Abnormal Spine Morphology and Enhanced LTP in LIMK-1 Knockout Mice

AbstractIn vitro studies indicate a role for the LIM kinase family in the regulation of cofilin phosphorylation and actin dynamics. In addition, abnormal expression of LIMK-1 is associated with Williams syndrome, a mental disorder with profound deficits in visuospatial cognition. However, the in vivo function of this family of kinases remains elusive. Using LIMK-1 knockout mice, we demonstrate a significant role for LIMK-1 in vivo in regulating cofilin and the actin cytoskeleton. Furthermore, we show that the knockout mice exhibited significant abnormalities in spine morphology and in synaptic function, including enhanced hippocampal long-term potentiation. The knockout mice also showed altered fear responses and spatial learning. These results indicate that LIMK-1 plays a critical role in dendritic spine morphogenesis and brain function

Stability analysis of PV generators with consideration of P&O-based power control

Photovoltaic (PV) generators have continuously increased in recent years, whose power is usually controlled through the perturbation and observation (P&O) method. In essence, the P&O method is nonlinear and discontinuous. Hence, the conventional small-signal stability analysis is not suitable anymore when the influence of the P&O-based power control is considered. Focusing on this problem, this paper adopts the nonlinear describing function (DF) method to conduct the accurate stability analysis of PV generators with consideration of P&O-based power control. The detailed procedures about the DF method are introduced, and then the related influence factors like perturbation size, filters, and so on are analyzed quantitatively. Furthermore, the comparison with the conventional stability analysis methods is made, which suggests that the DF method can effectively enhance the accuracy of the stability analysis. All the conclusions are verified by the real-time hardware-in-loop tests

A Novel Postconditioning Approach Attenuates Myocardial Ischaemia-Reperfusion Injury in Rats

Background: Ischaemia-reperfusion injury (IRI) is the damage that occurs when blood flow is restored to a tissue or organ after a period of ischaemia. Postconditioning is a therapeutic strategy aimed at reducing the tissue damage caused by IRI. Postconditioning in rodents is a useful tool to investigate the potential mechanisms of postconditioning. Currently, there is no convenient approach for postconditioning rodents. Methods: Rats were subjected to a balloon postconditioning procedure. A balloon was used to control the flow in the vessel. This allowed for easy and precise manipulation of perfusion. Evans blue and triphenyltetrazolium chloride (TTC) double staining were used to determine the infarct size. Apoptosis in the myocardium was visualised and quantified by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Western blotting was performed to assess the expression of key apoptotic proteins, i.e., B-cell lymphoma 2 (Bcl-2), Bcl-2 Associated X (Bax), and cleaved caspase-3. Results: The balloon control approach to postconditioning provided accurate control of coronary blood flow and simplified the postconditioning manipulation. Infarct size reduction was observed in IRI rats after post-conditioning. There was a decrease in cardiac apoptosis in IRI rats after conditioning, as detected by TUNEL staining. IRI rats showed increased Bcl-2 levels and decreased Bax and cleaved caspase-3 levels in the myocardium. Conclusions: Postconditioning was successfully applied in rats using this novel approach. Postconditioning with this approach reduced infarct size and apoptosis in the area at risk

Distributed Coordination Control Based on State-of-Charge for Bidirectional Power Converters in a Hybrid AC/DC Microgrid

This paper proposes a distributed coordination control for multiple bidirectional power converters (BPCs) in a hybrid AC/DC microgrid with consideration of state-of-charge (SOC) of storages. The researched hybrid AC/DC microgrid is composed of both AC and DC subgrids connected by multiple parallel BPCs. In the literature, the storages of a hybrid microgrid are considered to allocate in only the AC subgrid or DC subgrid, which reduces the reliability of the whole system, especially during the islanded mode. Besides, the SOC management has not been considered in BPCs’ operating strategy. This paper considers a hybrid microgrid topology which has energy storages in both AC side and DC side. This ensures the reliability while increasing the complexity of the control strategy at the same time. Further, a distributed coordination control method for multiple BPCs based on SOC was proposed to enhance the reliability of hybrid microgrid. Finally, the performance of the proposed control methods was verified by real-time hardware-in-loop (HIL) tests

