Autism spectrum disorder (ASD) is induced by complex hereditary and environmental factors. However, the mechanisms of ASD development are poorly understood. The purpose of this study was to identify ...standard indicators of this condition by comparing clinical, pathophysiological, and neurobehavioral features in an autism-like animal model. A total of 22 male Sprague-Dawley rats were randomly divided into control and 500 mg/kg propionic acid (PPA)-treated groups. Rats were subjected to behavioral tests, gene expression analyses, and histological analyses to detect pathophysiological and neurobehavioral alterations. Exploratory activity and non-aggressive behavior were significantly reduced in PPA-treated rats, whereas enhanced aggressive behavior during adjacent interactions was observed on day 14 after PPA administration. To evaluate gene expression after PPA administration, we analyzed hippocampal tissue using reverse transcription PCR. Glial fibrillary acidic protein was augmented in the PPA-treated group on day 14 after appearance of ASD-like behaviors by PPA administration, whereas octamer-binding transcription factor 4 expression was significantly decreased in the PPA-treated group. Histological evaluation revealed significantly reduced diameter and layer thickness of granule cells in PPA-treated rats compared with control rats. We conclude that PPA administration induced abnormal neural cell organization, which may have led to autism-like neurobehaviors, including increased aggressive behavior, reduced exploratory activity, and isolative and passive behaviors.
The symbiotic microbiota profoundly affect many aspects of host physiology; however, the molecular mechanisms underlying host-microbe cross-talk are largely unknown. Here, we show that the ...pyrroloquinoline quinone-dependent alcohol dehydrogenase (PQQ-ADH) activity of a commensal bacterium, Acetobacter pomorum, modulates insulin/insulin-like growth factor signaling (IIS) in Drosophila to regulate host homeostatic programs controlling developmental rate, body size, energy metabolism, and intestinal stem cell activity. Germ-free animals monoassociated with PQQ-ADH mutant bacteria displayed severe deregulation of developmental and metabolic homeostasis. Importantly, these defects were reversed by enhancing host IIS or by supplementing the diet with acetic acid, the metabolic product of PQQ-ADH.
Climate change is a main driving force that affects the hydrological cycle, leading to an increase in natural hazards. Among these natural hazards, drought is one of the most destructive and becomes ...more complex considering climate change. Therefore, it is necessary to investigate the effect of climate change on different types of drought. In this study, we examined the propagation probability of meteorological drought into hydrological drought using a probabilistic graphical model across South Korea. We performed correlation analyses among meteorological drought represented by Standardized Precipitation Index (SPI) and Standardized Precipitation Evapotranspiration Index (SPEI) and hydrological drought by Standardized Runoff Index (SRI) on different time scales. Drought characteristics were examined under a baseline period, RCP 4.5, and 8.5 climate change scenarios, and the results illustrated that drought characteristics varied spatially. On average, drought severity of SPI increased in P1 (2011–2040) and then deceased in P2 (2041–2070) and P3 (2071–2099) under RCP 4.5, whereas drought severity also increased in P1 under RCP 8.5. However, average drought severity of SPEI increased in P3, whereas that of SRI showed a decreasing trend for all the periods. Finally, propagation occurrence probabilities of different states of meteorological drought resulting in different states of hydrological drought were examined under climate change scenarios. The average propagation probability of extreme state of meteorological drought resulting in moderate and severe condition of hydrological drought increased by 13% and 2%, respectively, under RCP 4.5; while average propagation probability of extreme state of meteorological drought resulting in severe and extreme conditions of hydrological drought increased by 1.5% and 84%, respectively, under RCP 8.5. We concluded that propagation probability of meteorological drought into hydrological drought increased significantly under climate change. These findings will be helpful for early mitigation of hydrological drought.
Recent advances in 3D culture systems have led to the generation of brain organoids that resemble different human brain regions; however, a 3D organoid model of the midbrain containing functional ...midbrain dopaminergic (mDA) neurons has not been reported. We developed a method to differentiate human pluripotent stem cells into a large multicellular organoid-like structure that contains distinct layers of neuronal cells expressing characteristic markers of human midbrain. Importantly, we detected electrically active and functionally mature mDA neurons and dopamine production in our 3D midbrain-like organoids (MLOs). In contrast to human mDA neurons generated using 2D methods or MLOs generated from mouse embryonic stem cells, our human MLOs produced neuromelanin-like granules that were structurally similar to those isolated from human substantia nigra tissues. Thus our MLOs bearing features of the human midbrain may provide a tractable in vitro system to study the human midbrain and its related diseases.
