Typhoon Faxai hit Japan in 2019 and severely damaged the Tokyo metropolitan area. To mitigate such damages, a good track forecast is necessary even before the typhoon formation. To investigate the ...predictability of the genesis and movement of a precursor vortex and its relationship with the synoptic‐scale flow, 100‐member ensemble simulations of Typhoon Faxai were performed using a 14‐km mesh global nonhydrostatic atmospheric model, which started from 16 different initial days (i.e., 1,600 members in total). The results show that the model could predict an enhanced risk of a Faxai‐like vortex heading toward Japan 2 weeks before landfall, which was up to 70%. The reason for the enhancement was a rapid increase in the members reproducing a precursor vortex from 15 to 12 days before landfall in Japan. In addition, the upper‐tropospheric vortex played an essential role in the track simulation of Faxai.
Plain Language Summary
Tropical cyclones severely damage coastal regions yearly. Typhoon Faxai hit Japan in 2019 and severely damaged buildings, power grids, and cell phone networks in the Tokyo metropolitan area. To mitigate such damages, better track forecast is necessary even from the timing before typhoon formation. A large ensemble member (1,600‐member in total) and high‐resolution (14‐km) simulation was performed to investigate the genesis and movement of the precursor vortex of Faxai in 2019 and its relationship with the synoptic‐scale environmental flow using a global nonhydrostatic atmospheric model on the Supercomputer Fugaku. The results show the model could predict an enhanced risk of a Faxai‐like vortex heading toward Japan 2 weeks before landfall. A reason for the enhancement was a rapid increase in the members reproducing a precursor vortex from 15 to 12 days before landfall in Japan. In addition, the upper‐tropospheric vortex played an essential role in the movement of the Faxai‐like vortex.
Key Points
A 1,600‐member ensemble simulation in total for Typhoon Faxai (2019) was performed using a 14‐km mesh nonhydrostatic atmospheric model
The model successfully predicts the risk of Faxai's landfall in Japan 2 weeks in advance
Reproducibilities of the precursor vortex and upper‐tropospheric vortex yield good prediction of the formation and track of Faxai
Bisphenol A (BPA) is an estrogen‐like compound, and an environmental hormone, that is commonly used in daily life. Therefore, it may enter the human body through food or direct contact, causing BPA ...residues in blood and urine. Because most studies focused on the analysis of BPA in reproductive cells or tissues, regarding evidence the effect of BPA on human retinal pigment epithelium (ARPE‐19) cells unavailable. Accordingly, the present study explored the cytotoxicity of BPA on ARPE‐19 cells. After BPA treatment, the expression of Bcl‐XL an antiapoptotic protein, in the mitochondria decreased, and the expression of Bax, a proapoptotic protein increased. Then the mitochondrial membrane potential was affected. BPA changed in mitochondrial membrane potential led to the release of cytochrome C, which activated caspase‐9 to promote downstream caspase‐3 leading to cytotoxicity. The nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) and heme oxygenase 1 (HO‐1) pathway play a major role in age‐related macular degeneration. Our results showed that expression of HO‐1 and Nrf2 suppressed by BPA. Superoxide dismutase and catalase, which Nrf2 downstream antioxidants, were degraded by BPA. AMP‐activated kinase (AMPK), which can regulate the phosphorylation of Nrf2, and the phosphorylation of AMPK expression was reduced by BPA. Finally, BPA‐induced ROS generation and cytotoxicity were reduced by N‐acetyl‐l‐cysteine. Taken together, these results suggest that BPA induced ARPE‐19 cells via oxidative stress, which was associated with down regulated Nrf2/HO‐1 pathway, and the mitochondria dependent apoptotic signaling pathway.
