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Standardization of the Agar Plate Method for Bacteriophage Production
No full textThe growing threat of antimicrobial resistance (AMR), exacerbated by the COVID-19 pandemic, highlights the urgent need for alternative treatments such as bacteriophage (phage) therapy. Phage therapy offers a targeted approach to combat bacterial infections, particularly those resistant to conventional antibiotics. This study aimed to standardize an agar plate method for high-mix, low-volume phage production, suitable for personalized phage therapy. Plaque assays were conducted with the double-layer agar method, and plaque sizes were precisely measured using image analysis tools. Regression models developed with Minitab software established correlations between plaque size and phage production, optimizing production while minimizing resistance development. The resulting Plaque Size Calculation (PSC) model accurately correlated plaque size with inoculum concentration and phage yield, establishing specific plaque-forming unit (PFU) thresholds for optimal production. Using phages targeting pathogens such as Escherichia, Salmonella, Staphylococcus, Pseudomonas, Chryseobacterium, Vibrio, Erwinia, and Aeromonas confirmed the model's accuracy across various conditions. The model's validation showed a strong inverse correlation between plaque size and minimum-lawn cell clearing PFUs (MCPs; R-2 = 98.91%) and identified an optimal inoculum density that maximizes yield while minimizing the evolution of resistant mutants. These results highlight that the PSC model offers a standardized and scalable method for efficient phage production, which is crucial for personalized therapy and AMR management. Furthermore, its adaptability across different conditions and phages positions it as a potential standard tool for rapid and precise phage screening and propagation in both clinical and industrial settings.Y
Celecoxib Enhances Oxidative Muscle Fibre Formation and Improves Muscle Functions Through Prokr1 Activation in Mice
No full textBackground Muscle diseases are serious challenges to human health. Prokineticin receptor 1 (PROKR1) has emerged as a potential target to improve muscle function through increasing oxidative muscle fibres, but there are no clinically applicable synthetic PROKR1 agonists. Methods Drugs with biological properties of prokineticin 2 (PK2) were discovered through connectivity map (CMap) analysis. Their effects on PROKR1 were evaluated using molecular docking, PROKR1 signalling and competitive binding assays. Pregnant dams were fed diets containing varying celecoxib concentrations (0, 500, 1000 and 1500 ppm) from gestation day 5 through weaning. Offspring were given high-fat diets (HFD) from weaning until 20 weeks old, and body composition, insulin resistance, energy expenditure, exercise performance and histological analysis of muscle tissues were evaluated. Results Celecoxib, with a connectivity score of 64.19 to PK2 and a docking score of -9.0 to PROKR1, selectively activated Gs signalling at 4 mu M of EC50 and increased NR4A2 protein levels by 1.6-fold (p < 0.01) in PROKR1-overexpressing cells. It competitively inhibited PK2 binding to PROKR1 and reduced cAMP accumulation. In murine and human myotubes, celecoxib increased Prokr1 protein levels by 1.8-fold (p < 0.05), pCreb by 1.5-fold (p < 0.05) and Nr4a2 by 1.3-fold (p < 0.05). It also elevated Myh7 index by 2.2-fold (p < 0.0001), mitochondrial content by 1.6-fold (p < 0.001) and fatty acid oxidation (FAO) activity by 4.1-fold (p < 0.05). Offspring exposed to celecoxib during pre- and postnatal muscle development exhibited activated Prokr1 signalling, enhanced oxidative muscle fibre formation and improved muscle phenotype despite HFD. At weaning, both male and female offspring showed dose-dependent increases in lean mass (> 9.35%, p < 0.001) and grip strength (< 18.0%, p < 0.01). At 12 weeks old, mice displayed a dose-dependent decrease in weight loss (> 13.3%, p < 0.05), increased lean mass (> 16.2%, p < 0.05), improved insulin resistance (> 70.4%, p < 0.0001), energy expenditure (> 173%, p < 0.0001) and grip strength (> 23.5%, p < 0.001). Celecoxib also increased Myh7-positive muscle fibre composition (> 10.8%, p < 0.05) and mitochondrial mass (> 32.8%, p < 0.05) in the gastrocnemius and soleus muscles, accompanied by significant Prokr1 signalling activation. These effects persisted in both male and female mice at 20 weeks old. ConclusionsCelecoxib shows promise as a PROKR1 agonist and clinically applicable exercise mimetic for the treatment of muscular disorders.Y
Systematic ocular phenotyping of 8,707 knockout mouse lines identifies genes associated with abnormal corneal phenotypes
