- by Nguyen, N. T., Truong, V. H., Myung, J.Study Objectives: Chronotype, typically defined by the mid-sleep phase on free days, is often interpreted as a direct proxy for circadian phase. However, a fundamental paradox challenges this assumption: worldwide chronotype distributions show a heavy right skew, whereas circadian period distributions show a slight left skew. We investigated whether fast, noisy cortical processes in homeostatic sleep pressure dynamics could resolve this paradox. Methods: Drawing upon the classical two-process model of sleep regulation, we simulated how interindividual differences in sleep homeostasis […]
- by Wang, R., Hnin, T., Feng, Y., Valm, A. M.Fluorescence imaging with spectrally variant fluorophores allows the spatial mapping of biological structures with exquisite cellular and molecular specificity. However, the ability to robustly discriminate multiple fluorophores in any single imaging experiment is greatly hindered by the broad emission spectra of bio-compatible fluorophores and the large contribution of noise in low-energy regime fluorescence microscopy. In this study, we propose a novel machine learning framework, Bleaching-Excitation-Emission Photodynamics (BEEP) learning, that exploits multiple discriminatory features of fluorescent dyes to greatly expand the […]
- by Fujita, Y., Kage, A., Nishizaka, T.The raphidophyte Chattonella marina is a harmful algal bloom (HAB) species known for its distinct diurnal vertical migration (DVM), a behavior important for its survival and bloom formation. However, the single-cell mechanisms governing this migration remain unclear. In this study, we investigated the swimming characteristics of individual C. marina cells during day (light) and night (dark) phases. We observed a strong positive correlation between the length of the propulsive anterior flagellum and the cell's swimming speed. We discovered that the […]
- by Rooney, L. M., Christopher, J., Foylan, S., Butterworth, C., Walker, L. D., Copeland, L., Coubrough, K., The SOMC 2025 Consortium,, Gould, G. W., Cunningham, M. R., Bauer, R., McConnell, G.Solid immersion lenses (SILs) enhance the spatial resolution of an optical microscope by increasing the effective numerical aperture (NA) without physical modification of the objective lens. However, SIL application remains limited by cost, fragility, and accessibility. We present a rapid, single-step fabrication process to create optical quality hemispherical SILs using consumer-grade UV-curable transparent resin which reduces material costs by over five orders of magnitude relative to commercial glass counterparts. Our method produced resin SILs within seconds which can be easily […]
- by Mallick, A., Pfanzelter, J., Pimpale, L. G., Grill, S. W.Left-right (LR) asymmetries are a defining feature of bilaterian body plans, but the mechanisms that convert molecular chirality into a conserved body-axis handedness remain unclear. In C. elegans, LR axis specification proceeds via a chiral spindle skew that establishes a handed cell-cell contact pattern (CCP) at the 6-cell stage; an arrangement that, when reversed, leads to situs inversus nematodes. Chiral acto-myosin flows that arise from active chiral torques have been previously identified as the driver of this LR asymmetric spindle […]
- by Ball, D. A., Wagh, K., Stavreva, D. A., Hoang, L., Schiltz, R. L., Chari, R., Raziuddin, R., Mazza, D., Upadhyaya, A., Hager, G. L., Karpova, T. S.Linking the spatiotemporal dynamics of proteins in live cells to physiological functions is a fundamental challenge in biology and robust quantification of protein dynamics is a major step towards this endeavor. Single molecule tracking (SMT) has emerged as a powerful technique to investigate protein dynamics at the single molecule level in living cells. Most SMT analyses require familiarity with biophysical models and programming and the results from different analyses cannot be easily integrated. To mitigate these shortcomings, we developed QuantiTrack […]
- by Laan, D. M., Kourkoulou, A. M., Ramirez-San-Juan, G. R.Free-living unicellular organisms known as ciliates rely on fluid flows to perform essential functions. These flows emerge from the coordinated activity of thousands of cilia organized into arrays with highly diverse architectures. Despite the importance of mesoscale cilia organization for flow generation, the relationship between the architecture of the ciliary array and the flow function it performs remains poorly understood. Here, we investigate how the ciliary array in the ciliate Paramecium tetraurelia enables this organism to feed and swim simultaneously. […]
