Tropical Origins for Recent North Atlantic Climate Change

Evidence is presented that North Atlantic climate change since 1950 is linked to a progressive warming of tropical sea surface temperatures, especially over the Indian and Pacific Oceans. The ocean changes alter the pattern and magnitude of tropical rainfall and atmospheric heating, the atmospheric response to which includes the spatial structure of the North Atlantic Oscillation (NAO). The slow, tropical ocean warming has thus forced a commensurate trend toward one extreme phase of the NAO during the past half-century

Pik3r1 Is Required for Glucocorticoid-Induced Perilipin 1 Phosphorylation in Lipid Droplet for Adipocyte Lipolysis.

Glucocorticoids promote lipolysis in white adipose tissue (WAT) to adapt to energy demands under stress, whereas superfluous lipolysis causes metabolic disorders, including dyslipidemia and hepatic steatosis. Glucocorticoid-induced lipolysis requires the phosphorylation of cytosolic hormone-sensitive lipase (HSL) and perilipin 1 (Plin1) in the lipid droplet by protein kinase A (PKA). We previously identified Pik3r1 (also called p85α) as a glucocorticoid receptor target gene. Here, we found that glucocorticoids increased HSL phosphorylation, but not Plin1 phosphorylation, in adipose tissue-specific Pik3r1-null (AKO) mice. Furthermore, in lipid droplets, the phosphorylation of HSL and Plin1 and the levels of catalytic and regulatory subunits of PKA were increased by glucocorticoids in wild-type mice. However, these effects were attenuated in AKO mice. In agreement with reduced WAT lipolysis, glucocorticoid- initiated hepatic steatosis and hypertriglyceridemia were improved in AKO mice. Our data demonstrated a novel role of Pik3r1 that was independent of the regulatory function of phosphoinositide 3-kinase in mediating the metabolic action of glucocorticoids. Thus, the inhibition of Pik3r1 in adipocytes could alleviate lipid disorders caused by excess glucocorticoid exposure

Repression of glucocorticoid-stimulated angiopoietin-like 4 gene transcription by insulin.

Angiopoietin-like 4 (Angptl4) is a glucocorticoid receptor (GR) primary target gene in hepatocytes and adipocytes. It encodes a secreted protein that inhibits extracellular LPL and promotes adipocyte lipolysis. In Angptl4 null mice, glucocorticoid-induced adipocyte lipolysis and hepatic steatosis are compromised. Markedly, insulin suppressed glucocorticoid-induced Angptl4 transcription. To unravel the mechanism, we utilized small molecules to inhibit insulin signaling components and found that phosphatidylinositol 3-kinase and Akt were vital for the suppression in H4IIE cells. A forkhead box transcription factor response element (FRE) was found near the 15 bp Angptl4 glucocorticoid response element (GRE). Mutating the Angptl4 FRE significantly reduced glucocorticoid-induced reporter gene expression in cells. Moreover, chromatin immunoprecipitation revealed that GR and FoxO1 were recruited to Angptl4 GRE and FRE in a glucocorticoid-dependent manner, and cotreatment with insulin abolished both recruitments. Furthermore, in 24 h fasted mice, significant occupancy of GR and FoxO1 at the Angptl4 GRE and FRE was found in the liver. In contrast, both occupancies were diminished after 24 h refeeding. Finally, overexpression of dominant negative FoxO1 mutant abolished glucocorticoid-induced Angptl4 expression, mimicking the insulin suppression. Overall, we demonstrate that both GR and FoxO1 are required for Angptl4 transcription activation, and that FoxO1 negatively mediates the suppressive effect of insulin

The glucocorticoid-Angptl4-ceramide axis induces insulin resistance through PP2A and PKCζ.