No full textPurposeCorneal dysmorphologies (CDs) are typically classified as either regressive degenerative corneal dystrophies (CDtrs) or defective growth and differentiation-driven corneal dysplasias (CDyps). Both eye disorders have multifactorial etiologies. While previous work has elucidated many aspects of CDs, such as presenting symptoms, epidemiology, and pathophysiology, the genetic mechanisms remain incompletely understood. The purpose of this study was to analyze phenotype data from 8,707 knockout mouse lines to identify new genes associated with the development of CDs in humans. Methods8,707 knockout mouse lines phenotyped by the International Mouse Phenotyping Consortium were queried for genes associated with statistically significant (P < 0.0001) abnormal cornea morphology to identify candidate CD genes. Corneal abnormalities were investigated by histopathology. A literature search was used to determine the proportion of candidate genes previously associated with CDs in mice and humans. Phenotypes of human orthologues of mouse candidate genes were compared with known human CD genes to identify protein-protein interactions and molecular pathways using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Protein Analysis Through Evolutionary Relationships (PANTHER), and Kyoto Encyclopedia of Genes and Genomes. ResultsAnalysis of data from 8,707 knockout mouse lines identified 213 candidate CD genes. Of these, 37 (17%) genes were previously known to be associated with CD, including 14 in the mouse, 16 in humans, and 7 in both. The remaining 176 (83%) genes have not been previously implicated in CD. We also searched publicly available RNAseq data and found that 131 of the total 213 (61.5%) were expressed in adult human corneal tissue. STRING analysis showed several interactions within and between candidate and established CD proteins. All cellular pathways of the established genes were found in the PANTHER analysis of the candidate genes. Several of the candidate genes were implicated in corneal disease, such as TGF-ss signaling. We also identified other possible underappreciated mechanisms relevant to the human cornea. ConclusionsWe identified 213 mouse genes that resulted in statistically significant abnormal corneal phenotypes in knockout mice, many of which have not previously been implicated in corneal pathology. Bioinformatic analyses implicated candidate genes in several signaling pathways which are potential therapeutic targets.Y
A process-based evaluation of biases in extratropical stratosphere-troposphere coupling in subseasonal forecast systems
No full textTwo-way coupling between the stratosphere and troposphere is recognized as an important source of subseasonal-to-seasonal (S2S) predictability and can open windows of opportunity for improved forecasts. Model biases can, however, lead to a poor representation of such coupling processes; drifts in a model's circulation related to model biases, resolution, and parameterizations have the potential to feed back on the circulation and affect stratosphere-troposphere coupling. We introduce a set of diagnostics using readily available data that can be used to reveal these biases and then apply these diagnostics to 22 S2S forecast systems.In the Northern Hemisphere, nearly all S2S forecast systems underestimate the strength of the observed upward coupling from the troposphere to the stratosphere, downward coupling within the stratosphere, and the persistence of lower-stratospheric temperature anomalies. While downward coupling from the lower stratosphere to the near surface is well represented in the multi-model ensemble mean, there is substantial intermodel spread likely related to how well each model represents tropospheric stationary waves.In the Southern Hemisphere, the stratospheric vortex is oversensitive to upward-propagating wave flux in the forecast systems. Forecast systems generally overestimate the strength of downward coupling from the lower stratosphere to the troposphere, even as most underestimate the radiative persistence in the lower stratosphere. In both hemispheres, models with higher lids and a better representation of tropospheric quasi-stationary waves generally perform better at simulating these coupling processes.Y
[Editors note] Domestic Politics and International Relations of Japans Cultural Heritage
No full textRegional Inequality through the Nuclear Power Plant Affected Areas: Focusing on the Case of the TEPCOs Kashiwazaki-Kariwa Nuclear Power Plant Site and the
No full textCausal interaction and effect modification: a randomization-based approach to inference
