STAT3 Regulates Monocyte TNF-Alpha Production in Systemic Inflammation Caused by Cardiac Surgery with Cardiopulmonary Bypass

BACKGROUND: Cardiopulmonary bypass (CPB) surgery initiates a controlled systemic inflammatory response characterized by a cytokine storm, monocytosis and transient monocyte activation. However, the responsiveness of monocytes to Toll-like receptor (TLR)-mediated activation decreases throughout the postoperative course. The purpose of this study was to identify the major signaling pathway involved in plasma-mediated inhibition of LPS-induced tumor necrosis factor (TNF)-α production by monocytes. METHODOLOGY/PRINCIPAL FINDINGS: Pediatric patients that underwent CPB-assisted surgical correction of simple congenital heart defects were enrolled (n = 38). Peripheral blood mononuclear cells (PBMC) and plasma samples were isolated at consecutive time points. Patient plasma samples were added back to monocytes obtained pre-operatively for ex vivo LPS stimulations and TNF-α and IL-6 production was measured by flow cytometry. LPS-induced p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB activation by patient plasma was assessed by Western blotting. A cell-permeable peptide inhibitor was used to block STAT3 signaling. We found that plasma samples obtained 4 h after surgery, regardless of pre-operative dexamethasone treatment, potently inhibited LPS-induced TNF-α but not IL-6 synthesis by monocytes. This was not associated with attenuation of p38 MAPK activation or IκB-α degradation. However, abrogation of the IL-10/STAT3 pathway restored LPS-induced TNF-α production in the presence of suppressive patient plasma. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that STAT3 signaling plays a crucial role in the downregulation of TNF-α synthesis by human monocytes in the course of systemic inflammation in vivo. Thus, STAT3 might be a potential molecular target for pharmacological intervention in clinical syndromes characterized by systemic inflammation

Optimal foraging and community structure: implications for a guild of generalist grassland herbivores

A particular linear programming model is constructed to predict the diets of each of 14 species of generalist herbivores at the National Bison Range, Montana. The herbivores have body masses ranging over seven orders of magnitude and belonging to two major taxa: insects and mammals. The linear programming model has three feeding constraints: digestive capacity, feeding time and energy requirements. A foraging strategy that maximizes daily energy intake agrees very well with the observed diets. Body size appears to be an underlying determinant of the foraging parameters leading to diet selection. Species that possess digestive capacity and feeding time constraints which approach each other in magnitude have the most generalized diets. The degree that the linear programming models change their diet predictions with a given percent change in parameter values (sensitivity) may reflect the observed ability of the species to vary their diets. In particular, the species which show the most diet variability are those whose diets tend to be balanced between monocots and dicots. The community-ecological parameters of herbivore body-size ranges and species number can possibly be related to foraging behavior.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47765/1/442_2004_Article_BF00377109.pd

Survey of protected vascular plants on the Oak Ridge Reservation, Oak Ridge, Tennessee

Vascular plant surveys were initiated during fiscal year 1992 by the environmentally sensitive areas program to determine the baseline condition of threatened and endangered (T&E) vascular plant species on the Oak Ridge Reservation (ORR). T&E species receive protection under federal and state regulations. In addition, the National Environmental Policy Act (NEPA) requires that federally-funded projects avoid or mitigate impacts to listed species. T&E plant species found on or near the U.S. Department of Energy`s (DOE) Oak Ridge Reservation (ORR) are identified. Twenty-eight species identified on the ORR are listed by the Tennessee Department of Environment and Conservation as either endangered, threatened, or of special concern. Four of these have been under review by the U.S. Fish and Wildlife Service for possible listing (listed in the formerly-used C2 candidate category). Additional species listed by the state occur near and may be present on the ORR. A range of habitats support the rare taxa on the ORR: river bluffs, sinkholes, calcareous barrens, wetlands, utility corridors, and forests. The list of T&E plant species and their locations on the ORR should be considered provisional because the entire ORR has not been surveyed, and state and federal status of all species continues to be updated. The purpose of this document is to present information on the listed T&E plant species currently known to occur on the ORR as well as listed species potentially occurring on the ORR based on geographic range and habitat availability. For the purpose of this report, {open_quotes}T&E species{close_quotes} include all federal- and state-listed species, including candidates for listing, and species of special concern. Consideration of T&E plant habitats is an important component of resource management and land-use planning; protection of rare species in their natural habitat is the best method of ensuring their long-term survival