- by Beiter, J. R., Tsai, F.-C., Bassereau, P., Voth, G. A.The NBAR-domain containing protein endophilin, as a major player in many endocytic pathways, has offered considerable insight into BAR-domain driven membrane remodeling. However, understanding the interaction of the different subdomains of endophilin and their abilities to sense and generate negative Gaussian curvature are yet unanswered questions, with significant implications for the mechanisms and regulation of unconventional endocytic pathways. Using coarse-grained molecular dynamics simulation, we demonstrate the synergistic remodeling capabilities of the NBAR remodeling unit, as well as its ability to […]
- by Bartoelke, R., Henbest, K. B., Schmidt, J., Kasahara, T., Cubbin, D. R., Gravell, J., Bassetto, M., Dautaj, G., Pitcher, T. L., Murton, P. D. F., Saberamoli, G., Forst, J. J., Khazani, M., Apte, S., Olavesen, C., Hayward, H., Pare-Labrosse, O., Antill, L. M., Xu, J., Hore, P. J., Timmel, C. R., Mackenzie, S. R., Mouritsen, H.Magnetoreception, the ability of animals to sense the Earth's magnetic field, is a fascinating biological phenomenon. Cryptochromes, in particular cryptochrome 4a (CRY4a), have emerged as potential key players in mediating magnetic sensing in various bird species. Building on an earlier investigation of magnetic field effects on European robin (Erithacus rubecula) CRY4a, we focus here on CRY4a from the common/Japanese quail (Coturnix coturnix/japonica). Japanese quail is one of the very small number of domesticated bird species whose wild forms are migratory. […]
- by Francis, E. A., Sarikhani, E., Naghsh-Nilchi, H., Jahed, Z., Rangamani, P.Nuclear envelope stretch and rupture are common to cell spreading and migration in a variety of microenvironments, leading to marked changes in nucleocytoplasmic transport. Predicting cell response to different mechanochemical cues that are transmitted to the nucleus remains an open problem in the field of mechanomedicine. We developed a predictive modeling framework to examine how nuclear deformation on substrates with different nanotopographies influences nucleocytoplasmic transport and rearrangement of the nuclear lamina. Using the finite element method, we simulated nuclear compression […]
- by Senthilazhagan, K., Das, A.Cell-cell junctions (CCJs) are dynamic biopolymeric systems essential for adherence of biological cells or- ganizing into a tissue or organ. In vertebrate organisms, CCJs present in stable epithelial tissues are maintained primarily by cell-to-cell protein bridges made of an adhesion receptor E-cadherin. CCJs are destabilized dur- ing Epithelial (E) to mesenchymal (M) transformation (EMT), an essential step in cancer metastasis, where cells switch states and acquire migratory features. An essential trigger for EMT is a cadherin switch process from E-cadherins […]
- by Kuznetsov, A. V.AA amyloidosis is a severe complication of chronic inflammatory diseases characterized by fibrillar protein deposition in the kidneys, leading to progressive organ failure. This study presents a mathematical model coupling SAA-HDL binding dynamics with renal amyloid aggregation kinetics to elucidate disease pathogenesis. Under normal conditions, Serum Amyloid A (SAA) circulates bound to high-density lipoprotein (HDL), which acts as a molecular chaperone preventing misfolding. However, during chronic inflammation, SAA production exceeds HDL binding capacity, resulting in free SAA that undergoes renal […]
- by Jin, D., Li, Z., Roke, S., Klein, J.Membrane fusion is ubiquitous in myriad biological processes, including presynaptic neurotransmitter release, myoblast fusion, virus entry, and fertilization. It is often considered in the presence of fusogenic proteins, which mediate the fusion by pulling the membranes into contact to overcome the high energy barrier imposed by hydration repulsion. Here we uncover an alternative pathway: membrane fusion arising from electroporation induced by transmembrane potentials in absence of proteins. Using biased molecular dynamics simulations to carry out extensive potential-of-mean-force calculations, we show […]
