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The northern Hikurangi subduction margin hosts slow slip events (SSEs), which are exceptionally shallow (<15 km). The sedimentary sequence on the incoming plate is therefore representative of the shallow fault material where the SSEs will take place once they enter the subduction zone. Knowledge about the frictional behavior of these sediments is required to know which lithologies are capable of hosting SSEs, and what mechanisms are causing them. Frictional behavior is material specific and depends on sliding velocity, but it is unknown how these natural sediments behave at plate‐rate velocities. We performed laboratory shearing experiments testing the major lithologies sampled during International Ocean Discovery Program (IODP) Expedition 375, at velocities ranging from the plate convergence rate at the Hikurangi margin (5 cm/year), up to those characteristics of the shallow SSEs (160 and 530 cm/year), under simulated in‐situ as well as standardized conditions. We find that the calcite‐rich pelagic sediments are relatively strong and display the velocity‐weakening frictional behavior required for slip events, whereas other lithologies are weaker and show velocity‐neutral to velocity‐strengthening friction. We observe spontaneous laboratory SSEs in the calcareous pelagic sediments, which show partial locking in between sliding events, consistent with the interpretation of SSEs within the spectrum of slow to fast earthquakes. For the Hikurangi margin, our results suggest that SSE occurrence requires the stronger carbonate‐rich unit to be incorporated into the plate‐boundary fault zone, which we suggest occurs because the rough incoming plate introduces geometrical complexity into the fault zone. Plain Language Summary: In the Hikurangi subduction zone, located offshore the east coast of the North Island of New Zealand, the movement between the downgoing and overriding tectonic plates can occur as slow slip events (SSEs). During SSEs the two plates move relative to each other, a process in many aspects similar to ordinary earthquakes, except SSEs take weeks instead of seconds and no ground‐shaking can be felt on the surface. SSEs occur in many subduction zones worldwide, but at the Hikurangi margin they occur shallow, relatively often and close to many mostly land‐based GPS stations that track the movement of the two plates, which makes them ideal to study. A recent research expedition (IODP Expedition 375) drilled the stack of sediments going into the subduction zone to learn more about the circumstances that control where and when SSEs occur. In this paper, we test all the major different sediment types going into the subduction fault zone to find out which one of them is responsible for the SSEs. Using a laboratory device that mimics the subduction zone, we find that sediments containing the mineral calcite cause slip events that are similar to the SSEs observed in the Hikurangi margin. Key Points: Spontaneous laboratory slow slip events (SSEs) suggest the shallow Hikurangi SSEs are favored in carbonate‐rich sedimentsRate‐and‐state friction and critical stiffness theory can partly explain SSEs, but they can occur under velocity‐strengthening conditionsSSE generation in Hikurangi is probably related to heterogeneity in the plate‐boundary fault zone [ABSTRACT FROM AUTHOR]

While analysis of glacial seismicity continues to be a widely used method for interpreting glacial processes, the underlying mechanics controlling glacial stick‐slip seismicity remain speculative. Here, we report on laboratory shear experiments of debris‐laden ice slid over a bedrock asperity under carefully controlled conditions. By modifying the elastic loading stiffness, we generated the first laboratory icequakes. Our work represents the first comprehensive lab observations of unstable ice‐slip events and replicates several seismological field observations of glacier slip, such as slip velocity, stress drop, and the relationship between stress drop and recurrence interval. We also observe that stick‐slips initiate above a critical driving velocity and that stress drop magnitude decreases with further increases in velocity, consistent with friction theory and rock‐on‐rock friction laboratory experiments. Our results demonstrate that glacier slip behavior can be accurately predicted by the constitutive rate‐and‐state friction laws that were developed for rock friction. Plain Language Summary: Glacier beds and tectonic faults may at first appear to be quite different, but they share important characteristics. In both cases, motion may be smooth (aseismic creep) or earthquake‐producing "stick‐slip." A powerful physical constitutive relationship called rate‐and‐state friction has been developed to understand earthquakes and smooth slip on tectonic faults. Laboratory experiments reported here simulate glacier‐bed motion by sliding debris‐bearing ice over a rock plate under conditions that are typical for glacier beds. They produce the first laboratory icequakes. Transitions between steady and stick‐slip motions are generated by controlling shearing velocity and other conditions, as predicted by rate‐and‐state friction theory. Future studies can thus apply this physical framework to glacier slip, helping to understand ice motion and its potential to accelerate sea level rise in a warming world. Furthermore, because motion at the glacier bed is often much easier to study than tectonic faults, additional observations of glaciers may provide useful insights into earthquake behavior. Key Points: The first laboratory "icequakes" were generated and slip stability was predicted well by rate‐and‐state frictionLaboratory icequake attributes such as peak slip velocity, stress drop and healing agree well with other laboratory and field observationsThe laboratory icequake events suggest that debris‐bed contacts dominate the sudden slip mechanics [ABSTRACT FROM AUTHOR]

