What state of the world are we in? Targeted monitoring to detect transitions in vegetation restoration projects.

Monitoring vegetation restoration is challenging because monitoring is costly, requires long-term funding, and involves monitoring multiple vegetation variables that are often not linked back to learning about progress toward objectives. There is a clear need for the development of targeted monitoring programs that focus on a reduced set of variables that are tied to specific restoration objectives. In this paper, we present a method to progress the development of a targeted monitoring program, using a pre-existing state-and-transition model. We (1) use field data to validate an expert-derived classification of woodland vegetation states; (2) use these data to identify which variable(s) help differentiate woodland states; and (3) identify the target threshold (for the variable) that signifies if the desired transition has been achieved. The measured vegetation variables from each site in this study were good predictors of the different states. We show that by measuring only a few of these variables, it is possible to assign the vegetation state for a collection of sites, and monitor if and when a transition to another state has occurred. For this ecosystem and state-and-transition models, out of nine vegetation variables considered, the density of immature trees and percentage of exotic understory vegetation cover were the variables most frequently specified as effective to define a threshold or transition. We synthesize findings by presenting a decision tree that provides practical guidance for the development of targeted monitoring strategies for woodland vegetation.

A novel thiol oxidation-based mechanism for adriamycin-induced cell injury in human macrophages.

Adriamycin is a widely used antitumor antibiotic, but its use has been limited by its cytotoxicity in both cardiomyocytes and non-cardiac tissues. While adriamycin's ability to redox cycle via one-electron transfer reactions and generate ROS is thought to promote cardiotoxicity, the mechanisms involved in non-cardiac tissue injury are not clear. Here we show that prolonged exposure (48 h) of human monocyte-derived macrophages to adriamycin at concentrations as low as 1 microM promotes caspase-independent cell death. Treatment of cells with scavengers of superoxide and peroxyl radicals blocked adriamycin-induced oxidation of dichlorodihydrofluorescein (DCFH) but did not prevent macrophage injury. Macrophages treated with either adriamycin or the thiol oxidant diamide showed elevated levels of glutathione disulfide and increased protein-S-glutathionylation prior to cell injury, indicating that thiol oxidation is involved in adriamycin-induced macrophage death. Furthermore, inhibition of glutathione reductase (GR) with 1,3-bis[2-chloroethyl]-1-nitrosourea or transfection of macrophages with small inhibitory RNA (siRNA) directed against GR or glutaredoxin (Grx) potentiated adriamycin-induced macrophage injury. Thus, both GR and Grx appear to play a crucial role in protecting macrophages from adriamycin-induced cell injury. These findings suggest a new mechanism for adriamycin-induced tissue injury whereby thiol oxidation, rather than one-electron redox cycling and ROS generation, mediates adriamycin-induced cell damage.

Oxidized LDL promotes peroxide-mediated mitochondrial dysfunction and cell death in human macrophages: a caspase-3-independent pathway.

Several studies suggest that macrophage death and subsequent lysis contribute to the development of advanced atherosclerotic lesions. Although oxidized LDL (OxLDL) is thought to contribute to lesion formation and induces macrophage apoptosis, the mechanisms underlying macrophage lysis have not been well defined. To determine if induction of apoptosis in human macrophages also promotes cell lysis, we studied caspase-3 activation by OxLDL and activating anti-Fas antibodies. We found that Fas-induced activation of caspase-3 does not promote macrophage lysis and caspase-3 activation is not required for OxLDL-induced macrophage lysis. OxLDL induces the formation of peroxides, but not superoxide, and decreases mitochondrial membrane potential. Scavengers of peroxyl radicals restore mitochondrial membrane potential and prevent macrophage lysis, implicating peroxyl radicals in both mitochondrial dysfunction and macrophage lysis induced by OxLDL. We conclude that macrophage death induced by OxLDL results in cell lysis, but it does not require activation of Fas or caspase-3. The full text of this article is available at http://www.circresaha.org.

Lipoprotein aggregation protects human monocyte-derived macrophages from OxLDL-induced cytotoxicity.

Oxidative modifications render low density lipoprotein cytotoxic and enhance its propensity to aggregate and fuse into particles similar to those found in atherosclerotic lesions. We showed previously that aggregation of oxidized LDL (OxLDL) promotes the transformation of human macrophages into lipid-laden foam cells (Asmis, R., and J. Jelk. 2000. Large variations in human foam cell formation in individuals. A fully autologous in vitro assay based on the quantitative analysis of cellular neutral lipids. Atherosclerosis. 148: 243-253). Here, we tested the hypothesis that aggregation of OxLDL enhances its clearance by human macrophages and thus may protect macrophages from OxLDL-induced cytotoxicity. We found that increased aggregation of OxLDL correlated with decreased macrophage injury. Using 3H-labeled and Alexa546-labeled OxLDL, we found that aggregation enhanced OxLDL uptake and increased cholesteryl ester accumulation but did not alter free cholesterol levels in macrophages. Acetylated LDL was a potent competitor of aggregated oxidized LDL (AggOxLDL) uptake, suggesting that scavenger receptor A plays an important role in the clearance of AggOxLDL. Inhibitors of actin polymerization, cytochalasin B, cytochalasin D, and latrunculin A, also prevented AggOxLDL uptake and restored OxLDL-induced cytotoxicity. This suggests that OxLDL-induced macrophage injury does not require OxLDL uptake and may occur on the cell surface. Our data demonstrate that aggregation of cytotoxic OxLDL enhances its clearance by macrophages without damage to the cells, thus allowing macrophages to avoid OxLDL-induced cell injury.