Discovery of YS-1 as a cell line of gastric inflammatory cancer-associated fibroblasts.

BACKGROUND: Inflammatory cancer-associated fibroblasts (iCAFs) was first identified by co-culture of pancreatic stellate cells and tumor organoids. The key feature of iCAFs is IL-6high/αSMAlow. We examine this phenomenon in gastric cancer using two cell lines of gastric fibroblasts (HGF and YS-1). METHODS AND RESULTS: HGF or YS-1 were co-cultured with MKN7 (a gastric adenocarcinoma cell line) in Matrigel. IL-6 protein levels in the culture supernatant were measured by ELISA. The increased production of IL-6 was not observed in any of the combinations. Instead, the supernatant of YS-1 exhibited the higher levels of IL-6. YS-1 showed IL-6high/αSMA (ACTA2)low in real-time PCR, mRNA-seq and immunohistochemistry. In mRNA-seq, iCAFs-associated genes and signaling pathways were up-regulated in YS-1. No transition to myofibroblastic phenotype was observed by monolayer culture, or the exposure to sonic hedgehog (SHH) or TGF-ß. YS-1 conditioned medium induced changes of morphology and stem-ness/differentiation in NUGC-3 (a human gastric adenocarcinoma cell line) and UBE6T-15 (a human bone marrow-derived mesenchymal stem cell line). CONCLUSIONS: YS-1 is a stable cell line of gastric iCAFs. This discovery will promote further research on iCAFs for many researchers.

Air kerma reference field with high energy photons using a 15 MeV electron beam from a clinical linear accelerator.

In the medical and nuclear fields, there are environments where exposure to photons with energies above several MeV can result in problems. The National Metrology Institute of Japan has developed a high-energy photon field using a 15 MeV electron beam of a clinical linear accelerator with a copper target and an aluminium filter unit to facilitate dosimeter calibration in terms of air kerma. To determine the air kerma rate, the energy fluence distribution at a reference point was calculated, and both calculations and experiments evaluated the effective energy and spatial dose distribution. Moreover, to validate the air kerma measurement, two commercial cavity chambers were calibrated in a developed photon field. The results obtained exhibited a 4% difference compared with those in a Co-60γ-ray reference field.

Harmonic radiation contribution and X-ray transmission at the Small Quantum Systems instrument of European XFEL.

Transmission measurements of the soft X-ray beamline to the Small Quantum Systems (SQS) scientific instrument at the SASE3 undulator of European XFEL are presented. Measurements are reported for a wide range of photon energies (650 eV to 2400 eV), using X-ray gas monitors as well as a bolometric radiometer. The results are in good agreement with simulations for the beam transport and show a transmission of up to 80% over the whole photon energy range. The contribution of second- and third-harmonic radiation of the soft X-ray undulator is determined at selected photon energies by performing transmission measurements using a gas absorber to provide variable attenuation of the incoming photon flux. A comparison of the results with semi-analytic calculations for the generation of free-electron laser pulses in the SASE3 undulator reveals an influence of apertures along the beam transport on the exact harmonic content to be accounted for at the experiment. The second-harmonic content is measured to be in the range of 0.1% to 0.3%, while the third-harmonic contributed a few percent to the SASE3 emission. For experiments at the SQS instrument, these numbers can be reduced through specific selections of the mirror reflection angles.

Morphological and optical properties of α- and ß-phase zinc (∥) phthalocyanine thin films for application to organic photovoltaic cells.

We have investigated the morphological and optical properties of α- and ß-phase Zinc Phthalocyanine (ZnPc) thin films for application to organic photovoltaic cells (OPVs). It was found that the α-phase is completely converted to the ß-phase by thermal annealing at 220 °C under ultrahigh vacuum conditions. When the α- to ß-phase transition takes place, the surface roughness of the ZnPc film became flat uniformly with a nanometer order of unevenness by anisotropic growth of crystalline grains along a lateral direction to substrates. Correspondingly, the optical absorbance of the ß-phase film became greater by 1.5-2 times than that of the α-phase one in an ultraviolet-visible-near infrared (UV-vis-NIR) wavelength range, which plays a role in increasing the number of photogenerated excitons. On the contrary, time-resolved photoluminescence measurements showed that the average lifetime of excitons for the ß-phase film became shorter by 1/6-1/7 than that for the α-phase one, which plays a role in decreasing the number of excitons achieving the donor/acceptor interface where excitons are separated to carriers (holes and electrons). Both the increase in the number and the shortening in the average lifetime have a trade-off relationship with each other for contribution to the photoelectric conversion efficiency of OPVs. Then, we examined an external quantum efficiency (EQE) of OPVs using the α- and ß-phase films as a donor and obtained that the former OPV (α-phase) exhibits a higher EQE by ∼2 times than the latter one (ß-phase) in the wavelength range of 400 nm-800 nm.

