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The kinetic mechanism of amyloid fibril formation by a peptide fragment containing seven residues of the amyloid-β protein Aβ-(16-22) was investigated. We found that the N- and C-terminal unprotected Aβ-(16-22), containing no aggregation nuclei, showed rapid fibrillation within seconds to minutes in a neutral aqueous buffer solution. The fibrillation kinetics were well described by the nucleation-elongation model, suggesting that primary nucleation was the rate-limiting step. On the basis of both experimental and theoretical analyses, the aggregated nucleus was estimated to be composed of 6-7 peptide molecules, wherein the two β-sheets were associated with their hydrophobic surfaces. Thin fibers with widths of 10-20 nm were formed, which increased their length and thickness, attaining a width of20 nm over several tens of minutes, probably owing to the lateral association of the fibers. Electrostatic and hydrophobic interactions play important roles in aggregation. These results provide a basis for understanding the fibrillation of short peptides.

Amphipathic α-helical peptides have been reported to form discoidal particles or nanodiscs with phospholipids, in which a lipid bilayer patch is encircled by peptides. Peptide-based nanodiscs have broad applicability because of their ease of preparation, size flexibility, and structural plasticity. We previously revealed that the nanodiscs formed by apolipoprotein-A-I-derived peptide 18A showed temperature-dependent structural destabilization above the gel-to-liquid-crystalline phase transition temperature of the lipid bilayer. It has been suggested that this destabilization is due to the migration of peptides bound to the edge of the discs to the bilayer surface. In this study, we designed a peptide that could stabilize nanodisc structures against the phase transition of lipid bilayers by disulfide cross-linking of peptides. An 18A-dimer cross-linked by a proline residue, 37pA (Ac-18A-P-18A-CONH

Self-assembling peptides form aggregates with various nanostructures such as spheres, sheets, and fibers and have potential applications in nanomedicine and drug delivery. The alkylation of peptides is a promising strategy for controlling the self-assembly of peptides. In this study, we investigated the thermodynamic properties associated with the aggregation of alkyl-chain-modified self-assembling peptides. The tripeptide sequence, KYF, which has been reported to form fibrous aggregates via self-assembly, was modified with various fatty acids at the N-terminus. The fibrous morphology of the aggregates was observed by transmission electron microscopy and atomic force microscopy. Thioflavin T fluorescence and circular dichroism spectroscopy revealed the formation of β-sheet structures. The critical micelle concentration and its temperature dependence were determined to obtain the thermodynamic parameters for aggregation. The results showed that the aggregation was an entropy-driven process at low temperatures, whereas it was enthalpy-driven at high temperatures. The negative heat capacity changes for aggregation suggested that hydrophobic interactions were the major driving force for self-assembly. Other entropic and enthalpic interactions were also contributed in part to the self-assembly. We individually identified the contributions of the peptide and alkyl chain moiety to the self-assembly. These contributions can be explained by the theoretical values for the self-assembly of each component. The results of this study provide fundamental insights into the design of self-associating peptides.

Near-field thermal radiation transfer overcoming the blackbody limit has attracted significant attention in recent years owing to its potential for drastically increasing the output power and conve...

Titanium disulfide TiS$_2$, which is a member of the layered transition-metal dichalcogenides with the 1T-CdI$_2$-type crystal structure, is known to exhibit a wide variety of magnetism through intercalating various kinds of transition-metal atoms of different concentrations. Among them, Fe-intercalated titanium disulfide Fe$_x$TiS$_2$ is known to be ferromagnetic with strong perpendicular magnetic anisotropy (PMA) and large coercive fields ($H_\text{c}$). In order to study the microscopic origin of the magnetism of this compound, we have performed X-ray absorption spectroscopy (XAS) and X-ray magnetic circular dichroism (XMCD) measurements on single crystals of heavily intercalated Fe$_x$TiS$_2$ ($x\sim0.5$). The grown single crystals showed a strong PMA with a large $H_\text{c}$ of $\mu_0H_\text{c} \simeq 1.0\ \text{T}$. XAS and XMCD spectra showed that Fe is fully in the valence states of 2+ and that Ti is in an itinerant electronic state, indicating electron transfer from the intercalated Fe atoms to the host TiS$_2$ bands. The Fe$^{2+}$ ions were shown to have a large orbital magnetic moment of $\simeq 0.59\ \mu_\text{B}\text{/Fe}$, to which, combined with the spin-orbit interaction and the trigonal crystal field, we attribute the strong magnetic anisotropy of Fe$_x$TiS$_2$., Comment: 24 pages, 8 figures