The Hikurangi subduction zone hosts shallow slow‐slip events, possibly extending to the seafloor. The mechanisms allowing for this behavior are poorly understood but are likely a function of the frictional properties of the downgoing seafloor sediments. We conducted friction experiments at a large range of effective stresses, temperatures, and velocities on incoming sediment to the Hikurangi subduction zone to explore the possible connection of frictional properties to slow‐slip events. These experiments were conducted on multiple apparatuses, allowing us to access a wider range of deformation conditions than is available on any one machine. We find that the material frictionally weakens and becomes less velocity strengthening with increasing effective stress, whereas temperature has only a small effect on both friction and frictional stability. When driven at the plate convergence rate, the sediment exhibits velocity‐weakening behavior. These results imply that the frictional properties of the sediment package subducting at Hikurangi could promote slow‐slip events at the pressures, temperatures, and strain rates expected along the plate boundary thrust up to 10‐km depth without requiring elevated pore fluid pressures. The transition to velocity‐strengthening behavior at faster slip rates could provide a mechanism for limiting unstable slip to slow‐sliding velocities, rather than accommodating deformation through ordinary earthquakes. Key Points: Sediments subducting at the Hikurangi Trench become weaker and less velocity strengthening with increasing depthSediments exhibit a cutoff velocity of 1 μm/s, possibly explaining the presence of shallow slow slip at the Hikurangi TrenchSlow slip at the Hikurangi Trench could result from frictional instability, in addition to factors such as elevated pore fluid pressures [ABSTRACT FROM AUTHOR]

In contrast to intracellular gene transfer, the direct delivery of expressed proteins is a significantly challenging yet essential technique for elucidating cellular functions, including protein complex structure, liquid-liquid phase separation, therapeutic applications, and reprogramming. In this study, we developed a hybrid nanotube (HyNT) stamp system that physically inserts the HyNTs into adhesive cells, enabling the injection of target molecules through HyNT ducts. This system demonstrates the capability to deliver multiple proteins, such as lactate oxidase (LOx) and ubiquitin (UQ), to approximately 1.8 × 10 7 adhesive cells with a delivery efficiency of 89.9% and a viability of 97.1%. The delivery of LOx enzyme into HeLa cancer cells induced cell death, while enzyme-delivered healthy cells remained viable. Furthermore, our stamp system can deliver an isotope-labeled UQ into adhesive cells for detection by nuclear magnetic resonance (NMR).

Since the establishment of Japan's publicly supported pediatric home medical care (PHMC) system in 2012, the number of technology-dependent children (TDC) who are supported by PHMC has been increasing. We expected care to become easier as TDC mobility increased. However, many family caregivers complained of the opposite, that the burden of care increased as TDC's mobility increased. Therefore, we aimed to study the problems of the care burden of families in relation to the improvement of mobility of TDC with a focus on respiratory support. We conducted a survey among caregivers of TDC in two parts: a first survey was done between 2018 and 2020, and a follow-up survey in 2023. In each medical procedure, the correlation of TDC's motor function level with care burden was analyzed by using correlation analysis. In 15 households, caregivers' activities were monitored to elucidate the problems of the care objectively. The second survey was conducted in February 2023 in TDC whose medical records were available. Analysis of 418 cases showed that care-burden increased with improvements in the children's motor ability in tracheostomy, or remained the same in other procedures. A follow-up study in 262/418 cases of this group showed that part of these TDC with high mobility aged 1-8, after passing through the mobile phase with increased burden of care, had a high potential to be weaned from medical devices.  Conclusion: For TDC who acquire motor skills during PHMC, the burden of care for caregivers either increases or remains the same. It is important to maintain social support for TDC on the recovering mobile stage. What is Known: • There was no clear information on the care burden when TDC become mobile. What is New: • We did a qualitative study to show that the care burden increases when TDC become mobile. • In addition, mobike TDC showed a high potential for recovery., (© 2023. The Author(s).)

