A putative structural mechanism underlying the antithetic effect of homologous RND1 and RhoD GTPases in mammalian plexin regulation

Plexins are semaphorin receptors that play essential roles in mammalian neuronal axon guidance and in many other important mammalian biological processes. Plexin signaling depends on a semaphorin-induced dimerization mechanism, and is modulated by small GTPases of the Rho family, of which RND1 serves as a plexin activator yet its close homolog RhoD an inhibitor. Using molecular dynamics (MD) simulations we showed that RND1 reinforces the plexin dimerization interface whereas RhoD destabilizes it due to their differential interaction with the cell membrane. Upon binding plexin at the Rho-GTPase binding domain (RBD), RND1 and RhoD interact differently with the inner leaflet of the cell membrane, and exert opposite effects on the dimerization interface via an allosteric network involving the RBD, RBD linkers, and a buttress segment adjacent to the dimerization interface. The differential membrane interaction is attributed to the fact that, unlike RND1, RhoD features a short C-terminal tail and a positively charged membrane interface.

Electrostatic Interaction Between NS1 and Negatively Charged Lipids Contributes to Flavivirus Replication Organelles Formation

Flavivirus replication occurs in membranous replication compartments, also known as replication organelles (ROs) derived from the host ER membrane. Our previous study showed that the non-structural (NS) protein 1 (NS1) is the essential factor for RO creation by hydrophobic insertion into the ER membrane. Here, we found that the association of NS1 with the membrane can be facilitated by the electrostatic interaction between NS1 and negatively charged lipids. NS1 binds to a series of negatively charged lipids, including PI4P, and a positively charged residue, R31, located on the membrane-binding face of NS1, plays important roles in this interaction. The NS1 R31E mutation significantly impairs NS1 association with negatively charged membrane and its ER remodeling ability in the cells. To interfere with the electrostatic interaction between NS1 and negatively charged lipids, intracellular phosphatidylinositol phosphates (PIPs) level was downregulated by the overexpression of Sac1 or treatment with PI3K and PI4K inhibitors to attenuate flavivirus replication. Our findings emphasize the importance of electrostatic interaction between NS1 and negatively charged lipids in flavivirus RO formation.

Migration of ions near charged surface

Detailed understanding of ionic behavior in the region near a charged surface is important for the enhancement of water filtration mechanisms. In this study, a highly charged membrane is hypothesized to form an ion depletion zone (IDZ) without an external power supply. The formation of IDZ was experimentally investigated using membranes with varying surface zeta potential (SZP) values to confirm the hypothesis. The surface zeta potential of the charged membrane was controlled by layer-by-layer deposition method. Our results indicate that indicated that the fluorescent intensity near the charged surface becomes weaker with an increased absolute magnitude of SZP. Ionic surfactants enhance the formation of IDZ by increasing SZP magnitude, and by forming a secondary filtration layer. These findings provide information that is helpful in understanding the ionic behavior near the highly charged surface. In addition, the information provided by the findings would be helpful in fabricating a small-scale water filtration device.

Insights into the Action Mechanism of the Antimicrobial Peptide Lasioglossin III

Lasioglossin III (LL-III) is a cationic antimicrobial peptide derived from the venom of the eusocial bee Lasioglossum laticeps. LL-III is extremely toxic to both Gram-positive and Gram-negative bacteria, and it exhibits antifungal as well as antitumor activity. Moreover, it shows low hemolytic activity, and it has almost no toxic effects on eukaryotic cells. However, the molecular basis of the LL-III mechanism of action is still unclear. In this study, we characterized by means of calorimetric (DSC) and spectroscopic (CD, fluorescence) techniques its interaction with liposomes composed of a mixture of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-rac-phosphoglycerol (POPG) lipids as a model of the negatively charged membrane of pathogens. For comparison, the interaction of LL-III with the uncharged POPC liposomes was also studied. Our data showed that LL-III preferentially interacted with anionic lipids in the POPC/POPG liposomes and induces the formation of lipid domains. Furthermore, the leakage experiments showed that the peptide could permeabilize the membrane. Interestingly, our DSC results showed that the peptide-membrane interaction occurs in a non-disruptive manner, indicating an intracellular targeting mode of action for this peptide. Consistent with this hypothesis, our gel-retardation assay experiments showed that LL-III could interact with plasmid DNA, suggesting a possible intracellular target.

Highly selective and high-performance osmotic power generators in subnanochannel membranes enabled by metal-organic frameworks

The electric organs of electric eels are able to convert ionic gradients into high-efficiency electricity because their electrocytes contain numerous “subnanoscale” protein ion channels that can achieve highly selective and ultrafast ion transport. Despite increasing awareness of blue energy production through nanochannel membranes, achieving high-performance energy output remains considerably unexplored. Here, we report on a heterogeneous subnanochannel membrane, consisting of a continuous UiO-66-NH2 metal-organic framework (MOF) and a highly ordered alumina nanochannel membrane. In the positively charged membrane, the angstrom-scale windows function as ionic filters for screening anions with different hydrated sizes. Driven by osmosis, the subnanochannel membrane can produce an exceptionally high Br−/NO3− selectivity of ~1240, hence yielding an unprecedented power of up to 26.8 W/m2 under a 100-fold KBr gradient. Achieving ultrahigh selective and ultrafast osmotic transport in ion channel–mimetic MOF-based membranes opens previously unexplored avenues toward advanced separation technologies and energy-harvesting devices.

Low-Latency Spiking Neural Networks Using Pre-Charged Membrane Potential and Delayed Evaluation

Spiking neural networks (SNNs) have attracted many researchers’ interests due to its biological plausibility and event-driven characteristic. In particular, recently, many studies on high-performance SNNs comparable to the conventional analog-valued neural networks (ANNs) have been reported by converting weights trained from ANNs into SNNs. However, unlike ANNs, SNNs have an inherent latency that is required to reach the best performance because of differences in operations of neuron. In SNNs, not only spatial integration but also temporal integration exists, and the information is encoded by spike trains rather than values in ANNs. Therefore, it takes time to achieve a steady-state of the performance in SNNs. The latency is worse in deep networks and required to be reduced for the practical applications. In this work, we propose a pre-charged membrane potential (PCMP) for the latency reduction in SNN. A variety of neural network applications (e.g., classification, autoencoder using MNIST and CIFAR-10 datasets) are trained and converted to SNNs to demonstrate the effect of the proposed approach. The latency of SNNs is successfully reduced without accuracy loss. In addition, we propose a delayed evaluation method (DE), by which the errors during the initial transient are discarded. The error spikes occurring in the initial transient is removed by DE, resulting in the further latency reduction. DE can be used in combination with PCMP for further latency reduction. Finally, we also show the advantages of the proposed methods in improving the number of spikes required to reach a steady-state of the performance in SNNs for energy-efficient computing.