Serum canine thymus and activation-regulated chemokine (TARC/CCL17) concentrations correlate with disease severity and therapeutic responses in dogs with atopic dermatitis.

BACKGROUND: Thymus and activation-regulated chemokine (TARC/CCL17) has been implicated in the pathogenesis of canine atopic dermatitis (cAD). Serum TARC concentrations are a reliable biomarker for human atopic dermatitis; however, their potential as a biomarker for cAD has not been investigated. HYPOTHESIS/OBJECTIVES: To investigate whether serum TARC concentrations correlate with disease severity and therapeutic responses for cAD. ANIMALS: Thirty-nine dogs with cAD and 42 healthy dogs were recruited. METHODS AND MATERIALS: Serum TARC concentrations in dogs with cAD and healthy dogs were measured by sandwich ELISA with anti-canine TARC antibodies. The clinical severity of cAD was scored using the validated Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04). Serum TARC concentrations were compared between dogs with cAD and healthy controls, and their relationship with CADESI-04 was examined. Serum TARC concentrations also were measured in 20 dogs with cAD treated with prednisolone or oclacitinib for four weeks. RESULTS: Serum TARC concentrations were significantly higher in dogs with cAD than in healthy dogs (P < 0.001). In dogs with cAD, serum TARC concentrations correlated with CADESI-04 scores (ρ = 0.457, P < 0.01). Furthermore, serum TARC concentrations significantly decreased in treated dogs with the attenuation of clinical signs (P < 0.001). Changes in serum TARC concentrations before and after treatment correlated with those in CADESI-04 scores (ρ = 0.746, P < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: Serum TARC concentrations have potential as a clinical and research tool for the objective evaluation of disease severity and therapeutic responses for cAD.

Measurement of the absolute number of photons of the hard X-ray beamline at the Linac Coherent Light Source.

X-ray free-electron lasers provide intense pulses of coherent X-rays with a short pulse duration. These sources are chaotic by nature and therefore, to be used at their full potential, require that every X-ray pulse is characterized in terms of various relevant properties such as intensity, photon energy, position and timing. Diagnostics are for example installed on an X-ray beamline to specifically monitor the intensity of individual X-ray pulses. To date, these can however only provide a single-shot value of the relative number of photons per shot. Here are reported measurements made in January 2015 of the absolute number of photons in the hard X-ray regime at LCLS which is typically 3.5 × 1011 photons shot-1 between 6 and 9.5 keV at the X-ray Pump-Probe instrument. Moreover, an average transmission of ≉62% of the hard X-ray beamline over this energy range is measured and the third-harmonic content of ≉0.47% below 9 keV is characterized.

Evaluation of Measures against Exposure during Administration of Hazardous Drugs through a Feeding Tube.

Hazardous drugs (HD), which need to be handled with care, may be administered through a feeding tube using the simple suspension method. However, instrument contamination during HD administration with the simple suspension method remains unclear. Therefore, to minimize such contamination during the simple suspension method using an injector, we propose the following exposure countermeasures method: (1) Wear two layers of gloves. (2) Prepare injectors for administration and flushing. (3) Use caps. (4) Replace outer gloves after the removal of tablets from the press-through package (PTP) sheet. (5) Handle drugs on a tray. (6) Inject while wrapping the connection site between the injector for administration and the tube with gauze. (7) Wrap the connection site between the injector and tube with gauze. (8) Do not point the injector downward. To establish whether these countermeasures method are effective, 16 ward nurses who routinely administer drugs via a feeding tube were enrolled as subjects. By visual evaluation, we compared differences in instrument contamination between a suspension using a medicine cup and administration via a feeding tube (the conventional method) and the exposure countermeasures method. Exposure with the countermeasures method under our instruction was markedly lower than that with the conventional method. Furthermore, after implementing the exposure countermeasures method, most nurses noted that caution and awareness of exposure countermeasures increased. Thus, to minimize exposure, we recommend the implementation of the exposure countermeasures method and increasing knowledge and awareness of measures against exposure.

Prognostic factors for long-term improvement from stroke-related aphasia with adequate linguistic rehabilitation.