No full textUnderstanding causal interactions is critical in observational studies but often challenging due to confounding and methodological limitations. While these concepts have been extensively studied in randomized experiments, their application in observational data remains limited, particularly in settings requiring stratification to evaluate interactions. We propose a novel randomization-based inference framework utilizing matching methods to investigate causal interactions. Additionally, we provide a comprehensive review of causal interaction, explaining its unique focus on joint causal effects and distinguishing it from statistical interaction and effect modification. Using a real-world dataset, we analyze the joint effects of two treatments: residential fire safety equipment and fire response time. Our approach demonstrates how matching can mitigate confounding and identify interaction effects, offering a robust alternative to traditional methods. The findings highlight the importance of considering causal interaction in public safety interventions and provide actionable insights for fire safety policy and fire response optimization.Y
Analyzing Perceptions and Educational Needs of Elementary School Teachers for AI-integrated Education
No full text본 연구는 초등교사들이 AI 융합 교육에 대해 가지는 인식과 요구를 파악하는 것을 목적으로현직 초등교사 125명 대상의 설문조사를 실시하였다. 연구 결과, 설문에 참여한 대부분의 초등교사는 AI 융합 교육과 관련된 연수나 교육 경험은 있으나, AI 이해 교육과 활용 교육을 AI 융합 교육과 명확하게 구분하지 못함을 확인하였다. 또한 AI 융합 교육의 필요성에 대해서는대체로 동의하였으나, 교사의 역량 부족, 수업자료 제작 어려움과 같은 내적 및 기존 교과 수업의 진도 부담, 기자재 부족과 노후화와 같은 외적 방해 요인에 직면해 있는 것으로 나타났다. 또한 초등학교에서 효과적인 AI 융합 교육을 위해 AI 융합 교육에 대한 이해 향상, AI 기반 학습환경 조성 등의 요소를 고려해야 함을 확인하였다. 본 연구는 초등교사들의 AI 융합교육에 대한 인식과 요구를 기반으로 AI 융합 교육의 활성화를 위한 시사점을 논의한다.N
Remediating zinc-contaminated groundwater with calcium polysulfide using model porous media and simulated groundwater
No full textThis study demonstrates the feasibility of using calcium polysulfide (CPS) for in-situ redox manipulation (CPS-ISRM) to remediate Zn-contaminated groundwater, focusing on concentrations exceeding 10,000 mg/L at a zinc smelting site in South Korea. Experiments with sand-only and sand-clay columns revealed that subsurface heterogeneity significantly impacts CPS transport, reactivity, and removal efficiency. Homogeneous sand conditions allowed rapid CPS migration and over 99 % Zn removal, albeit within a shorter reactive time frame. In contrast, heterogeneous sand-clay media enabled prolonged localized reactions due to CPS retention, although with less than 50 % Zn removal due to restricted distribution. CPS interactions with groundwater and geochemical constituents varied based on subsurface conditions, influencing permeability and chemical evolution. Precipitation including the formation of ZnS(s) and CaSO4(s) drove localized clogging and changes in hydraulic conductivity, particularly in confined zones of the sand-clay column. These findings highlight the importance of subsurface characterization and tailored CPS injection protocols, considering site-specific factors such as subsurface heterogeneity, groundwater chemistry, and interactions between CPS, groundwater constituents, and the targeted contaminants. Understanding these system dynamics is imperative for optimizing CPS-ISRM technology for field-scale groundwater remediation.N
Intakes of saturated and unsaturated fat and circulating levels of inflammatory markers among breast cancer survivors
No full textWe investigated whether dietary intakes of saturated fat (SFA), monounsaturated fat (MUFA), or polyunsaturated fat (PUFA) were associated with plasma inflammatory markers among breast cancer survivors in Korea. This cross-sectional study included 419 female breast cancer survivors aged 30 to 78 years. Dietary intake was assessed using 3-day dietary records (DRs) or food frequency questionnaires (FFQs). Plasma levels of adiponectin, high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha were measured. We calculated an inflammatory composite score by summing the z-scores of each inflammatory marker, with adiponectin assigned a negative sign. Least-squares means (LS-means) and 95% confidence intervals (CIs) of inflammatory markers were estimated according to SFA, MUFA, and PUFA intakes using the generalized linear models. We found that increasing dietary MUFA intake was associated with increasing levels of adiponectin, but decreasing levels of hs-CRP (p for trend = 0.042 and 0.032, respectively). Similarly, higher dietary PUFA intake was associated with higher levels of adiponectin (p for trend = 0.023), but lower levels of hs-CRP and inflammatory composite score (p for trend < 0.001 and 0.036, respectively). However, no significant associations were found between SFA intake and plasma inflammatory markers. In conclusion, our results suggest that a higher intake of MUFA or PUFA is associated with a more favorable inflammatory profile among Korean female breast cancer survivors, which may potentially help in managing chronic inflammation.Y