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Abstract Biologically produced protein drugs are generally susceptible to degradation by proteases and often exhibit immunogenicity. To address this issue, mirror-image peptide/protein binders consisting of D-amino acids have been developed so far through the mirror-image phage display technique. Here, we develop a mirror-image protein binder derived from a monobody, one of the promising protein scaffolds, utilizing two notable technologies: chemical protein synthesis and TRAP display, an improved version of mRNA display. A sequential workflow of initial screening followed by affinity maturation, facilitated by TRAP display, generates an L-monobody with high affinity (K D = 1.3 nM) against monocyte chemoattractant protein-1 (MCP-1) D-enantiomer. The chemically synthesized D-monobody demonstrates strong and specific binding to L-MCP-1 and exhibits pharmaceutically favorable properties such as proteolytic resistance, minimal immune response, and a potent inhibitory effect on MCP-1-induced cell migration. This study elevates the value of mirror-image peptide/protein binders as an alternative modality in drug discovery.

Abstract Local ensemble transform Kalman filter (LETKF)‐based Ocean Research Analysis (LORA) version 1.0 datasets for western North Pacific (WNP) and Maritime Continent (MC) regions (LORA‐WNP and ‐MC, respectively) are released through the JAXA‐RIKEN Ocean Analysis website. The LORA datasets are created using an eddy‐resolving LETKF‐based ocean data assimilation system with satellite sea‐surface temperature, salinity, and height data and with in‐situ temperature and salinity data assimilated daily. The LORA datasets include 128‐member ensemble analyses at the sea surface (2D), each term of mixed‐layer temperature and salinity budget equations, and the related variables (2D) such as mixed‐layer depth and heat and freshwater fluxes as well as system grid information and analysis ensemble mean and spread (3D), from August 2015 to January 2024 (as of June 2024). The LORA datasets are useful for geoscience research and practical applications, especially for particle tracking, boundary conditions of atmospheric models, and research on spatiotemporal variations in sea‐surface temperature and salinity.

Abstract The Ser/Leu-swapped genetic code can act as a genetic firewall, mitigating biohazard risks arising from horizontal gene transfer in genetically modified organisms. Our prior work demonstrated the orthogonality of this swapped code to the standard genetic code using a cell-free translation system comprised of 21 in vitro transcribed tRNAs. In this study, to advance this system for protein engineering, we introduce a natural/in vitro transcribed-hybrid tRNA set. This set combines natural tRNAs from Escherichia coli (excluding Ser, Leu, and Tyr) and in vitro transcribed tRNAs, encompassing anticodon-swapped tRNASer GAG and tRNALeu GGA. This approach reduces the number of in vitro transcribed tRNAs required from 21 to only 4. In this optimized system, the production of a model protein, superfolder green fluorescent protein, increases to 3.5-fold. With this hybrid tRNA set, the Ser/Leu-swapped cell-free translation system will stand as a potent tool for protein production with reduced biohazard concerns in future biological endeavors.

The X-ray binary system Cygnus X-3 (4U 2030+40, V1521 Cyg) is luminous but enigmatic owing to the high intervening absorption. High-resolution X-ray spectroscopy uniquely probes the dynamics of the photoionized gas in the system. In this Letter, we report on an observation of Cyg X-3 with the XRISM/Resolve spectrometer, which provides unprecedented spectral resolution and sensitivity in the 2–10 keV band. We detect multiple kinematic and ionization components in absorption and emission whose superposition leads to complex line profiles, including strong P Cygni profiles on resonance lines. The prominent Fe xxv He α and Fe xxvi Ly α emission complexes are clearly resolved into their characteristic fine-structure transitions. Self-consistent photoionization modeling allows us to disentangle the absorption and emission components and measure the Doppler velocity of these components as a function of binary orbital phase. We find a significantly higher velocity amplitude for the emission lines than for the absorption lines. The absorption lines generally appear blueshifted by ∼−500–600 km s ^−1 . We show that the wind decomposes naturally into a relatively smooth and large-scale component, perhaps associated with the background wind itself, plus a turbulent, denser structure located close to the compact object in its orbit.

We present an analysis of the first two XRISM/Resolve spectra of the well-known Seyfert-1.5 active galactic nucleus (AGN) in NGC 4151, obtained in 2023 December. Our work focuses on the nature of the narrow Fe K _α emission line at 6.4 keV, the strongest and most common X-ray line observed in AGN. The total line is found to consist of three components. Even the narrowest component of the line is resolved with evident Fe K _α _,1 (6.404 keV) and K _α _,2 (6.391 keV) contributions in a 2:1 flux ratio, fully consistent with neutral gas with negligible bulk velocity. Subject to the limitations of our models, the narrowest and intermediate-width components are consistent with emission from optically thin gas, suggesting that they arise in a disk atmosphere and/or wind. Modeling the three line components in terms of Keplerian broadening, they are readily associated with (1) the inner wall of the “torus,” (2) the innermost optical “broad-line region” (or “X-ray BLR”), and (3) a region with a radius of r ≃ 100 GM / c ^2 that may signal a warp in the accretion disk. Viable alternative explanations of the broadest component include a fast-wind component and/or scattering; however, we find evidence of variability in the narrow Fe K _α line complex on timescales consistent with small radii. The best-fit models are statistically superior to simple Voigt functions, but when fit with Voigt profiles the time-averaged lines are consistent with a projected velocity broadening of FWHM $\,=\,{1600}_{-200}^{+400}\,\mathrm{km}\,{{\rm{s}}}^{-1}$ . Overall, the resolution and sensitivity of XRISM show that the narrow Fe K line in AGN is an effective probe of all key parts of the accretion flow, as it is currently understood. We discuss the implications of these findings for our understanding of AGN accretion, future studies with XRISM, and X-ray-based black hole mass measurements.

