Activation of PI3-Kinase Is Required for AMPA Receptor Insertion during LTP of mEPSCs in Cultured Hippocampal Neurons

AbstractHippocampal CA1 homosynaptic long-term potentiation (LTP) is expressed specifically at activated synapses. Increased insertion of postsynaptic α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptors (AMPARs) appears to be crucial for CA1 LTP. However, the mechanism underlying AMPAR insertion during LTP remains largely unknown. We now report that phosphatidylinositol 3-kinase (PI3K) is complexed with AMPARs at synapses and activated by selective stimulation of synaptic N-methyl-D-aspartate (NMDA) receptors. Activation of the AMPAR-associated PI3K is required for the increased cell surface expression of AMPARs and LTP. Thus, our results strongly suggest that the AMPAR-PI3K complex may constitute a critical molecular signal responsible for AMPAR insertion at activated CA1 synapses during LTP, and consequently, this lipid kinase may serve to determine the polarity of NMDA receptor-dependent synaptic plasticity

Attribution of extreme precipitation in the lower reaches of the Yangtze River during May 2016

May 2016 was the third wettest May on record since 1961 over central eastern China based on station observations, with total monthly rainfall 40% more than the climatological mean for 1961–2013. Accompanying disasters such as waterlogging, landslides and debris flow struck part of the lower reaches of the Yangtze River. Causal influence of anthropogenic forcings on this event is investigated using the newly updated Met Office Hadley Centre system for attribution of extreme weather and climate events. Results indicate that there is a significant increase in May 2016 rainfall in model simulations relative to the climatological period, but this increase is largely attributable to natural variability. El Ni ̃no years have been found to be correlatedwith extreme rainfall in the Yangtze River region in previous studies—the strong El Ni ̃no of 2015–2016 may account for the extreme precipitation event in 2016. However, on smaller spatial scales we find that anthropogenic forcing has likely played a role in increasing the risk of extreme rainfall to the north of the Yangtze and decreasing it to the south

Lenalidomide or bortezomib as maintenance treatment remedy the inferior impact of high-risk cytogenetic abnormalities in non-transplant patients with newly diagnosed multiple myeloma: a real-world multi-centered study in China

Maintenance treatment is a pivotal part in the whole process management of multiple myeloma (MM), which further deepens response and improves survival. However, evidence of maintenance in non-transplant MM patients is inadequate in real-world practice. Here, we retrospectively analyzed the efficacy and survival of 375 non-transplant MM patients from 11 centers between 2010 and 2021 in north China. After a median of seven cycles of front-line regimens, there were 141, 79, and 155 patients receiving lenalidomide maintenance (L-MT), bortezomib maintenance (B-MT), or thalidomide maintenance (T-MT), respectively. Patients on L-MT and B-MT had significantly greater proportions of high-risk cytogenetic abnormalities (HRCAs) detected by fluorescence in situ hybridization (FISH), which was defined as 1q21 gain, 17p deletion, adverse immunoglobulin heavy chain (IgH) translocations. Although the progression-free survival (PFS) and overall survival (OS) were comparable among the three groups, L-MT and B-MT remedied the negative impact of HRCAs on survival (PFS of patients with HRCAs vs. patients without HRCAs: L-MT, 26.9 vs. 39.2 months, p=0.19; B-MT, 20.0 vs. 29.7 months, p=0.36; OS not reached in all groups). Patients with HRCAs in the T-MT group presented inferior clinical outcomes compared to standard-risk patients (PFS, 12.1 vs. 22.8 months, p=0.02, HR=1.8, 95% CI 1.0–3.4; OS, 54.9 months vs. NR, p<0.001, HR=3.2, 95% CI 1.5–7.0). Achieving complete response (CR) after induction therapy led to superior PFS compared to other degrees of response, regardless of maintenance medication. Furthermore, maintenance duration over 24 months correlated with favorable survival. Due to the large gap of transplant eligibility in China, optimizing maintenance therapy is important for non-transplant MM patients. In this real-world multi-centered study, our findings suggest that clinicians prefer to prescribe lenalidomide or bortezomib as maintenance therapy in high-risk settings, which are superior to thalidomide in non-transplant MM patients. Achievement of CR and maintenance duration over 2 years are positive factors that influence survival

500-yr. precipitation variability in Southern Taihang Mountains, China, and its linkages to ENSO and PDO

