ADAM10 Cell Surface Expression but Not Activity Is Critical for Staphylococcus aureus α-Hemolysin-Mediated Activation of the NLRP3 Inflammasome in Human Monocytes

The Staphylococcus aureus toxin, α-hemolysin, is an important and well-studied virulence factor in staphylococcal infection. It is a soluble monomeric protein that, once secreted by the bacterium, forms a heptameric pore in the membrane of a broad range of host cell types. Hemolysin was recently discovered to bind and activate a disintegrin and metalloprotease 10 (ADAM10). In epithelial and endothelial cells, ADAM10 activation is required for the toxin’s activity against these cells. In host monocytic cells, α-hemolysin activates the nucleotide-binding domain and leucine-rich repeat containing gene family, pyrin domain containing 3 (NLRP3) inflammasome leading to production of pro-inflammatory cytokines and cell death. We now show that ADAM10 is critical for α-hemolysin-mediated activation of the NLRP3 inflammasome in human monocytes as siRNA knockdown or chemical blockade of ADAM10-α-hemolysin interaction leads to diminished inflammasome activation and cell death by reducing the available ADAM10 on the cell surface. Unlike epithelial cell and endothelial cell damage, which requires α-hemolysin induced ADAM10 activation, ADAM10 protease activity was not required for NLRP3 inflammasome activation. This work confirms the importance of ADAM10 in immune activation by α-hemolysin, but indicates that host cell signal induction by the toxin is different between host cell types

Perioperative Management of Patients Undergoing Total Pancreatectomy with/without Islet Cell Autotransplantation: A Single Center Experience

Total pancreatectomy (TP) and islet cell autotransplantation (IAT) are complex operations that require intensive postoperative monitoring with standardized protocols. There are few studies detailing immediate perioperative management. The purpose of this study was to describe the perioperative management of post-pancreatectomy patients in the first week following surgery to guide clinicians in addressing salient points from different organ systems. This is a retrospective cohort review of prospectively collected data from September 2017 to September 2022 at a single institution, including patients 16 years and older who underwent TP or TPIAT for chronic pancreatitis. Patients were maintained on a heparin drip (TPIAT), insulin drip, and ketamine infusion. Primary outcomes were complications in the first 5 days following surgery and ICU length of stay (LOS). Secondary outcomes included overall LOS and mortality. Of 31 patients, 26 underwent TPIAT, and 5 underwent TP. Median ICU LOS was five days (IQR 4–6). The most common immediate postoperative complications were reintubation [n = 5 (16%)] and bleeding [n = 2 (6%)]. Median insulin drip use was 70 h (IQR 20–124). There was no mortality. Patients were extubated quickly and progressed well on the protocol. Immediate postoperative complications were generally minor and without long-term effects

Pollen percentages, Charcoal flux, Mg/Ca-based SST and Benthic foraminiferal δ18O records of site GeoB16602

Vegetation dynamics during previous warm interglacial periods shed light on the human impacts on natural ecosystems during the Holocene. However, reliable terrestrial records that span such periods are rare and provide little information on regional scale. Here we present a high-resolution marine pollen record from the northern South China Sea, which reveals that during five peak interglacial periods, Marine Isotope Stages 13a, 11c, 9c, 5e and 1 (the Holocene), the vegetation successions in southern China were similar. At the beginning of each interglacial period, tropical rainforest conifers, which include Dacrydium, Dacrycarpus and Podocarpus, and associated broadleaved taxa, such as Altingia, expanded quickly at the expense of the subtropical/temperate montane conifer Pinus. Near the end of the warm periods, Pinus recovered and the tropical taxa retreated. However, the Holocene displays subtle but significant differences in which the species turnover was interrupted and the rainforest conifers did not fully expanded. The Mg/Ca-based sea surface temperature record from the same site reveals that temperature was the major control of the rise and fall of the peak interglacial vegetation. However, exceptionally high charcoal fluxes during the Holocene suggest that human activities through land-use modifications completely, and possibly permanently, altered the natural vegetation trend five to six thousand years ago

Pollen and spore percentage data of composite sediment core GeoB16602 over the past 140 kyr

Cores of marine site GeoB16602 (18.95°N, 113.71°E, water depth, 953 m) were recovered during the 2012 RV SONNE cruise SO-221 “INVERS”, northern South China Sea. Pollen samples were processed via standard hydrochloric-hydrofluoric acid procedure. Pollen and spore percentages were calculated based on the pollen sum (>300 grains per sample) and spore sum (>100 grains) respectively. The data set cover the whole last glacial cycle (140 kyr) with an average temporal resolution of ~600 years, revealing vegetation evolution history of the Pearl River catchment area in southern China. In general, the results reveal three different evolution patterns of vegetation at the tropical-subtropical flora ecotone: the zonal forest exhibited a clear glacial-interglacial cycle and weak response to stadial cooling; the fern communities exhibited similar glacial-interglacial variations but more sensitivity to low-amplitude temperature fluctuations; the glacial-interglacial trend in coastal wetland vegetation was ambiguous whereas a series of millennial-scale expansion events were closely related with sea-level rises

ADAM10 Cell Surface Expression but Not Activity Is Critical for Staphylococcus aureus α-Hemolysin-Mediated Activation of the NLRP3 Inflammasome in Human Monocytes

The Staphylococcus aureus toxin, α-hemolysin, is an important and well-studied virulence factor in staphylococcal infection. It is a soluble monomeric protein that, once secreted by the bacterium, forms a heptameric pore in the membrane of a broad range of host cell types. Hemolysin was recently discovered to bind and activate a disintegrin and metalloprotease 10 (ADAM10). In epithelial and endothelial cells, ADAM10 activation is required for the toxin’s activity against these cells. In host monocytic cells, α-hemolysin activates the nucleotide-binding domain and leucine-rich repeat containing gene family, pyrin domain containing 3 (NLRP3) inflammasome leading to production of pro-inflammatory cytokines and cell death. We now show that ADAM10 is critical for α-hemolysin-mediated activation of the NLRP3 inflammasome in human monocytes as siRNA knockdown or chemical blockade of ADAM10-α-hemolysin interaction leads to diminished inflammasome activation and cell death by reducing the available ADAM10 on the cell surface. Unlike epithelial cell and endothelial cell damage, which requires α-hemolysin induced ADAM10 activation, ADAM10 protease activity was not required for NLRP3 inflammasome activation. This work confirms the importance of ADAM10 in immune activation by α-hemolysin, but indicates that host cell signal induction by the toxin is different between host cell types