Plants and animals rely on innate immunity to prevent infections by detection of microbe-associated molecular patterns (MAMPs) through pattern-recognition receptors (PRRs). The plant PRR FLS2, a leucine-rich repeat-receptor kinase, recognizes bacterial flagellin and initiates immune signaling by association with another leucinerich repeat-receptor-like kinase, BAK1. It remains unknown how the FLS2/BAK1 receptor complex activates intracellular signaling cascades. Here we identified the receptor-like cytoplasmic kinase BIK1 that is rapidly phosphorylated upon flagellin perception, depending on both FLS2 and BAK1. BIK1 associates with FLS2 and BAK1 in vivo and in vitro. BIK1 is phosphorylated by BAK1, and BIK1 also directly phosphorylates BAK1 and FLS2 in vitro. The flagellin phosphorylation site Thr 237 of BIK1 is required for its phosphorylation on BAK1 and FLS2, suggesting that BIK1 is likely first phosphorylated upon flagellin perception and subsequently transphosphorylates FLS2/ BAK1 to propagate flagellin signaling. Importantly, bik1 mutants are compromised in diverse flagellin-mediated responses and immunity to the nonpathogenic bacterial infection. Thus, BIK1 is an essential component in MAMP signal transduction, which links the MAMP receptor complex to downstream intracellular signaling.pathogen-associated molecular pattern/microbe-associated molecular pattern-triggered immunity | phosphorylation | pattern recognition receptor | BRI1-associated receptor kinase | flagellin sensing 2 P lants and animals live in an environment with a diverse array of microorganisms and have developed the capacity to timely detect potential infectious agents without destroying their own tissues. Innate immunity, the first line of inducible defense, is triggered instantaneously upon the detection of conserved pathogen-or microbe-associated molecular patterns (PAMP/ MAMPs) (1-5). In plants, MAMPs are usually perceived by cellsurface pattern-recognition receptors (PRRs) and mount PAMP/ MAMP-triggered immunity (PTI). Different MAMPs likely trigger convergent immune signaling events, including changes in cytoplasmic Ca 2+ levels, activation of MAP kinase (MAPK) cascades, induction of defense-related genes, production of reactive oxygen species and nitric oxide, deposition of callose to reinforce the cell wall, and stomatal closure to prevent pathogen entry (1-5). PTI is important for plants to thwart off a broad spectrum of potential pathogens.One of the best-characterized plant MAMP receptors is the leucine-rich repeat receptor kinase (LRR-RK) protein FLS2 that recognizes a conserved 22-amino-acid peptide (flg22) from bacterial flagellin (6). Upon flagellin perception, FLS2 rapidly associates with another LRR-receptor-like kinase (RLK), BAK1, thereby initiating downstream signaling (7,8). BAK1 was originally identified as a BRI1-associated receptor kinase mediating brassinosteroid signaling (9, 10). Brassinosteroids (BRs), a class of plant hormone with essential roles in plant growth and development, are perceived by LRR-RK BRI1, ...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to respiratory illness and multi-organ failure in critically ill patients. Although the virus-induced lung damage and inflammatory cytokine storm are believed to be directly associated with coronavirus disease 2019 (COVID-19) clinical manifestations, the underlying mechanisms of virus-triggered inflammatory responses are currently unknown. Here we report that SARS-CoV-2 infection activates caspase-8 to trigger cell apoptosis and inflammatory cytokine processing in the lung epithelial cells. The processed inflammatory cytokines are released through the virus-induced necroptosis pathway. Virus-induced apoptosis, necroptosis, and inflammation activation were also observed in the lung sections of SARS-CoV-2-infected HFH4-hACE2 transgenic mouse model, a valid model for studying SARS-CoV-2 pathogenesis. Furthermore, analysis of the postmortem lung sections of fatal COVID-19 patients revealed not only apoptosis and necroptosis but also massive inflammatory cell infiltration, necrotic cell debris, and pulmonary interstitial fibrosis, typical of immune pathogenesis in the lung. The SARS-CoV-2 infection triggered a dual mode of cell death pathways and caspase-8-dependent inflammatory responses may lead to the lung damage in the COVID-19 patients. These discoveries might assist the development of therapeutic strategies to treat COVID-19.