Stability Analysis and Stability Enhancement Based on Virtual Harmonic Resistance for Meshed DC Distributed Power Systems with Constant Power Loads

This paper addresses the stability issue of the meshed DC distributed power systems (DPS) with constant power loads (CPLs) and proposes a stability enhancement method based on virtual harmonic resistance. In previous researches, the network dynamics of the meshed DC DPS are often ignored, which affects the derivation of the equivalent system impendence. In addition, few of them have considered the meshed DC DPS including multiple sources with voltage-controlled converters and CPLs. To tackle the aforementioned challenge, this paper mainly makes the following efforts. The component connection method (CCM) is employed and expanded to derive the stability criterion of the meshed DC DPS with CPLs. This stability criterion can be simplified to relate only with the network node admittance matrix, the output impendences of the sources, and the input admittances of the CPLs. A virtual harmonic resistance through the second-order generalized integrator (SOGI) is added in the source with the voltage-controlled converter to lower the peak of the source output impendence, which can enhance the stability of the meshed DC DPS. The effectiveness of the proposed stability criterion and stability enhancement method are verified by nonlinear dynamic simulations

MALAT1 Mediates α-Synuclein Expression through miR-23b-3p to Induce Autophagic Impairment and the Inflammatory Response in Microglia to Promote Apoptosis in Dopaminergic Neuronal Cells

Background. Parkinson’s disease (PD) is a very common neurodegenerative disease that adversely affects the physical and mental health of many patients, but there is currently no effective treatment. Objective. To this end, this study focused on investigating the potential mechanisms leading to dopaminergic neuronal apoptosis in PD. Methods. Rotenone induces damage in dopaminergic neuronal MN9D cells. Apoptosis was detected by flow cytometry, and the expression of apoptosis-related proteins was detected by western blot. RT-qPCR was used to detect the expression of MALAT1 and miR-23b-3p. The expression of α-synuclein was detected by ELISA. A dual luciferase gene reporter assay was used to determine the targeted regulatory relationship between MALAT1 and miR-23b-3p and miR-23b-3p and α-synuclein. MN9D supernatant was cocultured with BV-2 cells, or BV-2 cells were treated with exogenous α-synuclein and then treated with an autophagy inhibitor (3-MA) and autophagy activator (RAPA). The expression of α-synuclein in BV-2 cells was detected by immunofluorescence. The expression of MIP-1α, a marker of microglial activation, was detected by ELISA. The nuclear translocation of NF-κB p65 was detected by immunofluorescence. The expression of proinflammatory cytokines was detected by ELISA. Western blotting was used to detect the expression of autophagy-related proteins. Apoptosis of MN9D cells was detected after coculture of BV-2 supernatant with MN9D. Results. The expression of MALAT1 and α-synuclein was upregulated, while the expression of miR-23b-3p was downregulated in damaged MN9D cells, resulting in cell apoptosis. MALAT1 can negatively regulate the expression of miR-23b-3p, while miR-23b-3p negatively regulates the expression of α-synuclein. α-synuclein can enter BV-2 cells through cell phagocytosis. Coculture of BV-2 cells with α-synuclein or with MN9D supernatant overexpressing MALAT1 resulted in a decrease in the autophagy level of BV-2 cells and an inflammatory reaction. However, miR-23b-3p mimics and knockdown of α-synuclein reversed the effect of MALAT1 on autophagy and the inflammatory response of BV-2 cells. In addition, after coculture of BV-2 cells with α-synuclein, the level of autophagy further decreased when 3-MA was added, while the opposite result occurred when RAPA was added. After coculture of α-synuclein-treated BV-2 cell supernatant with MN9D cells, autophagy-impaired BV-2 promoted the apoptosis of MN9D cells, and 3-MA aggravated the autophagy disorder of BV-2 and further promoted the apoptosis of MN9D cells, while RAPA reversed the autophagy disorder of BV-2 and alleviated the apoptosis of MN9D cells. Conclusion. MALAT1 can promote α-synuclein expression by regulating miR-23b-3p, thereby inducing microglial autophagy disorder and an inflammatory response leading to apoptosis of dopaminergic neurons. This newly discovered molecular mechanism may provide a potential target for the treatment of PD