Phosphorylation by p38 MAPK as an alternative pathway for GSK3beta inactivation

Glycogen synthase kinase 3beta (GSK3beta) is involved in metabolism, neurodegeneration, and cancer. Inhibition of GSK3beta activity is the primary mechanism that regulates this widely expressed active kinase. Although the protein kinase Akt inhibits GSK3beta by phosphorylation at the N terminus, preventing Akt-mediated phosphorylation does not affect the cell-survival pathway activated through the GSK3beta substrate beta-catenin. Here, we show that p38 mitogen-activated protein kinase (MAPK) also inactivates GSK3beta by direct phosphorylation at its C terminus, and this inactivation can lead to an accumulation of beta-catenin. p38 MAPK-mediated phosphorylation of GSK3beta occurs primarily in the brain and thymocytes. Activation of beta-catenin-mediated signaling through GSK3beta inhibition provides a potential mechanism for p38 MAPK-mediated survival in specific tissues.     

Seasonal speedup along the western flank of the Greenland Ice Sheet

It has been widely hypothesized that a warmer climate in Greenland would increase the volume of lubricating surface meltwater reaching the ice-bedrock interface, accelerating ice flow and increasing mass loss. We have assembled a data set that provides a synoptic-scale view, spanning ice-sheet to outlet-glacier flow, with which to evaluate this hypothesis. On the ice sheet, these data reveal summer speedups (50 to 100%) consistent with, but somewhat larger than, earlier observations. The relative speedup of outlet glaciers, however, is far smaller (<15%). Furthermore, the dominant seasonal influence on Jakobshavn Isbrae's flow is the calving front's annual advance and retreat. With other effects producing outlet-glacier speedups an order of magnitude larger, seasonal melt's influence on ice flow is likely confined to those regions dominated by ice-sheet flow.     

凉瓜热风干燥动力学研究

研究一定条件下风速与风温对经烫漂预处理的凉瓜薄层热风干燥过程的影响,拟合干燥曲线方程,并计算临界含水量、传热膜系数α与传质系数kH等动力学参数.结果表明:于燥方程符合Page模型;随风速增大,α与kH均增大,但风温对两者影响不大.在温度75℃、风机频率50 Hz的条件下干燥得到的凉瓜成品质地硬脆,呈暗绿或褐黄色,品质好.     

Dependence of water-binding properties of ground meat on change in active acidity

The effect of pH value on water activity and water-binding capacity of ground meat is established. The water-binding properties of ground meat change at different levels of the sodium chloride content in it.     

哺乳母猪的颗粒日粮

共采用76头母猪(1～4 胎)进行试验,来确定颗粒日粮对母猪及其仔猪生产性能的影响.在21 d的哺乳试验中,母猪喂粉状(玉米磨碎至粒度500～600 μm)或颗粒(直径0.48 cm)形式的玉米-豆粕基础日粮.结果,日粮形状不会影响酸性洗涤纤维摄取量(ADFI)或哺乳期失重(P≥0.15).同时,每窝猪的断奶仔猪头数、仔猪存活率、每窝仔猪增重,断奶至发情的天数不受处理的影响(P≥0.15).然而,喂颗粒饲料的母猪失去较少的背膘(0.13 cm,P＜0.02).同时,喂颗粒饲料的母猪,其干物质(DM)、氮(N)和总能(GE)消化率分别提高6%、9%和9%,而每天排出的DM和N分别减少90 g和2 g(P＜0.001).总之,在不分胎次母猪中,使用颗粒饲料不仅不会影响其仔猪的生产性能,而且可提高母猪的养分消化率、减少养分的排出.     

Aurasperone A Inhibits SARS CoV-2 In Vitro: An Integrated In Vitro and In Silico Study

Several natural products recovered from a marine-derived Aspergillus niger were tested for their inhibitory activity against SARS CoV-2 in vitro. Aurasperone A (3) was found to inhibit SARS CoV-2 efficiently (IC₅₀ = 12.25 µM) with comparable activity with the positive control remdesivir (IC₅₀ = 10.11 µM). Aurasperone A exerted minimal cytotoxicity on Vero E6 cells (CC₅₀ = 32.36 mM, SI = 2641.5) and it was found to be much safer than remdesivir (CC₅₀ = 415.22 µM, SI = 41.07). To putatively highlight its molecular target, aurasperone A was subjected to molecular docking against several key-viral protein targets followed by a series of molecular dynamics-based in silico experiments that suggested M^pro to be its primary viral protein target. More potent anti-SARS CoV-2 M^pro inhibitors can be developed according to our findings presented in the present investigation.     

Neoechinulin A as a Promising SARS-CoV-2 Mpro Inhibitor: In Vitro and In Silico Study Showing the Ability of Simulations in Discerning Active from Inactive Enzyme Inhibitors

The COVID-19 pandemic and its continuing emerging variants emphasize the need to discover appropriate treatment, where vaccines alone have failed to show complete protection against the new variants of the virus. Therefore, treatment of the infected cases is critical. This paper discusses the bio-guided isolation of three indole diketopiperazine alkaloids, neoechinulin A (1), echinulin (2), and eurocristatine (3), from the Red Sea-derived Aspergillus fumigatus MR2012. Neoechinulin A (1) exhibited a potent inhibitory effect against SARS-CoV-2 M^pro with IC₅₀ value of 0.47 μM, which is comparable to the reference standard GC376. Despite the structural similarity between the three compounds, only 1 showed a promising effect. The mechanism of inhibition is discussed in light of a series of extensive molecular docking, classical and steered molecular dynamics simulation experiments. This paper sheds light on indole diketopiperazine alkaloids as a potential structural motif against SARS-CoV-2 M^pro. Additionally, it highlights the potential of different molecular docking and molecular dynamics simulation approaches in the discrimination between active and inactive structurally related M^pro inhibitors.