agglomerans and Erwinia toletana. Our findings highlight the relevance of LysM proteins in maintaining bacterial integrity, motility, and competitive fitness, which are crucial for successful host infection. This study expands the functional repertoire of LysM-containing proteins and reveals their broader impact on bacterial virulence and adaptation to the plant-associated niche.
### Competing Interest Statement
The authors have declared no competing interest.
"Infection dynamics and virulence potential of clinical Pseudomonas aeruginosa isolates in a human airway epithelium model system"
https://www.biorxiv.org/content/10.1101/2025.04.11.644308v1?rss=1 #Dynamics #Cell
bioRxiv · Infection dynamics and virulence potential of clinical Pseudomonas aeruginosa isolates in a human airway epithelium model systemPersistent bacterial infections constitute an increasing health problem, which is often associated with antibiotic resistance. However, investigations of chronic lung inflammation and persistent infections with Pseudomonas aeruginosa in people with cystic fibrosis (pwCF) show that treatment failures may instead be rooted in host-microbe interactions developing after bacterial colonization of the CF airways. Using a laboratory infection model based on human airway epithelial tissues, cultured in an Air-Liquid Interface (ALI) system, we simulated the infection process of various P. aeruginosa strains to investigate the colonisation dynamics and the virulence potential during infection of nasal epithelial cultures from both non-CF and CF donors in addition to an immortalized bronchial cell line, BCi-NS1.1. Infections by P. aeruginosa reference strains and clinical isolates from pwCF were employed. While reference and patients' early strains exhibited high virulence and increased epithelial disruption, clinically adapted strains showed reduced virulence potential and limited epithelial damage regardless of the host cell type or clonal lineage. Dual RNA-seq analysis revealed that colonization of ALI cultures with virulent PAO1 significantly upregulated inflammatory pathways in host cells, an effect that was dampened in the less virulent pscC mutant strain lacking the type III secretion system. Simultaneously, while bacterial gene expression was similar in wild-type and BCi-NS1.1 cultures, in CF cells, the pscC strain showed dysregulation of genes involved in iron starvation, respiration, and quorum sensing pathways. Altogether, our results summarize the infection dynamics in the ALI model system and in pwCF, and provide a snapshot of the interplay between the airway epithelium and P. aeruginosa.
### Competing Interest Statement
The authors have declared no competing interest.
"Mechanical control of tissue growth during limb regeneration"
https://www.biorxiv.org/content/10.1101/2025.04.07.647008v1?rss=1 #Mechanical #Cell
bioRxiv · Mechanical control of tissue growth during limb regenerationThe axolotl is a highly regenerative species, capable of restoring full limbs, regardless of the amputation site. However, the regeneration rate is adjusted with the plane of amputation along the proximo-distal (PD) axis, leading to equivalent regeneration times regardless of the extent of tissue removal. We hypothesized that this phenomenon could be partly explained by differences in tissue mechanical properties. In this work, we describe tissue growth mathematically and evaluate cell cycle parameters of regenerating limbs amputated at different levels along the PD axis, demonstrating a linear correlation between the cell cycle length and the amputation site during early regeneration phases. We show as well, that blastema cells require their endogenous context to retain such proliferation differences. We measured mechanical properties in regenerating limbs with in vivo optical and standard indentation-based techniques and demonstrated that distal blastema cells are stiffer than proximal ones. Accordingly, we demonstrated that axolotl cells decrease their proliferation with increased extracellular matrix stiffness in vitro. Next, we evaluated the activity of the mechanotransducers YAP/TAZ in vivo by using a GTIIC-based reporter line combined with target gene expression data, which indicated that their activity peaks during the blastema stage, with higher activity after proximal amputations. Hence, our findings strongly suggest a mechanical dependence for the position-dependent regulation of cell proliferation during axolotl limb regeneration, where YAP/TAZ likely plays a role in the mechanotransduction mechanism.