Abstract Aims/Introduction Equol, which is produced by enteric bacteria from soybean isoflavones, has a chemical structure similar to estrogen. Both in vivo and in vitro studies have shown the beneficial metabolic effects of equol. However, its effects on type 2 diabetes remain unclear. We investigated the association between the equol producers/non‐producers and type 2 diabetes. Materials and Methods The participants included 147 patients with type diabetes mellitus aged 70–89 years, and 147 age‐ and sex‐matched controls. To ascertain the equol producers or non‐producers, we used the comparative logarithm between the urinary equol and daidzein concentrations (cut‐off value −1.75). Results The urinary equol concentration was significantly lower in the diabetes group compared with the non‐diabetes group (P = 0.01). A significant difference in the proportion of equol producers was observed among all participants (38.8% in the diabetes group and 53.1% in the non‐diabetes group; P = 0.01). The proportion of equol producers among women was significantly lower in the diabetes group (31.4%) than in the non‐diabetes group (52.8%; P

Abstract Microwaves (MWs) are widely used for heating food, accelerating chemical reactions, drying materials, therapies, and so on. Water molecules absorb MWs and produce heat because of their substantial electric dipole moments. Recently, increasing attention has been paid to accelerating various catalytic reactions in water-containing porous materials using MW irradiation. Here, a critical question is whether water in nanoscale pores generates heat in the same way as liquid water. Is it valid that MW-heating behaviors of nanoconfined water are estimated solely by a dielectric constant of liquid water? There are almost no studies regarding this question. Here, we address it using reverse micellar (RM) solutions. Reverse micelles are water-containing nanoscale cages formed by self-assembled surfactant molecules in oil. We measured real-time temperature changes of liquid samples within a waveguide under MW irradiation at 2.45 GHz and at MW intensities of ~ 3 to ~ 12 W/cm2. We found that the heat production and its rate per unit volume of water in the RM solution are about one order of magnitude larger than those of liquid water at all the MW intensities examined. This indicates that water spots that are much hotter than liquid water under MW irradiation at the same intensity, are formed in the RM solution. Our findings will give fundamental information to develop effective and energy-saving chemical reactions in nanoscale reactors with water under MW irradiation, and to study MW effects on various aqueous mediums with nanoconfined water. Furthermore, the RM solution will serve as a platform to study the impact of nanoconfined water on MW-assisted reactions.

Abstract Purpose Japan, with an increasing number of elderly people needing long-term care in a super-aged society, urgent needs to develop the clinical guidelines on implant maintenance for elderly people with declining independence. The purpose is to categorize the troubles encountered in the care of patients with dental implants and to indicate actual practices and points of note. Methods From the members of the Japanese Society of Oral Implantology, 12 expert panelists who were experienced with many problems of implant maintenance during dental visits and were familiar with their solutions were selected. Through repeated discussions in the many panel meetings, the problems of implant maintenance during dental visits were distilled. Results During a dental visit, the oral cavity, general conditions, and background of elderly patients who cannot orally care for themselves must be grasped, and medical staff, care managers, and patients should understand the changes in these factors as time goes by. The solutions and responses that can be made differ greatly depending on the medical care facilities, the environment, differences in the experience of medical staff, and the patient’s background. Thus, it is necessary to select safe treatments appropriate to each situation. Conclusions This paper features many opinions based on clinical experiences. However, clinical guidelines on implant management during dental visits should be formulated in the future based on the accumulation of evidence through the implementation of clinical research.

Cyclins are degraded by the anaphase-promoting complex/cyclosome (APC/C)-mediated proteasome in normal mitosis. We showed that Cdc13 (cyclin B) is also degraded by macroautophagy/autophagy in sulfur-deficient fission yeast. Sulfur depletion causes G2 cell cycle arrest and reduces cell size; however, the associated mechanisms are unknown. We found that autophagy is required for the degradation of Cdc13, which is associated with cell cycle arrest and reduced cell size, by examining cell morphology under sulfur depletion. The analysis of the Cdc13-GFP fusion protein supported the conclusion that Cdc13 is degraded by autophagy. Moreover, we showed that sulfur depletion results in the inactivation of target of rapamycin complex 1 (TORC1) activity via Ecl1-family proteins. Our data indicate that the cyclin is degraded by two different systems: APC/C-mediated proteasome and autophagy. The latter is induced under nutrient-depleted situations. This switch in degradation systems will contribute to appropriate cell cycle arrest when resources are depleted. Abbreviations: APC, anaphase-promoting complex; CDK, cyclin-dependent kinase; DB, destruction box; EMM, Edinburgh minimal medium; GFP, green fluorescent protein; PCR, polymerase chain reaction; TOR, target of rapamycin; UPS, ubiquitin-proteasome system

Summary: Conventional competitive enzyme-linked immunosorbent assay (ELISA) to measure the cortisol level in body fluid consumes a large amount of time, owing to complicated operations involved and requirement for precise control of reagent addition. We developed an automatic microfluidic system to detect salivary cortisol rapidly, and an electrospun polystyrene (PS) microfiber-based reactor providing considerable binding sites for antibody immobilization, thus resolving the time limitations of competitive ELISA. Cortisol sample, horseradish peroxidase (HRP)-conjugated cortisol, and 3,3′,5,5′-tetramethylbenzidine (TMB) substrate were delivered to the PS reactor from containers in sequence by pumps automatically. The color variation due to oxidized TMB complex reflects the cortisol concentration level measured using an RGB phototransistor. In addition, the entire procedure from sample introduction to obtaining the photocurrent took only 15 min. This system can be implemented to quantify cortisol from 0.37 ng/mL to 30 ng/mL, and the limit of detection was estimated at 0.37 ng/mL.