In the past decade, several studies have reported potential prognostic factors for aphasia after stroke. However, these reports covered no more than 1 year after stroke onset, even though patients often continue to improve over longer periods. The present study included 121 patients with aphasia who received cognitive-based linguistic rehabilitation for at least 2 years post-onset. All were right-handed and had a lesion only in the left hemisphere. Aphasia outcome was predicted using multiple linear regression analysis. Age at onset, lesion in the left superior temporal gyrus including Wernicke's area, and baseline linguistic abilities including aphasia severity and both phonological and semantic functions were significant predictors of long-term aphasia outcome. These findings suggest that the long-term outcome of aphasia following adequate linguistic rehabilitation can be predicted by age at onset, lesion area, and baseline linguistic abilities and that linguistic rehabilitation is particularly recommended for younger individuals with aphasia.

Two new genera of Podostemaceae from northern Central Laos: saltational evolution and enigmatic morphology.

Podostemaceae, the river-weeds, are characterized by remarkable differences between species and genera, which resulted from saltational evolution. This paper presents additional cases of such two genera, which are described here from the Phou Khao Khouay National Protected Area in northern Central Laos. Molecular phylogenetic data show that Ctenobryum mangkonense (gen. & sp. nov.) is sister to Hydrodiscus koyamae, while Laosia ramosa (gen. & sp. nov.) is isolated from all Asian genera of subfamily Podostemoideae. Ctenobryum mangkonense is distinct from Hydrodiscus koyamae in the crustose roots (versus rootless in the latter), scattered flowers on the root (versus alternate on the shoot), and pectinate bracts (versus simple, sheath-like). Laosia ramosa is distinct from all the genera in the columnar, endogenously branched axes and single style-stigma complex. The axis is an enigmatic organ with combined characteristics of root, stem and leaf, pending further study. Laos, together with Thailand, is a center of diversity of the Southeast and East Asian Podostemoideae. The three monotypic genera, i.e., Ctenobryum, Hydrodiscus and Laosia, occur in neighboring and closely similar aquatic habitats within the Area. The new taxa are formally described.

Morphological characterization of infra-generic lineages in Deparia (Athyriaceae: Polypodiales).

Deparia, including the previously recognized genera Lunathyrium, Dryoathyrium (=Parathyrium), Athyriopsis, Triblemma, and Dictyodroma, is a fern genus comprising about 70 species in Athyriaceae. In this study, we inferred a robust Deparia phylogeny based on a comprehensive taxon sampling (~81% of species) that captures the morphological diversity displayed in the genus. All Deparia species formed a highly supported monophyletic group. Within Deparia, seven major clades were identified, and most of them were characterized by inferring synapomorphies using 14 morphological characters including leaf architecture, petiole base, rhizome type, soral characters, spore perine, and leaf indument. These results provided the morphological basis for an infra-generic taxonomic revision of Deparia.

Airbag deployment and cervical spine injury in restrained drivers following motor vehicle collisions.

PURPOSE: Seatbelts and airbags are the most important devices protecting drivers from cervical spine injury (CSI) following motor vehicle collisions (MVCs). However, there have been few reports on the radiographic characteristics of CSI sustained by restrained, airbag-deployed drivers. METHODS: A single-center, retrospective observational study was conducted using prospectively acquired data. Between January 2011 and December 2017, 564 restrained drivers, whose vehicle had been severely damaged in MVCs, underwent whole-body computed tomography for evaluation of bodily injuries. The drivers were dichotomized into airbag (+) group (n = 218) and airbag (-) group (n = 139), after excluding 207 drivers in whom airbag deployment status was unknown. RESULTS: Eight and nine drivers sustained CSIs in the airbag (+) and airbag (-) group, respectively. The frequency of CSI did not differ significantly between the two groups (3.7% vs. 6.5%, p = 0.31). All eight CSIs in the airbag (+) group were classified as hyperextension injuries, and four of them sustained concomitant spinal cord injuries caused by dislocation. Within the airbag (+) group, the drivers with CSIs were significantly older than those without CSIs (65.2 ± 18.5 vs. 44.8 ± 18.7 years, p = 0.002). CONCLUSION: Although it is without doubt that the combination of seatbelt and airbag reduces the frequency and severity of CSIs following MVCs, the CSIs sustained in restrained, airbag (+) drivers may not always be mild, and elderly drivers may be at an elevated risk of CSI. In addition, the possibility of a causal role of airbags in CSI requires consideration in this population.

Columnar Liquid Crystals from a Giant Macrocycle Mesogen.