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•Self-organizing midbrain-like organoids (hMLOs) develop from hPSCs in 3D culture•hMLOs, but not mouse MLOs or human cerebral organoids, produce neuromelanin•hMLOs secrete dopamine (DA) and neurons within the hMLOs form functional synapses•Neurons within hMLOs exhibit SNpc DA neuron-like electrophysiological properties
Jo et al. report a method for generating human midbrain-like organoids (hMLOs) from hPSCs in 3D culture. The hMLOs contain distinct layers of neuronal cells expressing human midbrain markers, such as neuromelanin, are electrically active, form functional synapses, and produce dopamine, suggesting that they may be useful for studying human midbrain.
Background
Allergic inflammation affects the epithelial cell populations resulting in goblet cell hyperplasia and decreased ciliated cells. Recent advances in single‐cell RNA sequencing (scRNAseq) ...have enabled the identification of new cell subtypes and genomic features of single cells. In this study, we aimed to investigate the effect of allergic inflammation in nasal epithelial cell transcriptomes at the single‐cell level.
Methods
We performed scRNAseq in cultured primary human nasal epithelial (HNE) cells and in vivo nasal epithelium. The transcriptomic features and epithelial cell subtypes were determined under IL‐4 stimulation, and cell‐specific marker genes and proteins were identified.
Results
We confirmed that cultured HNE cells were similar to in vivo epithelial cells through scRNAseq. Cell‐specific marker genes were utilized to cluster the cell subtypes, and FOXJ1+‐ciliated cells were sub‐classified into multiciliated and deuterosomal cells. PLK4 and CDC20B were specific for deuterosomal cells, and SNTN, CPASL, and GSTA2 were specific for multiciliated cells. IL‐4 altered the proportions of cell subtypes, resulting in a decrease in multiciliated cells and loss of deuterosomal cells. The trajectory analysis revealed deuterosomal cells as precursor cells of multiciliated cells and deuterosomal cells function as a bridge between club and multiciliated cells. A decrease in deuterosomal cell marker genes was observed in nasal tissue samples with type 2 inflammation.
Conclusion
The effects of IL‐4 appear to be mediated through the loss of the deuterosomal population, resulting in the reduction in multiciliated cells. This study also newly suggests cell‐specific markers that might be pivotal for investigating respiratory inflammatory diseases.
This study investigates the effect of allergic inflammation in nasal epithelial cell transcriptomes at the single‐cell level. The effects of IL‐4 appear to be mediated through the loss of the deuterosomal population, resulting in the reduction in multiciliated cells. The trajectory analysis reveals deuterosomal cells as precursor cells of multiciliated cells. Common ciliated cell marker (FOXJ1), multiciliated cell marker (CCNO), and deuterosomal cell markers (CDC20 and CDK1) are reduced by IL‐4 treatment; IL‐13 shows similar inhibitory effect.Abbreviations: CCNO, cyclin O; CDC20, cell division cycle 20; CDK1, cyclin‐dependent kinase 1; CTRL, control; FOXJ1, forkhead box J1; IL, interleukin; RNAseq, RNA sequencing
Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory airway disease involving non-eosinophilic and eosinophilic phenotypes, which translate to various endotypes. Activated eosinophils and ...neutrophils are known to generate extracellular traps consisting of DNA and cytotoxic granule proteins. We sought to investigate the presence of eosinophil and neutrophil extracellular traps (EETs and NETs, respectively) in human CRS tissues and to clarify the associations with their clinical features. Nasal polyp (NP) or ethmoid tissue slides of 43 subjects from endoscopic sinus surgery for CRS were analysed. Quantitative analysis of EETs and NETs was performed by confocal microscopy using immunofluorescent staining. For correlation study, the presence of NPs, number of infiltrating tissue eosinophils, preoperative Lund-Mackay scores, and other comorbidities were analysed. EET formation was observed to varying degrees in all CRS groups and was correlated with the number of tissue eosinophils (r = 0.83, p < 0.001) regardless of the presence of NPs. Patients with more EETs demonstrated higher Lund-Mackay scores (r = 0.51, p = 0.009), blood eosinophilia (r = 0.80, p < 0.001), and decreased olfactory function (r = -0.65, p < 0.001). No correlation between the extent of EET formation and the presence of atopy or asthma was apparent. However, none of the CRS groups containing neutrophils formed NETs in this study. Eosinophilic CRS indicates the presence of EETs. Formation of EETs could have a role in clinical decision-making and prediction of treatment outcome of CRS, regardless of NP status.
In the face of changing water environment due to climate change, the assessment of water demand and water supply capacity by region is needed to prevent and mitigate droughts. Herein, we propose a ...quantitative approach to identify high drought risk areas in South Korea by applying future climate and socio‐economic change scenarios to calculate the demand and supply of municipal, agricultural, and industrial water. Three Coupled Model Intercomparison Project 5 Global Climate Models were selected to assess future drought risk under different climate change scenarios by combining meteorological and socio‐economic factors. The drought hazard was assessed by calculating the severity and frequency of drought based on a rating method. Drought vulnerability was assessed by calculating water shortages in domestic, industrial, and agricultural waters based on water demand and supply capacity and applying entropy weightings. According to future climate change scenarios, the Youngsan River Basin was more vulnerable to drought than other basins. The results of the IPSL‐CM5‐LR model also suggest that the drought risk in the Youngsan River Basin will increase during the period 2071–2099. By demonstrating the relative sensitivity of drought risk on the Korean Peninsula to various future emission scenarios, our work provides valuable information to update mid‐ to long‐term drought mitigation strategies.