### Competing Interest Statement
The authors have declared no competing interest.
"CRTAP-Null Osteoblasts Have Increased Proliferation, Protein Secretion, and Skeletal Morphogenesis Gene Expression with Downregulation of Cellular Adhesion"
https://doi.org/doi:10.3390/cells14070518
https://pubmed.ncbi.nlm.nih.gov/40214472/
#Morphogenesis #Adhesion #Cell
"Alginate-hydroxyapatite scaffolds: A comprehensive characterization study"
https://doi.org/doi:10.1016/j.jobcr.2025.03.010
https://pubmed.ncbi.nlm.nih.gov/40212102/
#Mechanical #Cell
"Non-uniform temporal scaling of neurogenesis for species-specific dosing of cortical excitatory subtypes"
https://www.biorxiv.org/content/10.1101/2025.04.10.648214v1?rss=1 #Dynamics #Cell
bioRxiv · Non-uniform temporal scaling of neurogenesis for species-specific dosing of cortical excitatory subtypesMammals share a laminar cerebral cortex, with excitatory neuron subtypes organized in distinct tangential layers. Although this framework is conserved, subtype balance varies markedly between species due to unknown mechanisms. This study shows that non-uniform scaling of temporal neurogenetic dynamics shapes species-specific neuronal composition. Comparing mice and rats, we show that rats produce more deep layer (DL) neurons but similar numbers of upper layer (UL) neurons. This difference results from a specific extension of early neurogenetic phase for DL production before transitioning to UL production in rats, as confirmed by birthdating and single-cell transcriptomics. The duration of DL production is regulated by a genetic program controlling progenitor aging, including Ccnd1. Knocking down Ccnd1 in rat progenitors induces a precocious shift to UL production, mirroring the mouse pattern. Thus, while sequential cortical neurogenesis is conserved, its progression is non-uniformly scaled in each species. Such precise heterochronic fine-tuning allows evolutionary refinement of cellular configuration without drastic remodeling of the conserved corticogenesis program.
### Competing Interest Statement
The authors have declared no competing interest.
"The ORF6 accessory protein contributes to SARS-CoV-2 virulence and pathogenicity in the naturally susceptible feline model of infection"
https://www.biorxiv.org/content/10.1101/2025.04.09.647941v1?rss=1 #Dynamics #Cell
"Single-Cell Trajectory Reconstruction Reveals Migration Potential of Cell Populations"
https://arxiv.org/abs/2504.07553 #Physics.Bio-Ph #CellMigration #Cell
arXiv.orgSingle-Cell Trajectory Reconstruction Reveals Migration Potential of Cell PopulationsCell migration, which is strictly regulated by intracellular and extracellular cues, is crucial for normal physiological processes and the progression of certain diseases. However, there is a lack of an efficient approach to analyze super-statistical and time-varying characteristics of cell migration based on single trajectories. Here, we propose an approach to reconstruct single-cell trajectories, which incorporates wavelet transform, power spectrum of an OU-process, and fits of the power spectrum to analyze statistical and time-varying properties of customized target-finding and migration metrics. Our results reveal diverse relationships between motility parameters and dynamic metrics, especially the existence of an optimal parameter range. Moreover, the analysis reveals that the loss of Arpin protein enhances the migration potential of D. discoideum, and a previously reported result that the rescued amoeba is distinguishable from the wild-type amoeba. Significantly, time-varying dynamic metrics emerge periodic phenomena under the influence of irregularly changing parameters, which correlates with migration potential. Our analysis suggests that the approach provides a powerful tool for estimating time-dependent migration potential and statistical features of single-cell trajectories, enabling a better understanding of the relationship between intracellular proteins and cellular behaviors. This also provides more insights on the migration dynamics of single cells and cell populations.