It has been demonstrated that peripheral inflammation induces cognitive dysfunction. Several histone deacetylase (HDAC) inhibitors ameliorate cognitive dysfunction in animal models of not only peripheral inflammation but also Alzheimer's disease. However, it is not clear which HDAC expressed in the central nervous system or peripheral tissues is involved in the therapeutic effect of HDAC inhibition on cognitive dysfunction. Hence, the present study investigated the effect of peripheral HDAC inhibition on peripheral inflammation-induced cognitive dysfunction. Suberoylanilide hydroxamic acid (SAHA), a pan-HDAC inhibitor that is mainly distributed in peripheral tissues after intraperitoneal administration, was found to prevent peripheral inflammation-induced cognitive dysfunction. Moreover, pretreatment with SAHA dramatically increased mRNA expression of interleukin-10, an anti-inflammatory cytokine, in peripheral and central tissues and attenuated peripheral inflammation-induced microglial activation in the CA3 region of the hippocampus. Minocycline, a macrophage/microglia inhibitor, also ameliorated cognitive dysfunction. Furthermore, as a result of treatment with liposomal clodronate, depletion of peripheral macrophages partially ameliorated the peripheral inflammation-evoked cognitive dysfunction. Taken together, these findings demonstrate that inhibition of peripheral HDAC plays a critical role in preventing cognitive dysfunction induced by peripheral inflammation via the regulation of anti-inflammatory cytokine production and the inhibition of microglial functions in the hippocampus. Thus, these findings could provide support for inhibition of peripheral HDAC as a novel therapeutic strategy for inflammation-induced cognitive dysfunction.

Understanding how lipid dynamics change with membrane curvature is important given that biological membranes constantly change their curvature and morphology through membrane fusion and endo-/exocytosis. Here, we used time-resolved small-angle neutron scattering and time-resolved fluorescence to characterize the properties and dynamics of phospholipids in vesicles with different curvatures. Dissociation of phospholipids from vesicles required traversing an energy barrier comprising positive enthalpy and negative entropy. However, lipids in membranes with high positive curvature have dense acyl chain packing and loose headgroup packing, leading to hydrophobic hydration due to water penetration into the membrane. These properties were found to lower the hydrophobic hydration enhancement associated with phospholipid dissociation and mitigate the acyl chain packing of lipids adjacent to the space created by the lipid dissociation, resulting in an increase in activation entropy. The results of this study provide important insights into the functions of biomembranes in relation to their dynamic structural changes.

Phospholipid scramblases that catalyze lipid transbilayer movement are associated with intercellular signaling and lipid homeostasis. Although several studies have shown that the hydrophilic residue-rich groove of the proteins mediates lipid scrambling, the interactions between the groove and the lipid bilayers remain poorly understood. Here we have revealed the structural features of model transmembrane peptides that conduct lipid scrambling as well as the interactions between the peptides and the surrounding lipids by means of experimental and simulation techniques. Peptides with two strongly hydrophilic residues located on the same side of the helices and at a deeper position in the membrane exhibited high scramblase activities. All-atom molecular dynamics simulations showed that the interactions between the hydrophilic residues and lipid head groups regulate the membrane thinning and disorder near the peptides in an order that correlates with the scramblase activity of the peptides. These results provide a basis for understanding the lipid scrambling mechanisms by transmembrane regions.