Mitochondrial dysfunction, a common cellular hallmark in both familial and sporadic forms of Parkinson's disease (PD), is assumed to play a significant role in pathologic development and progression ...of the disease. Teaghrelin, a unique bioactive compound in some oolong tea varieties, has been demonstrated to protect SH‐SY5Y cells against 1‐methyl‐4‐phenylpyridinium induced neurotoxicity by binding to the ghrelin receptor to activate the AMPK/SIRT1/PGC‐1α pathway. In this study, an animal model was established using a neurotoxin, 1‐methyl‐4phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), a byproduct of a prohibited drug, to evaluate the oral efficacy of teaghrelin on PD by monitoring motor dysfunction of mice in open field, pole, and bean walking tests. The results showed that MPTP‐induced motor dysfunction of mice was significantly attenuated by teaghrelin supplementation. Tyrosine hydroxylase and dopamine transporter protein were found reduced in the striatum and midbrain of MPTP‐treated mice, and significantly mitigated by teaghrelin supplementation. Furthermore, teaghrelin administration enhanced mitophagy and mitochondria biogenesis, which maintained cell homeostasis and prevented the accumulation of αSyn and apoptosis‐related proteins. It seemed that teaghrelin protected dopaminergic neurons in MPTP‐treated mice by increasing PINK1/Parkin‐mediated mitophagy and AMPK/SIRT1/PGC‐1α‐mediated mitochondria biogenesis, highlighting its potential therapeutic role in maintaining dopaminergic neurons function in PD. Mitochondrial dysfunction, a common cellular hallmark in both familial and sporadic forms of Parkinson's disease (PD), is assumed to play a significant role in pathologic development and progression of the disease. Teaghrelin, a unique bioactive compound in some oolong tea varieties, has been demonstrated to protect SH‐SY5Y cells against 1‐methyl‐4‐phenylpyridinium induced neurotoxicity by binding to the ghrelin receptor to activate the AMPK/SIRT1/PGC‐1α pathway. In this study, an animal model was established using a neurotoxin, 1‐methyl‐4phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), a byproduct of a prohibited drug, to evaluate the oral efficacy of teaghrelin on PD by monitoring motor dysfunction of mice in open field, pole, and bean walking tests. The results showed that MPTP‐induced motor dysfunction of mice was significantly attenuated by teaghrelin supplementation. Tyrosine hydroxylase and dopamine transporter protein were found reduced in the striatum and midbrain of MPTP‐treated mice, and significantly mitigated by teaghrelin supplementation. Furthermore, teaghrelin administration enhanced mitophagy and mitochondria biogenesis, which maintained cell homeostasis and prevented the accumulation of αSyn and apoptosis‐related proteins. It seemed that teaghrelin protected dopaminergic neurons in MPTP‐treated mice by increasing PINK1/Parkin‐mediated mitophagy and AMPK/SIRT1/PGC‐1α‐mediated mitochondria biogenesis, highlighting its potential therapeutic role in maintaining dopaminergic neurons function in PD.
Blood–brain barrier (BBB) characteristics are induced and maintained by crosstalk between brain microvascular endothelial cells and neighboring cells. Using in vitro cell models, we previously found ...that a bystander effect was a cause for Japanese encephalitis‐associated endothelial barrier disruption. Brain astrocytes, which neighbor BBB endothelial cells, play roles in the maintenance of BBB integrity. By extending the scope of relevant studies, a potential mechanism has been shown that the activation of neighboring astrocytes could be a cause of disruption of endothelial barrier integrity during the course of Japanese encephalitis viral (JEV) infection. JEV‐infected astrocytes were found to release biologically active molecules that activated ubiquitin proteasome, degraded zonula occludens‐1 (ZO‐1) and claudin‐5, and disrupted endothelial barrier integrity in cultured brain microvascular endothelial cells. JEV infection caused astrocytes to release vascular endothelial growth factor (VEGF), interleukin‐6 (IL‐6), and matrix metalloproteinases (MMP‐2/MMP‐9). Our data demonstrated that VEGF and IL‐6 released by JEV‐infected astrocytes were critical for the proteasomal degradation of ZO‐1 and the accompanying disruption of endothelial barrier integrity through the activation of Janus kinase‐2 (Jak2)/signal transducer and activator of transcription‐3 (STAT3) signaling as well as the induction of ubiquitin–protein ligase E3 component, n‐recognin‐1 (Ubr 1) in endothelial cells. MMP‐induced endothelial barrier disruption was accompanied by MMP‐mediated proteolytic degradation of claudin‐5 and ubiquitin proteasome‐mediated degradation of ZO‐1 via extracellular VEGF release. Collectively, these data suggest that JEV infection could activate astrocytes and cause release of VEGF, IL‐6, and MMP‐2/MMP‐9, thereby contributing, in a concerted action, to the induction of Japanese encephalitis‐associated BBB breakdown. GLIA 2015;63:1915–1932
Main Points
JEV‐infected astrocytes disrupted endothelial barrier integrity.
JEV infection caused astrocytes to release MMP‐2/MMP‐9, IL‐6, and VEGF.
IL‐6 and VEGF activated Jak2/STAT3/Ubr 1 leading to ZO‐1 degradation and endothelial barrier disruption.