"The Role of Buffer Gas in Shaping the D1 Line Spectrum of Potassium Vapour"
https://arxiv.org/abs/2504.07888 #Physics.Atom-Ph #Physics.Optics #Pressure #Cell
arXiv.orgThe Role of Buffer Gas in Shaping the D1 Line Spectrum of Potassium VapourIn this study, we investigate the effect of buffer gas and magnetic field on the spectral line shapes of the potassium D1 transition using sealed vapour cells filled with varying amounts of neon as a buffer gas. Employing a dual-temperature control system, we independently manipulate the cell body and stem temperatures to explore Doppler and collisional effects on the spectrum. Our results show how the Voigt spectral profile changes from Gaussian- to Lorentzian-dominated forms due to pressure broadening and shifts caused by collisions between potassium atoms and neon. Our measurements are in excellent agreement with the literature values for potassium-neon collisions. For the first time we were able to incorporate the buffer-gas shift and broadening into the modified Voigt profile via the ElecSus code, and found excellent agreement between the predicted and measured line profiles. We also analyse the potassium D1 spectral lines in the hyperfine Paschen-Back regime using strong magnetic fields, demonstrating how Zeeman splitting modifies the pressure-broadened line shape. This work provides valuable insights into collision-induced broadening and shifts, enhancing our understanding of potassium spectroscopy and its application in the development of advanced magneto-optical filters for solar physics and other applications.
"Phenotype structuring in collective cell migration:a tutorial of mathematical models and methods"
https://arxiv.org/abs/2410.13629 #CellMigration #Dynamics #Q-Bio.Cb #Math.Ap #Cell
arXiv.orgPhenotype structuring in collective cell migration:a tutorial of mathematical models and methodsPopulations are heterogeneous, deviating in numerous ways. Phenotypic diversity refers to the range of traits or characteristics across a population, where for cells this could be the levels of signalling, movement and growth activity, etc. Clearly, the phenotypic distribution -- and how this changes over time and space -- could be a major determinant of population-level dynamics. For instance, across a cancerous population, variations in movement, growth, and ability to evade death may determine its growth trajectory and response to therapy. In this review, we discuss how classical partial differential equation (PDE) approaches for modelling cellular systems and collective cell migration can be extended to include phenotypic structuring. The resulting non-local models -- which we refer to as phenotype-structured partial integro-differential equations (PS-PIDEs) -- form a sophisticated class of models with rich dynamics. We set the scene through a brief history of structured population modelling, and then review the extension of several classic movement models -- including the Fisher-KPP and Keller-Segel equations -- into a PS-PIDE form. We proceed with a tutorial-style section on derivation, analysis, and simulation techniques. First, we show a method to formally derive these models from underlying agent-based models. Second, we recount travelling waves in PDE models of spatial spread dynamics and concentration phenomena in non-local PDE models of evolutionary dynamics, and combine the two to deduce phenotypic structuring across travelling waves in PS-PIDE models. Third, we discuss numerical methods to simulate PS-PIDEs, illustrating with a simple scheme based on the method of lines and noting the finer points of consideration. We conclude with a discussion of future modelling and mathematical challenges.
"Gas Vesicle-Expressing Human Pluripotent Stem Cells Enable Multimodal Ultrasound and Optical Coherence Tomographic Imaging"
https://www.biorxiv.org/content/10.1101/2025.04.10.648235v1?rss=1 #Pressure #Cell
bioRxiv · Gas Vesicle-Expressing Human Pluripotent Stem Cells Enable Multimodal Ultrasound and Optical Coherence Tomographic ImagingGenetically encoded imaging reporters are critical tools for tracking cell fate and function in regenerative medicine. Gas vesicles (GVs), air-filled protein nanostructures derived from bacteria, offer unique advantages for noninvasive imaging due to their acoustic and optical properties. In this study, we engineered human pluripotent stem cells (hPSCs) to express GVs using a doxycycline-inducible system. Upon doxycycline (Dox) treatment, GVs formed intracellularly and enabled enhanced contrast in both ultrasound and optical coherence tomography (OCT) imaging. Dynamic ultrasound imaging revealed pressure-dependent GV buckling and harmonic signal generation, while OCT imaging confirmed high sensitivity and depth-resolved detection in both in vitro and ex vivo retinal models. Our work establishes a multimodal GV-based reporter platform compatible with human stem cells and clinically relevant imaging modalities. This approach offers a powerful and versatile tool for noninvasively visualizing and tracking therapeutic cells in real time, advancing the development and monitoring of cell-based therapies.