Abstract Many genes responsible for Malignant mesothelioma (MM) have been identified as tumor suppressor genes and it is difficult to target these genes directly at a molecular level. We searched for the gene which showed synthetic lethal phenotype with LATS2, one of the MM causative genes and one of the kinases in the Hippo pathway. Here we showed that knockdown of SMG6 results in synthetic lethality in LATS2-inactivated cells. We found that this synthetic lethality required the nuclear translocation of YAP1 and TAZ. Both are downstream factors of the Hippo pathway. We also demonstrated that this synthetic lethality did not require SMG6 in nonsense-mediated mRNA decay (NMD) but in regulating telomerase reverse transcriptase (TERT) activity. In addition, the RNA-dependent DNA polymerase (RdDP) activity of TERT was required for this synthetic lethal phenotype. We confirmed the inhibitory effects of LATS2 and SMG6 on cell proliferation in vivo. The result suggests an interaction between the Hippo and TERT signaling pathways. We also propose that SMG6 and TERT are novel molecular target candidates for LATS2-inactivated cancers such as MM.

Abstract In December 2019, a new activity started at Nishinoshima volcano in the southern part of the Izu–Ogasawara arc, Japan. This is now referred to as Episode 4 of a series of activities that began in 2013. We analyzed the eruption sequence, including erupted volume and effusion rate, based on combined observations of thermal anomalies by Himawari-8 and topographic changes by ALOS-2. The total eruption volume during Episode 4 was ~ 132 × 106 m3, and the average effusion rate over the entire period was 0.51 × 106 m3 day−1 (5.9 m3 s−1), which was two to three times higher than that of Episode 1. Episode 4 had three stages. In Stage 1, effusive activity was dominant, and most of the lava erupted from a northeast vent at the foot of the pyroclastic cone to cover the northern half of the island. The average effusion rate was estimated to be 0.46 × 106 m3 day−1 (5.3 m3 s−1). In Stage 2, an intensive lava fountain with a high discharge rate developed, and it increased the size of the pyroclastic cone rapidly. The effusion rate temporarily reached 2.6 × 106 m3 day−1 (30 m3 s−1). Pyroclastic rocks accounted for 45–88% of the total erupted volume in this stage. Lava flows with rafted cone material were generated, and those possibly caused by intensive spatter falls on the slope were also formed. These lavas flowed down the southern half of the island. In Stage 3, continuous phreatomagmatic eruptions released ash and spread it over a wide area. The high effusion rate and the drastic change in the activity style in Episode 4 can be explained by deep volatile-rich magma being supplied to a shallower magma chamber prior to Episode 4. When the volatile-rich magma reached a shallow part of the conduit in Stage 2, fragmentation occurred due to rapid volume expansion to eject large amounts of magma and form the intensive lava fountain. Observations by satellite-borne ultraviolet–visible image sensors detected a rapid increase in SO2 emissions in response to the intensive lava-fountain activity. The less-differentiated nature of the ash fragments collected during Stage 2 may reflect the composition of the volatile-rich magma. Large-scale discolored-seawater areas appeared during the late period of Stage 1, which may have been caused by ascent of the volatile-rich magma. Graphical Abstract

Wide-awake local anesthesia has many advantages. We describe a new method to use wide-awake local anesthesia with more flexibility. A 32-year-old man with a severe right-hand contracture after an iatrogenic tourniquet accident during an anterolateral thigh flap for a partial hand amputation underwent contracture release using external fixation after proximal row carpectomy and subsequent tenolysis. We performed most of the tenolysis procedure under general anesthesia and the final stage with an intraoperative assessment of active finger movement and dissection under local anesthesia. He regained his grip strength 2.5 years post-injury. General anesthesia is useful to treat a surgical site with extensive hard scars, whereas local anesthesia is useful for adjusting tension in an awake patient. The indication for wide-awake surgery is yet to be established; our method of combining general and local anesthesia in the tenolysis procedure illustrates the possibilities in expanding this method.

A generic methodology is presented to cross-calibrate satellite ocean-color sensors in polar orbit via an intermediary geostationary sensor of reference. In this study, AHI onboard Hiwamari-8 is used as the intermediary sensor to cross-calibrate SGLI onboard GCOM-C and MODIS onboard Aqua and Terra (MODIS-A and MODIS-T) after system vicarious calibration (SVC). Numerous coincidences were obtained near the Equator using 3 days of imagery, i.e., 11 May 2018, 22 January 2019, and 25 January 2020. Spectral matching to AHI spectral bands was first performed for a wide range of angular geometry, aerosol conditions, and Case 1 waters using a single band or multiple bands of SGLI, MODIS-A and MODIS-T, yielding root mean square differences of 0.1–0.7% in the blue and green and 0.7%–3.7% in the red depending on the band combination. Limited by the inherent AHI instrument noise and the system vicarious calibration of individual polar-orbiting sensors, cross-calibration was only performed for equivalent AHI bands centered on at 471, 510, and 639 nm. Results show that MODIS-A and MODIS-T are accurately cross-calibrated, with cross-calibration ratios differing by 0.1%–0.8% in magnitude. These differences are within or slightly outside the estimated uncertainties of ±0.6% to ±1.0%. In contrast, SGLI shows larger cross-calibration differences, i.e., 1.4%, 3.4%, and 1.1% with MODIS-A and 1.5%, 4.6%, and 1.5% with MODIS-T, respectively. These differences are above uncertainties of ±0.8–1.0% at 471 and 510 nm and within uncertainties of ±2.3% and ±1.9% at 639 nm. Such differences may introduce significant discrepancies between ocean-color products generated from SGLI and MODIS data, although some compensation may occur because different atmospheric correction schemes are used to process SGLI and MODIS imagery, and SVC is based on the selected scheme. Geostationary sensors with ocean color capability have potential to improve the spectral matching and reduce uncertainties, as long as they provide imagery at sufficient cadence over equatorial regions. The methodology is applicable to polar-orbiting optical sensors in general and can be implemented operationally to ensure consistency of products generated by individual sensors in establishing long-term data records for climate studies.