Chronic glucocorticoid exposure is associated with the development of insulin resistance. We showed that glucocorticoid-induced insulin resistance was attenuated upon ablation of Angptl4, a glucocorticoid target gene encoding the secreted protein angiopoietin-like 4, which mediates glucocorticoid-induced lipolysis in white adipose tissue. Through metabolomic profiling, we revealed that glucocorticoid treatment increased hepatic ceramide concentrations by inducing enzymes in the ceramide synthetic pathway in an Angptl4-dependent manner. Angptl4 was also required for glucocorticoids to stimulate the activities of the downstream effectors of ceramide, protein phosphatase 2A (PP2A) and protein kinase Cζ (PKCζ). We further showed that knockdown of PP2A or inhibition of PKCζ or ceramide synthesis prevented glucocorticoid-induced glucose intolerance in wild-type mice. Moreover, the inhibition of PKCζ or ceramide synthesis did not further improve glucose tolerance in Angptl4-/- mice, suggesting that these molecules were major downstream effectors of Angptl4. Overall, our study demonstrates the key role of Angptl4 in glucocorticoid-augmented hepatic ceramide production that induces whole-body insulin resistance

Transcriptional regulation of FoxO3 gene by glucocorticoids in murine myotubes.

Glucocorticoids and FoxO3 exert similar metabolic effects in skeletal muscle. FoxO3 gene expression was increased by dexamethasone (Dex), a synthetic glucocorticoid, both in vitro and in vivo. In C2C12 myotubes the increased expression is due to, at least in part, the elevated rate of FoxO3 gene transcription. In the mouse FoxO3 gene, we identified three glucocorticoid receptor (GR) binding regions (GBRs): one being upstream of the transcription start site, -17kbGBR; and two in introns, +45kbGBR and +71kbGBR. Together, these three GBRs contain four 15-bp glucocorticoid response elements (GREs). Micrococcal nuclease (MNase) assay revealed that Dex treatment increased the sensitivity to MNase in the GRE of +45kbGBR and +71kbGBR upon 30- and 60-min Dex treatment, respectively. Conversely, Dex treatment did not affect the chromatin structure near the -17kbGBR, in which the GRE is located in the linker region. Dex treatment also increased histone H3 and/or H4 acetylation in genomic regions near all three GBRs. Moreover, using chromatin conformation capture (3C) assay, we showed that Dex treatment increased the interaction between the -17kbGBR and two genomic regions: one located around +500 bp and the other around +73 kb. Finally, the transcriptional coregulator p300 was recruited to all three GBRs upon Dex treatment. The reduction of p300 expression decreased FoxO3 gene expression and Dex-stimulated interaction between distinct genomic regions of FoxO3 gene identified by 3C. Overall, our results demonstrate that glucocorticoids activated FoxO3 gene transcription through multiple GREs by chromatin structural change and DNA looping

Exposure assessment of dietary cadmium: findings from shanghainese over 40 years, China

BACKGROUND: Environmental exposure to cadmium causes renal dysfunction and bone damage. Cadmium contamination in food is regarded as the main environmental source of non-occupational exposure. The aim of this study was to assess the contribution of dietary cadmium exposure in environmental cadmium exposure and its health risk among adults in Shanghai, China. METHODS: A cross-sectional survey about food consumption was conducted in 2008 among 207 citizens aged over 40 years in Shanghai, China. The food frequency questionnaire was combined with food, tobacco and water cadmium exposure to estimate the daily environmental cadmium exposure in both point and probabilistic estimations. Urine and blood samples of the participants were analyzed for internal exposure to total cadmium. Correlation analysis was conducted between the internal cadmium exposure and environmental cadmium exposure. RESULTS: According to the point estimation, average daily environmental cadmium exposure of the participants was 16.7 μg/day and approached 33.8% of the provisional tolerable daily intake (PTDI). Dietary and tobacco cadmium exposure approached 25.8% and 7.9% of the PTDI, respectively. Males had higher levels of dietary cadmium exposure than females (p?=?0.002). The probabilistic model showed that 93.4% of the population did not have any health risks from dietary cadmium exposure. By sensitivity analysis, tobacco consumption, tobacco cadmium level, cadmium in vegetables and cadmium in rice accounted for 27.5%, 24.9%, 20.2% and 14.6% of the total cadmium exposure, respectively. The mean values of urinary and blood cadmium among the study population were 0.5 μg/L and 1.9 μg/L, respectively. Positive correlations were observed between environmental cadmium exposure and blood cadmium (R?=?0.52, P<0.01), tobacco cadmium intake and blood cadmium excluding non-smokers (R?=?0.26, P?=?0.049<0.05), and urine cadmium and age (R?=?0.15, P?=?0.037). CONCLUSIONS: It has been suggested that there is no increased health risk among adult residents in Shanghai, China because of recent total cadmium exposure. Vegetables and rice were the main sources of dietary cadmium intake. Tobacco cadmium exposure, which accounted for approximately 25% of the total dietary cadmium exposure, was another important source of non-occupational cadmium exposure