### Competing Interest Statement
The authors have declared no competing interest.
"Fixation and extinction in time-fluctuating spatially structured metapopulations"
https://www.biorxiv.org/content/10.1101/2025.04.10.648186v1?rss=1 #CellMigration #Cell
bioRxiv · Fixation and extinction in time-fluctuating spatially structured metapopulationsBacteria evolve in volatile environments and complex spatial structures. Migration, fluctuations and environmental variability therefore have a significant impact on the evolution of microbial populations. Here, we consider a class of spatially explicit metapopulation models arranged as regular (circulation) graphs where cells of a wild-type and mutant strain compete in a time-fluctuating environment where demes (subpopulations) are connected by slow cell migration. The carrying capacity is the same at each deme and endlessly switches between two values associated to harsh and mild environmental conditions. When the rate of switching is intermediate, the dynamics is characterised by bottlenecks and the population is prone to fluctuations or extinction. We analyse how slow migration, spatial structure, and fluctuations affect the phenomena of fixation and extinction on clique, cycle, and square lattice metapopulations. When the carrying capacity remains large, bottlenecks are weak and deme extinction can be ignored. The dynamics is thus captured by a coarse-grained description within which the probability and mean time of fixation are obtained analytically. This allows us to show that, in contrast to what happens in static environments, the mutant fixation probability depends on the rate of migration. We also show that the fixation probability and mean fixation time can exhibit a non-monotonic dependence on the switching rate When the carrying capacity is small under harsh conditions, bottlenecks are strong, and the metapopulation evolution is shaped by the coupling of deme extinction and strain competition. This yields rich dynamical scenarios, among which we identify the best conditions to eradicate mutants without dooming the metapopulation to extinction. We offer an interpretation of these findings in the context of an idealised treatment and discuss possible generalisations of our models.
### Competing Interest Statement
The authors have declared no competing interest.
"A Morpho-Proteomic Atlas of Mitosis at Sub-Minute Resolution"
https://www.biorxiv.org/content/10.1101/2025.04.09.647158v1?rss=1 #CellDivision #Mitosis #Cell
bioRxiv · A Morpho-Proteomic Atlas of Mitosis at Sub-Minute ResolutionPrecise spatiotemporal protein organization is critical for fundamental biological processes including cell division. Indeed, aberrant mitosis and mitotic factors are involved in diverse diseases, including various cancers, Alzheimer's disease, and rare diseases. During mitosis, complex spatial rearrangements and regulation ensure the accurate separation of replicated sister chromatids to produce genetically identical daughter cells. Previous studies employed high-throughput methodologies to follow specific proteins during mitosis. Still a temporally refined systems-level approach capable of monitoring morphological and proteomic changes throughout mitosis has been lacking. Here, we achieved unprecedented resolution by phenotypically decomposing mitosis into 40 subsections of a regression plane for proteomic analysis using deep learning and regression techniques. Our deep visual proteomics (DVP) workflow, revealed rapid, dynamic proteomic changes throughout mitosis. We quantified 4,350 proteins with high confidence, demonstrating that 147 show significant dynamic abundance changes during mitotic progression. Clustering revealed coordinated patterns of protein regulation, while network analysis uncovered tight regulation of core cell cycle proteins and a link between cell cycle and cancer-linked mutations. Immunofluorescence validated abundance changes and linked previously uncharacterised proteins, like C19orf53, to mitosis. To facilitate data navigation, we developed Mito-Omix, a user-friendly online platform that integrates intricate morphological and molecular data. Our morphological and proteomic dataset spans mitosis at high resolution, providing a rich resource for understanding healthy and aberrant cell division.
