A Safe, Simple, and Facile Staining Method Using Polysiloxanes for High-Contrast Visualization of Gelator Aggregates by Transmission Electron Microscopy

The staining of TEM samples using Si atoms was investigated using aggregates of loose gels formed by twelve structurally different gelators in several solvents. Thirteen commercially available siloxanes were used as stains. TEM images of non-stained and OsO4-stained samples of molecular aggregates formed by the dodecamethylenediamide of N-methacryloyl-oxyethylaminocarbonyl-L-isoleucine in 1-propanol were poorly defined and low-contrast. However, the image of a methacryloyloxypropyl-terminated polydimethylsiloxane (S1)-stained sample was characterized by very clear bundles of fine fibers. The staining effect was explained by the wrapping of fibers, the stabilizing of the individual fibers, and reinforcing by S1. An S1 concentration of more than 5 mgmL(-1) was found to be necessary for satisfactory contrast. S1 was successfully applied to the observation of aggregates of eleven other gelators. S1 worked universally as an aggregate stain regardless of the gelator or solvent polarity. The staining effect was observed for other siloxanes. This effect was found to depend on the molecular weight of the siloxane (>1,000) rather than the kind of siloxane employed. Energy-dispersive X-ray spectroscopy indicated that the molecules of S1 gather on the surface of the fibers during drying, wrapping them. The results indicate that the present staining method guarantees reproducibility and universality.ArticleBULLETIN OF THE CHEMICAL SOCIETY OF JAPAN.91(7):1176-1185(2018)journal articl

Transcriptomic Interpretation on Explainable AI-Guided Intuition Uncovers Premonitory Reactions of Disordering Fate in Persimmon Fruit

Deep neural network (DNN) techniques, as an advanced machine learning framework, have allowed various image diagnoses in plants, which often achieve better prediction performance than human experts in each specific field. Notwithstanding, in plant biology, the application of DNNs is still mostly limited to rapid and effective phenotyping. The recent development of explainable CNN frameworks has allowed visualization of the features in the prediction by a convolutional neural network (CNN), which potentially contributes to the understanding of physiological mechanisms in objective phenotypes. In this study, we propose an integration of explainable CNN and transcriptomic approach to make a physiological interpretation of a fruit internal disorder in persimmon, rapid over-softening. We constructed CNN models to accurately predict the fate to be rapid softening in persimmon cv. Soshu, only with photo images. The explainable CNNs, such as Gradient-weighted Class Activation Mapping (Grad-Class Activation Mapping (CAM)) and guided Grad-CAM, visualized specific featured regions relevant to the prediction of rapid softening, which would correspond to the premonitory symptoms in a fruit. Transcriptomic analyses to compare the featured regions of the predicted rapid-softening and control fruits suggested that rapid softening is triggered by precocious ethylene signal–dependent cell wall modification, despite exhibiting no direct phenotypic changes. Further transcriptomic comparison between the featured and non-featured regions in the predicted rapid-softening fruit suggested that premonitory symptoms reflected hypoxia and the related stress signals finally to induce ethylene signals. These results would provide a good example for the collaboration of image analysis and omics approaches in plant physiology, which uncovered a novel aspect of fruit premonitory reactions in the rapid-softening fate

Increase of Pro-opiomelanocortin mRNA Prior to Tyrosinase, Tyrosinase-Related Protein 1, Dopachrome Tautomerase, Pmel-17/gp100, and P-Protein mRNA in Human Skin After Ultraviolet B Irradiation

