Transient information input to the brain leads to persistent changes in synaptic circuits, contributing to the formation of memory engrams. Pre- and postsynaptic structures undergo coordinated ...functional and structural changes during this process, but how such changes are achieved by their component molecules remains largely unknown. We found that activated CaMKII, a central player of synaptic plasticity, undergoes liquid-liquid phase separation with the NMDA-type glutamate receptor subunit GluN2B. Due to CaMKII autophosphorylation, the condensate stably persists even after Ca
is removed. The selective binding of activated CaMKII with GluN2B cosegregates AMPA receptors and the synaptic adhesion molecule neuroligin into a phase-in-phase assembly. In this way, Ca
-induced liquid-liquid phase separation of CaMKII has the potential to act as an activity-dependent mechanism to crosslink postsynaptic proteins, which may serve as a platform for synaptic reorganization associated with synaptic plasticity.
It remains unclear whether the necessity of calcified mellitus induced by high inorganic phosphate (Pi) is required and the roles of autophagy plays in aldosterone (Aldo)‐enhanced vascular ...calcification (VC) and vascular smooth muscle cell (VSMC) osteogenic differentiation. In the present study, we found that Aldo enhanced VC both in vivo and in vitro only in the presence of high Pi, alongside with increased expression of VSMC osteogenic proteins (BMP2, Runx2 and OCN) and decreased expression of VSMC contractile proteins (α‐SMA, SM22α and smoothelin). However, these effects were blocked by mineralocorticoid receptor inhibitor, spironolactone. In addition, the stimulatory effects of Aldo on VSMC calcification were further accelerated by the autophagy inhibitor, 3‐MA, and were counteracted by the autophagy inducer, rapamycin. Moreover, inhibiting adenosine monophosphate‐activated protein kinase (AMPK) by Compound C attenuated Aldo/MR‐enhanced VC. These results suggested that Aldo facilitates high Pi‐induced VSMC osteogenic phenotypic switch and calcification through MR‐mediated signalling pathways that involve AMPK‐dependent autophagy, which provided new insights into Aldo excess‐associated VC in various settings.
Kv2 family "delayed-rectifier" potassium channels are widely expressed in mammalian neurons. Kv2 channels activate relatively slowly and their contribution to action potential repolarization under ...physiological conditions has been unclear. We explored the function of Kv2 channels using a Kv2-selective blocker, Guangxitoxin-1E (GxTX-1E). Using acutely isolated neurons, mixed voltage-clamp and current-clamp experiments were done at 37°C to study the physiological kinetics of channel gating and action potentials. In both rat superior cervical ganglion (SCG) neurons and mouse hippocampal CA1 pyramidal neurons, 100 nm GxTX-1E produced near-saturating block of a component of current typically constituting ∼60-80% of the total delayed-rectifier current. GxTX-1E also reduced A-type potassium current (IA), but much more weakly. In SCG neurons, 100 nm GxTX-1E broadened spikes and voltage clamp experiments using action potential waveforms showed that Kv2 channels carry ∼55% of the total outward current during action potential repolarization despite activating relatively late in the spike. In CA1 neurons, 100 nm GxTX-1E broadened spikes evoked from -70 mV, but not -80 mV, likely reflecting a greater role of Kv2 when other potassium channels were partially inactivated at -70 mV. In both CA1 and SCG neurons, inhibition of Kv2 channels produced dramatic depolarization of interspike voltages during repetitive firing. In CA1 neurons and some SCG neurons, this was associated with increased initial firing frequency. In all neurons, inhibition of Kv2 channels depressed maintained firing because neurons entered depolarization block more readily. Therefore, Kv2 channels can either decrease or increase neuronal excitability depending on the time scale of excitation.
Advances in microscopy techniques have revealed the details of synaptic nanodomains as defined by the segregation of specific molecules on or beneath both presynaptic and postsynaptic membranes. ...However, it is yet to be clarified how such segregation is accomplished without demarcating membrane and how nanodomains respond to the neuronal activity. It was recently discovered that proteins at the synapse undergo liquid–liquid phase separation (LLPS), which not only contributes to the accumulation of synaptic proteins but also to further segregating the proteins into subdomains by forming phase-in-phase structures. More specifically, CaMKII, a postsynaptic multifunctional kinase that serves as a signaling molecule, acts as a synaptic cross-linker which segregates certain molecules through LLPS in a manner triggered by Ca2+. Nanodomain formation contributes to the establishment of trans-synaptic nanocolumns, which may be involved in the optimization of spatial arrangement of the transmitter release site and receptor, thereby serving as a new mechanism of synaptic plasticity.
•The hot-dry environment of different temperatures was simulated in a laboratory.•The influence of surrounding rock temperature on concrete property of was analyzed.•The correlation analysis between ...temperature and pore structure was carried out.
In view of the temperature distribution of the high-temperature geothermal tunnels, the surrounding rock temperature was divided into four grades (40 °C, 60 °C, 80 °C and 100 °C) to simulate the hot-dry environment. Using the standard curing environment as a reference condition, the mechanical properties and pore structure characteristics of concrete for shotcrete use under hot-dry environments at different temperatures were studied by mechanical and mercury intrusion porosimetry (MIP) tests. Fractal dimension of pore structure was calculated through the fractal model based on thermodynamic method. Bivariate correlation analysis was conducted on the curing temperature and the pore structure parameters. The results show that the 40 °C hot-dry environment is conducive to enhance the mechanical properties of concrete and optimize its pore structure at the age of 1d. However, the hot-dry environments after 7 days will deteriorate the mechanical properties and pore structure of concrete, and the higher the temperature, the more obvious the deterioration. There is a significant correlation between curing temperature and porosity of capillary pores, median pore diameter, average pore diameter and fractal dimension.