Abstract
This study examines projections of high clouds related to sea surface temperature (SST) change using 14-km simulation output from NICAM, a global cloud system–resolving model. This study ...focuses on the vertical and horizontal structure of high cloud response to the SST pattern and how these cloud responses are linked to ice hydrometeors, such as cloud ice, snow, and graupel, which are not resolved by conventional general circulation models (GCMs). Under the present climate, the vertical and horizontal structure of the simulated increase in tropical high cloud amount for positive tropical mean HadISST SST anomalies has similar behavior to that of the GCM-Oriented
CALIPSO
Cloud Product (GOCCP) cloud fraction for HadISST SST. We further show that cloud ice is the main contributor to the simulated high cloud amount. Under a warming climate, the composite vertical and horizontal structure of the tropical high cloud response to the SST shows similar behavior to that under the present climate, but the amplitude of the variation is greater by a factor of 1.5 and the variation is more widespread. This amplification contributes to the high cloud increase under the warming climate, which is directly linked to the wider spatial extent of cloud ice in the eastern Pacific region. This study specifically reveals the similarity of the patterns of the responses of the high cloud fraction and cloud ice to global warming, indicating that an appropriate treatment of the complete spectrum of ice hydrometeors in global climate models is key to simulating high clouds and their response to global warming.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In wireless rechargeable sensor networks (WRSNs), there is a way to use mobile vehicles to charge node and collect data. It is a rational pattern to use two types of vehicles, one is for energy ...charging, and the other is for data collecting. These two types of vehicles, data collection vehicles (DCVs) and wireless charging vehicles (WCVs), are employed to achieve high efficiency in both data gathering and energy consumption. To handle the complex scheduling problem of multiple vehicles in large-scale networks, a twice-partition algorithm based on center points is proposed to divide the network into several parts. In addition, an anchor selection algorithm based on the tradeoff between neighbor amount and residual energy, named AS-NAE, is proposed to collect the zonal data. It can reduce the data transmission delay and the energy consumption for DCVs' movement in the zonal. Besides, we design an optimization function to achieve maximum data throughput by adjusting data rate and link rate of each node. Finally, the effectiveness of proposed algorithm is validated by numerical simulation results in WRSNs.
Cyclizine, an over‐the‐counter and prescription antihistamine, finds widespread application in the prevention and treatment of motion sickness, encompassing symptoms such as nausea, vomiting, ...dizziness, along with its effectiveness in managing vertigo. However, the overuse or misuse of cyclizine may lead to hallucinations, confusion, tachycardia, and hypertension. The molecular mechanisms underlying cyclizine‐induced cytotoxicity and apoptosis remain unclear. During the 24 h incubation duration, RAW264.7 macrophages were exposed to different concentrations of cyclizine. Cytotoxicity was assessed through the lactate dehydrogenase assay. Flow cytometry employing annexin V‐fluorescein isothiocyanate and propidium iodide was utilized to evaluate apoptosis and necrosis. Caspase activity and mitochondrial dysfunction were evaluated through a fluorogenic substrate assay and JC‐1 dye, respectively. Flow cytometry employing fluorogenic antibodies was utilized to evaluate the release of cytochrome c and expression of death receptor, including tumor necrosis factor‐α receptor and Fas receptor. Western blotting was utilized to evaluate the expression of the Bcl2 and Bad apoptotic regulatory proteins. The findings unveiled from the present study demonstrated that cyclizine exerted a concentration‐dependent effect on RAW264.7 macrophages, leading to the induction of cytotoxicity, apoptosis, and necrosis. This compound further activated the intrinsic apoptotic pathway by inducing mitochondrial dysfunction, Bcl2/Bad exchange expression, cytochrome c liberation, and activation of caspases contained caspase 3, 8, and 9. Moreover, the activation of the extrinsic apoptotic pathway was observed as cyclizine induced the upregulation of death receptors and increased caspase activities. Based on our investigations, it can be inferred that cyclizine prompts cytotoxicity and apoptosis in RAW264.7 macrophages in a concentration‐dependent manner by triggering both the intrinsic and extrinsic apoptotic pathways.