The oceanic waters of the Southwest Tropical Pacific occupy a vast region including multiple Pacific Island Countries. The state of these waters is determinant for fisheries and the blue economy. Ocean color remote sensing is the main tool to survey the variability and long-term evolution of these large areas that are important for economic development but are affected by climate change. Unlike vast oligotrophic gyres, tropical waters are characterized by numerous archipelagos and islands, with deep and shallow lagoons subjected to the large impacts of the land. Strikingly large dendritic phytoplankton (Trichodesmium) blooms with high levels of chlorophyll, developing within archipelagos, as well as coastal enrichments from various origins may be observed. Algorithms to detect the presence of Trichodesmium have been developed or adapted, as well as algorithms to estimate the chlorophyll concentration ([Chl-a)]. Adapting existing [Chl-a] algorithms does not always yield high, i.e., sufficient, accuracy. A review of published regional bio-optical algorithms developed taking into account the specific phytoplankton composition and minimizing the adverse impacts of particles and the seabed bottom on [Chl-a] determination is presented, as well the bio-optical database that allowed their development. The interest of such algorithms for a variety of applications and scientific accomplishments is highlighted, with a view to further addressing the main biology and biogeochemistry questions, e.g., to determine the true impact of diazotrophs and assess lagoon [Chl-a] variability with the highest confidence. This work anticipates the use of future coarse and high-spatial-resolution and multi- and hyper-spectral satellite imagery in the Pacific.

Objective Maintaining cervical lordosis (CL) after laminoplasty is important for indirect decompression of the spinal cord. This study aimed to identify preoperative dynamic radiographic predictors for the loss of CL after laminoplasty. Methods We retrospectively analyzed 141 consecutive patients who underwent cervical laminoplasty for cervical myelopathy. The following radiographic parameters were measured before surgery and at 1 year of follow-up: CL, C7 slope, C2–7 sagittal vertical axis (SVA), C2–7 range of motion (ROM), CL in flexion, CL in extension, ROM of flexion (Flex ROM), and ROM of extension. The CL ratio (CLR) was defined as 100 × Flex ROM/C2–7 ROM. ΔCL was defined as postoperative CL minus preoperative CL. Patients were classified into 2 groups: group K (kyphotic change group, ΔCL ≤ -10) and group C (control group, ΔCL > -10). Results The patient population comprised 94 men and 47 women (mean age, 70.9 ± 9.4 years), with 24 patients (17.0%) classified into group K. CL, C7 slope, and CLR were significantly higher in group K than in group C. The groups did not significantly differ in age, sex, C2–7 SVA, and C2–7 ROM. On multivariable analysis, the CLR was significantly associated with postoperative kyphotic changes. On receiver-operating characteristic curve analysis (area under the curve = 0.717, p < 0.001), the cutoff value for CLR was 68.9%, with sensitivity and specificity of 87.5% and 57.3%, respectively. Conclusion The CLR, reflecting the balance between flexion and extension mobility, was identified as a novel predictor for CL loss after laminoplasty, with a cutoff value of 68.9%.

A previously well 15-year-old male presented with a history of gross rectal prolapse (GRP) involving full-thickness rectal prolapse of increasing severity and incidence over 6 months that occurred with every bowel motion, varying from 10 to 40 cm. He denied constipation and passed a soft motion once daily, adeptly reducing his prolapsed rectum after each motion. This case illustrates technical challenges and planning for surgical intervention for optimal treatment in keeping with an FDA alert issued April, 2019 banning surgical mesh for pelvic organ prolapse. Preoperative fluoroscopic defecography confirmed rectal prolapse beginning with eversion of the anal verge identified on inspection. For surgery, general anesthesia was induced, he was placed in a Trendelenburg position, and four ports were inserted. The peritoneum was incised and blunt dissection used to expose the levator ani complex (LAC) taking care to prevent lateral nerve injury and preserve regional vascularity. Seven polypropylene sutures were used to fix the seromuscular posterior wall of the rectum to the median raphe of the LAC, the presacral fascia, and the periosteum of the sacral promontory. Operative time was 170 min. Postoperative recovery and progress were unremarkable. Currently, 5 years postoperatively, defecation is regular without recurrence of prolapse. For prolapse involving protrusion of the upper rectum without eversion of the anal verge, rectal fixation to the sacral promontory without further dissection beyond the peritoneal reflection is adequate, but when extensive prolapse is associated with eversion of the anal verge, more extensive blunt dissection from the peritoneal reflection to the LAC with multiple rectopexy sutures is valid for reducing risks for recurrence and eliminating mesh-related complications.

