The effects of Asian summer monsoon on algal blooms in reservoirs

An important characteristic of lakes and reservoirs in the East Asian summer monsoon region is the dramatic seasonal difference in hydrologic inputs, with annual rainfall commonly concentrated in a few heavy rain events. In this study, we surveyed the monthly variations of phytoplankton density in 3 large deep reservoirs and 7 small shallow reservoirs and analyzed the effect of large precipitation events on phytoplankton. During heavy rains, stream phosphorus concen¬trations increased sharply, and phosphorus loadings into reservoirs were not continuous but episodic shock loadings. In deep stratified reservoirs, however, the concentrations of phosphorus and chlorophyll a were much lower than expected from the high total phosphorus levels in the storm runoff. Inflowing storm waters laden with phosphorus flowed into metalimnetic layers because deep reservoirs had strong thermal stratification and the storm water was cooler than the epilimnion. The result was the formation of an ecosystem resilient to phosphorus shock loadings during monsoon. Nutrients in the metalimnion seemed to be dispersed gradually toward the epilimnion, and phytoplankton reached maximum densities, called “monsoon blooms,” after the monsoon. By contrast, shallow reservoirs with short hydraulic residence times had lower chlorophyll a concentrations during the monsoon season because the high flushing rate was the major limiting factor of phytoplankton growth. In conclusion, summer monsoon is the major determinant of phyto¬plankton density in reservoirs of the East Asian region, but their responses can vary widely depending on hydrologic characteristics

Editorial: The Role of HMGB1 in Immunity

High mobility group box 1 (HMGB1) is an evolutionarily conserved nuclear protein that can be released by almost all cell types. Scientists have uncovered a variety of molecular mechanisms by which HMGB1 in both immune and non-immune cells modulates the nature and magnitude of immune responses (1–3). In recent years, HMGB1-targeted therapies have been exploited in multiple preclinical studies of inflammatory conditions and there is robust clinical evidence for HMGB1 levels as a potential biomarker for early prediction or progression of various diseases. However, it is not presently possible to specifically target HMGB1 in any clinical setting. A significant obstacle to developing therapeutics lies in gaps in knowledge of the post-translational modification of HMGB1 as well as the timing and type of microenvironments to which HMGB1 is exposed. This Research Topic provides a comprehensive overview of current understanding of the contribution of HMGB1 to various diseases and HMGB1 specific therapeutics. Nine articles are included: five original articles, three review articles, and one mini-review. The authors invited the scientific contributors to this collection based on their unique and pioneering discoveries on the role of HMGB1 in physiological and pathological conditions including: (i) HMGB1-related immune functions (ii) Post-translational modification and secretion mechanisms of HMGB1 (iii) Molecular pathways activated by HMGB1 in acute lung injury, lupus, cancers, and other diseases (iv) Agents to modulate HMGB1 function.11Nsci

High-mobility group box 1-induced complement activation causes sterile inflammation

High-mobility group box 1 (HMGB1), a well-known danger-associated molecular pattern molecule, acts as a pro-inflammatory molecule when secreted by activated immune cells or released after necrotic cell damage. HMGB1 binds to immunogenic bacterial components and augments septic inflammation. In this study, we show how HMGB1 mediates complement activation, promoting sterile inflammation. We show that HMGB1 activates the classical pathway of complement system in an antibody-independent manner after binding to C1q. The C3a complement activation product in human plasma and C5b-9 membrane attack complexes on cell membrane surface are detected after the addition of HMGB1. In an acetaminophen (APAP)-induced hepatotoxicity model, APAP injection reduced HMGB1 levels and elevated C3 levels in C1q-deficient mouse serum samples, compared to that in wild-type (WT) mice. APAP-induced C3 consumption was inhibited by sRAGE treatment in WT mice. Moreover, in a mouse model of brain ischemia-reperfusion injury based on middle cerebral arterial occlusion, C5b-9 complexes were deposited on vessels where HMGB1 was accumulated, an effect that was suppressed upon HMGB1 neutralization. We propose that the HMGB1 released after cell necrosis and in ischemic condition can trigger the classical pathway of complement activation to exacerbate sterile inflammation. © 2018 Kim, Son, Lee, Kwak, Han, Lee, Park, Kim, Kim, Lee, Choi, Diamond and Shi