Though rosmarinic acid possesses nutritional, pharmaceutical, and toxic properties and shows therapeutic potential on liver diseases, its therapeutic effects against cholestatic liver diseases have ...not been proven. Using an extrahepatic cholestasis rat model by bile-duct ligation (BDL), daily oral administration of rosmarinic acid showed improvement effects on liver histology, serum biochemicals, ductular reaction, oxidative stress, inflammation, and fibrosis. Rosmarinic acid alleviated BDL-induced transforming growth factor beta-1 (TGF-β1) production and hepatic collagen deposition, and the anti-fibrotic effects were accompanied by reductions in matrix-producing cells and Smad2/3. BDL rats showed increased hepatic NF-κB/AP-1 activities, inflammatory cell infiltration/accumulation, and cytokine production, and these signs of hepatic inflammation were ameliorated by rosmarinic acid. Mechanistic study revealed an inhibitory effect of rosmarinic acid on the axis of the high mobility group box-1 (HMGB1)/toll-like receptor-4 (TLR4) in BDL rats. Results of cultured hepatic stellate cells further showed the impacts of rosmarinic acid which attenuated TGF-β1-induced stellate cell mitogenic and fibrogenic activation. Our findings support the concept that rosmarinic acid could serve as a hepatoprotective agent, and dietary rosmarinic acid supplementation may be beneficial in terms of improving cholestasis-related liver injury via mechanisms involving resolution of oxidative burden and down-regulation of HMGB1/TLR4, NF-κB, AP-1, and TGF-β1/Smad signaling.
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•Bile duct ligation caused extrahepatic cholestasis in rodents.•Rosmarinic acid showed improvement effects against cholestasis.•Rosmarinic acid attenuated hepatic TGF-β1 signaling in BDL rats.•Rosmarinic acid attenuated hepatic NF-κB/AP-1 activities in BDL rats.•Rosmarinic acid attenuated hepatic HMGB1/TLR4 signaling in BDL rats.
Adequate stress on the Endoplasmic Reticulum (ER) with the Unfolded Protein Response (UPR) could maintain glioma malignancy. Uncontrolled ER stress, on the other hand, predisposes an ...apoptosis-dominant UPR program. We studied here the proapoptotic actions of the Epidermal Growth Factor Receptor (EGFR) inhibitor gefitinib, with the focus on ER stress. The study models were human H4 and U87 glioma cell lines. We found that the glioma cell-killing effects of gefitinib involved caspase 3 apoptotic cascades. Three branches of ER stress, namely Activating Transcription Factor-6 (ATF6), Protein Kinase R (PKR)-Like ER Kinase (PERK), and Inositol-Requiring Enzyme 1 (IRE1), were activated by gefitinib, along with the elevation of intracellular free Ca
, Reactive Oxygen Species (ROS), and NADPH Oxidase2/4 (NOX2/4). Specifically, elevated IRE1 phosphorylation, Tumor Necrosis Factor (TNF) Receptor-Associated Factor-2 (TRAF2) expression, Apoptosis Signal-Regulating Kinase-1 (Ask1) phosphorylation, c-Jun N-Terminal Kinase (JNK) phosphorylation, and Noxa expression appeared in gefitinib-treated glioma cells. Genetic, pharmacological, and biochemical studies further indicated an active ROS/ER stress/Ask1/JNK/Noxa axis causing the glioma apoptosis induced by gefitinib. The findings suggest that ER-stress-based therapeutic targeting could be a promising option in EGFR inhibitor glioma therapy, and may ultimately achieve a better patient response.
Fucoxanthin is a natural pigment widely distributed in macroalgae and microalgae. An orange‐colored xanthophyll, it has several bioactive effects, including anticancer, anti‐obesity, oxidative stress ...reduction, and anti‐inflammation. Acute lung injury (ALI) caused by acute infections or injurious stimuli to the lung tissues is a severe pulmonary inflammatory disease. To date, no evidence has shown ALI to be reduced by fucoxanthin through activation of Ras homolog family member A (RhoA) and the nuclear factor (NF)‐κB pathway in lipopolysaccharide (LPS)‐treated mice. Pretreatment with fucoxanthin inhibited histopathological changes in lung tissues and neutrophil infiltration into bronchoalveolar lavage fluid induced by LPS in ALI mice. Moreover, LPS‐induced proinflammatory cytokine expression and neutrophil infiltration were inhibited by fucoxanthin in a concentration‐dependent manner. Pretreatment of mice with fucoxanthin inhibited NF‐κB phosphorylation and IκB degradation in the lungs of mice with LPS‐induced ALI. We further found that phosphorylation of Akt and p38 mitogen‐activated protein KINASE (MAPK) was inhibited by fucoxanthin. By contrast, the phosphorylation of extracellular signal‐regulated kinase and c‐Jun N‐terminal kinase was not inhibited by fucoxanthin. Furthermore, we found that the activation of RhoA was inhibited by fucoxanthin in LPS‐induced ALI. On the basis of these results, we propose that fucoxanthin disrupts the RhoA activation‐mediated phosphorylation of Akt and p38 MAPK, leading to NF‐κB activation in mice with LPS‐induced ALI.
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