Summary: Two flaps, namely the free vascularized iliac bone graft supplied by the deep circumflex iliac artery (DCIA) and the superficial circumflex iliac artery perforator flap supplied by the superficial circumflex iliac artery (SCIA), can be individually harvested from a single surgical field. We report two cases treated by these free flaps for severe hand injury with large skin defect and osteomyelitis. Sequential chimeric flaps were anastomosed between the ascending branch of the DCIA and the SCIA. The advantage of this method is more freedom in the flap insetting for complex tissue defects. For this reason, this method is also excellent for cosmetic appearance. Furthermore, donor site morbidity can be minimized because the flaps are harvested from the same site.

Abstract Aims/Objectives Glycemic control varies according to stress level and the efficacy of control measures, affecting the outcomes of diabetes. Although detailed coping styles have not been well studied in patients with type 2 diabetes mellitus, problem‐focused coping strategies are believed to be related to better control of blood glucose. Associations between coping profiles/dimensions and blood glucose control were examined in individuals with type 2 diabetes. Materials and Methods The participants included 503 Japanese patients (mean age 63.9 ± 12.6 years) with type 2 diabetes. The average glycated hemoglobin A1c (HbA1c) levels were calculated from HbA1c levels measured more than four times within the 12 months before the assessment. Coping profiles were assessed using the Brief Scale for Coping Profile. Lifestyle factors were also included in the analyses. Results Factors other than age were not associated with HbA1c levels in patients who used insulin. Conversely, habitual alcohol consumption, single status, the adaptive emotion‐focused coping dimension, and changing mood and changing one’s point of view profiles were associated with HbA1c levels. Conclusions These findings suggest that adaptive emotion‐focused coping supports glycemic control in type 2 diabetes patients who do not use insulin. Additional studies using a longitudinal design are required to further examine the relationships between psychological factors and glycemic control.

Abstract Non-alcoholic fatty liver disease (NAFLD) is associated with a high risk of type 2 diabetes (DM), therefore, early diagnosis of NAFLD is important to prevent incident DM. FIB-4 index, a biomarker, often used to evaluate severity of NAFLD, may be useful to evaluate risk for incident DM in ordinary clinical setting. Here, we determined the association of FIB-4 index with changes in indices representing glucose metabolism with aging in a non-diabetic population. From among the participants of the population-based Iwaki study of Japanese people conducted during 2014–2017, 1,268 non-diabetic individuals with complete data sets (age: 51.4 ± 15.9 years; men/women: 485/773) were enrolled in a cross-sectional study. In addition, of the participants, 439 who attended consecutive appointments between 2014 and 2017 were enrolled in a longitudinal study that aimed to evaluate the changes in insulin secretion and resistance with aging (age: 53.1 ± 13.7 years; men/women: 178/261). The cross-sectional study showed significant correlations of FIB-4 index with homeostasis model of assessment (HOMA) indices, even after adjustment for multiple factors (HOMA-β: β = − 0.254, p

Abstract The GCOM-C (SHIKISAI) satellite was developed to understand the mechanisms of global climate change. The second-generation global imager (SGLI) onboard GCOM-C is an optical sensor observing wavelengths from 380 nm to 12.0 μm in 19 bands. One of the notable features is that the resolution of the 1.63, 10.8, and 12.0 µm bands is 250 m, with an observation frequency of 2–3 days. To investigate the effective use and potential of the 250 m resolution of these SGLI bands in the study of eruptive activities, we analyzed four practical cases. As an example of large-scale effusive activity, we studied the 2018 Kilauea eruption. By analyzing the series of 10.8 μm band images using cumulative thermal anomaly maps, we could observe that the lava effused on the lower East Rift Zone, initially flowed down the southern slope to the sea, and then moved eastward. As an example of lava dome growth and generation of associated pyroclastic flows, the activity at Sheveluch between December 2018 and December 2019 was analyzed. The 1.63 and 10.8 µm bands were shown to be suitable for observing growth of the lava dome and occurrence of pyroclastic flows, respectively. We found that the pyroclastic flows occurred during periods of rapid lava dome expansion. For the study of an active crater lake, the activity of Ijen during 2019 was analyzed. The lake temperature was found to rise rapidly in mid-May and reach 38 °C in mid-June. We also analyzed the intermittent activities of small-scale vulcanian eruptions at Sakurajima in 2019. The 1.63 µm band was useful for detecting activities that are associated with vulcanian eruptions. Analytical results for these case studies demonstrated that the GCOM-C SGLI images are beneficial for observing various aspects of volcanic activity, and their real-time use may contribute to reducing eruption-related disasters.

The EPIC/DSCOVR observations of the Earth’s surface lit by the Sun made from the first Lagrange point several times during the day in spectral bands centered on 443, 551, and 680 nm are used to estimate daily mean photosynthetically available radiation (PAR) at the ice-free ocean surface. The PAR algorithm uses a budget approach, in which the solar irradiance reaching the surface is obtained by subtracting from the irradiance arriving at the top of the atmosphere (known), the irradiance reflected to space (estimated from the EPIC Level 1b radiance data), taking account of atmospheric transmission and surface albedo (modeled). Clear and cloudy regions within a pixel do not need to be distinguished, which dismisses the need for often-arbitrary assumptions about cloudiness distribution within a pixel and is therefore adapted to the relatively large EPIC pixels. A daily mean PAR is estimated on the source grid for each EPIC instantaneous daytime observation, assuming no cloudiness changes during the day, and the individual estimates are remapped and weight-averaged using the cosine of the Sun zenith angle. In the computations, wind speed, surface pressure, and water vapor amount are extracted from NCEP Reanalysis 2 data, aerosol optical thickness and Angström coefficient from MERRA-2 data, and ozone amount from EPIC Level 2 data. Areas contaminated by Sun glint are excluded using a threshold on Sun glint reflectance calculated using wind data. Ice masking is based on NSIDC near-real-time ice fraction data. The product is evaluated against in situ measurements at various locations and compared with estimates from sensors in polar and geostationary orbits (MODIS, AHI). Unlike with MODIS, the EPIC PAR product does not exhibit gaps at low and middle latitudes. Accuracy is satisfactory for long-term studies of aquatic photosynthesis, especially given the much larger uncertainties on the fraction of PAR absorbed by live algae and the quantum yield of carbon fixation. The EPIC daily mean PAR product is generated operationally on a Plate Carrée (equal-angle) grid with 18.4 km resolution at the equator and on an 18.4 km equal-area grid, i.e., it is fully compatible with the NASA Greenbelt OBPG ocean-color products. Data are available since the beginning of the DSCOVR mission (i.e., June 2015) from the NASA Langley ASDC website.