### Competing Interest Statement
P.H. is the founder and a shareholder of Single-Cell Technologies Ltd., a biodata analysis company that owns and develops the BIAS software. The remaining authors declare no competing interests.
"Gene regulatory network determinants of rapid recall in human memory CD4+ T cells"
https://www.biorxiv.org/content/10.1101/2025.04.06.646912v1?rss=1 #Dynamics #Cell
bioRxiv · Gene regulatory network determinants of rapid recall in human memory CD4+ T cellsRapid recall is the hallmark of memory T cells. While naive T cells require days to mount an effector response to a new threat, antigen-experienced memory T cells can produce cytokines within hours of the repeat encounter. The establishment of memory and control of rapid recall across lifespan is poorly understood, yet the mechanisms are fundamental to pathogen defense and immunological diseases. Epigenetic poising was proposed as a likely mechanism. Indeed, compared to naive, memory cells exhibit enhanced chromatin accessibility proximal to rapid recall genes, but the transcription factors (TFs) that establish, maintain and utilize these putative regulatory elements are unknown. Here, we leverage single-nuclei (sn)multiome-seq (simultaneous snRNA-seq and snATAC-seq) to (1) characterize the dynamic activation responses of naive and memory CD4+ T cell subsets and (2) reconstruct the underlying gene regulatory networks, at genome scale. Our analysis uncovered thousands of genes and putative regulatory elements with rapid-recall dynamics, shared and unique across the memory populations. A core of memory-associated TFs (MAF, PRDM1, RUNX2, RBPJ and KLF6) is predicted to orchestrate rapid recall and maintain accessible chromatin at rapid-recall gene enhancers in resting memory cells. We integrate GWAS to link our T cell populations and their dynamic chromatin landscapes to human phenotypes, nominating CD4+ T cell populations, rapid recall responses and gene regulatory mechanisms that might mediate genetic risk to autoimmune and inflammatory diseases.
### Competing Interest Statement
A.B. is a co-founder of Datirium, LLC, the developer of SciDAP.com. M.K. and A.B. developed CWL-Airflow, which is licensed to Datirium, LLC.
"4D mitochondrial network assumes distinct and predictive phenotypes through human lung and intestinal epithelial development"
https://www.biorxiv.org/content/10.1101/2025.04.09.648043v1?rss=1 #Dynamics #Cell
bioRxiv · 4D mitochondrial network assumes distinct and predictive phenotypes through human lung and intestinal epithelial developmentMitochondria form a dynamic three-dimensional network within the cell that exhibits a wide range of morphologies and behaviors. Depending on cell state, cell type, and cell fate, a cell's mitochondrial phenotype might range from relatively isolated mitochondrial segments to complex branching networks, and from stationary mitochondria to highly motile structures. While isolated mitochondrial phenotypes have been described for a subset of cell states, types, and fates, an integrated map of how mitochondrial phenotypes change over the full course of tissue development has so far been lacking. Here, we identify the mitochondrial phenotypes that appear throughout the course of lung and intestinal epithelial development from stem cells to differentiated tissue. Using human stem cell-derived intestinal and branching lung organoids that mimic developing human organs as model systems, we extract and analyze key mitochondrial biophysical phenotypes in human development. To achieve this, we employ lattice light-sheet microscopy (LLSM), which enables high-resolution, 4D (x, y, z, time) imaging of mitochondria in organoid tissues with minimal damage to the sample. We image at key developmental time points from stem cell differentiation into mature organoid tissue. For data processing, we utilize the MitoGraph and MitoTNT software packages along with our developed custom computational tools. These tools allow for automated 4D organoid to single cell image processing and quantitative 4D single cell mitochondrial temporal network tracking. This work represents the first 4D high spatiotemporal-resolution quantification of live human organoid tissues at the single-cell level through development. We identified distinct mitochondrial phenotypes unique to each organoid type and found correlations between mitochondrial phenotypes, cellular age, and cell type. Furthermore, we demonstrate that mitochondrial network characteristics can predict both organoid type and cell age. Our findings reveal fundamental aspects of mitochondrial biology that were previously unobservable, offering new insights into cell-type-specific mitochondrial dynamics and enabling new findings in relevant human model systems. We believe that our findings and methods will be essential for advancing 4D cell biology, providing a powerful framework for characterizing organelles in organoid tissues.