Disruptions as Opportunities

Disruptions as Opportunities: Governing Chinese Society with Interactive Authoritarianism addresses the long-standing puzzle of why China outlived other one-party authoritarian regimes with particular attention to how the state manages an emerging civil society. Drawing upon over 1,200 survey responses conducted in 126 villages in the Sichuan province, as well as 70 interviews conducted with Civil Society Organization (CSO) leaders and government officials, participant observation, and online research, the book proposes a new theory of interactive authoritarianism to explain how an adaptive authoritarian state manages nascent civil society. Sun argues that when new phenomena and forces are introduced into Chinese society, the Chinese state adopts a three-stage interactive approach toward societal actors: toleration, differentiation, and legalization without institutionalization. Sun looks to three disruptions—earthquakes, internet censorship, and social-media-based guerilla resistance to the ride-sharing industry—to test his theory about the three-stage interactive authoritarian approach and argues that the Chinese government evolves and consolidates its power in moments of crisis

Civil society under authoritarian rule: disasters, social capital, and their consequences in Chinese state-society relations

This dissertation addresses the question “how disasters change state-society relations under authoritarian rule?” Specifically, I investigate how space and social capital were created after major earthquakes and the relationships between local governments and civil society organizations (CSOs). Based on four years of interviews conducted with government officials and CSO leaders and two rounds of surveys in 126 villages in rural Sichuan province, utilizing experiments, focus groups, and interviews, I argue that social capital and space for CSOs were created after major earthquakes. Adding to the literature of consultative authoritarianism and graduated control, I demonstrate that within the newly created space, local governments use a deliberate differentiation strategy towards different CSOs. Such differentiation is more driven by the state’s interest to extract productivity and outsource responsibility for public goods provision by regime-supporting CSOs, and less dictated by the state’s need to acquire information from regime-challenging CSOs with collective action potential. Such approach contributes to the authoritarian resilience in China. Despite the interference from the state from above, the newly created space also faces challenges from the private sphere with individual citizens being skeptical of the CSO sector due to limited interactions, mismatch of criteria, institutional constraints, and lack of civility. I then draw from the qualitative data and construct a dynamic framework of state-society relations under an authoritarian state after disasters by starting from co-operational, complementary, competitive, and confrontational relations, and end up in either co-optation or confrontation in the long run. Finally, I trace the development of the newly drafted charity law and the foreign NGO law. I argue that the state-organized legalization process would first allow the state to use the “zone of indifference” to get to know the new developments in the public sphere. Then, through a process of toleration, participation, initiation, replication, and bifurcation, the state manages to extract productivity from, and outsource responsibility to, the regime-supporting players, and drive out the regime challenging ones. The laws, made through this process, is also vulnerable to state intervention at any time, and therefore, prevents China from having a meaningful civil society.2020-02-22T00:00:00

Disruptions as Opportunities

Disruptions as Opportunities: Governing Chinese Society with Interactive Authoritarianism addresses the long-standing puzzle of why China outlived other one-party authoritarian regimes with particular attention to how the state manages an emerging civil society. Drawing upon over 1,200 survey responses conducted in 126 villages in the Sichuan province, as well as 70 interviews conducted with Civil Society Organization (CSO) leaders and government officials, participant observation, and online research, the book proposes a new theory of interactive authoritarianism to explain how an adaptive authoritarian state manages nascent civil society. Sun argues that when new phenomena and forces are introduced into Chinese society, the Chinese state adopts a three-stage interactive approach toward societal actors: toleration, differentiation, and legalization without institutionalization. Sun looks to three disruptions—earthquakes, internet censorship, and social-media-based guerilla resistance to the ride-sharing industry—to test his theory about the three-stage interactive authoritarian approach and argues that the Chinese government evolves and consolidates its power in moments of crisis