Columnar liquid crystals composed of a giant macrocyclic mesogen were prepared. The giant macrocyclic mesogen has a square hollow with a 2.5 nm diagonal, which was bounded by diindolo[3,2-b:2',3'-h]carbazole (diindolocarbazole) moieties as the edges and bis(salicylidene)-o-phenylenediamine (salphen) moieties as the corners. The shape and size of the macrocycle were directly observed by scanning tunneling microscopy (STM). Each side of the bright square in the STM image corresponds to a diindolocarbazole moiety, and the length of the sides was consistent with the result of the single crystal analysis of diindolocarbazole. Finally, we successfully obtained a giant macrocycle with long and branched side chains, which exhibited a rectangular columnar LC phase over a wide temperature range. To the best of our knowledge, it contained the largest discrete inner space of any thermotropic columnar liquid crystal composed of macrocyclic mesogens.

Compact bolometric radiometer for free-electron lasers in a wavelength range from extreme-ultraviolet to x-rays.

A reliable diagnostic device for free-electron lasers (FELs) is essential for both users and the evaluation of FEL sources and beamline optics. Here, we propose a compact bolometric radiometer (CBR) that can operate at room temperature. The CBR is mainly designed for FELs in the wavelength range from the extreme-ultraviolet (EUV) to x-rays; moreover, we confirmed that the proposed device can also be applied to synchrotron radiation. As an application of the CBR, we evaluated an FEL beamline transmission by means of bolometric technique in the EUV range for the first time, to the best of our knowledge. This indicates that the CBR is an effective diagnostic device for FELs.

Male mice ultrasonic vocalizations enhance female sexual approach and hypothalamic kisspeptin neuron activity.

Vocal communication in animals is important for ensuring reproductive success. Male mice emit song-like "ultrasonic vocalizations (USVs)" when they encounter female mice, and females show approach to the USVs. However, it is unclear whether USVs of male mice trigger female behavioral and endocrine responses in reproduction. In this study, we first investigated the relationship between the number of deliveries in breeding pairs for 4months and USVs syllables emitted from those paired males during 3min of sexual encounter with unfamiliar female mice. There was a positive correlation between these two indices, which suggests that breeding pairs in which males could emit USVs more frequently had more offspring. Further, we examined the effect of USVs of male mice on female sexual behavior. Female mice showed more approach behavior towards vocalizing males than devocalized males. Finally, to determine whether USVs of male mice could activate the neural system governing reproductive function in female mice, the activation of kisspeptin neurons, key neurons to drive gonadotropin-releasing hormone neurons in the hypothalamus, was examined using dual-label immunocytochemistry with cAMP response element-binding protein phosphorylation (pCREB). In the arcuate nucleus (Arc), the number of kisspeptin neurons expressing pCREB significantly increased after exposure to USVs of male as compared with noise exposure group. In conclusion, our results suggest that USVs of male mice promote fertility in female mice by activating both their approaching behavior and central kisspeptin neurons.

Habitat specificity enhances genetic differentiation in two species of aquatic Podostemaceae in Japan.

PREMISE OF THE STUDY: Species with habitat specificity show restricted distribution, and the limited dispersal provides opportunity for long-term isolation. Aquatic Podostemaceae grow on rocks in river rapids, which are extreme habitats for angiosperms. To infer the diversification process of the podostemad species in such specific habitats, we investigated environmental factors shaping their distribution and the relationship between their distribution and genetic structure. METHODS: We used Hydrobryum japonicum and Cladopus doianus, which have contrasting distributions (i.e., narrower and wider, respectively) in southern Kyushu, Japan. Environmental factors contributing to their distribution were estimated by ecological niche modeling. Using polymorphisms in chloroplast DNA, we performed population genetic analyses of 13 H. japonicum populations occurring in nearby river basins and eight C. doianus populations in distant rivers. KEY RESULTS: Estimation of distribution probability showed great contributions of geology and temperature to the distribution of these populations, suggesting that the species grow on volcanic rocks in relatively warm areas. Genetic analyses revealed higher interpopulational genetic diversity than intrapopulational diversity and strong differentiation between rivers in both species. No correlation between genetic and geographic distances was detected among the C. doianus populations, in contrast to the significant correlation observed in the H. japonicum populations. CONCLUSIONS: The high-level genetic differentiations among populations of the two species may result from their limited dispersal. Their restricted habitats, which are primarily characterized by volcanic rocks in rapids and lower temperatures in winter, may enhance isolation among populations in distant rivers.

Multidisciplinary studies of the diversity and evolution in river-weeds.