### Competing Interest Statement
The authors have declared no competing interest.
"Protein diffusion controls how single cells respond to electric fields"
https://www.biorxiv.org/content/10.1101/2025.04.09.647627v1?rss=1 #Dynamics #Cell
bioRxiv · Protein diffusion controls how single cells respond to electric fieldsCells sense and respond to electric fields, using these fields as a guidance cue in wound healing and development. This sensing is done by redistribution of charged membrane proteins on the cell's surface ("sensors") via electrophoresis and electroosmotic flow. If membrane proteins have to physically rearrange on the cell's surface, how quickly can a cell respond to an applied signal? What limits the cell's ability to respond? Are galvanotaxing cells, like chemotaxing cells, limited by stochasticity from the finite number of molecules? Here, we develop a model for the response dynamics of galvanotaxing cells and show that, for weak enough field strengths, two relevant timescales emerge: the time for the cell's sensors to rearrange, which depends on their diffusion across the cell, and the time for the cell's orientation to respond to an applied field, which may be very different. We fit this model to experimental measurements on the recently-identified sensor galvanin (TMEM154) in neutrophil-like HL-60 cells, finding that given the dynamics of a cell responding to an applied field, we can predict the dynamics of the cell after the field is turned off. This fit constrains the noise of the galvanotaxis process, demonstrating that HL-60 is not limited by the stochasticity of finite sensor number. Our model also allows us to explain the effect of media viscosity on cell dynamics, and predict how cells respond to pulsed DC fields. These results place constraints on the ability to guide cells with pulsed fields, predicting that a field on half of the time is no better than a field that is always on with half the magnitude.
### Competing Interest Statement
The authors have declared no competing interest.
"Whole-cell particle-based digital twin simulations from 4D lattice light-sheet microscopy data"
https://www.biorxiv.org/content/10.1101/2025.04.09.647865v1?rss=1 #Dynamics #Cell
bioRxiv · Whole-cell particle-based digital twin simulations from 4D lattice light-sheet microscopy dataWe present a framework for performing whole-cell digital twin simulations which integrates 4D (x,y,z,t) lattice light-sheet microscopy (LLSM) data with particle-based reaction-diffusion modeling to capture intracellular organelle dynamics. Using imaging data from Cal27 cells, we construct digital twins that incorporate mitochondrial networks, microtubule networks, dynein and kinesin motors, the plasma membrane, and the nucleus. Passive diffusive mitochondrial dynamics are parameterized using stochastic reaction-diffusion simulations in ReaDDy, while active transport is modeled explicitly by incorporating motor-driven transport along a diffusing, polarized microtubule network. Our simulations accurately reproduce experimentally observed mitochondrial dynamics across pharmacological microtubule depolymerization conditions and reproduce the mitochondrial response to intermediate perturbations without explicit re-parameterization. This novel meso-scale digital twin framework offers a bridge between atomic-scale whole-cell simulations and experimental time and length scales.
### Competing Interest Statement
The authors have declared no competing interest.