High-Mobility Group Box 1-Induced Complement Activation Causes Sterile Inflammation

High-mobility group box 1 (HMGB1), a well-known danger-associated molecular pattern molecule, acts as a pro-inflammatory molecule when secreted by activated immune cells or released after necrotic cell damage. HMGB1 binds to immunogenic bacterial components and augments septic inflammation. In this study, we show how HMGB1 mediates complement activation, promoting sterile inflammation. We show that HMGB1 activates the classical pathway of complement system in an antibody-independent manner after binding to C1q. The C3a complement activation product in human plasma and C5b-9 membrane attack complexes on cell membrane surface are detected after the addition of HMGB1. In an acetaminophen (APAP)-induced hepatotoxicity model, APAP injection reduced HMGB1 levels and elevated C3 levels in C1q-deficient mouse serum samples, compared to that in wild-type (WT) mice. APAP-induced C3 consumption was inhibited by sRAGE treatment in WT mice. Moreover, in a mouse model of brain ischemia–reperfusion injury based on middle cerebral arterial occlusion, C5b-9 complexes were deposited on vessels where HMGB1 was accumulated, an effect that was suppressed upon HMGB1 neutralization. We propose that the HMGB1 released after cell necrosis and in ischemic condition can trigger the classical pathway of complement activation to exacerbate sterile inflammation

Data_Sheet_1.PDF

<p>High-mobility group box 1 (HMGB1), a well-known danger-associated molecular pattern molecule, acts as a pro-inflammatory molecule when secreted by activated immune cells or released after necrotic cell damage. HMGB1 binds to immunogenic bacterial components and augments septic inflammation. In this study, we show how HMGB1 mediates complement activation, promoting sterile inflammation. We show that HMGB1 activates the classical pathway of complement system in an antibody-independent manner after binding to C1q. The C3a complement activation product in human plasma and C5b-9 membrane attack complexes on cell membrane surface are detected after the addition of HMGB1. In an acetaminophen (APAP)-induced hepatotoxicity model, APAP injection reduced HMGB1 levels and elevated C3 levels in C1q-deficient mouse serum samples, compared to that in wild-type (WT) mice. APAP-induced C3 consumption was inhibited by sRAGE treatment in WT mice. Moreover, in a mouse model of brain ischemia–reperfusion injury based on middle cerebral arterial occlusion, C5b-9 complexes were deposited on vessels where HMGB1 was accumulated, an effect that was suppressed upon HMGB1 neutralization. We propose that the HMGB1 released after cell necrosis and in ischemic condition can trigger the classical pathway of complement activation to exacerbate sterile inflammation.</p

SOCS-6 Negatively Regulates T Cell Activation through Targeting p56lck to Proteasomal Degradation*

The T cell-specific tyrosine kinase, p56lck, plays crucial roles in T cell receptor (TCR)-mediated T cell activation. Here, we report that SOCS-6 (suppressor of cytokine signaling-6) is a negative regulator of p56lck. SOCS-6 was identified as a protein binding to the kinase domain of p56lck through yeast two-hybrid screening. SOCS-6 bound specifically to p56lck (F505), which mimics the active form of p56lck, but not to wild type p56lck. In Jurkat T cells, SOCS-6 binding to p56lck was detected 1–2 h after TCR stimulation. Confocal microscopy showed that upon APC-T cell conjugation, SOCS-6 was recruited to the immunological synapse and colocalized with the active form of p56lck. SOCS-6 promoted p56lck ubiquitination and its subsequent targeting to the proteasome. Moreover, SOCS-6 overexpression led to repression of TCR-dependent interleukin-2 promoter activity. These results establish that SOCS-6 acts as a negative regulator of T cell activation by promoting ubiquitin-dependent proteolysis