Thiol catalysts are essential in native chemical ligation (NCL) to increase the reaction efficiency. In this paper, we report the use of thiocholine in chemical protein synthesis, including NCL-based peptide ligation and metal-free desulfurization. Evaluation of thiocholine peptide thioester in terms of NCL and hydrolysis kinetics revealed its practical utility, which was comparable to that of other alkyl thioesters. Importantly, thiocholine showed better reactivity as a thiol additive in desulfurization, which is often used in chemical protein synthesis to convert Cys residues to more abundant Ala residues. Finally, we achieved chemical synthesis of two differently methylated histone H3 proteins via one-pot NCL and desulfurization with thiocholine.

We have been developing a measurement system for microstructures using a small-diameter optical fiber probe. The contact detection method using a threshold value may cause a large error due to the time lag between the real contact time and the time detected by the measurement system. In this paper, we investigated a method for detecting the starting point of contact using an AR model and LSTM, a type of deep learning when the stylus tip contacts the measured surface. The results of measurement experiments using an inclined surface showed that the detection accuracy using AR model decreased as the inclination angle increased, but the LSTM was able to detect the contact point with high accuracy even when the inclination angle increased. It was also confirmed that the method using LSTM can detect contact with high accuracy without being affected by drift over time and various noises (other than random noise).

The precise measurement of microstructures and other micron-sized materials has garnered considerable interest in recent years. We have developed a measurement system that uses an etched small diameter optical fiber as a stylus to measure microstructures with low contact force. However, when the diameter of the stylus tip is less than a few tens of micrometers, the surface forces between the measured surface and the stylus tip become larger than the gravity of the stylus tip, causing the stylus tip to stick to the measured surface. This adhesion leads to an increase in measurement time and a decrease in measurement accuracy. In this study, we fabricated a high-function stylus with water-repellent and antistatic coatings applied to the stylus tip to reduce the adhesion between the stylus tip and measured surface due to surface forces, and conducted performance evaluation tests. As a result, the average separation distance was 13.8 µm when a fluorinated resin coating with a contact angle of 105° was used, confirming that the influence of liquid bridge forces could be reduced by approximately 78%. Additionally, when static elimination experiments were conducted by scanning the charged surface at a pitch of 0.5 µm using an antistatic coating stylus with a gold on the stylus surface, the average adsorption distance was 3.6 µm, confirming that the effect of electrostatic force could be reduced by 71%.

Kinetochores drive chromosome segregation by mediating chromosome interactions with the spindle. In higher eukaryotes, sister kinetochores are separately positioned on opposite sides of sister centromeres during mitosis, but associate with each other during meiosis I. Kinetochore association facilitates the attachment of sister chromatids to the same pole, enabling the segregation of homologous chromosomes toward opposite poles. In the fission yeast, Schizosaccharomyces pombe, Rec8-containing meiotic cohesin is suggested to establish kinetochore associations by mediating cohesion of the centromere cores. However, cohesinmediated kinetochore associations on intact chromosomes have never been demonstrated directly. In the present study, we describe a novel method for the direct evaluation of kinetochore associations on intact chromosomes in live S. pombe cells, and demonstrate that sister kinetochores and the centromere cores are positioned separately on mitotic chromosomes but associate with each other on meiosis I chromosomes. Furthermore, we demonstrate that kinetochore association depends on meiotic cohesin and the cohesin regulators Moa1 and Mrc1, and requires mating-pheromone signaling for its establishment. These results confirm cohesinmediated kinetochore association and its regulatory mechanisms, along with the usefulness of the developed method for its analysis. [ABSTRACT FROM AUTHOR]

Abstract Aims/Introduction To examine the three‐dimensional morphology and vascular endothelial growth factor (VEGF) expression of skin microvasculature in patients with type 2 diabetes in relation to neuropathy, retinopathy and nephropathy. Materials and Methods The present study enrolled 17 individuals with type 2 diabetes and 16 without. Skin sections were double‐immunostained for type IV collagen and VEGF‐A or protein gene product 9.5. Projected images from confocal microscopy served to quantify the occupancy rate of subepidermal type IV collagen‐immunoreactive microvascular basement membrane area (OR‐T4MBM), subepidermal VEGF‐A‐immunoreactive area and the VEGF/T4MBM ratio, as well as the protein gene product 9.5‐immunoreactive intraepidermal nerve fiber density. Reduced intraepidermal nerve fiber density was applied for the diagnosis of neuropathy, fundic ophthalmoscopy and fluorescein angiography for retinopathy, and microalbuminuria or persistent proteinuria for nephropathy. Results A total of 12 patients with diabetes had neuropathy, 10 had retinopathy and eight had nephropathy. Regardless of the presence or absence of neuropathy, retinopathy or nephropathy, OR‐T4MBM was significantly increased in patients with diabetes compared with individuals without diabetes. In contrast, VEGF/T4MBM ratio was significantly decreased in those with neuropathy and retinopathy, as well as in those with and without nephropathy, whereas a trend toward a decreased VEGF/T4MBM ratio was seen in patients without retinopathy, as compared with individuals without diabetes. Conclusions The present study is the first report to show that cutaneous microangiopathy, as indicated by subepidermal microvascular proliferation and impaired VEGF expression, appears to occur before the development of overt clinical neuropathy, retinopathy or nephropathy in patients with type 2 diabetes.

