Sanderlin2266

Our model predicts that the level of macrophage activation can be negatively correlated with the level of viral load when viral infectivity is sufficiently high. We further identify that temporary depletion of resting macrophages in response to viral infection is a major driver in our model for the negative relationship between the level of macrophage activation and viral load, providing new insight into the mechanisms that regulate macrophage activation. Our model serves as a framework to study the complex dynamics of virus-macrophage interactions and provides a mechanistic explanation for existing experimental observations, contributing to an enhanced understanding of the role of macrophages in influenza viral infection.The biological interactions underpinning the Arabidopsis circadian clock have been systematically uncovered and explored by biological experiments and mathematical models. This is captured by a series of published ordinary differential equation (ODE) models, which describe plant clock dynamics in response to light/dark conditions. However, understanding the role of temperature in resetting the clock (entrainment) and the mechanisms by which circadian rhythms maintain a near-24 h period over a range of temperatures (temperature compensation) is still unclear. Understanding entrainment and temperature compensation may elucidate the principles governing the structure of the circadian clock network. Here we explore the design principles of the Arabidopsis clock and its responses to changes in temperature. selleck chemicals llc We analyse published clock models of Arabidopsis, spanning a range of complexity, and incorporate temperature-dependent dynamics into the parameters of translation rates in these models, to discern which regulatory patterns may best explain clock function and temperature compensation. We additionally construct three minimal clock models and explore what key features govern their rhythmicity and temperature robustness via a series of random parameterisations. Results show that the highly repressive interactions between the components of the plant clock, together with autoregulation patterns and three-node feedback loops, are associated with circadian function of the clock in general, and enhance its robustness to temperature variation in particular. However, because the networks governing clock function vary with time due to light and temperature conditions, we emphasise the importance of studying plant clock functionality in its entirety rather than as a set of discrete regulation patterns.Plants can adjust their competitive traits for acquiring resources in response to the relatedness of their neighbours. Recently, it has been found that plants can alter their investment in traits of attracting pollinators based on kin-interaction. We build a mathematical model to study the optimal floral display to attract pollinators in a patch with kin structure. We show that when plants can attract pollinators to a whole patch through the magnet effect, the floral display should increase with the increasing relatedness of the plants in the patch. Our model also indicates that increasing investment into attracting pollinators is a form of altruism, reducing a plant's own seed production but increasing the contribution of other plants to its fitness. We also predict that seed production should increase with increasing relatedness in the patch. Our model provides the explicit conditions when resource allocation to attract pollinators in response to neighbour relatedness can be favoured by kin selection, and a possible mechanism for the plants to deal with the consequent loss of pollinator diversity and abundance.Sleep loss causes decrements in cognitive performance, which increases risks to those in safety-sensitive fields, including medicine and aviation. Mathematical models can be formulated to predict performance decrement in response to sleep loss, with the goal of identifying when an individual may be at highest risk for an accident. This work produces an Ensemble Mixed Effects Model that combines a traditional Linear Mixed Effects (LME) model with a semi-parametric, nonlinear model called Mixed Effects Random Forest (MERF). Using this model, we predict performance on the Psychomotor Vigilance Task (PVT), a test of sustained attention, using biologically motivated features extracted from a dataset containing demographic, sleep, and cognitive test data from 44 healthy participants studied during inpatient sleep loss laboratory experiments. Our Ensemble Mixed Effects Model accurately predicts an individual's trend in PVT performance, and fits the data better than prior published models. The ensemble successfully cuations in which people work at different circadian times (e.g., night- or shift-work).Assembly of KU and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) at DNA double strand breaks (DSBs) forms DNA-PK holoenzyme as a critical initiating step for non-homologous end joining (NHEJ) repair of DSBs produced by radiation and chemotherapies. Advanced cryo-electron microscopy (cryo-EM) imaging together with breakthrough macromolecular X-ray crystal (MX) structures of KU and DNA-PKcs recently enabled visualization of the ∼600 kDa DNA-PK assembly at near atomic resolution. These important static structures provide the foundation for definition and interpretation of functional movements crucial to mechanistic understanding that can be tested through solution state structure analysis. We herein therefore leverage Cryo-EM and MX structures for the interpretation of synchrotron small-angle X-ray scattering (SAXS) data on DNA-PK conformations in solution to inform the structural mechanism for NHEJ initiation. SAXS, which measures thermodynamic solution-state conformational states and assemblies outside of cryo- and solid-state conditions, unveils the inherent flexibility of KU, DNA-PKcs and DNA-PK. The combined structural measurements reveal mobility of KU80 C-terminal region (KU80CTR), motion/plasticity of HEAT (DNA-PKcs Huntingtin, Elongation Factor 3, PP2 A, and TOR1) regions, allosteric switching upon DNA-PKcs autophosphorylation, and dimeric arrangements of DNA-PK assembly. Importantly, the results uncover displacement of the N-terminal HEAT domain during autophosphorylation as suitable for a regulated release mechanism of DNA-PKcs from DNA-PK to control unproductive access to toxic and mutagenic DNA repair intermediates. These integrated analyses show that the marriage of SAXS with cryo-EM leverages the strengths of both techniques to enable assessment of functional conformations and flexibility defining atomic-resolution molecular mechanisms for DSB repair.