Redefining the Moral and Legal Roles of the State in Everyday Life: The New Life Movement in China in the Mid-1930s

Chiang Kai-shek launched the New Life Movement in Nanchang in February 1934 to revive traditional morality by reforming people’s daily behavior. In response to civil leader Wang Jingwei’s challenge, Chiang agreed to deploy moral suasion to urge the Chinese people to observe the New Life directives, but he still integrated the movement into government routine and relied on government agents, especially policemen, to implement it. Contemporary politicians and commentators understood this movement as an effective way to cultivate qualified citizens and to maintain social order in the power void caused by the retreat of the traditional rule of morality and the deficiency of the rule of law, so the New Life Movement was located in a new domain of state control between morality and law. Although this new domain was similar to the Western state apparatus of disciplining the population to produce “docile bodies” in the Foucauldian sense, it was actually an integral part of China’s own modernizing process, in which the state redefined its moral and legal role in people’s everyday lives in order to build a modern nation-state

Deep Variational Luenberger-type Observer for Stochastic Video Prediction

Considering the inherent stochasticity and uncertainty, predicting future video frames is exceptionally challenging. In this work, we study the problem of video prediction by combining interpretability of stochastic state space models and representation learning of deep neural networks. Our model builds upon an variational encoder which transforms the input video into a latent feature space and a Luenberger-type observer which captures the dynamic evolution of the latent features. This enables the decomposition of videos into static features and dynamics in an unsupervised manner. By deriving the stability theory of the nonlinear Luenberger-type observer, the hidden states in the feature space become insensitive with respect to the initial values, which improves the robustness of the overall model. Furthermore, the variational lower bound on the data log-likelihood can be derived to obtain the tractable posterior prediction distribution based on the variational principle. Finally, the experiments such as the Bouncing Balls dataset and the Pendulum dataset are provided to demonstrate the proposed model outperforms concurrent works

Stimulation of the D5 Dopamine Receptor Acidifies the Lysosomal pH of Retinal Pigmented Epithelial Cells and Decreases Accumulation of Autofluorescent Photoreceptor Debris

Optimal neuronal activity requires that supporting cells provide both efficient nutrient delivery and waste disposal. The incomplete processing of engulfed waste by their lysosomes can lead to accumulation of residual material and compromise their support of neurons. As most degradative lysosomal enzymes function best at an acidic pH, lysosomal alkalinization can impede enzyme activity and increase lipofuscin accumulation. We hypothesize that treatment to reacidify compromised lysosomes can enhance degradation. Here, we demonstrate that degradation of ingested photoreceptor outer segments by retinal pigmented epithelial (RPE) cells is increased by stimulation of D5 dopamine receptors. D1/D5 receptor agonists reacidified lysosomes in cells alkalinized by chloroquine or tamoxifen, with acidification dependent on protein kinase A. Knockdown with siRNA confirmed acidification was mediated by the D5 receptor. Exposure of cells to outer segments increased lipofuscin-like autofluorescence, but SKF 81297 reduced autofluorescence. Likewise, SKF 81297 increased the activity of lysosomal protease cathepsin D in situ. D5DR stimulation also acidified lysosomes of RPE cells from elderly ABCA4−/− mice, a model of recessive Stargardt’s retinal degeneration. In conclusion, D5 receptor stimulation lowers compromised lysosomal pH, enhancing degradation. The reduced accumulation of lipofuscin-like autofluorescence implies the D5 receptor stimulation may enable cells to better support adjacent neurons

Stimulation of the D5 Dopamine Receptor Acidifies the Lysosomal pH of Retinal Pigmented Epithelial Cells and Decreases Accumulation of Autofluorescent Photoreceptor Debris