In ultraviolet-induced tanning, the protein levels of various gene products critical for pigmentation (including tyrosinase and tyrosinase-related protein-1) are increased in response to ultraviolet B irradiation, but changes in mRNA levels of these factors have not been investigated in vivo. We have established an in situ hybridization technique to investigate mRNA levels of pro-opiomelanocortin, tyrosinase, tyrosinase-related protein-1, dopachrome tautomerase, P-protein, Pmel-17/gp100, and microphthalmia-associated transcription factor, and have analyzed the changes in mRNA levels in the ultraviolet B-exposed skin in vivo. The right or left forearm of each volunteer was irradiated with ultraviolet B, and skin biopsies were obtained at 2 and 5 d postirradiation. mRNA level of pro- opiomelanocortin was increased 2 d after ultraviolet B irradiation, and returned to a near-basal level after 5 d, whereas the mRNA levels of tyrosinase, tyrosinase-related protein-1, dopachrome tautomerase, P-protein, and Pmel-17/gp100 showed some or no increase at 2 d, but were significantly increased 5 d after ultraviolet B irradiation. Microphthalmia-associated transcription factor mRNA was slightly increased on days 2 and 5 after ultraviolet B irradiation. Our results suggest that the mechanism of the tanning response of human skin may involve the transcriptional regulation of certain pigmentary genes, and that pro-opiomelanocortin-derived melanocortins such as α-melanocyte-stimulating hormone and adrenocorticotropic hormone may play a part in regulating these genes in vivo

Interaction between caesium iodide particles and gaseous boric acid in a flowing system through a thermal gradient tube (1030 K–450 K) and analysis with ASTEC/SOPHAEROS

International audienceThe present work aimed at studying the interaction between caesium iodide particles and gaseous boric acidthrough a Thermal Gradient Tube (TGT) from 1023 K to 453 K under Ar/H2O. Particles size range of transportedparticles was measured by ELPI and the fraction of gaseous compounds by ICP-MS and UV–visible spectroscopy.Reaction between the two compounds was deduced by measuring a significant fraction of gaseous iodine at theoutlet of the facility, representing more than 80% of the total iodine sampled at the outlet. The reaction rate wasshown to be lower when the flow rate inside the facility was increased. Analysis with SOPHAEROS module ofASTEC code was performed. The ASTEC fission products models allowed performing the evaluation of theexperimentally observed results for the analysis of the transport of pure compounds. However, the heterogeneousinteraction between the caesium iodide particles and the gaseous boric acid was not reproduced, as the modelsare not taken into account in the version v2.1_1_6 of the ASTEC/SOPHAEROS module. The next step would be toidentify the mechanism of the reaction by comparing the results with other studies and to determine the reactionrates. Then, a first development in SOPHAEROS would be to implement such phenomena

Inhibition of NF-κB and Akt pathways by an antibody-avidin fusion protein sensitizes malignant B-cells to cisplatin-induced apoptosis

Multiple myeloma (MM) is an incurable disease of malignant plasma cells. Recent therapeutic advancements have resulted in improved response rates, however, there is no improvement in overall survival, therefore, new therapeutics are needed. Since the transferrin receptor is upregulated on the surface of MM cells, we previously developed an antibody fusion protein consisting of an IgG3 specific for the human transferrin receptor 1 (TfR1, CD71) genetically fused to avidin at its carboxy-terminus (ch128.1Av). We have previously shown that ch128.1Av exhibits intrinsic cytotoxicity against certain malignant B-cells by disrupting the cycling of the TfR and decreasing TfR cell surface expression resulting in lethal iron starvation. In addition, ch128.1Av can sensitize malignant cells to apoptosis induced by gambogic acid, a herbal drug used in Chinese medicine. In this study, we hypothesized that ch128.1Av may also sensitize drug-resistant malignant B-cells to chemotherapeutic agents by inhibiting key survival pathways. In this study we show that ch128.1Av sensitizes malignant B-cells to apoptosis induced by cisplatin (CDDP). The sensitization by ch128.1Av resulted in the inhibition of the constitutively activated Akt and NF-κB survival/antiapoptotic pathways and downstream decreased expression of antiapoptotic gene products such as BclxL and survivin. The direct role of the inhibition of the Akt and NF-κB pathways by ch128.1Av in CDDP-mediated cytotoxicity was demonstrated by the use of specific chemical inhibitors and siRNA which mimicked the effects of ch128.1Av. Overall, this study provides evidence of the therapeutic potential of ch128.1Av as a chemo-sensitizing agent in drug-resistant tumor cells.Fil: Suzuki, Eriko. Keio University; JapónFil: Daniels, Tracy R.. University of California at Los Angeles; Estados UnidosFil: Helguera, Gustavo Fernando. University of California at Los Angeles; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Penichet, Manuel L.. University of California at Los Angeles; Estados UnidosFil: Umezawa, Kazuo. Keio University; JapónFil: Bonavida, Benjamín. University of California at Los Angeles; Estados Unido

