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Obstructive sleep apnea (OSA) is a prevalent sleep disorder that is associated with increased incidence of chronic musculoskeletal pain. We investigated the mechanism of this association in a mouse model of chronic intermittent hypoxia (CIH) that mimics the repetitive hypoxemias of OSA. After 14 days of CIH, both male and female mice exhibited behaviors indicative of persistent pain, with biochemical markers in the spinal cord dorsal horn and sensory neurons of the dorsal root ganglia consistent with hyperalgesic priming. CIH, but not sleep fragmentation alone, induced an increase in macrophage recruitment to peripheral sensory tissues (sciatic nerve and dorsal root ganglia), an increase in inflammatory cytokines in the circulation, and nociceptor sensitization. Peripheral macrophage ablation blocked CIH-induced hyperalgesic priming. The findings suggest that correcting the hypoxia or targeting macrophage signaling might suppress persistent pain in patients with OSA. Editor's summary: Chronic pain is associated with both obstructive sleep apnea and sleep deprivation, which is a consequence of sleep apnea. Chivers et al. found that mice exposed during sleep to chronic episodes of hypoxia—but not those merely roused from sleep as often—were more sensitive to heat and touch. Hypoxia activated peripheral macrophages in the circulation and promoted their recruitment into sensory nerve tissues, whose sensitivity was increased by macrophage-released cytokines. The findings identify a target to potentially reduce chronic pain in patients with sleep apnea. —Leslie K. Ferrarelli [ABSTRACT FROM AUTHOR]

This study aims to investigate how assimilating GOES‐16 ABI infrared brightness temperature (BT) with different microphysics schemes affects the convection‐allowing analysis and prediction of the 3 May 2020 bow echo case. The Gridpoint Statistical Interpolation‐based Ensemble Kalman Filter (GSI‐EnKF) system and Weather Research and Forecasting (WRF) model are utilized to conduct data assimilation (DA) experiments using Thompson, WDM6, NSSL, and Morrison microphysics schemes. Correlation structures between BT and model state variables indicate that assimilating infrared BT can adjust bowing MCS dynamics via latent cooling and the rear inflow jet. Such corrections during DA cycling enhance the rear inflow jet and bow echo size, primarily for microphysics schemes featuring faster hydrometeor fall velocity and stronger latent cooling. The improved analyses lead to better forecasts of the bow echo's shape, size, timing of the bowing process, and wind speeds. Substituting a larger microphysics‐dependent effective radius for a constant default value increases prior BT, the magnitude of BT innovations, and accumulated impact on the rear inflow jet, especially for the WDM6 and Morrison schemes. In the subsequent forecasts, incorporating microphysics‐dependent effective radius further improves the experiment using the Morrison scheme but degrades it when using the WDM6 scheme. Plain Language Summary: Past studies have shown that incorporating infrared radiance observations, sensitive to water vapor and cloud top, into weather prediction models enhances the analysis of current weather conditions and the forecast accuracy for severe weather events. However, previous studies focused only on a single method to parameterize cloud particles and did not explore how cloud particle characteristics—such as falling speed, phase changes, and scattered size—affect the assimilation of these infrared radiance observations into model states. This study investigates how different cloud parameterization methods affect the analysis and forecast of a severe weather event on 3 May 2020. Our findings illustrate that using infrared radiance observations from the GOES‐16 satellite adjusts the dynamics of a bow echo, enhancing evaporation and circulation within the storm. These adjustments notably improve the forecast accuracy for the bow echo's shape, size, timing, and wind speeds. Employing parameterization methods with faster cloud falling speeds and stronger evaporation intensifies the storm's circulation, resulting in a wider bow echo and a subsequent area of severe wind damage in the forecast. Furthermore, assigning large scattered particle sizes based on the applied cloud parameterization methods can either enhance or degrade the severe storm forecast. Key Points: Assimilation of all‐sky infrared radiance improves analysis and forecast of bow echo dynamicsMicrophysics schemes affect assimilating all‐sky radiance through latent cooling and hydrometeor fall velocity assumptionImproving consistency in effective radius between forward operator and microphysics scheme also affects assimilation results of all‐sky radiances depending on schemes [ABSTRACT FROM AUTHOR]