Abstract Objective Type 2 diabetes mellitus (T2DM) is associated with a high prevalence of depression, which is influenced by personality traits and coping style. However, these psychological factors have not been well studied in individuals with T2DM. The association between coping behaviors and the reported levels of depressive symptoms was examined in individuals with T2DM. Methods The subjects were 435 T2DM patients (mean age 63.1 ± 12.6 years). Depressive status, personality traits and coping behaviors were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Brief Scale for Coping Profile (BSCP). Lifestyle factors and glycated hemoglobin A1c (HbA1c) levels in the patients were also included in the analyses. Results Among the 435 subjects with T2DM, 130 (29.9%) exhibited possible depression, and 68 (15.6%) displayed probable depression. After adjustment for confounders, logistic and multiple regression analyses revealed that certain coping profile scores, such as Changing one’s point of view, Emotional expression involving others and Avoidance and suppression, were consistently and significantly associated with the presence and severity of depression. No relationship was found between depression and HbA1c. Conclusion These findings indicate that Maladaptive emotion-focused coping strategies, such as Emotional expression involving others and Avoidance and suppression, are protective factors and that Adaptive emotion-focused coping, such as Changing one’s point of view, is a risk factor for depression in T2DM patients. Psychological intervention focusing on the coping profile may reduce depressive symptoms. Additional studies are needed to examine the relationships between psychological factors and depressive symptoms using a longitudinal study design.

Abstract Aims/Introduction Insomnia is associated with type 2 diabetes mellitus, and results in a low quality of life. There are several known relationships between insomnia and personality. Thus, we clarified the association between some personality traits and insomnia among Japanese type 2 diabetes mellitus patients. Materials and Methods The participants were 504 type 2 diabetes mellitus patients (mean age 63.9 ± 12.5 years). Sleep disturbance and personality traits were evaluated using the Pittsburgh Sleep Quality Index‐Japanese version and the Ten‐Item Personality Inventory Japanese version, respectively. Lifestyle factors, glycated hemoglobin levels and depressive status of the patients were also included in the analyses. Results Among the 504 participants with type 2 diabetes mellitus, 154 (30.6%) showed probable insomnia. After adjustment for confounders, being female, living alone, high body mass index and “high neuroticism” were found to be significantly correlated with current insomnia. No other relationships between insomnia and glycated hemoglobin or lifestyle factors, such as smoking, drinking alcohol or exercise frequency, were found. Conclusions The prevalence of insomnia in individuals with type 2 diabetes mellitus was high, and the risk factors included some personality factors. Future prospective studies are required to confirm the therapeutic effects of behavioral interventions for insomnia in patients with type 2 diabetes mellitus.

Recently, we developed transcription/translation coupled with the association of puromycin linker (TRAP) display as a quick in vitro selection method to obtain antibody-like proteins. For the in vitro selection, it is important to prepare mRNA libraries among which the diversity is high. Here, we describe a method for the preparation of monobody mRNA libraries with greater than 1013 theoretical diversity. First, we synthesized two long single-stranded DNAs that corresponded to fragments of monobody DNA, with random codons in the BC and FG loops. These oligonucleotides were ligated by T4 DNA ligase with the support of guide oligonucleotides containing 3′ ends that were protected by a modification. After amplifying the product DNAs by PCR, one end of each DNA fragment was digested with the type II restriction enzyme BsaI, and the resulting DNA fragments were ligated using T4 DNA ligase. After amplification of the DNA product, mRNAs were synthesized by T7 RNA polymerase. This method is simple and could be used for the preparation of mRNA libraries for various antibody-like proteins.Graphic abstract:Construction of a highly diverse mRNA library.

Introduction Given an increasing use of dipeptidyl peptidase-4 (DPP-4) inhibitors to treat patients with type 2 diabetes mellitus in the real-world setting, we conducted a prospective observational study (Japan-based Clinical Research Network for Diabetes Registry: J-BRAND Registry) to elucidate the safety and efficacy profile of long-term usage of alogliptin.Research design and methods We registered 5969 patients from April 2012 through September 2014, who started receiving alogliptin (group A) or other classes of oral hypoglycemic agents (OHAs; group B), and were followed for 3 years at 239 sites nationwide. Safety was the primary outcome. Symptomatic hypoglycemia, pancreatitis, skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major adverse events (AEs). Efficacy assessment was the secondary outcome and included changes in hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin and urinary albumin.Results Of the registered, 5150 (group A: 3395 and group B: 1755) and 5096 (3358 and 1738) were included for safety and efficacy analysis, respectively. Group A patients mostly (>90%) continued to use alogliptin. In group B, biguanides were the primary agents, while DPP-4 inhibitors were added in up to ~36% of patients. The overall incidence of AEs was similar between the two groups (42.7% vs 42.2%). Kaplan-Meier analysis revealed the incidence of cancer was significantly higher in group A than in group B (7.4% vs 4.8%, p=0.040), while no significant incidence difference was observed in the individual cancer. Multivariate Cox regression analysis revealed that the imbalanced patient distribution (more elderly patients in group A than in group B), but not alogliptin usage per se, contributed to cancer development. The incidence of other major AE categories was with no between-group difference. Between-group difference was not detected, either, in the incidence of microvascular and macrovascular complications. HbA1c and fasting glucose decreased significantly at the 0.5-year visit and nearly plateaued thereafter in both groups.Conclusions Alogliptin as a representative of DPP-4 inhibitors was safe and durably efficacious when used alone or with other OHAs for patients with type 2 diabetes in the real world setting.