The outbreak of 2019 novel coronavirus (2019-nCoV) pneumonia was reported in Wuhan, Hubei Province, China in December 2019 and has spread internationally. This article discusses how radiology ...departments can most effectively respond to this public health emergency.
This study evaluated the capability of satellite precipitation estimates from five products derived from Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks ...(including PERSIANN, PERSIANN-CCS, PERSIANN-CDR, PERSIANN-CCS-CDR, and PDIR-Now) to represent precipitation characteristics over Luzon. The analyses focused on monthly and daily timescales from 2003–2015 and adopted surface observations from the Asian Precipitation Highly Resolved Observational Data Integration Towards Evaluation of Water Resources (APHRODITE) platform as the evaluation base. Among the five satellite precipitation products (SPPs), PERSIANN-CDR was observed to possess a better ability to qualitatively and quantitatively estimate spatiotemporal variations of precipitation over Luzon for the majority of the examined features with the exception of the extreme precipitation events, for which PERSIANN-CCS-CDR is superior to the other SPPs. These results highlight the usefulness of the addition of the cloud patch approach to PERSIANN-CDR to produce PERSIANN-CCS-CDR to depict the characteristics of extreme precipitation events over Luzon. A similar advantage of adopting the cloud patch approach in producing extreme precipitation estimates was also revealed from the comparison of PERSIANN, PERSIANN-CCS, and PDIR-Now. Our analyses also highlighted that all PERSIANN-series exhibit improved skills in regard to detecting precipitation characteristics over west Luzon compared to that over east Luzon. To overcome this weakness, we suggest that an adjustment in the cloud patch approach (e.g., using different cloud temperature thresholds or different brightness temperature and precipitation rate relationships) over east Luzon may be helpful.
Summary
Artemisinin, isolated from Artemisia annua, is recommended as the preferred drug to fight malaria. Previous research showed that jasmonate (JA)‐mediated promotion of artemisinin accumulation ...depended on light. However, the mechanism underlying the interaction of light and JA in regulating artemisinin accumulation is still unknown.
We identified a WRKY transcription factor, AaWRKY9, using transcriptome analysis. The glandular trichome‐specific AaWRKY9 positively regulates artemisinin biosynthesis by directly binding to the promoters of AaDBR2 and AaGSW1.
The key regulator in the light pathway AaHY5 activates the expression of AaWRKY9 by binding to its promoter. In addition, AaWRKY9 interacts with AaJAZ9, a repressor in the JA signalling pathway. AaJAZ9 represses the transcriptional activation activity of AaWRKY9 in the absence of methyl jasmonate. Notably, in the presence of methyl jasmonate, the transcriptional activation activity of AaWRKY9 is increased.
Taken together, our results reveal a novel molecular mechanism underlying AaWRKY9 contributes to light‐mediated and jasmonate‐mediated to regulate the biosynthesis of artemisinin in A. annua. Our study provides new insights into integrating the two signalling pathways to regulate terpene biosynthesis in plants.
•Relationships between regional economic sectors and water consumption are analysed.•The changes in water use indicators over a decade are tracked.•The effects of water-saving policies on water use ...indicators are examined.•A case study area of virtual water assessment in a water-scarce region.•The produced policy recommendations are useful for water planning in northern China.
Northern China has been facing severe water scarcity as a result of vigorous economic growth, population expansion and changing lifestyles. A typical case is Shandong province whose water resources per capita is approximately only a sixth of the national average and a twentieth of the global average. It is useful to assess the implications of the province’s growth and trade patterns for water use and water conservation strategies. This study quantitatively analyses relationships between regional economic sectors and water use in Shandong using an input–output model for virtual water resources. The changes in key indicators for 1997–2007 are tracked and the effects of water-saving policies on these changes are examined. The results highlight the benefits of applying a virtual water trade analysis on a water-scarce region where water resources exhibit highly heterogeneous temporal and geographical distributions. The net export of virtual water in Shandong was initially large, but this declined over the years and the province has recently become a net importer. Between 1997 and 2002, water use in most sectors increased due to rapid urbanisation and industrialisation. Since then, water use in all Shandong economic sectors exhibit a downward trend despite continued increases in goods and services net exports, a trend which can be attributed to the vigorous implementation of water-saving policies and measures, especially water use quotas. Economic sectors consume water directly and indirectly and understanding the pattern of virtual water trade implied by sectoral relationships is important for managing water scarcity problems. This study fills the knowledge gap in the existing literature created by the lack of case studies that dynamically assess virtual water trade and analyse the effects of water-saving policies and measures. The study draws policy recommendations that are relevant for future water planning in Shandong and other regions in northern China.
•Results are represented in terms of LMIs, easily verified by convex optimization techniques.•Proposed criteria are computationally attractive, providing less conservative results than the existing ...ones.•Numerical examples are given to illustrate effectiveness of our theoretical results.
This study considers the robust absolute stability criteria for Lur'e systems with time-varying delay and sector-bounded nonlinearity. Using a delayed decomposition approach that splits the overall delay time into three subintervals and by introducing a new Lyapunov–Krasovskii functional, some new delay-dependent and robust absolute stability criteria are obtained in terms of linear matrix inequalities. Numerical examples from four benchmark problems are presented to illustrate the superior performance of the proposed approach compared with previously reported methods.
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