Arteries adapt to their mechanical environment by undergoing remodeling of the structural scaffold via the action of matrix metalloproteinases (MMPs). Cell culture studies have shown that stretching vascular smooth muscle cells (VSMCs) positively correlates to the production of MMP-2 and -9. In tissue level studies, the expressions and activations of MMP-2 and -9 are generally higher in the outer media. However, homogeneous mechanical models of arteries predict lower stress and strain in the outer media, which appear inconsistent with experimental findings. The effects of heterogeneity may be important to our understanding of VSMC function since arteries exhibit structural heterogeneity across the wall. We hypothesized that local stresses, computed using a heterogeneous mechanical model of arteries, positively correlate to the levels of MMP-2 and -9 in situ. We developed a model of the arterial wall accounting for nonlinearity, residual strain, anisotropy and structural heterogeneity. The distributions of elastin and collagen fibers in situ, measured in the media of porcine carotid arteries, showed significant nonuniformities. Anisotropy was represented by the direction of collagen fibers measured by the helical angle of VSMC nuclei. The points at which the collagen fibers became load bearing were computed, assuming a uniform fiber strain and orientation under physiological loading conditions, an assumption motivated by morphological measurements. The distributions of circumferential stresses, computed using both heterogeneous and homogeneous models, were correlated to the distributions of expressions and activations of MMP-2 and -9 in porcine common carotid arteries incubated in an ex vivo perfusion organ culture system under physiological conditions for 48 h. While strains computed using incompressibility were identical in both models, the heterogeneous model, unlike the homogeneous model, predicted higher circumferential stresses in the outer layer correlated to the expressions and activations of MMP-2 and -9. This implies that localized remodeling occurs in the areas of high stress and agrees with results from cell culture studies. The results support the role of mechanical stress in vascular remodeling and the importance of structural heterogeneity in understanding mechanobiological responses. [DOI: 10.1115/1.3005163] Keywords: modeling, blood vessels, vascular smooth muscle cells, matrix metalloproteinase, vascular remodeling

As the outermost barrier tissue of the body, the skin harbors a large number of innate lymphoid cells (ILCs) that help maintain local homeostasis in the face of changing environments. How skin-resident ILCs are regulated and function in local homeostatic maintenance is poorly understood. We here report the discovery of a cold-sensing neuron-initiated pathway that activates skin group 2 ILCs (ILC2s) to help maintain thermal homeostasis. In stearoyl-CoA desaturase 1 (SCD1) knockout mice whose skin is defective in heat maintenance, chronic cold stress induced excessive activation of CCR10−CD81+ST2+ skin ILC2s and associated inflammation. Mechanistically, stimulation of the cold-sensing receptor TRPM8 expressed in sensory neurons of the skin led to increased production of IL-18, which, in turn, activated skin ILC2s to promote thermogenesis. Our findings reveal a neuroimmune link that regulates activation of skin ILC2s to support thermal homeostasis and promotes skin inflammation after hyperactivation. Skin ILC2s turn up the heat: Skin is a critical barrier tissue that supports organismal homeostasis through multiple pathways including maintenance of skin temperature in cold environments. Xu et al. analyzed how defects in the skin lipid barrier of stearoyl-CoA desaturase-1 (SCD-1) knockout mice that impaired maintenance of thermal homeostasis led to increased skin inflammation. Cold ambient temperatures activated TRPM8+ sensory neurons, triggering increased release of IL-18 and activation of dermal group 2 innate lymphoid cells (ILC2s). The activated ILC2s, in turn, released IL-5 enhancing expression of uncoupling protein-1 (UCP1) by dermal cells, resulting in increased thermogenesis. The neuroimmune circuit identified in this study that connects cold sensing to activation of skin ILC2s provides fresh mechanistic insights into how changes in environmental temperatures can regulate the inflammatory tone of the skin. [ABSTRACT FROM AUTHOR]

Author(s): Sang Jeong Kim [1, 2]; Yu Shin Kim [1]; Joseph P. Yuan [1]; Ronald S. Petralia [3]; Paul F. Worley [1]; David J. Linden (corresponding author) [1] Group I [...]