The aim of this study is to examine the proposed control method of the assist suit with a Velocity-Based Mechanical Safety Device (VBMSD) for patients with difficulty moving their lower legs by themselves. The proposed control method for the assist suit assists the patients as if the patients move their knee joint under zero gravity. A physical simulation model is used to examine whether the gravitational torque of the subject's lower leg and foot was canceled by the torque generated by the assist suit. Experimental results indicated that the gravitational torque of the subject's lower leg and foot is canceled by the torque generated by the assist suit. The control of the assist suit was not adversely influenced by the VBMSD. That is, the VBMSD did not prevent the control of the assist suit. The proposed control method makes the assist suit assist the patient in moving his/her knee joint in a zero gravity-like environment. However, a weight of 3kg was used instead of an actual patient in the experiment. Experiments with actual patients should be conducted to verify the effectiveness of the proposed control method in clinical use. Furthermore, it will be necessary to take into consideration the patients' general conditions and symptoms.

Molecular networks containing various proteins mediate many types of cellular processes. Elucidation of how the proteins interact will improve our understanding of the molecular integration and physiological and pharmacological propensities of the network. One of the most complicated and unexplained interactions between proteins is the inter-G protein-coupled receptor (GPCR) interaction. Recently, many studies have suggested that an interaction between neurotransmitter GPCRs may mediate diverse modalities of neural responses. The B-type gamma-aminobutyric acid (GABA) receptor (GBR) and type-1 metabotropic glutamate receptor (mGluR1) are GPCRs for GABA and glutamate, respectively, and each plays distinct roles in controlling neurotransmission. We have previously reported the possibility of their functional interaction in central neurons. Here, we examined the interaction of these GPCRs using stable cell lines and rat cerebella. Cell-surface imaging and coimmunoprecipitation analysis revealed that these GPCRs interact on the cell surface. Furthermore, fluorometry revealed that these GPCRs mutually modulate signal transduction. These findings provide solid evidence that mGluR1 and GBR have intrinsic abilities to form complexes and to mutually modulate signaling. These findings indicate that synaptic plasticity relies on a network of proteins far more complex than previously assumed.

Investigation of ultrafast dynamic behaviors can provide novel insights about the coupling mechanisms among multiple degrees of freedom, such as lattice, magnetism and electronic structure, in condensed matters. Here we investigate both the ferromagnetic (FM) and antiferromagnetic (AFM) ultrafast dynamics of a strongly correlated oxide system, GdBaCo2O5.5 thin film by time-resolved x-ray magnetic circular dichroism in reflectivity (XMCDR) and resonant magnetic x-ray diffraction (RMXD). A photo-induced AFM-FM transition characterized by an increase of the transient XMCDR (sensitive to FM order) beyond the unpumped value and a decay of RMXD (sensitive to AFM order) was observed. The photon-energy dependence of the transient XMCDR and reflectivity could be interpreted as a concomitant photo-induced spin-state transition (SST). The AFM-FM transition and SST couple with each other in the time domain, resulting in unusual dynamic behaviors of the magnetism.

The discoveries of intrinsic ferromagnetism in atomically-thin van der Waals crystals have opened up a new research field enabling fundamental studies on magnetism at two-dimensional (2D) limit as well as development of magnetic van der Waals heterostructures. To date, a variety of 2D ferromagnetism has been explored mainly by mechanically exfoliating 'originally ferromagnetic (FM)' van der Waals crystals, while bottom-up approach by thin film growth technique has demonstrated emergent 2D ferromagnetism in a variety of 'originally non-FM' van der Waals materials. Here we demonstrate that V5Se8 epitaxial thin films grown by molecular-beam epitaxy (MBE) exhibit emergent 2D ferromagnetism with intrinsic spin polarization of the V 3d electrons despite that the bulk counterpart is 'originally antiferromagnetic (AFM)'. Moreover, thickness-dependence measurements reveal that this newly-developed 2D ferromagnet could be classified as an itinerant 2D Heisenberg ferromagnet with weak magnetic anisotropy, broadening a lineup of 2D magnets to those potentially beneficial for future spintronics applications.

