Background/Aims: MicroRNA (miRNA) is a small non-coding RNA molecule that functions in regulation of gene expression by targeting mRNA to affect its stability and/or translation. The aim of this study was to evaluate the miRNAs involvement in gestational diabetes mellitus (GDM), a well known risk factor for fetal overgrowth. Methods: Differential microRNA expression in placental tissues of normal controls and women with GDM were identified by miRNA micorarray analysis and further confirmed by quantitative real-time PCR (qRT-PCR) on an independent set of normal and GDM placental tissues. Target genes of microRNAs were bioinformatically predicted and verified in vitro by Western blotting. Results: Our results uncovered 9 miRNAs that were significantly deregulated in GDM samples: miR-508-3p was up-regulated and miR-27a, miR-9, miR-137, miR-92a, miR-33a, miR-30d, miR-362-5p and miR-502-5p were down-regulated. Bioinformatic approaches revealed that the microRNAs signature identifies gene targets involved in EGFR (epidermal growth factor receptor)-PI3K (phosphoinositide 3-Kinase)-Akt (also known as protein kinase B) pathway, a signal cascade which plays important roles in placental development and fetal growth. We found that the protein levels of EGFR, PI3K and phospho-Akt were up-regulated and PIKfyve (a FYVE finger-containing phosphoinositide kinase), a negative regulator of EGFR signaling, was down-regulated significantly in GDM tissues. We also confirmed PIKfyve was a direct target of miR-508-3p. Conclusion: Our data identified a miRNA signature involvement in GDM which may contribute to macrosomia through enhancing EGFR signaling.
East Asian dust and its radiative feedbacks are analyzed by the use of the fourth version of the Community Atmosphere Model (CAM4) with a bulk aerosol model parameterization (BAM) for the dust size distribution (CAM4‐BAM). Two numerical experiments are conducted and intercompared: one with (Active) and one without (Passive) the radiative effects of dust aerosols. This CAM4‐BAM captures the main spatial distribution of the dust aerosol optical depth (AOD) and the dust surface concentrations over East Asia, with positive correlations with the local observational data on annual and seasonal means. A comparative analysis of the Active and Passive experiments reveals that consideration of the dust‐radiation interaction can significantly reduce dust emissions, loading, transport, and dry and wet depositions over East Asia, which is opposite to the enhanced dust cycle over North Africa. Further analysis of the contrasting dust‐radiation feedbacks between North Africa and East Asia shows that over North Africa, the dust radiative forcing significantly increases the surface temperature and 10 m wind speed, whereas it decreases the surface temperature and the surface wind speeds over East Asia. These contrasting radiative effects, in turn, result in distinct dust cycle changes over these two regions. Mechanistic analysis reveals that the radiative contrasts between East Asia and North Africa are mainly due to the differences in their regional surface albedo, dust vertical distribution, and size distribution.
The outputs of the Chinese Academy of Sciences (CAS) Flexible Global Ocean-Atmosphere-Land System (FGOALS-f3-L) model for the baseline experiment of the Atmospheric Model Intercomparison Project simulation in the Diagnostic, Evaluation and Characterization of Klima common experiments of phase 6 of the Coupled Model Intercomparison Project (CMIP6) are described in this paper. The CAS FGOALS-f3-L model, experiment settings, and outputs are all given. In total, there are three ensemble experiments over the period 1979-2014, which are performed with different initial states. The model outputs contain a total of 37 variables and include the required three-hourly mean, six-hourly transient, daily and monthly mean datasets. The baseline performances of the model are validated at different time scales. The preliminary evaluation suggests that the CAS FGOALS-f3-L model can capture the basic patterns of atmospheric circulation and precipitation well, including the propagation of the Madden-Julian Oscillation, activities of tropical cyclones, and the characterization of extreme precipitation. These datasets contribute to the benchmark of current model behaviors for the desired continuity of CMIP.