Ras acts as a molecular switch to control intracellular signaling on the plasma membrane (PM). Elucidating how Ras associates with PM in the native cellular environment is crucial for understanding its control mechanism. Here, we used in-cell nuclear magnetic resonance (NMR) spectroscopy combined with site-specific 19 F-labeling to explore the membrane-associated states of H-Ras in living cells. The site-specific incorporation of p -trifluoromethoxyphenylalanine (OCF 3 Phe) at three different sites of H-Ras, i.e., Tyr32 in switch I, Tyr96 interacting with switch II, and Tyr157 on helix α5, allowed the characterization of their conformational states depending on the nucleotide-bound states and an oncogenic mutational state. Exogenously delivered 19 F-labeled H-Ras protein containing a C-terminal hypervariable region was assimilated via endogenous membrane-trafficking, enabling proper association with the cell membrane compartments. Despite poor sensitivity of the in-cell NMR spectra of membrane-associated H-Ras, the Bayesian spectral deconvolution identified distinct signal components on three 19 F-labeled sites, thus offering the conformational multiplicity of H-Ras on the PM. Our study may be helpful in elucidating the atomic-scale picture of membrane-associated proteins in living cells., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Ficifolidione, a natural insecticidal compound isolated from the essential oils of Myetaceae species, is a spiro phloroglucinol with an isobutyl group at the C-4 position. We found that ficifolidione showed cytotoxicity against cancer cells via apoptosis. Replacement of the isobutyl group by n -propyl group did not influence the potency, but the effect of the replacement of this group by a shorter or longer alkyl group on the biological activity remains unknown. In this study, ficifolidione derivatives with alkyl groups such as methyl, n -pentyl, and n -heptyl group-instead of the isobutyl group at the C-4 position-were synthesized to evaluate their cytotoxicity against the human promyelocytic leukaemia cell line HL60 and their insecticidal activity against mosquito larvae. The biological activities of their corresponding 4-epimers were also evaluated. As a result, the conversion of the isobutyl group to another alkyl group did not significantly influence the cytotoxicity or insecticidal activity. In HL60 cells treated with the n -heptyl-ficifolidione derivative, the activation of caspase 3/7 and the early stages of apoptosis were detected by using immunofluorescence and flow cytometric techniques, respectively, suggesting that the cytotoxicity should be induced by apoptosis even though the alkyl group was changed.

To obtain biocontrol agents for suppression of food-deteriorating fungi during storage of agricultural products, bacteria producing volatile organic compounds (VOCs) with strong antifungal activity were screened and isolated from various environmental samples. Among 136 bacterial isolates, strain TM-R showed the strongest and broadest antifungal activity. Based on physiological and genetical characterization, the bacterium was identified as Bacillus pumilus . The effects of VOCs produced by the bacterium, which was grown on four types of agar media (nutrient, Trypto-Soya, Luria-Bertani, and TM Enterprise), were examined against six species of fungi ( Alternaria alternata , Aspergillus niger, Cladosporium cladosporioides , Curvularia lunata , Fusarium oxysporum , and Penicillium italicum) in both small- and large-scale tests (plate and 12-L tests, respectively). In the plate test, the bacterium markedly suppressed the mycelial growth of five fungi ( Alternaria alternata , Cladosporium cladosporioides , Curvularia lunata , F. oxysporum , and P. italicum ) but promoted the growth of Aspergillus niger . In the 12-L test, the degree of growth inhibitiondecreased; however, the bacterium grown on TMEA still exhibited the strongest inhibition, especially against P. italicum (growth inhibition rate of 93%). Surprisingly, the growth of Aspergillus niger was promoted even more strongly (-36%) by the bacterium on TMEA than in the plate test (-9%). Twenty-two of 32 VOCs detected by GC-MS were identified using three databases (NIST 2011, AromaOffice, and AroChemBase). The species and concentration of detected VOCs differed greatly among growth media. To identify causative antifungal VOCs, we estimated the correlation between growth inhibition of P. italicum by the bacterium grown on each of the four media vs. the relative abundance of individual VOCs. As a result, four VOCs (methyl isobutyl ketone, ethanol, 5-methyl-2-heptanone, and S-(-)-2-methylbutylamine) were determined to be the predominant antifungal VOCs. To the best of our knowledge, this study is the first to specify causative antifungal VOCs using such an approach.

By using in-cell NMR experiments, we have demonstrated that the protein folding state in cells is significantly influenced by the cellular health conditions. hAK1 was denatured in cells under stressful culture conditions, while it remained functional and properly folded in cells continuously supplied with a fresh medium.