- by Weikl, T. R.Adhesion of spherical nanoparticles or virus-like particles to membranes can lead to membrane tubules in which linear chains of adhering particles are cooperatively wrapped by the membrane. This cooperative wrapping of spherical particles in tubules is energetically favourable compared to the individual wrapping of the particles because of a favourable interplay of bending and adhesion energies in the contact regions in which the membrane detaches from the particles, and because a particle in a tubule has two such contact regions […]
- by Keshavanarayana, P., Brown, E., Luthert, P. J., Shipley, R. J., Walker-Samuel, S.Purpose: To investigate the interplay between biomechanics, fluid dynamics, and solute transport in Diabetic Macular Oedema (DMO) using a theory of porous media-based multiphysics computational model, aiming to elucidate mechanisms behind variable treatment outcomes. Methods: We developed a multiphysics model of the retina within a porous media framework. The model integrates OCT-derived geometry, vascular leakage, retinal biomechanics (including Müller cell fibre architecture), retinal pigment epithelium (RPE) function, and anti-VEGF transport. We simulated oedema development and therapeutic response by varying vascular […]
- by Kitashov, A. V.Space weather exerts profound effects on Earth's technological systems, yet its influence on the terrestrial biosphere remains largely unexplored at the global scale. While local experiments suggest magnetic sensitivity in plants, observational evidence for a planetary-scale vegetative response to geomagnetic disturbances is lacking. Here, we analyze a decade of satellite-derived solar-induced chlorophyll fluorescence (SIF) data alongside geomagnetic indices to isolate non-seasonal physiological anomalies. Using temperature-stratified cumulative correlation analysis and multivariate models controlling for radiative and hydrological drivers, we identify a […]
- by Mitra, M., Mukherjee, R., Jurinovic, K., Ouldridge, T. E.Catalytic molecular templating, wherein a copolymer molecule serves as a sequence specific template to propagate genetic information to a daughter copolymer, is fundamental to cells. Templating underlies DNA replication, RNA transcription and protein translation, underpinning the molecular basis of heredity, evolution, and biological function, and allowing staggering complexity to arise from simple building blocks. It has hitherto been challenging to emulate templating without highly evolved enzymes, largely due to product inhibition of catalytic turnover, which is a major challenge for […]
- by Shi, Y., Li, J.A fully physical, non-alchemical framework is presented for absolute binding free energy (ABFE) calculations for protein-ligand complexes. Incorporation of a regularization potential eliminates unphysical artifacts and provides several key advantages: no endpoint catastrophes, fast convergence, robust performance for charged and neutral ligands, and rapid upfront verification. Validated on 30 diverse systems, the method improves predictive accuracy by 15.6% and numerical stability by 17.1% over leading alchemical approaches. This non-alchemical ABFE framework can be a potentially accurate and robust tool, carrying […]
- by Martin, M., Bolognesi, B.Amyloid formation, typically associated with neurodegeneration, can also serve essential biological functions. RIPK1 and RIPK3 kinases assemble functional amyloids via their RHIM domains to drive necrosome formation and necroptosis. Here, we systematically map the sequence-function relationship of these domains using deep mutagenesis combined with massively parallel assays that directly report on amyloid nucleation and necroptotic signaling. Analysis of ~3,000 mutations across RIPK1 and RIPK3 reveals that both proteins rely on a conserved aliphatic tetrad to nucleate amyloids, but diverge mechanistically: […]
- by Ross, B. L., Lodesani, A., Aiello, C. D.MagLOV2 is an engineered flavoprotein designed to have large changes in fluorescence intensity in response to weak magnetic fields. Here, we characterize the magnitude of these fluorescence changes, known as the "magnetic field effect," as a function of the strength of an externally applied magnetic field in E. coli colonies expressing MagLOV2. We observe that the magnetic field effect is positive at low magnetic fields, reaches a maximum positive value near 1 mT, and then decreases, reversing sign at approximately […]
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