Dual-Organ Transcriptomic Analysis of Rainbow Trout Infected With Ichthyophthirius multifiliis Through Co-Expression and Machine Learning

Ichthyophthirius multifiliis is a major pathogen that causes a high mortality rate in trout farms. However, systemic responses to the pathogen and its interactions with multiple organs during the course of infection have not been well described. In this study, dual-organ transcriptomic responses in the liver and head kidney and hemato-serological indexes were profiled under I. multifiliis infection and recovery to investigate systemic immuno-physiological characteristics. Several strategies for massive transcriptomic interpretation, such as differentially expressed genes (DEGs), Poisson linear discriminant (PLDA), and weighted gene co-expression network analysis (WGCNA) models were used to investigate the featured genes/pathways while minimizing the disadvantages of individual methods. During the course of infection, 6,097 and 2,931 DEGs were identified in the head kidney and liver, respectively. Markers of protein processing in the endoplasmic reticulum, oxidative phosphorylation, and the proteasome were highly expressed. Likewise, simultaneous ferroptosis and cellular reconstruction was observed, which is strongly linked to multiple organ dysfunction. In contrast, pathways relevant to cellular replication were up-regulated in only the head kidney, while endocytosis- and phagosome-related pathways were notably expressed in the liver. Moreover, interestingly, most immune-relevant pathways (e.g., leukocyte trans-endothelial migration, Fc gamma R-mediated phagocytosis) were highly activated in the liver, but the same pathways in the head kidney were down-regulated. These conflicting results from different organs suggest that interpretation of co-expression among organs is crucial for profiling of systemic responses during infection. The dual-organ transcriptomics approaches presented in this study will greatly contribute to our understanding of multi-organ interactions under I. multifiliis infection from a broader perspective.publishedVersio

A Case of Intramuscular Hemangioma Presenting with Large-angle Hypertropia

Purpose: To report the case of a patient with large-angle hypertropia of an intramuscular hemangioma of the right superior rectus muscle (SR). Methods: A 63-year-old man with progressive vertical deviation of the right eye for the past 6 months visited our strabismus department; his condition was not painful. An examination indicated that he had 60PD of right hypertropia at distance and near in primary gaze. Additionally, a significant limitation of his downgaze was noted. The right eye appeared mildly proptotic, and the upper and lower eyelids were slightly edematous. Corrected vision was 20/20 in both eyes. Results: Orbital magnetic resonance imaging (MRI) studies revealed fusiform enlargement of the right superior rectus muscle, with prominent but irregular enhancement following gadolinium administration. Incisional biopsy revealed an intramuscular hemangioma in the superior rectus muscle with cavernous-type vessels. Conclusions: This case demonstrates that intramuscular hemangioma should be considered in the differ-ential diagnosis of isolated extraocular muscle enlargement and unusual strabismus. Korean Journal o

Intracellular Membrane Association of the Aplysia cAMP Phosphodiesterase Long and Short Forms via Different Targeting Mechanisms

Phosphodiesterases (PDEs) play key roles in cAMP compartmentalization, which is required for intracellular signaling processes, through specific subcellular targeting. Previously, we showed that the long and short forms of Aplysia PDE4 (ApPDE4), which are localized to the membranes of distinct subcellular organelles, play key roles in 5-hydroxytryptamineinduced synaptic facilitation in Aplysia sensory and motor synapses. However, the molecular mechanism of the isoform-specific distinct membrane targeting was not clear. In this study, we further investigated the molecular mechanism of the membrane targeting of the ApPDE4 long and short forms. We found that the membrane targeting of the long form was mediated by hydrophobic interactions, mainly via 16 amino acids at the N-terminal region, whereas the short form was targeted solely to the plasma membrane, mainly by nonspecific electrostatic interactions between theirNtermini and the negatively charged lipids such as the phosphatidylinositol polyphosphates PI4P and PI(4,5)P<inf>2</inf>, which are embedded in the inner leaflet of the plasma membrane. Moreover, oligomerization of the long or short form by interaction of their respective upstream conserved region domains, UCR1 and UCR2, enhanced their plasma membrane targeting. These results suggest that the long and short forms of ApPDE4 are distinctly targeted to intracellular membranes through their direct association with the membranes via hydrophobic and electrostatic interactions, respectively. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.1