Optimal neuronal activity requires that supporting cells provide both efficient nutrient delivery and waste disposal. The incomplete processing of engulfed waste by their lysosomes can lead to accumulation of residual material and compromise their support of neurons. As most degradative lysosomal enzymes function best at an acidic pH, lysosomal alkalinization can impede enzyme activity and increase lipofuscin accumulation. We hypothesize that treatment to reacidify compromised lysosomes can enhance degradation. Here, we demonstrate that degradation of ingested photoreceptor outer segments by retinal pigmented epithelial cells is increased by stimulation of D5 dopamine receptors. D1/D5 receptor agonists reacidified lysosomes in cells alkalinized by chloroquine or tamoxifen, with acidification dependent on protein kinase A. Knockdown with siRNA confirmed acidification was mediated by the D5 receptor. Exposure of cells to outer segments increased lipofuscin-like autofluorescence, but SKF 81297 reduced autofluorescence. Likewise, SKF 81297 increased the activity of lysosomal protease cathepsin D in situ. D5DR stimulation also acidified lysosomes of retinal pigmented epithelial cells from elderly ABCA4-/- mice, a model of recessive Stargardt\u27s retinal degeneration. In conclusion, D5 receptor stimulation lowers compromised lysosomal pH, enhancing degradation. The reduced accumulation of lipofuscin-like autofluorescence implies the D5 receptor stimulation may enable cells to better support adjacent neurons. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry

Single cell cortical bone transcriptomics define novel osteolineage gene sets altered in chronic kidney disease

IntroductionDue to a lack of spatial-temporal resolution at the single cell level, the etiologies of the bone dysfunction caused by diseases such as normal aging, osteoporosis, and the metabolic bone disease associated with chronic kidney disease (CKD) remain largely unknown.MethodsTo this end, flow cytometry and scRNAseq were performed on long bone cells from Sost-cre/Ai9+ mice, and pure osteolineage transcriptomes were identified, including novel osteocyte-specific gene sets.ResultsClustering analysis isolated osteoblast precursors that expressed Tnc, Mmp13, and Spp1, and a mature osteoblast population defined by Smpd3, Col1a1, and Col11a1. Osteocytes were demarcated by Cd109, Ptprz1, Ramp1, Bambi, Adamts14, Spns2, Bmp2, WasI, and Phex. We validated our in vivo scRNAseq using integrative in vitro promoter occupancy via ATACseq coupled with transcriptomic analyses of a conditional, temporally differentiated MSC cell line. Further, trajectory analyses predicted osteoblast-to-osteocyte transitions via defined pathways associated with a distinct metabolic shift as determined by single-cell flux estimation analysis (scFEA). Using the adenine mouse model of CKD, at a time point prior to major skeletal alterations, we found that gene expression within all stages of the osteolineage was disturbed.ConclusionIn sum, distinct populations of osteoblasts/osteocytes were defined at the single cell level. Using this roadmap of gene assembly, we demonstrated unrealized molecular defects across multiple bone cell populations in a mouse model of CKD, and our collective results suggest a potentially earlier and more broad bone pathology in this disease than previously recognized

PIMT is a Novel and Potent Suppressor of Endothelial Activation

Proinflammatory agonists provoke the expression of cell surface adhesion molecules on endothelium in order to facilitate leukocyte infiltration into tissues. Rigorous control over this process is important to prevent unwanted inflammation and organ damage. Protein L-isoaspartyl O-methyltransferase (PIMT) converts isoaspartyl residues to conventional methylated forms in cells undergoing stress-induced protein damage. The purpose of this study was to determine the role of PIMT in vascular homeostasis. PIMT is abundantly expressed in mouse lung endothelium and PIMT deficiency in mice exacerbated pulmonary inflammation and vascular leakage to LPS(lipopolysaccharide). Furthermore, we found that PIMT inhibited LPS-induced toll-like receptor signaling through its interaction with TNF receptor-associated factor 6 (TRAF6) and its ability to methylate asparagine residues in the coiled-coil domain. This interaction was found to inhibit TRAF6 oligomerization and autoubiquitination, which prevented NF-κB transactivation and subsequent expression of endothelial adhesion molecules. Separately, PIMT also suppressed ICAM-1 expression by inhibiting its N-glycosylation, causing effects on protein stability that ultimately translated into reduced EC(endothelial cell)-leukocyte interactions. Our study has identified PIMT as a novel and potent suppressor of endothelial activation. Taken together, these findings suggest that therapeutic targeting of PIMT may be effective in limiting organ injury in inflammatory vascular diseases