Variability of PDO identified by a last 300-year stalagmite delta O-18 record in Southwest China

Stalagmite oxygen isotope (delta O-18) record has been widely used in characterizing Asian Monsoon variations. In southwest (SW) China, although the stalagmite delta O-18 was usually suggested as a precipitation proxy, it remains a subject of debate. Here we present two replicated, high-precise-dated stalagmite delta O-18 records for the interval 1710-2003 AD from Yunnan province, SW China. The stalagmite delta O-18 shows no correlation with the local monsoon precipitation, but a significantly positive correlation with the Pacific Decadal Oscillation (PDO) index. It demonstrates that the stalagmite delta O-18 in SW China is most likely influenced by the atmospheric circulation associated with the PDO through the upstream depletion mechanism. During the warm (cold) PDO period, the deficit rainfall over India would make the delta O-18 of water vapor transporting to SW China less (more) negative due to the weaker Rayleigh distillation process, which would lead to the less (more) negative stalagmite delta O-18. Consequently, the stalagmite delta O-18 in SW China is suitable to reconstruct the PDO variations. It is important to note that the other factors, such as El Nino-Southern Oscillation (ENSO) or sea surface temperature (SST) also possibly affect the stalagmite delta O-18 in SW China, and the relationship between them requires further studies. (C) 2021 Elsevier Ltd. All rights reserved

Ogt-mediated O-GlcNAcylation inhibits astrocytes activation through modulating NF-κB signaling pathway

Abstract Previous studies have shown that Ogt-mediated O-GlcNAcylation is essential for neuronal development and function. However, the function of O-GlcNAc transferase (Ogt) and O-GlcNAcylation in astrocytes remains largely unknown. Here we show that Ogt deficiency induces inflammatory activation of astrocytes in vivo and in vitro, and impairs cognitive function of mice. The restoration of O-GlcNAcylation via GlcNAc supplementation inhibits the activation of astrocytes, inflammation and improves the impaired cognitive function of Ogt deficient mice. Mechanistically, Ogt interacts with NF-κB p65 and catalyzes the O-GlcNAcylation of NF-κB p65 in astrocytes. Ogt deficiency induces the activation of NF-κB signaling pathway by promoting Gsk3β binding. Moreover, Ogt depletion induces the activation of astrocytes derived from human induced pluripotent stem cells. The restoration of O-GlcNAcylation inhibits the activation of astrocytes, inflammation and reduces Aβ plaque of AD mice in vitro and in vivo. Collectively, our study reveals a critical function of Ogt-mediated O-GlcNAcylation in astrocytes through regulating NF-κB signaling pathway

The neuroprotective role of metformin in advanced glycation end product treated human neural stem cells is AMPK-dependent

AbstractDiabetic neuronal damage results from hyperglycemia followed by increased formation of advanced glycosylation end products (AGEs), which leads to neurodegeneration, although the molecular mechanisms are still not well understood. Metformin, one of the most widely used anti-diabetic drugs, exerts its effects in part by activation of AMP-activated protein kinase (AMPK). AMPK is a critical evolutionarily conserved enzyme expressed in the liver, skeletal muscle and brain, and promotes cellular energy homeostasis and biogenesis by regulating several metabolic processes. While the mechanisms of AMPK as a metabolic regulator are well established, the neuronal role for AMPK is still unknown. In the present study, human neural stem cells (hNSCs) exposed to AGEs had significantly reduced cell viability, which correlated with decreased AMPK and mitochondria associated gene/protein (PGC1α, NRF-1 and Tfam) expressions, as well as increased activation of caspase 3 and 9 activities. Metformin prevented AGEs induced cytochrome c release from mitochondria into cytosol in the hNSCs. Co-treatment with metformin significantly abrogated the AGE-mediated effects in hNSCs. Metformin also significantly rescued hNSCs from AGE-mediated mitochondrial deficiency (lower ATP, D-loop level, mitochondrial mass, maximal respiratory function, COX activity, and mitochondrial membrane potential). Furthermore, co-treatment of hNSCs with metformin significantly blocked AGE-mediated reductions in the expression levels of several neuroprotective genes (PPARγ, Bcl-2 and CREB). These findings extend our understanding of the molecular mechanisms of both AGE-induced neuronal toxicity, and AMPK-dependent neuroprotection by metformin. This study further suggests that AMPK may be a potential therapeutic target for treating diabetic neurodegeneration

The spatio-temporal pattern of Asian summer monsoon during glacial Termination II recorded by Chinese stalagmite δ18O

The difficulty in constraining the large-scale Asian summer monsoon (ASM) variability in the Chinese monsoon region (CMR) during glacial Termination II lies in our limited knowledge of the western part, primarily due to sparse paleoclimate records. To get a better picture of the ASM during Termination II, we examined a precisely dated stalagmite δ18O record between 133.1 and 127.0 kyr B.P. from Wanxiang Cave located at the ASM's northern edge in western China. In combination with published δ18O data from this cave, we have identified the ‘Weak Monsoon Interval’ (WMI) in the Wanxiang δ18O record and confirmed that the Heinrich 11 cold event in the North Atlantic caused the weakened ASM over the CMR via reorganization of the large-scale ocean-atmospheric circulation. However, the post-WMI change in δ18O is gradual, in contrast with the abrupt shift shown in the other cave records from southern and northeastern China. The rapid northward migration of the westerly jet relative to the Qinghai-Tibet Plateau is probably responsible for this discrepancy. This northward-positioned westerly jet prevented the more 18O-depleted moisture from the Indian Ocean from reaching the study site. Simultaneously, it facilitated the earlier northward movement of the East Asian summer monsoon (EASM) rainband that carries positive precipitation δ18O to obscure the abrupt decrease in our δ18O record. After the onset of the last interglacial, no obvious Younger Dryas (YD)-like event was recorded in Wanxiang Cave. This result is consistent with most stalagmite δ18O records in the CMR and further suggests a minimal impact of the YD-like event on ASM variabilities. The relatively large amplitude of δ18O variations observed in Wanxiang Cave between the late penultimate glacial and the last interglacial corresponds to a dominant control of the Indian summer monsoon (ISM), whereas smaller δ18O amplitudes were recorded in cave sites mainly under the influence of both ISM and EASM. Therefore, we posit that the heterogeneity of the hydroclimate in the CMR during Termination II resulted from a combination of multiple processes, that is, the westerly jet, ISM and EASM, rather than a single one.Ministry of Education (MOE)Published versionThis work was supported by grants of the National Natural Science Foundation of China (No. 41873001, 41473009, 41273014, 42101024), China Scholarship Council (No. 202006180039), Department of Earth and Environmental Sciences, University of Minnesota, USA (U.S. NSF Grant 2202913 to R.L.E), and Isotope Laboratory of Xi'an Jiaotong University, China. X.F.W. acknowledges the financial support by the Ministry of Education, Singapore through an MOE Tier 2 grant (MOE2019-T2-1-174) and the Earth Observatory of Singapore (EOS)