Because industrial emissions of anthropogenic aerosols over East Asia have greatly increased in recent decades, the interactions between atmospheric aerosols and the East Asian summer monsoon (EASM) have attracted enormous attention. To further understand the aerosol‐EASM interaction, we investigate the impacts of anthropogenic aerosols on the EASM during the multidecadal strong (1950–1977) and weak (1978–2000) EASM stages using the Community Atmospheric Model 5.1. Numerical experiments are conducted for the whole period, including the two different EASM stages, with present day (PD, year 2000) and preindustrial (PI, year 1850) aerosol emissions, as well as the observed time‐varying aerosol emissions. A comparison of the results from PD and PI shows that, with the increase in anthropogenic aerosols, the large‐scale EASM intensity is weakened to a greater degree (−9.8%) during the weak EASM stage compared with the strong EASM stage (−4.4%). The increased anthropogenic aerosols also result in a significant reduction in precipitation over North China during the weak EASM stage, as opposed to a statistically insignificant change during the strong EASM stage. Because of greater aerosol loading and the larger sensitivity of the climate system during weak EASM stages, the aerosol effects are more significant during these EASM stages. These results suggest that anthropogenic aerosols from the same aerosol emissions have distinct effects on the EASM and the associated precipitation between the multidecadal weak and strong EASM stages.
Influenza A viruses (IAVs) rely on host factors to support their life cycle, as viral proteins hijack or interact with cellular proteins to execute their functions. Identification and understanding of these factors would increase our knowledge of the molecular mechanisms manipulated by the viruses. In this study, we searched for novel binding partners of the influenza A virus NS2 protein, the nuclear export protein responsible for overcoming host range restriction, by a yeast two-hybrid screening assay and glutathione S-transferase-pulldown and coimmunoprecipitation assays and identified AIMP2, a potent tumor suppressor that usually functions to regulate protein stability, as one of the major NS2-binding candidates. We found that the presence of NS2 protected AIMP2 from ubiquitin-mediated degradation in NS2-transfected cells and AIMP2 functioned as a positive regulator of IAV replication. Interestingly, AIMP2 had no significant effect on NS2 but enhanced the stability of the matrix protein M1. Further, we provide evidence that AIMP2 recruitment switches the modification of M1 from ubiquitination to SUMOylation, which occurs on the same attachment site (K242) on M1 and thereby promotes M1-mediated viral ribonucleoprotein complex nuclear export to increase viral replication. Collectively, our results reveal a new mechanism of AIMP2 mediation of influenza virus replication. IMPORTANCEAlthough the ubiquitination of M1 during IAV infection has been observed, the precise modification site and the molecular consequences of this modification remain obscure. Here, we demonstrate for the first time that ubiquitin and SUMO compete for the same lysine (K242) on M1 and the interaction of NS2 with AIMP2 facilitates the switch of the M1 modification from ubiquitination to SUMOylation, thus increasing viral replication. Influenza A virus (IAV) is a significant cause of morbidity and mortality in both humans and animal species owing to its ability to cause yearly epidemics and occasional pandemics (1-3). Like other viruses, IAV hijacks the host cellular machinery to support its life cycle. Thus, identification and characterization of the interactions between viral components and specific host factors would help provide an understanding of the mechanisms by which the viruses acquire human pandemic potential.IAV belongs to the Orthomyxoviridae family, and its genome consists of eight negative-sense RNA segments encoding up to 17 viral proteins (4-9). The viral RNA (vRNA) exists as a form of viral ribonucleoprotein complexes (vRNPs) containing vRNA, nucleoprotein (NP), and three viral polymerase proteins (PB1, PB2, and PA). Unlike most other RNA viruses, influenza virus transcribes and replicates its genome in the nucleus. Thus, after it enters a host cell, vRNPs enter the nucleus to complete transcription and replication (10). The newly synthesized vRNPs are exported from the nucleus for packaging into progeny virions (11). In this regard, efficient nuclear export of vRNPs is essential for productive infection.NS2, also kn...
We also examine the connections between the global energy and water balance and discuss the possible link between the two within the context of the findings from the reanalysis data. Finally, the model biases as well as possible solutions are discussed.
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