An annually resolved and absolutely dated ring-width chronology spanning 657 yrs. is constructed with Whitebark pine (Pinus bungeana Zucc.) samples from the southern Taihang Mountains, Eastern China. On the basis of a significant correlation between the tree-ring width index and observed instrumental data, precipitation in current May is reconstructed for the region since AD 1510, with predictor variables accounting for 37.9 % of the variance in precipitation data. In agreement with other drought reconstructions, notable dry spells occur in the 1630s–1650s, 1680s–1700s, and 1770s–1800s, whereas wet periods prevail in the 1530s–1570s, 1840s–1870s, and 1950s-present. Wavelet analysis reveals clear 2–8, 20–40, and 80–130 yrs cycles at the 95 % confidence level for the reconstructed series over the past 500 yrs, suggesting possible linkages with the El Niño-Southern Oscillation (ENSO) and the Pacific Decadal Oscillation (PDO). Correlation analysis between the tree-ring series, ENSO, and PDO index further demonstrates that precipitation is negatively correlated with PDO and ENSO in the long term

A dendroclimatic analysis of regional moisture variation in the northeastern Tibetan Plateau during the past 150 years

As a transitional zone between westerlies and the Asian Monsoon system, the northeastern part of the Tibetan Plateau (NETP) is highly sensitive to climate change. The record of historical regional moisture variation in the NETP is essential for understanding climatic variation and its relationship with different climate systems in this area. Using principal component analysis, a time series was extracted from sixteen moisture-sensitive tree-ring series to investigate the regional moisture variation in the NETP over the past 150 years. We find that the first principal component (PC1) represents 46. 9 % of the total variance, reflecting a common growth response to the climate factor. A spatial correlation analysis of PC1 with the gridded meteorological data demonstrated that the precipitation in May-June was the major factor in controlling tree-ring growth. Further analysis indicated that the westerlies had a sustained influence on rainfall in the NETP over the past 150 years. In addition, the rainfall in the NETP may be closely associated with the East Asian Monsoon (EAM). Severe drought years commonly correspond to years of a negative phase of the North Atlantic Oscillation and stronger EAM years over the past 150 years. 2012 Springer-Verlag Berlin Heidelberg

Tree-Ring Based Drought Reconstruction (A.D. 1855-2001) For The Qilian Mountains, Northwestern China

A juniper (Juniperus przewalskii Kom) tree-ring width chronology has been developed from the western-most forest of the Qilian Mountains. Our analyses demonstrate both temperature and precipitation have significant effects on tree growth and that both should be considered in climate reconstruction. Thus a regional drought history (A.D. 1855–2001) is reconstructed by calibrating with a linear interpolation through four Palmer Drought Severity Index (PDSI) grid values nearest the sampling site. Our reconstruction extends the drought history of this area and also reveals that the most severe drought occurred in the 1920s. In the context of the drought history of western China, this extreme drought between 1925–1931 is consistent over a large surrounding region of Northwestern China. Multi-taper spectral analysis reveals the existence of significant 40- to 46-year, 29-year, and 2.1- to 3-year periods of variability. Overall, our study provides reliable information for the research of past drought variability in the Qilian Mountains, Northwestern China.This item is part of the Tree-Ring Research (formerly Tree-Ring Bulletin) archive. For more information about this peer-reviewed scholarly journal, please email the Editor of Tree-Ring Research at [email protected]

Ripk3 promotes ER stress-induced necroptosis in cardiac IR injury: A mechanism involving calcium overload/XO/ROS/mPTP pathway

Receptor-interacting protein 3 (Ripk3)-mediated necroptosis contributes to cardiac ischaemia-reperfusion (IR) injury through poorly defined mechanisms. Our results demonstrated that Ripk3 was strongly upregulated in murine hearts subjected to IR injury and cardiomyocytes treated with LPS and H2O2. The higher level of Ripk3 was positively correlated to the infarction area expansion, cardiac dysfunction and augmented cardiomyocytes necroptosis. Function study further illustrated that upregulated Ripk3 evoked the endoplasmic reticulum (ER) stress, which was accompanied with an increase in intracellular Ca2+ level ([Ca2+]c) and xanthine oxidase (XO) expression. Activated XO raised cellular reactive oxygen species (ROS) that mediated the mitochondrial permeability transition pore (mPTP) opening and cardiomyocytes necroptosis. By comparison, genetic ablation of Ripk3 abrogated the ER stress and thus blocked the [Ca2+]c overload-XO-ROS-mPTP pathways, favouring a pro-survival state that ultimately resulted in the inhibition of cardiomyocytes necroptosis in the setting of cardiac IR injury. In summary, the present study helps to elucidate how necroptosis is mediated by ER stress, via the calcium overload /XO/ROS/mPTP opening axis. Keywords: Necroptosis, Ripk3, XO, ROS, mPTP, ER stres