The Mechanism of Na+/K+ Selectivity in Mammalian Voltage-Gated Sodium Channels Based on Molecular Dynamics Simulation

AbstractVoltage-gated sodium (Nav) channels and their Na+/K+ selectivity are of great importance in the mammalian neuronal signaling. According to mutational analysis, the Na+/K+ selectivity in mammalian Nav channels is mainly determined by the Lys and Asp/Glu residues located at the constriction site within the selectivity filter. Despite successful molecular dynamics simulations conducted on the prokaryotic Nav channels, the lack of Lys at the constriction site of prokaryotic Nav channels limits how much can be learned about the Na+/K+ selectivity in mammalian Nav channels. In this work, we modeled the mammalian Nav channel by mutating the key residues at the constriction site in a prokaryotic Nav channel (NavRh) to its mammalian counterpart. By simulating the mutant structure, we found that the Na+ preference in mammalian Nav channels is collaboratively achieved by the deselection from Lys and the selection from Asp/Glu within the constriction site

Association between behavioral patterns and depression symptoms: dyadic interaction between couples

BackgroundBehavioral patterns are sometimes associated with depression symptoms; however, few studies have considered the intra-couple effects. This study examined the effect of a spouses’ behavioral patterns on depression symptoms within themself and in their spouse.MethodsA total of 61,118 childbearing age participants (30,559 husband-wife dyads) were surveyed. The depression symptoms were assessed using the nine-item Patient Health Questionnaire (PHQ-9). The behavioral patterns were identified by the latent class analysis. The effects of behavioral patterns on the couple’s own depression symptoms (actor effect) and their partner’s depression symptoms (partner effect) were analyzed using the Actor-Partner Interdependence Model (APIM).ResultsThree behavioral patterns were identified: low-risk group, moderate-risk group, and high-risk group. The high risk of these behavior patterns would be associated with a higher score on the PHQ-9; for both husbands and wives, their behavioral patterns were positively associated with PHQ-9 scores (βhusband = 0.53, P < 0.01; βwife = 0.58, P < 0.01). Wives’ behavioral patterns were also positively associated with their husbands’ PHQ-9 scores (β = 0.14, P < 0.01), but husbands’ behavioral patterns were not associated with their wives’ PHQ-9 scores.ConclusionsWives’ depression symptoms were affected only by their own behavioral patterns, whereas husbands’ depression symptoms were influenced by both their own and their spouses’ behavioral patterns

Sign Retention in Classical MF-DFA

In this paper, we propose a one-dimensional (1D) multifractal sign retention detrending fluctuation analysis algorithm (MF-S-DFA). The proposed method is based on conventional multifractal detrending fluctuation analysis (MF-DFA). As negative values may exist in the calculation in the original MF-DFA model, sign retention is considered to improve performance. We evaluate the two methods based on time series constructed by p-model multiplication cascades. The results indicate that the generalized Hurst exponent H(q), the scale exponent τ(q) and the singular spectrum f(α) estimated by MF-S-DFA behave almost consistently with the theoretical values. Moreover, we also employ distance functions such as DH and Dτ. The results prove that MF-S-DFA achieves more accurate estimation. In addition, we present various numerical experiments by transforming parameters such as nmax, q and p. The results imply that MF-S-DFA obtains more excellent performance than that of conventional MF-DFA in all cases. Finally, we also verify the high feasibility of MF-S-DFA in ECG signal classification. Through classification of normal and abnormal ECG signals, we further corroborate that MF-S-DFA is more effective than conventional MF-DFA

Lysine and the Na+/K+ Selectivity in Mammalian Voltage-Gated Sodium Channels.