A Case of Focal Choroidal Excavation Development Associated with Multiple Evanescent White Dot Syndrome

Focal choroidal excavation (FCE) is described as an excavated lesion of the choroid that can be detected by optical coherence tomography (OCT). While the exact pathogenesis of FCE remains unclear, it has been proposed in some cases that there is an association with the inflammation in the outer retina. We present a case of FCE development that was detected by spectral domain OCT (SD-OCT) and found to be associated with multiple evanescent white dot syndrome (MEWDS). A 40-year-old Japanese woman was diagnosed with MEWDS based on multiple white dots observed from the posterior pole to the midperiphery, along with yellow granularity in the fovea. SD-OCT revealed separation between the retinal pigment epithelium (RPE) and Bruch’s membrane (BM) and discontinuations of the ellipsoid zone, RPE, and BM. At 4 weeks after onset, several of the white dots disappeared, the yellow granularity in the fovea became small, and we detected nonconforming choroidal excavation under the central fovea. The choroidal excavation gradually deepened and changed to a conforming pattern. These findings suggest that the degree of the impairment caused by inflammation and the plasticity of the BM and RPE complex may be associated with different types of acquired FCE

Exploring early discontinuation of mental health outpatient treatment: language, demographics and clinical characteristics among migrant populations in Japan.

BACKGROUND: The fast-growing migrant population in Japan and globally poses challenges in mental healthcare, yet research addressing migrants mental health treatment engagement remains limited. OBJECTIVE: This study examined language proficiency, demographic and clinical characteristics as predictors of early treatment discontinuation among migrants. METHODS: Electronic health record data from 196 adult migrants, identified from 14 511 patients who received mental health outpatient treatment during 2016 and 2019 at three central hospitals in the Tokyo-Yokohama metropolitan region of Japan, were used. We conducted multivariable regression models to identify predictors of early discontinuation within 3 months. FINDINGS: The study cohort (65% women, age range: 18-90 years, from 29 countries or regions) included 23% non-Japanese speakers. Japanese and non-Japanese speakers had similar discontinuation rates (26% vs 22%). Multivariable models revealed younger age (OR=0.97; 95% CI: 0.95, 0.99; p=0.016) and those with a primary diagnosis other than a schizophrenia spectrum disorder (OR=3.99; 95% CI: 1.36, 11.77; p=0.012) or a neurotic, stress-related and somatoform disorder (OR=2.79; 95% CI: 1.14, 6.84; p=0.025) had higher odds of early discontinuation. These effects were more pronounced among the Japanese speakers with significant language-by-age and language-by-diagnoses interactions. CONCLUSION: Younger age and having a primary diagnosis other than a schizophrenia spectrum disorder or a neurotic, stress-related and somatoform disorder increased vulnerability for discontinuing mental health treatment early in Japanese-speaking migrants but not for migrants with limited Japanese proficiency. CLINICAL IMPLICATIONS: Understanding language needs within a context of mental health treatment should go beyond assumed or observed fluency. Unmet language needs might increase vulnerability for treatment disengagement among migrants. Targeted clinical efforts are crucial for enhancing early treatment engagement and informing health practices in Japan and countries with growing migrant populations