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BMI1, also known as B lymphoma Mo-MLV insertion region 1, is a protein in the Polycomb group that is implicated in various cellular processes, including stem cell self-renewal and the regulation of cellular senescence. BMI1 plays a role in the regulation of retinal progenitor cells and the renewal of adult neuronal cells. However, the presence, location, and quantification of BMI1 in the adult human eye have never previously been reported. In this study, we collected 45 frozen globes from eye banks, and ocular tissues were dissected. Protein was quantified by utilizing a custom electrochemiluminescence (ECL) assay developed to quantify the BMI1 protein. BMI1 was found in all ocular tissues at the following levels: the retina (1483.6 ± 191.7 pg/mL) and the RPE (296.4 ± 78.1 pg/mL). BMI1 expression was noted ubiquitously in the GCL (ganglion cell layer), the INL (inner nuclear layer), the ONL (outer nuclear layer), and the RPE (retinal pigment epithelium) via immunofluorescence, with higher levels in the inner than in the outer retinal layers and the RPE. These data confirm that BMI1 is expressed in the human retina. Further studies will illuminate the role that BMI1 plays in ocular cells. BMI1 levels are lower in aged retinas, possibly reflecting changes in retinal somatic and stem cell maintenance and disease susceptibility. [ABSTRACT FROM AUTHOR]

Slag eyes are the upper exposed areas of molten steel in a refining ladle that are formed due to excessive bottom argon bubbling. This phenomenon frequently occurs in the steel-refining process and can lead to slag entrapment and re-oxidation of molten steel. Taking a 150-t industrial steel ladle as the research object, the effects of a dual-plug gas-blown process on the slag-eye size were studied using hydraulic modeling and large-eddy simulations. The experimental results showed that at higher gas flow rates such as 9.1 and 11.7 normal liters/min (Nl/min), the relative central angle of the two porous plugs had a significant effect on the slag-eye size; conversely, at lower gas flow rates, its influence could be ignored. Due to the tendency of the two small slag eyes to merge, the 0.6R–45° (R being the bottom radius of the ladle) case resulted in a larger total slag-eye area compared to the cases with other angles. The 0.6R–135° case showed the most beneficial results for reducing the slag-eye size. Additionally, the numerical simulations helped us to visualize the bubble-uplifting and slag-eye formation processes, and they allowed an exploration of the slag-entrapment mechanism. The simulation results showed that the symmetric gas-blown mode can reduce slag entrapment when compared with the asymmetric mode for the 135°–11.7 Nl/min case; this will be favorable to control the cleanliness of the molten steel. Additionally, analysis of both liquid-level fluctuations and turbulent-kinetic-energy distributions further confirmed the advantages of the symmetric gas-blown mode for suppressing slag entrapment. [ABSTRACT FROM AUTHOR]

Neural activation increases blood flow locally. This vascular signal is used by functional imaging techniques to infer the location and strength of neural activity (1,2). However, the precise spatial scale over which neural and vascular signals are correlated is unknown. Furthermore, the relative role of synaptic and spiking activity in driving haemodynamic signals is controversial (3-9). Previous studies recorded local field potentials as a measure of synaptic activity together with spiking activity and low-resolution haemodynamic imaging. Here we used two-photon microscopy to measure sensory-evoked responses of individual blood vessels (dilation, blood velocity) while imaging synaptic and spiking activity in the surrounding tissue using fluorescent glutamate and calcium sensors. In cat primary visual cortex, where neurons are clustered by their preference for stimulus orientation, we discovered new maps for excitatory synaptic activity, which were organized similarly to those for spiking activity but were less selective for stimulus orientation and direction. We generated tuning curves for individual vessel responses for the first time and found that parenchymal vessels in cortical layer 2/3 were orientation selective. Neighbouring penetrating arterioles had different orientation preferences. Pial surface arteries in cats, as well as surface arteries and penetrating arterioles in rat visual cortex (where orientation maps do not exist (10)), responded to visual stimuli but had no orientation selectivity. We integrated synaptic or spiking responses around individual parenchymal vessels in cats and established that the vascular and neural responses had the same orientation preference. However, synaptic and spiking responses were more selective than vascular responses--vessels frequently responded robustly to stimuli that evoked little to no neural activity in the surrounding tissue. Thus, local neural and haemodynamic signals were partly decoupled. Together, these results indicate that intrinsic cortical properties, such as propagation of vascular dilation between neighbouring columns, need to be accounted for when decoding haemodynamic signals., To determine how neural activity leads to changes in cerebral blood flow, the haemodynamic responses of individual vessels need to be compared to neural activity in the surrounding tissue (11). [...]