"Phloem-Specific Translational Regulation of Soybean Nodulation: Insights from a Phloem-Targeted TRAP-Seq Approach"
https://www.biorxiv.org/content/10.1101/2025.04.09.647652v1?rss=1 #Dynamics #Cell
bioRxiv · Phloem-Specific Translational Regulation of Soybean Nodulation: Insights from a Phloem-Targeted TRAP-Seq ApproachSoybean (Glycine max) root nodulation is a symbiotic process that requires complex molecular and cellular coordination. The phloem plays a crucial role not only in nutrient transport but also in long-distance signaling that regulates nodulation. However, the molecular mechanisms underlying phloem-specific regulation during nodulation remain poorly characterized. Here, we developed a phloem-specific Translating Ribosome Affinity Purification sequencing (TRAP-seq) system to investigate the translational dynamics of phloem-associated genes during nodulation. Using a phloem-specific promoter (Glyma.01G040700) combined with the GAL4-UAS amplification system, we successfully captured the translatome of soybean root phloem at early (72 hours post-inoculation, hpi) and late (21 days post-inoculation, dpi) nodulation stages. Differential expression analysis revealed dynamic translational reprogramming, with 2,636 differentially expressed genes (DEGs) at 72 hpi and 8,422 DEGs at 21 dpi. Gene ontology and pathway enrichment analyses showed stage-specific regulatory shifts, including early activation of ethylene and defense pathways and late-stage enhancement of nutrient transport and vascular development. Transcription factor analysis identified GmbHLH121 as a key phloem-specific regulator of nodulation. Functional validation using RNAi knockdown and overexpression experiments demonstrated that GmbHLH121 negatively regulates nodule formation, likely acting downstream of or independently from early nodulation signaling pathways. Additionally, we uncovered dynamic regulation of cell wall-modifying enzymes (PME and PMEI) in the phloem, implicating their role in modulating plasmodesmata permeability and facilitating symplastic connectivity during nodulation. Our findings highlight the critical role of phloem-mediated translational regulation in coordinating root nodulation, emphasizing the phloem as an active regulatory hub for long-distance signaling and symbiotic efficiency.
### Competing Interest Statement
The authors have declared no competing interest.
"Characterization of a Novel FKS1 Mutation in Candida lusitaniae Shows a Potential Critical Role for MKC1 in Echinocandin Resistance"
https://www.biorxiv.org/content/10.1101/2025.04.08.647726v1?rss=1 #Force #Cell
bioRxiv · Characterization of a Novel FKS1 Mutation in Candida lusitaniae Shows a Potential Critical Role for MKC1 in Echinocandin ResistanceCaspofungin is an echinocandin antifungal that inhibits glucan synthesis in the fungal cell wall. A Candida parapsilosis bloodstream isolate resistant to echinocandins was recovered from a patient who had undergone allogeneic hematopoietic stem cell transplantation. The FKS1 gene, encoding the target glucan synthase, contained a heterozygous mutation resulting in an I1380T amino acid change, in addition to the naturally occurring P660A polymorphism. When expressed at the equivalent position in the Fks1p protein of C. lusitaniae, P642A and I1359T, alone and in combination, led to 6-, 12-, and ≥256-fold increases in the minimal inhibitory concentration (MIC) of caspofungin, respectively. The caspofungin concentration needed to inhibit 50% of glucan synthase activity was increased 3-, 37-, and 270-fold, respectively. At high drug concentrations, and also in drug-free medium, infrared spectroscopy revealed a decrease in β-glucan content and an increase in chitin in the cell wall of the I1359T Fks1p mutants. Atomic force microscopy showed cell wall damage and cell swelling in both susceptible and resistant strains under caspofungin exposure. Analysis of susceptibility to cell-wall stressors and key factors in cell wall integrity (CWI) and high-osmolarity glycerol (HOG) pathways showed that all strains activated these pathways under caspofungin stress. In the I1359T Fks1p mutants, Mkc1p was constitutively activated even without caspofungin. Deletion of MKC1 restored caspofungin susceptibility, indicating that activation of the CWI pathway is a key molecular determinant of resistance in vitro to caspofungin in these mutants.