Effect of Gambisan on the Inhibition of Adipogenesis in 3T3-L1 Adipocytes

This study was conducted to explore the antiadipogenic effect and possible mechanism of Gambisan on 3T3-L1 cells. For quality control, Gambisan was standardized by HPLC and the standard compounds ephedrine, epigallocatechin-3-gallate, and caffeine were screened. Cultured 3T3-L1 cells that had been induced to differentiate were treated with various concentrations of Gambisan or its major component extracts (Ephedra intermedia Schrenk, Atractylodes lancea DC., and Thea sinensis L.) for 72 hours for MTT assay to determine cell viability or 10 days for LDH assay, triglyceride assay, DNA content measurement, Oil red O staining, RT-PCR, and western blot. Gambisan significantly inhibited adipogenesis in 3T3-L1 cells by reducing triglyceride contents and lipid accumulation in a dose-dependent manner without obvious cytotoxicity. Viability and DNA content in 3T3-L1 cells treated with Gambisan were significantly higher than cells treated with the major component extracts at every concentration. The anti-adipogenic effects of Gambisan appeared to be mediated by a significant downregulation of the expression of lipoprotein lipase mRNA and PPARγ, C/EBPα, and SREBP-1 protein apart from the expression of hormone-sensitive lipase. Gambisan could act as a possible therapeutic agent for obesity. However, further studies including in vivo assays and clinical trials are needed to confirm the efficacy, safety and mechanisms of the antiobesity effects of Gambisan

Automating Rey Complex Figure Test scoring using a deep learning-based approach: a potential large-scale screening tool for cognitive decline

Background The Rey Complex Figure Test (RCFT) has been widely used to evaluate the neurocognitive functions in various clinical groups with a broad range of ages. However, despite its usefulness, the scoring method is as complex as the figure. Such a complicated scoring system can lead to the risk of reducing the extent of agreement among raters. Although several attempts have been made to use RCFT in clinical settings in a digitalized format, little attention has been given to develop direct automatic scoring that is comparable to experienced psychologists. Therefore, we aimed to develop an artificial intelligence (AI) scoring system for RCFT using a deep learning (DL) algorithm and confirmed its validity. Methods A total of 6680 subjects were enrolled in the Gwangju Alzheimers and Related Dementia cohort registry, Korea, from January 2015 to June 2021. We obtained 20,040 scanned images using three images per subject (copy, immediate recall, and delayed recall) and scores rated by 32 experienced psychologists. We trained the automated scoring system using the DenseNet architecture. To increase the model performance, we improved the quality of training data by re-examining some images with poor results (mean absolute error (MAE) ≥ 5 [points]) and re-trained our model. Finally, we conducted an external validation with 150 images scored by five experienced psychologists. Results For fivefold cross-validation, our first model obtained MAE = 1.24 [points] and R-squared (R2 ) = 0.977. However, after evaluating and updating the model, the performance of the final model was improved (MAE = 0.95 [points], R2 = 0.986). Predicted scores among cognitively normal, mild cognitive impairment, and dementia were significantly different. For the 150 independent test sets, the MAE and R2 between AI and average scores by five human experts were 0.64 [points] and 0.994, respectively. Conclusion We concluded that there was no fundamental difference between the rating scores of experienced psychologists and those of our AI scoring system. We expect that our AI psychologist will be able to contribute to screen the early stages of Alzheimers disease pathology in medical checkup centers or large-scale community-based research institutes in a faster and cost-effective way.This research was supported by the Technology Innovation Program (20022810, Development and Demonstration of a Digital System for the evaluation of geriatric Cognitive impairment) funded By the Ministry of Trade, Industry & Energy(MOTIE, Korea), by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2020R1F1A1052932), by the Healthcare AI Convergence Research & Development Program through the National IT Industry Promotion Agency of Korea (NIPA) funded by the Ministry of Science and ICT(No.1711120216), by the KBRI basic research program through the Korea Brain Research Institute funded by the Ministry of Science and ICT (22-BR-03–05), and by the Korea National Institute of Health research project (project No. 2021-ER1007-01)