Chlorine oxidation followed by treatment with activated carbon was studied as a possible method for removing radioactive iodine from water. Chlorination time, chlorine dose, the presence of natural organic matter (NOM), the presence of bromide ion (Br⁻), and carbon particle size strongly affected iodine removal. Treatment with superfine powdered activated carbon (SPAC) after 10-min oxidation with chlorine (1 mg-Cl₂/L) removed 90% of the iodine in NOM-containing water (dissolved organic carbon concentration, 1.5 mg-C/L). Iodine removal in NOM-containing water increased with increasing chlorine dose up to 0.1 mg-Cl₂/L but decreased at chlorine doses of >1.0 mg-Cl₂/L. At a low chlorine dose, nonadsorbable iodide ion (I⁻) was oxidized to adsorbable hypoiodous acid (HOI). When the chlorine dose was increased, some of the HOI reacted with NOM to form adsorbable organic iodine (organic-I). Increasing the chlorine dose further did not enhance iodine removal, owing to the formation of nonadsorbable iodate ion (IO₃⁻). Co-existing Br⁻ depressed iodine removal, particularly in NOM-free water, because hypobromous acid (HOBr) formed and catalyzed the oxidation of HOI to IO₃⁻. However, the effect of Br⁻ was small in the NOM-containing water because organic-I formed instead of IO₃⁻. SPAC (median particle diameter, 0.62 μm) had a higher equilibrium adsorption capacity for organic-I than did conventional PAC (median diameter, 18.9 μm), but the capacities of PAC and SPAC for HOI were similar. The reason for the higher equilibrium adsorption capacity for organic-I was that organic-I was adsorbed principally on the exterior of the PAC particles and not inside the PAC particles, as indicated by direct visualization of the solid-phase iodine concentration profiles in PAC particles by field emission electron probe microanalysis. In contrast, HOI was adsorbed evenly throughout the entire PAC particle.

SWIRM is an evolutionarily conserved domain involved in several chromatin-modifying complexes. Recently, the LSD1 protein, which bears a SWIRM domain, was found to be a demethylase for Lys4-methylated histone H3. Here, we report a solution structure of the SWIRM domain of human LSD1. It forms a compact fold composed of 6 alpha helices, in which a 20 amino acid long helix (alpha4) is surrounded by 5 other short helices. The SWIRM domain structure could be divided into the N-terminal part (alpha1-alpha3) and the C-terminal part (alpha4-alpha6), which are connected to each other by a salt bridge. While the N-terminal part forms a SWIRM-specific structure, the C-terminal part adopts a helix-turn-helix (HTH)-related fold. We discuss a model in which the SWIRM domain acts as an anchor site for a histone tail.

Among the many PWWP-containing proteins, the largest group of homologous proteins is related to hepatoma-derived growth factor (HDGF). Within a well-conserved region at the extreme N-terminus, HDGF and five HDGF-related proteins (HRPs) always have a PWWP domain, which is a module found in many chromatin-associated proteins. In this study, we determined the solution structure of the PWWP domain of HDGF-related protein-3 (HRP-3) by NMR spectroscopy. The structure consists of a five-stranded beta-barrel with a PWWP-specific long loop connecting beta2 and beta3 (PR-loop), followed by a helical region including two alpha-helices. Its structure was found to have a characteristic solvent-exposed hydrophobic cavity, which is composed of an abundance of aromatic residues in the beta1/beta2 loop (beta-beta arch) and the beta3/beta4 loop. A similar ligand binding cavity occurs at the corresponding position in the Tudor, chromo, and MBT domains, which have structural and probable evolutionary relationships with PWWP domains. These findings suggest that the PWWP domains of the HDGF family bind to some component of chromatin via the cavity.

In this study, we attempted to analyze the peptide motifs recognized by 24822.111 and F9, monoclonal antibodies (mAbs) that inhibit the chemotactic activity of monocyte chemoattractant protein-1 (MCP-1), a member of the CC subfamily of chemokines. We isolated phage clones from a phage display library and identified six peptide motifs. One of these clones, C27, was strongly and specifically recognized by 24822.111 mAb, while another, G25, was similarly recognized by F9 mAb. Both the C27 motif and the G25 motif contain two cysteines in their sequences and have little homology to the primary amino acid sequence of MCP-1. These clones, however, bound to THP-1 cells, and the binding was competitively inhibited by MCP-1. The clones strongly inhibited the MCP-1-induced chemotaxis of human monocytes. The synthetic and intramolecularly disulfide-linked peptides of C27 and G25 (sC27 and sG25) also inhibited the chemotaxis induced by MCP-1, while their derivatives with serine in place of cysteine did not, suggesting the importance of the loop structure for the inhibition. These results suggest that sC27 and sG25 may mimic the MCP-1-binding domain to the MCP-1 receptor.