The Tibetan Plateau and its surroundings are known as the Third Pole (TP). This region is noted for its high rates of glacier melt and the associated hydrological shifts that affect water supplies in Asia. Atmospheric pollutants contribute to climatic and cryospheric changes through their effects on solar radiation and the albedos of snow and ice surfaces; moreover, the behavior and fates within the cryosphere and environmental impacts of environmental pollutants are topics of increasing concern. In this review, we introduce a coordinated monitoring and research framework and network to link atmospheric pollution and cryospheric changes (APCC) within the TP region. We then provide an up-to-date summary of progress and achievements related to the APCC research framework, including aspects of atmospheric pollution's composition and concentration, spatial and temporal variations, trans-boundary transport pathways and mechanisms, and effects on the warming of atmosphere and changing in Indian monsoon, as well as melting of glacier and snow cover. We highlight that exogenous air pollutants can enter into the TP’s environments and cause great impacts on regional climatic and environmental changes. At last, we propose future research priorities and map out an extended program at the global scale. The ongoing monitoring activities and research facilitate comprehensive studies of atmosphere–cryosphere interactions, represent one of China's key research expeditions to the TP and the polar regions and contribute to the global perspective of earth system science.
Chondrogenic differentiation of mesenchymal stem cells (MSCs) is accurately regulated by essential transcription factors and signaling cascades. However, the precise mechanisms involved in this process still remain to be defined. MicroRNAs (miRNAs) regulate various biological processes by binding target mRNA to attenuate protein synthesis. To investigate the mechanisms for miRNAs-mediated regulation of chondrogenic differentiation, we identified that miR-145 was decreased during transforming growth factor beta 3 (TGF-β3)-induced chondrogenic differentiation of murine MSCs. Subsequently, dual-luciferase reporter gene assay data demonstrated that miR-145 targets a putative binding site in the 3′-UTR of SRY-related high mobility group-Box gene 9 (Sox9) gene, the key transcription factor for chondrogenesis. In addition, over-expression of miR-145 decreased expression of Sox9 only at protein levels and miR-145 inhibition significantly elevated Sox9 protein levels. Furthermore, over-expression of miR-145 decreased mRNA levels for three chondrogenic marker genes, type II collagen (Col2a1), aggrecan (Agc1), cartilage oligomeric matrix protein (COMP), type IX collagen (Col9a2) and type XI collagen (Col11a1) in C3H10T1/2 cells induced by TGF-β3, whereas anti-miR-145 inhibitor increased the expression of these chondrogenic marker genes. Thus, our studies demonstrated that miR-145 is a key negative regulator of chondrogenic differentiation by directly targeting Sox9 at early stage of chondrogenic differentiation.
Black carbon (BC) is one of the key components causing global warming. Especially on the Tibetan Plateau (TP), reconstructing BC's historical trend is essential for better understanding its anthropogenic impact. Here, we present results from high altitude lake sediments from the central TP. The results provide a unique history of BC over the past 150 years, from the preindustrial to the modern period. Although BC concentration levels in the Nam Co Lake sediments were lower than those from other high mountain lakes, the temporal trend of BC fluxes clearly showed a recent rise, reflecting increased emissions from anthropogenic activities. The BC records were relatively constant until 1900, then began to gradually increase, with a sharp rise beginning around 1960. Recent decades show about 2.5-fold increase of BC compared to the background level. The emission inventory in conjunction with air mass trajectories further demonstrates that BC in the Nam Co Lake region was most likely transported from South Asia. Rapid economic development in South Asia is expected to continue in the next decades; therefore, the influence of BC over the TP merits further investigations.
Light‐absorbing impurities (LAIs) in snow of the southeastern Tibetan Plateau (TP) and their climatic impacts are of interest not only because this region borders areas affected by the South Asian atmospheric brown clouds but also because the seasonal snow and glacier melt from this region form important headwaters of large rivers. In this study, we collected surface snow and snowpit samples from four glaciers in the southeastern TP in June 2015 to investigate the comprehensive observational data set of LAIs. Results showed that the LAI concentrations were much higher in the aged snow and granular ice than in the fresh snow and snowpits due to postdepositional processes. Impurity concentrations fluctuated across snowpits, with maximum LAI concentrations frequently occurring toward the bottom of snowpits. Based on the SNow ICe Aerosol Radiative model, the albedo simulation indicated that black carbon and dust account for approximately 20% of the albedo reduction relative to clean snow. The radiative forcing caused by black carbon and dust deposition on the glaciers were between 1.0–141 W m−2 and 1.5–120 W m−2, respectively. Black carbon (BC) played a larger role in albedo reduction and radiative forcing than dust in the study area, enhancing approximately 15% of glacier melt. Analysis based on the Fire INventory from NCAR indicated that nonbiomass‐burning sources of BC played an important role in the total BC deposition, especially during the monsoon season. This study suggests that eliminating anthropogenic BC could mitigate glacier melt in the future of the southeastern TP.
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