This study provides a detailed assessment of future drought risk in South Korea based on future climate projections and socio‐economic scenarios affecting water demand up to 2099. We have developed a novel approach that accounts for both drought risk and drought vulnerability in the assessment of overall hazard. We categorize levels of risk based on projected changes in precipitation and the supply and demand of domestic, industrial, and agricultural water. Percentile changes in DRI for S1 (2011–2040), S2 (2041–2070), and S3 (2071–2099) under RCP 4.5 and 8.5 emission scenarios. For each panel, red (blue) indicates an increase (decrease) in drought risk compared to S0 (1976–2005) as a baseline.
Background Allergic rhinitis (AR) and asthma are 2 entities of allergic airway diseases that frequently occur together, which is referred to as united airways . In contrast to this general concept, ...we hypothesized that innate immunity of the upper and lower airways is respectively distinctive, because the immunologic conditions of the nasal and lung mucosa as well as the functions of the immune cells within their epithelia are different. Objective We wanted to identify distinctive mechanisms of innate immunity in the nose and lung mucosa, which are responsible for house dust mite (HDM)–induced AR and allergic asthma (AA), respectively. Methods We constructed a mouse model of AR or AA induced by sensitization and consequent provocation with HDM extracts. Results HDM-derived β-glucans, rather than LPS, were proven to be essential to activating innate immunity in the nasal mucosa and triggering AR, which depended on Toll-like receptor 2 (TLR2), but not on TLR4; however, the LPS/TLR4 signaling axis, rather than β-glucans/TLR2, was critical to HDM-induced AA. These differences were attributed to the specific role of β-glucans and LPS in inducing the surface expression of TLR2 and TLR4 and their translocation to lipid rafts in nasal and bronchial epithelial cells, respectively. We also showed that dual oxidase 2–generated reactive oxygen species mediate both β-glucan–induced TLR2 activation and LPS-induced TLR4 activation. Conclusions We describe a novel finding of distinctive innate immunity of the nose and lungs, respectively, which trigger AR and AA, by showing the critical role of HDM-induced TLR activation via dual oxidase 2–mediated reactive oxygen species.
This meta-analysis is aimed to investigate the association between the neutrophil-to-lymphocyte ratio (NLR) and obstructive sleep apnea (OSA). The PubMed, Web of Science, Google Scholar, and Cochrane ...Library databases were searched to collect all relevant articles. The pooled standardized mean difference (SMD) with a 95% confidence interval (CI) was calculated using the random effects model. In addition, subgroup analysis and meta-regression analysis were performed. Eleven eligible articles containing 2,259 patients with OSA were included in this study. Pooled outcomes revealed that the NLR was significantly higher in patients with OSA than in controls (SMD 0.62, 95% CI 0.29-0.94, P = 0.002). In subgroup analyses, differences in the NLR between patients and controls increased with worsening OSA grades. Furthermore, meta-regression analysis showed that differences in mean BMI exerted a significant effect on differences in the NLR (P = 0.0003). In summary, our meta-analysis demonstrated that the NLR in OSA patients was significantly higher than that in controls, and the difference was larger in patients with severe OSA. These results indicate that the NLR may be a reliable marker for detecting systemic inflammation and predicting disease severity in patients with OSA.
To prepare for the potential of extreme drought caused by climate change, both physical and socioeconomic factors need to be considered. In this study, three general circulation models were selected: ...IPSL‐CM5A‐LR, HadGEM2‐AO, and CanESM2 as representative scenarios for severe, moderate, and relatively weak droughts to assess the risk of droughts for future climate projections. Drought hazard was estimated using the meteorological drought index to determine drought frequency, severity, and probability. Population density, agricultural land area, and municipal, agricultural, and industrial water demand were used as drought vulnerability indicators. The Analytical Hierarchy Process technique was applied to determine the weight of each indicator, and the integrated drought risk was then estimated. HadGEM2‐AO and CanESM2 projected that drought risk would be reduced in the far future. IPSL‐CM5A‐LR projected an increased drought risk in the near and far future in the downstream area of the Nakdong River Basin. This study presented a quantitative approach to identify high drought‐risk areas that should be the focus of future extreme drought assessments and mid‐ to long‐term drought mitigation strategies.
Location of the study area and sub‐basin regions. The numbers shown on the map indicate basin identification numbers for the 33 sub‐basins of the Nakdong River, Korea.
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