Sec14, the major yeast phosphatidylcholine (PC)/phosphatidylinositol (PI) transfer protein (PITP), coordinates PC and PI metabolism to facilitate an appropriate and essential lipid signaling environment for membrane trafficking from trans-Golgi membranes. The Sec14 PI/PC exchange cycle is essential for its essential biological activity, but fundamental aspects of how this PITP executes its lipid transfer cycle remain unknown. To address some of these outstanding issues, we applied time-resolved small-angle neutron scattering for the determination of protein-mediated intervesicular movement of deuterated and hydrogenated phospholipids in vitro. Quantitative analysis by small-angle neutron scattering revealed that Sec14 PI- and PC-exchange activities were sensitive to both the lipid composition and curvature of membranes. Moreover, we report that these two parameters regulate lipid exchange activity via distinct mechanisms. Increased membrane curvature promoted both membrane binding and lipid exchange properties of Sec14, indicating that this PITP preferentially acts on the membrane site with a convexly curved face. This biophysical property likely constitutes part of a mechanism by which spatial specificity of Sec14 function is determined in cells. Finally, wild-type Sec14, but not a mixture of Sec14 proteins specifically deficient in either PC- or PI-binding activity, was able to effect a net transfer of PI or PC down opposing concentration gradients in vitro.

Near-field thermophotovoltaic (TPV) power generation has been attracting increasing attention as a promising approach for efficient conversion of heat into electricity with high output power density. Here, we numerically investigate near-field TPV devices with surrounding reflectors for efficient recycling of low-energy photons, which do not contribute to the power generation. We reveal that the conversion efficiency of a near-field TPV system can be drastically increased by introducing a pair of reflectors above and below the system, especially when the two mirrors are not in contact with the emitter and absorber. In addition, we investigate the influence of non-perfect photon recycling on the TPV efficiency and reveal that near-field TPV systems are more robust against the decrease of the reflectivity of the reflectors than the far-field TPV systems.

The strain effect from a substrate is an important experimental route to control electronic and magnetic properties in transition-metal oxide (TMO) thin films. Using hard x-ray photoemission spectroscopy, we investigate the strain dependence of the valence states in LaNiO$_{3}$ thin films, strongly correlated perovskite TMO, grown on four substrates: LaAlO$_{3}$, (LaAlO$_{3}$)$_{0.3}$(SrAl$_{0.5}$Ta$_{0.5}$O$_{3}$)$_{0.7}$, SrTiO$_{3}$, and DyScO$_{3}$. A Madelung potential analysis of core-level spectra suggests that the point-charge description is valid for the La ions while it breaks down for Ni and O ions due to a strong covalent bonding between the two. A clear x-ray photon-energy dependence of the valence spectra is analyzed by the density functional theory, which points to a presence of the La 5$p$ state near the Fermi level., 6 pages, 4 figures, and 2 tables

Liquid droplets of aggregation-prone proteins, which become hydrogels or form amyloid fibrils, are a potential target for drug discovery. In this study, we proposed an experiment-guided protocol for characterizing the design grammar of peptides that can regulate droplet formation and aggregation. The protocol essentially involves investigation of 19 amino acid additives and polymerization of the identified amino acids. As a proof of concept, we applied this protocol to fused in sarcoma (FUS). First, we evaluated 19 amino acid additives for an FUS solution and identified Arg and Tyr as suppressors of droplet formation. Molecular dynamics simulations suggested that the Arg additive interacts with specific residues of FUS, thereby inhibiting the cation–π and electrostatic interactions between the FUS molecules. Second, we observed that Arg polymers promote FUS droplet formation, unlike Arg monomers, by bridging the FUS molecules. Third, we found that the Arg additive suppressed solid aggregate formation of FUS, while Arg polymer enhanced it. Finally, we observed that amyloid-forming peptides induced the conversion of FUS droplets to solid aggregates of FUS. The developed protocol could be used for the primary design of peptides controlling liquid droplets and aggregates of proteins.