The Risk of Cytomegalovirus Infection in Non-myeloablative Peripheral Stem Cell Transplantation Compared with Conventional Bone Marrow Transplantation

Non-myeloablative allogeneic peripheral stem cell transplantation (NST) is a novel therapeutic strategy for patients with hematologic malignancies. Whether non-myeloablative transplants are associated with increased risk of cytomegalovirus (CMV) infections is unknown. To clarify this issue, we compared the outcome of CMV infection following 24 allogeneic non-myeloablative peripheral blood stem cell transplants and 40 conventional bone marrow transplants (CBT). The NST regimen consisted of busulfan (4mg/kg/day), fludarabine (30mg/m2) and anti-thymocyte globulin (10 mg/kg). Twelve patients (50%) in the NST group and 17 (43%) in the CBT group developed positive antigenemia before day 100 (p=0.60). The time to the first appearance of positive antigenemia was not different between these two groups (p=0.40), and two groups showed similar initial and maximal antigenemia values (p=0.56 and p=0.68, respectively). Only one case of CMV colitis developed in the CBT group whereas CMV disease did not develop in the NST group. Although statistically insignificant, the treatment response against CMV antigenemia using ganciclovir was in favor of NST group. In conclusion, there was no difference in the risk of CMV infection between NST group and CBT group. Further prospective and controlled study is needed to clarify the impact of non-myeloablative procedure on the outcome of CMV infection

Breath analyzer for personalized monitoring of exercise-induced metabolic fat burning

Dionisio V. Del Orbe recibió su Licenciatura en Ingeniería Aeronáutica de la Universidad de Western Michigan (2012), EE. UU., y una Maestría en Ingeniería de Manufactura Microelectrónica del Instituto de Tecnología de Rochester (2015), EE. UU. Recibió su doctorado en Ingeniería Mecánica KAIST (2022), Corea del Sur, y trabajó como investigador de posgrado en el Departamento de Investigación de TIC Médicas y de Bienestar en ETRI, Corea del Sur. Su investigación se centra en sensores de gases químicos para diversas aplicaciones, especialmente, análisis de aliento y detección de gases tóxicos/inflamables; también tiene intereses en dispositivos portátiles y flexibles. Actualmente, es docente e investigador en UNAPEC, República Dominicana.Obesity increases the risk of chronic diseases, such as type 2 diabetes mellitus, dyslipidemia, and cardiovascular diseases. Simple anthropometric measurements have time limitations in reflecting short-term weight and body fat changes. Thus, for detecting, losing or maintaining weight in short term, it is desirable to develop portable/ compact devices to monitor exercise-induced fat burn in real time. Exhaled breath acetone and blood-borne β-hydroxybutyric acid (BOHB) are both correlated biomarkers of the metabolic fat burning process that takes place in the liver, predominantly post-exercise. Here, we have fabricated a compact breath analyzer for convenient, noninvasive and personalized estimation of fat burning in real time in a highly automated manner. The analyzer collects end-tidal breath in a standardized, user-friendly manner and it is equipped with an array of four low-power MEMS sensors for enhanced accuracy; this device presents a combination of required and desirable design features in modern portable/compact breath analyzers. We analyzed the exhaled breath (with our analyzer) and the blood samples (for BOHB) in 20 participants after exercise; we estimated the values of BOHB, as indication of the fat burn, resulting in Pearson coefficient r between the actual and predicted BOHB of 0.8. The estimation uses the responses from the sensor array in our analyzer and demographic and anthropo- metric information from the participants as inputs to a machine learning algorithm. The system and approach herein may help guide regular exercise for weight loss and its maintenance based on individuals’ own metabolic changes