Aims/Introduction: Chronic kidney disease (CKD)-mineral and bone disorders (CKD-MBD) are an adverse outcome derived from decreases in kidney function, where abnormality of serum concentrations of calcium (Ca), phosphorus, parathyroid hormone (PTH), and vitamin D can be seen simultaneously. To identify individuals at risk for CKD-MBD or secondary hyperparathyroidism, the relationships between estimated glomerular filtration rate (eGFR) and serum PTH concentration were evaluated, allowing for confounding factors, in particular vitamin D status, in a general Japanese population.Materials and Methods: Nine-hundred-and-thirty participants in the population-based Iwaki study conducted in 2016 who were not on drugs affecting mineral metabolism nor hemodialysis, were included in the study (326 men and 604 women; age: 55.4 ± 15.9 years).Results: Regression analysis showed a significant correlation between eGFR and serum intact PTH concentration, after adjustment for possible confounding factors (β = −0.122, p < 0.001). The smoothed spline curve applied for the correlation analysis revealed a biphasic correlation, with a division at an eGFR of ~60 mL/min/1.73 m2, below which the correlation coefficient was higher (β = −0.405, p < 0.001). Stratification on the basis of vitamin D status showed that the correlation was present only in participants with vitamin D deficiency (25-dihydroxyvitamin D3:

Previously, we have succeeded in converting induced pluripotent stem cells (iPSCs) into cancer stem cells (CSCs) by treating the iPSCs with conditioned medium of Lewis lung carcinoma (LLC) cells. The converted CSCs, named miPS-LLCcm cells, exhibited the self-renewal, differentiation potential, and potential to form malignant tumors with metastasis. In this study, we further characterized miPS-LLCcm cells both in vivo and in vitro. The tumors formed by subcutaneous injection showed the structures with pathophysiological features consisting of undifferentiated and malignant phenotypes generally found in adenocarcinoma. Metastasis in the lung was also observed as nodule structures. Excising from the tumors, primary cultured cells from the tumor and the nodule showed self-renewal, differentiation potential as well as tumor forming ability, which are the essential characters of CSCs. We then characterized the epigenetic regulation occurring in the CSCs. By comparing the DNA methylation level of CG rich regions, the differentially methylated regions (DMRs) were evaluated in all stages of CSCs when compared with the parental iPSCs. In DMRs, hypomethylation was found superior to hypermethylation in the miPS-LLCcm cells and its derivatives. The hypo- and hypermethylated genes were used to nominate KEGG pathways related with CSC. As a result, several categories were defined in the KEGG pathways from which most related with cancers, significant and high expression of components was PI3K-AKT signaling pathway. Simultaneously, the AKT activation was also confirmed in the CSCs. The PI3K-Akt signaling pathway should be an important pathway for the CSCs established by the treatment with conditioned medium of LLC cells.

Tripodal extraction reagent with three phosphoric acid groups, together with the corresponding monopodal molecule has been prepared to investigate some metals extraction behavior, in particular, trivalent rare earth elements (REEs). The tripodal reagent exhibited extremely high selectivity for metals with high valency such as Zr(IV), In(III), Lu(III), and Fe(III). Tripodal reagent also exhibited exceptionally high extraction ability compared with the corresponding monopodal one in the extraction of trivalent rare earths. The result for the stoichiometry of tripodal reagent to heavy rare earths showed the inflection point between Er (2:1 for a ligand with ion) and Tm (1:1). The extraction reactions were determined for all rare earths with both reagents. The extraction equilibrium constants (Kex), the separation factors (β), half pH values (pH1/2), difference half pH values (ΔpH1/2) for extraction of REEs with both reagents are estimated.

Since activation of the sympathetic nervous system is associated with both impaired insulin secretion and insulin resistance, or namely with diabetes, evaluation of such activation in ordinary clinical settings may be important. Therefore, we evaluated the relationships between urinary concentrations of the catecholamine metabolites, urinary normetanephrine (U-NM) and urinary metanephrine (U-M), and glucose metabolism in a general population. From 1,148 participants in the 2016 population-based Iwaki study of Japanese, enrolled were 733 individuals (gender (M/F): 320/413; age: 52.1±15.1), who were not on medication affecting serum catecholamines, not diabetic, and had complete data-set and blood glucose levels appropriate for the evaluation of insulin secretion and resistance, using homeostasis model assessment (HOMA-β and HOMA-R, respectively). Univariate linear regression analyses revealed significant correlations between both U-NM and U-M, and HOMA-β, but adjustment for multiple factors correlated with HOMA indices abolished these (β = -0.031, p = 0.499, and β = -0.055, p = 0.135, respectively). However, the correlation between U-NM and HOMA-R observed using univariate linear regression analysis (β = 0.132, p1.6) determined by ROC analysis (0.2577 mg/gCr) showed that individuals at risk had an odds ratio of 2.65 (confidence interval: 1.42-4.97) after adjustment for the same factors used above. Higher U-NM concentrations within the physiologic range are a significant risk factor for increased insulin resistance in a general Japanese population.