The moss-like river-weeds or Podostemaceae offer a special opportunity to study the diversity and evolution of plants that are adapted to extreme environments. This paper reviews multidisciplinary studies on this subject. Based on field work in the four continents, we discovered many species and several genera that are new components of biodiversity, and revealed the Podostemaceae floras of East Asia, Southeast Asia, and Australia. The historical biogeography of the family, i.e., the change in distribution in space and time, is characterized by a few dispersals between continents, followed by diversification within each continent. Local species may be derived from parts of separated populations of parental species, which consequently are paraphyletic. The remarkable morphological adaptations of Podostemaceae include the development of the horizontal axis in plant body, with which the plants adhere to rock surfaces under violent current. The vertical axis is reduced or lost and the horizontal axis develops in the embryo and seedling. We also found saltational organ-level variation, such as presence or absence of shoot, shoot apical meristem, root, and root cap; the form of shoot and root; the mode of root branching and leaf production; and the number of cotyledons. Morphological evolution may not be always adaptive to the habitats, which are rocks periodically submerged across the distribution range. Analyses of shoot regulatory gene expression found that, in contrast to the expression pattern in primitive species with ordinary shoots, which is comparable with Arabidopsis, the unique pattern in derived species may result in 'fuzzy' morphology of the shoot and leaf. Finally, problems for future study are pointed out.

[Prediction of future cost savings in long-term care and medical care if Japan achieves the health expectancy target of Health Japan 21 (second term)].

OBJECTIVES: An earlier study using the data from the Japanese Long-term Care Insurance (LTCI) system reported a scenario for achieving the target of Health Japan 21 (the second term): future gains in health expectancy from 2011 to 2020 must be larger than gains in expectancy. According to this scenario (the Healthy Life Expectancy Extension Scenario), the proportion of disability (cases≥Care Level 2 in LTCI disability certification) will gradually decrease by 1% per year from 2011. The purpose of this study was to estimate the cost savings in long-term care and medical care if the Healthy Life Expectancy Extension Scenario is achieved. METHODS: We used data from Japanese national statistics and a survey conducted in Osaki city, Miyagi. The natural course of disability cases (≥Care Level 2) was estimated under the assumption that the future population composition would be equal to the population projections for Japan and the future proportion of disabilities for each age grade would be equal to that of 2010. Then, the decrease in the number of disabilities based on the Healthy Life Expectancy Extension Scenario was calculated. Finally, the cost savings in long-term care and medical care associated with the assumed decrease in the number of disability cases was calculated. RESULTS: When the disability cases (≥Care Level 2) were shifted to "no disability certification (not requiring care)," a total estimated cost reduction of 5,291 billion yen was achieved from 2011 to 2020. Furthermore, a total estimated reduction of 2,491 billion yen was achieved for the same period when all disability shifts to "Care Level 1" were accounted for. CONCLUSION: As a rough calculation, if the Health Japan 21 (second term) target is achieved, approximately 2,500-5,300 billion yen will be saved in the cost of long-term care and medical care.

Development of an in vitro assay for screening programmed death receptor-1/programmed cell death ligand 1 monoclonal antibody therapy in dogs.

Immunomodulatory antibody drugs that modulate the function of immune checkpoint molecules, such as programmed death receptor-1 (PD-1) and programmed cell death ligand 1 (PD-L1), have been established as new cancer treatments in human medicine. In recent years, there have also been reports on antibodies that inhibit immune checkpoint molecules in dogs, and clinical trials using such antibodies for canine cancer have been gradually increasing in number. Because inhibitory antibodies restore T-cell function by inhibiting the binding of PD-1 on T cells and its ligand PD-L1, the quality of antibody function has been evaluated using activated T cells or peripheral blood mononuclear cells isolated from healthy dogs; however, the assays and dogs used significantly vary. Therefore, in the present study, we developed a reporter gene assay using reporter cells (Jurkat/NFATluc/cPD1) and effector cells (CTAC/OKT3/cPDL1). Jurkat/NFATluc/cPD1 were generated by introducing both of the NFAT-responsive luciferase gene as a marker of T-cell signaling and canine PD-1, into a human T lymphoid cell line, Jurkat. CTAC/OKT3/cPDL1 were generated by introducing single-chain FV (scFV) of anti-human CD3 antibody (OKT3) and canine PD-L1 into a canine thyroid carcinoma cell line, CTAC. Ligation of PD-1 on Jurkat/NFATluc/cPD1 via binding of PD-L1 on CTAC/OKT3/cPDL1 suppressed NFAT luciferase activity induced by CD3 ligation by scFV of OKT3. The addition of anti-canine PD-1 and PD-L1 antibodies, both of which were previously developed in our laboratory, restored this suppression with high sensitivity, although the anti-human PD-L1 antibody atezolizumab induced a very weak restoration. This assay is an useful method for functionally evaluating the inhibition of canine PD-1 and PD-L1 binding.