Background: It has been well documented that metabolic syndrome (MetS) increases severity of periodontitis. In this study, we determined the effect of high‐fat diet (HFD)‐induced MetS on alveolar bone loss in a mouse model with ligature‐induced periodontitis. To understand how MetS increases bone loss, we tested our hypothesis that palmitic acid (PA), a most abundant saturated fatty acid in the HFD, interacts with lipopolysaccharide (LPS) to promote osteoclastogenesis. Methods: We induced MetS by feeding mice HFD for 18 weeks and induced periodontitis with ligature placement. After treatments, we assessed alveolar bone loss using micro‐computed tomography and determined osteoclastogenesis using tartrate‐resistant acid phosphatase (TRAP) staining. To explore the mechanisms, we treated macrophages with PA, LPS or both and analyzed the osteoclast formation and cytokine expression in macrophages. Results: While ligature robustly induced periodontitis in mice with or without MetS, the mice with MetS had more bone loss than those without MetS. PA and LPS cooperatively induced osteoclast formation and stimulated the expression of inflammatory cytokines involved in osteoclastogenesis potentially via a FAT/CD36‐dependent mechanism in macrophages. Conclusions: HFD‐induced MetS increases alveolar bone loss in mice with ligature‐induced periodontitis, and PA and LPS cooperatively stimulate osteoclast formation and proinflammatory gene expression in macrophages. [ABSTRACT FROM AUTHOR]

Background and objective: Clinical studies have shown that metabolic syndrome (MetS) exacerbates periodontitis. However, the underlying mechanisms remain largely unknown. Since our animal study has shown that high‐fat diet‐induced MetS exacerbates lipopolysaccharide (LPS)‐stimulated periodontitis in mouse model and our in vitro study showed that acid sphingomyelinase (aSMase) plays a key role in the amplification of LPS‐triggered pro‐inflammatory response by palmitic acid (PA) in macrophages, we tested our hypothesis that inhibitor of aSMase attenuates MetS‐exacerbated periodontitis in animal model. Furthermore, to explore the potential underlying mechanisms, we tested our hypothesis that aSMase inhibitor downregulates pro‐inflammatory and pro‐osteoclastogenic gene expression in macrophages in vitro. Material and methods: We induced MetS and periodontitis in C57BL/6 mice by feeding high‐fat diet (HFD) and periodontal injection of A. actinomycetemcomitans LPS, respectively, and treated mice with imipramine, a well‐established inhibitor of aSMase. Micro‐computed tomography (micro‐CT), tartrate‐resistant acid phosphatase staining, histological and pathological evaluations as well as cell cultures were performed to evaluate alveolar bone loss, osteoclast formation, periodontal inflammation and pro‐inflammatory gene expression. Results: Analysis of metabolic parameter showed that while HFD induced MetS by increasing bodyweight, insulin resistance, cholesterol and free fatty acids, imipramine reduced free fatty acids but had no significant effects on other metabolic parameters. MicroCT showed that either MetS or periodontitis significantly reduced bone volume fraction (BVF) of maxilla and the combination of MetS and periodontitis further reduced BVF. However, imipramine increased BVF in mice with both MetS and periodontitis to a level similar to that in mice with periodontitis alone, suggesting that imipramine abolished the synergy between MetS and periodontitis on alveolar bone loss. Consistently, results showed that imipramine inhibited osteoclast formation and periodontal inflammation in mice with both MetS and periodontitis. To elucidate the mechanisms by which imipramine attenuates MetS‐exacerbated periodontitis, we showed that imipramine inhibited the upregulation of pro‐inflammatory cytokines and transcription factor c‐FOS as well as ceramide production by LPS plus PA in macrophages. Conclusion: This study has shown that imipramine as an inhibitor of aSMase abolishes the synergy between MetS and periodontitis on alveolar bone loss in animal model and inhibits pro‐inflammatory and pro‐osteoclastogenic gene expression in macrophages in vitro. This study provides the first evidence that aSMase is a potential therapeutic target for MetS‐exacerbated periodontitis. [ABSTRACT FROM AUTHOR]

Background and objective: Metabolic syndrome (MetS) exacerbates periodontitis. Since saturated fatty acid (SFA) is increased in MetS and enhances lipopolysaccharide (LPS)‐induced proinflammatory cytokine expression in macrophages, it has been considered to play a role in MetS‐exacerbated periodontitis. However, it remains unknown how fatty acid receptors, which mediate the interaction of cells with SFA and uptake of SFA, are expressed and regulated in the periodontal tissue. In this study, we tested our hypothesis that the periodontal expression of fatty acid receptors GPR40 and CD36 is increased in patients with both MetS and periodontitis. We also determined the effect of SFA and LPS on GPR40 and CD36 expression in vitro. Material and methods: Periodontal tissue specimens were collected from 11 participants without MetS and periodontitis, 12 participants with MetS, 11 participants with periodontitis, and 14 participants with both MetS and periodontitis after surgeries. The tissues were processed, and GPR40 and CD36 were detected by immunohistochemistry. Furthermore, cultured macrophages and gingival fibroblasts were treated with LPS, palmitate, a major SFA, or LPS plus palmitate and the expression of GPR40 and CD36 was then quantified. Results: Analysis of clinical data showed that age, smoker, gender, and race/ethnicity were not significantly different among 4 groups. Immunohistochemistry showed that GPR40 and CD36 were expressed by epithelial cells, fibroblasts, and immune cells. Quantitative data showed that GPR40 expression is increased in patients with periodontitis, MetS, or both periodontitis and MetS while CD36 expression is increased only in patients with both periodontitis and MetS. The in vitro studies showed that the expression of GPR40 and CD36 in macrophages and fibroblasts was upregulated by the combination of LPS and palmitate. Conclusion: Periodontal expression of GPR40 and CD36 was upregulated in patients with both MetS and periodontitis, and GPR40 and CD36 in macrophages and fibroblasts were upregulated in vitro by the combination of LPS and palmitate, suggesting that GPR40 and CD36 may be involved in MetS‐exacerbated periodontitis. [ABSTRACT FROM AUTHOR]