Postsynaptic protein organization revealed by electron microscopy.

Neuronal synapses are key devices for transmitting and processing information in the nervous system. Synaptic plasticity, generally regarded as the cellular basis of learning and memory, involves changes of subcellular structures that take place at the nanoscale. High-resolution imaging methods, especially electron microscopy (EM), have allowed for quantitative analysis of such nanoscale structures in different types of synapses. In particular, the semi-ordered organization of neurotransmitter receptors and their interacting scaffolds in the postsynaptic density have been characterized for both excitatory and inhibitory synapses by studies using various EM techniques such as immuno-EM, electron tomography of high-pressure freezing and freeze-substituted samples, and cryo electron tomography. These techniques, in combination with new correlative approaches, will further facilitate our understanding of the molecular organization underlying diverse functions of neuronal synapses

Accumulation of Dense Core Vesicles in Hippocampal Synapses Following Chronic Inactivity.

The morphology and function of neuronal synapses are regulated by neural activity, as manifested in activity-dependent synapse maturation and various forms of synaptic plasticity. Here we employed cryo-electron tomography (cryo-ET) to visualize synaptic ultrastructure in cultured hippocampal neurons and investigated changes in subcellular features in response to chronic inactivity, a paradigm often used for the induction of homeostatic synaptic plasticity. We observed a more than 2-fold increase in the mean number of dense core vesicles (DCVs) in the presynaptic compartment of excitatory synapses and an almost 20-fold increase in the number of DCVs in the presynaptic compartment of inhibitory synapses after 2 days treatment with the voltage-gated sodium channel blocker tetrodotoxin (TTX). Short-term treatment with TTX and the N-methyl-D-aspartate receptor (NMDAR) antagonist amino-5-phosphonovaleric acid (AP5) caused a 3-fold increase in the number of DCVs within 100 nm of the active zone area in excitatory synapses but had no significant effects on the overall number of DCVs. In contrast, there were very few DCVs in the postsynaptic compartments of both synapse types under all conditions. These results are consistent with a role for presynaptic DCVs in activity-dependent synapse maturation. We speculate that these accumulated DCVs can be released upon reactivation and may contribute to homeostatic metaplasticity

Port safety evaluation from a captain's perspective: The Korean experience

There are many factors affecting navigational safety in ports, including weather, the characteristics of the channels and vessel types, etc. This paper aims to identify the factors influencing navigational safety in ports and to analyze the extent to which such factors affect the safety of ports from the perspective of ship captains through a real case study. A quantitative analysis is carried out using the data collected from 21 captains who have over 10. years experience in operating ships individually. The identified factors indicate risk implications in ports. A fuzzy analytical hierarchy process is used to evaluate the importance of the factors and to rank the safety levels of the targeted ports in Korea from a captain's perspective. Consequently, among Busan, Ulsan, Gwangyang, Incheon, and Mokpo, Busan is evaluated by captains as the safest port, while Mokpo is the most risky. The research also reveals that it is applicable to use domain expert knowledge when historical failure data is unavailable or difficult to access to evaluate port safety. The result shows great research significance in terms of providing relevant stakeholders, such as port authorities and shipping companies, with an insight into port safety performance and thus facilitating the development of the associated risk control measures. © 2014 Elsevier Ltd

Cooperative multivalent receptor binding promotes exposure of the SARS-CoV-2 fusion machinery core

The molecular events that permit the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to bind, fuse, and enter cells are important to understand for both fundamental and therapeutic reasons. Spike proteins consist of S1 and S2 domains, which recognize angiotensin-converting enzyme 2 (ACE2) receptors and contain the viral fusion machinery, respectively. Ostensibly, the binding of spike trimers to ACE2 receptors promotes the preparation of the fusion machinery by dissociation of the S1 domains. We report the development of bottom-up coarse-grained (CG) models validated with cryo-electron tomography (cryo-ET) data, and the use of CG molecular dynamics simulations to investigate the dynamical mechanisms involved in viral binding and exposure of the S2 trimeric core. We show that spike trimers cooperatively bind to multiple ACE2 dimers at virion-cell interfaces. The multivalent interaction cyclically and processively induces S1 dissociation, thereby exposing the S2 core containing the fusion machinery. Our simulations thus reveal an important concerted interaction between spike trimers and ACE2 dimers that primes the virus for membrane fusion and entry

The true amphipathic nature of graphene flakes: a versatile 2D stabilizer

The fundamental colloidal properties of pristine graphene flakes remain incompletely understood, with conflicting reports about their chemical character, hindering potential applications that could exploit the extraordinary electronic, thermal, and mechanical properties of graphene. Here, the true amphipathic nature of pristine graphene flakes is demonstrated through wet‐chemistry testing, optical microscopy, electron microscopy, and density functional theory, molecular dynamics, and Monte Carlo calculations, and it is shown how this fact paves the way for the formation of ultrastable water/oil emulsions. In contrast to commonly used graphene oxide flakes, pristine graphene flakes possess well‐defined hydrophobic and hydrophilic regions: the basal plane and edges, respectively, the interplay of which allows small flakes to be utilized as stabilizers with an amphipathic strength that depends on the edge‐to‐surface ratio. The interactions between flakes can be also controlled by varying the oil‐to‐water ratio. In addition, it is predicted that graphene flakes can be efficiently used as a new‐generation stabilizer that is active under high pressure, high temperature, and in saline solutions, greatly enhancing the efficiency and functionality of applications based on this materia

Probing the isospin dependent mean field and nucleon nucleon cross section in the medium by the nucleon emissions

We study the isospin effects of the mean field and two-body collision on the nucleon emissions at the intermediate energy heavy ion collisions by using an isospin dependent transport theory. The calculated results show that the nucleon emission number $N_{n}$ depends sensitively the isospin effect of nucleon nucleon cross section and weakly on the isospin dependent mean field for neutron-poor system in higher beam energy region . In particular, the correlation between the medium correction of two-body collision and the momentum dependent interaction enhances the dependence of nucleon emission number $N_{n}$ on the isospin effect of nucleon nucleon cross section. On the contrary, the ratio of the neutron proton ratio of the gas phase to the neutron proton ratio of the liquid phase, i.e., the degree of isospin fractionation $_{b}/_{b}$ depends sensitively on the isospin dependent mean field and weakly on the isospin effect of two-body collision for neutron-rich system in the lower beam energy region. In this case, $N_{n}$ and $_{b}/_{b}$ are the probes for extracting the information about the isospin dependent nucleon nucleon cross section in the medium and the isospin dependent mean field,respectively.Comment: 4 pages,4 figure

Top-mass effects in differential Higgs production through gluon fusion at order \alpha_s^4

Effects from a finite top quark mass on differential distributions in the Higgs+jet production cross section through gluon fusion are studied at next-to-leading order in the strong coupling, i.e. $O(\alpha_s^4)$. Terms formally subleading in $1/m_t$ are calculated, and their influence on the transverse momentum and rapidity distribution of the Higgs boson are evaluated. We find that, for the differential K-factor, the heavy-top limit is valid at the 2-3% level as long as the transverse momentum of the Higgs remains below about 150 GeV.Comment: 21 pages, 12 figure