Voltage-gated sodium (Nav) channels are critical in the generation and transmission of neuronal signals in mammals. The crystal structures of several prokaryotic Nav channels determined in recent years inspire the mechanistic studies on their selection upon the permeable cations (especially between Na+ and K+ ions), a property that is proposed to be mainly determined by residues in the selectivity filter. However, the mechanism of cation selection in mammalian Nav channels lacks direct explanation at atomic level due to the difference in amino acid sequences between mammalian and prokaryotic Nav homologues, especially at the constriction site where the DEKA motif has been identified to determine the Na+/K+ selectivity in mammalian Nav channels but is completely absent in the prokaryotic counterparts. Among the DEKA residues, Lys is of the most importance since its mutation to Arg abolishes the Na+/K+ selectivity. In this work, we modeled the pore domain of mammalian Nav channels by mutating the four residues at the constriction site of a prokaryotic Nav channel (NavRh) to DEKA, and then mechanistically investigated the contribution of Lys in cation selection using molecular dynamics simulations. The DERA mutant was generated as a comparison to understand the loss of ion selectivity caused by the K-to-R mutation. Simulations and free energy calculations on the mutants indicate that Lys facilitates Na+/K+ selection by electrostatically repelling the cation to a highly Na+-selective location sandwiched by the carboxylate groups of Asp and Glu at the constriction site. In contrast, the electrostatic repulsion is substantially weakened when Lys is mutated to Arg, because of two intrinsic properties of the Arg side chain: the planar geometric design and the sparse charge distribution of the guanidine group

Research on online teaching platform system based on microservice architecture

The traditional online teaching adopts the single architecture to develop and implement the system, which facilitates the data sharing and testing of the system. However, due to the increasing complexity of the system's business functions, the system based on monolithic architecture has become increasingly complex, its scalability has deteriorated, and its concurrency performance has decreased. Based on these problems, this paper puts forward combining microservice architecture and online teaching platform, using microservice architecture independent deployment, concurrent performance characteristics such as high technology selection and flexible, the complex business function is divided into several small service module, solve the challenges faced by the traditional system, at the same time improve the efficiency of the use of online teaching platform and students' learning autonomy, The system function design, architecture design, safety design and so on are expounded to build an efficient and perfect online teaching platform

Research on copyright appointment registration microplatform system based on vue

With the rapid development of copyright industry, people’s copyright awareness of their own creation of software and works is constantly improving, the number of applications for software copyright registration and works copyright is increasing. Therefore, how to make copyright registration business becomes more convenient and efficient is imminent. Existing copyright registration system need to first fill through PC and then make an appointment through the phone to deal with relevant business. This model is not only complicated operations, but also poor user experience. Therefore, based on the analysis of multiple needs of users and enterprises, this paper proposes to use Vue,SpringBoot, MyBatis and other technologies to develop a copyright appointment registration system based on microplatform. The development of this system can not only for the user to create a more convenient way of operation, give users a better experience, but also can change, rich business approach, bring more profits

Preparation and Properties of Partial-Degradable ZrO₂–Chitosan Particles–GelMA Composite Scaffolds

In the field of bone repair, the inorganic–organic composite scaffold is a promising strategy for mimicking the compositions of the natural bone. In addition, as implants for repairing load-bearing sites, an inert permanent bone substitute composites with bioactive degradable ingredients may make full use of the composite scaffold. Herein, the porous zirconia (ZrO2) matrix was prepared via the template replication method, and the partial degradable ZrO2–chitosan particles–GelMA composite scaffolds with different chitosan/GelMA volume ratios were prepared through the vacuum infiltration method. Dynamic light scattering (DLS) and the scanning electron microscope (SEM) were adopted to observe the size of the chitosan particles and the morphologies of the composites scaffold. The mechanical properties, swelling properties, and degradation properties of the composite scaffolds were also characterized by the mechanical properties testing machine and immersion tests. The CCK-8 assay was adopted to test the biocompatibility of the composite scaffold preliminarily. The results show that chitosan particles as small as 60 nm were obtained. In addition, the ratio of chitosan/GelMA can influence the mechanical properties and the swelling and degradation behaviors of the composites scaffold. Furthermore, improved cell proliferation performance was obtained for the composite scaffolds