Inflammation triggers degradation of intervertebral disc extracellular matrix (ECM), a hallmark of disc degeneration that contributes to back pain. Mechanosensitive nucleus pulposus cells are responsible for ECM production, yet the impact of a proinflammatory microenvironment on cell mechanobiology is unknown. Using gain- and loss-of-function approaches, we show that tumor necrosis factor-α (TNFα)-induced inflammation alters cell morphology and biophysical properties (circularity, contractility, cell stiffness, and hydraulic permeability) in a mechanism dependent on actomyosin contractility in a three-dimensional (3D) culture. We found that RhoA activation rescued cells from TNFα-induced mechanobiological disruption. Using a novel explant-in-hydrogel culture system, we demonstrate that nuclear factor kappa-B nuclear translocation and transcription are mechanosensitive, and its downstream effects on ECM degradation are regulated by actomyosin contractility. Results define a scaling relationship between circularity, contractility, and hydraulic permeability that is conserved from healthy to inflammatory microenvironments and is indicative of cell mechanobiological control across scales in 3D.While N6-methyladenosine (m6A) is the most prevalent modification of eukaryotic messenger RNA (mRNA) involved in various cellular responses, its role in modulating bacteria-induced inflammatory response remains elusive. Here, we showed that loss of the m6A reader YTH-domain family 2 (YTHDF2) promoted demethylation of histone H3 lysine-27 trimethylation (H3K27me3), which led to enhanced production of proinflammatory cytokines and facilitated the deposition of m6A cotranscriptionally. Mechanistically, the mRNA of lysine demethylase 6B (KDM6B) was m6A-modified and its decay mediated by YTHDF2. YTHDF2 deficiency stabilized KDM6B to promote H3K27me3 demethylation of multiple proinflammatory cytokines and subsequently enhanced their transcription. Furthermore, we identified H3K27me3 as a barrier for m6A modification during transcription. KDM6B recruits the m6A methyltransferase complex to facilitate the methylation of m6A in transcribing mRNA by removing adjacent H3K27me3 barriers. These results revealed cross-talk between m6A and H3K27me3 during bacterial infection, which has broader implications for deciphering epitranscriptomics in immune homeostasis.Brownian motion of particles in fluid is the most common form of collective behavior in physical and biological systems. Here, we demonstrate through both experiment and numerical simulation that the movement of vortices in a rotating turbulent convective flow resembles that of inertial Brownian particles, i.e., they initially move ballistically and then diffusively after certain critical time. Moreover, the transition from ballistic to diffusive behaviors is direct, as predicted by Langevin, without first going through the hydrodynamic memory regime. The transitional timescale and the diffusivity of the vortices can be collapsed excellently onto a master curve for all explored parameters. In the spatial domain, however, the vortices exhibit organized structures, as if they are performing tethered random motion. Our results imply that the convective vortices have inertia-induced memory such that their short-term movement can be predicted and their motion can be well described in the framework of Brownian motions.Maternal immune activation increases the risk of neurodevelopmental disorders. Elevated cytokines, such as interferon-γ (IFN-γ), in offspring's brains play a central role. IFN-γ activates an antiviral cellular state, limiting viral entry and replication. Moreover, IFN-γ is implicated in brain development. https://www.selleckchem.com/products/gsk-3008348-hydrochloride.html We tested the hypothesis that IFN-γ signaling contributes to molecular and cellular phenotypes associated with neurodevelopmental disorders. Transient IFN-γ treatment of neural progenitors derived from human induced pluripotent stem cells increased neurite outgrowth. RNA sequencing analysis revealed that major histocompatibility complex class I (MHCI) genes were persistently up-regulated through neuronal differentiation-an effect that was mediated by IFN-γ-induced promyelocytic leukemia protein (PML) nuclear bodies. Critically, IFN-γ-induced neurite outgrowth required both PML and MHCI. We also found evidence that IFN-γ disproportionately altered the expression of genes associated with schizophrenia and autism, suggesting convergence between genetic and environmental risk factors. Together, these data implicate IFN-γ signaling in neurodevelopmental disorder etiology.Urban theory models cities as spatial equilibria to derive their aggregate properties as functions of extensive variables, such as population size. However, this assumption seems at odds with cities' most interesting properties as engines of fast and variable processes of growth and change. Here, we build a general statistical dynamics of cities across scales, from single agents to entire urban systems. We include agents' strategic behavior to produce predictable growth rates, which requires balancing relative incomes and costs over time. We implement these dynamics using stochastic differential equations and control theory to demonstrate a number of general emergent properties of cities deriving from limit theorems applied to growth rates. This framework establishes necessary conditions for scaling to be conserved by urban dynamics and shows how exponent corrections can be calculated. These ideas are tested using stochastic simulations and a long timeseries for 382 US Metropolitan Areas over nearly five decades. Cystic fibrosis (CF) is a high-yield undergraduate medical education topic that lends itself to adaptability of content. We used a CF case paired with activities to deliver content in a near-peer teaching session. First-year (M1) and second-year (M2) medical students contributed acquired knowledge of protein structure and obstructive lung disease, respectively, to generate a concept map and address discussion questions. Combined groups of M1 and M2 students reviewed a CF case and a concept map prompt. For 30 minutes, they created a concept map describing connections between molecular biology and clinical manifestations. We summarized by reviewing concept maps and discussion questions. The efficacy of the session was determined by comparing exam performance of class attenders and nonattenders (M2) and performance on questions related and unrelated to the exercise (M1). We also determined students' perception of the session and incorporation of additional core competencies. M2 students' performance was 3.