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Glob Chang Biol ; 28(2): 665-684, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34543495


Terrestrial ecosystems regulate Earth's climate through water, energy, and biogeochemical transformations. Despite a key role in regulating the Earth system, terrestrial ecology has historically been underrepresented in the Earth system models (ESMs) that are used to understand and project global environmental change. Ecology and Earth system modeling must be integrated for scientists to fully comprehend the role of ecological systems in driving and responding to global change. Ecological insights can improve ESM realism and reduce process uncertainty, while ESMs offer ecologists an opportunity to broadly test ecological theory and increase the impact of their work by scaling concepts through time and space. Despite this mutualism, meaningfully integrating the two remains a persistent challenge, in part because of logistical obstacles in translating processes into mathematical formulas and identifying ways to integrate new theories and code into large, complex model structures. To help overcome this interdisciplinary challenge, we present a framework consisting of a series of interconnected stages for integrating a new ecological process or insight into an ESM. First, we highlight the multiple ways that ecological observations and modeling iteratively strengthen one another, dispelling the illusion that the ecologist's role ends with initial provision of data. Second, we show that many valuable insights, products, and theoretical developments are produced through sustained interdisciplinary collaborations between empiricists and modelers, regardless of eventual inclusion of a process in an ESM. Finally, we provide concrete actions and resources to facilitate learning and collaboration at every stage of data-model integration. This framework will create synergies that will transform our understanding of ecology within the Earth system, ultimately improving our understanding of global environmental change, and broadening the impact of ecological research.

Planeta Tierra , Ecosistema , Ecología , Incertidumbre , Agua
PLoS One ; 7(2): e32527, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22389707


Signal transduction pathways that are modulated by thiol oxidation events are beginning to be uncovered, but these discoveries are limited by the availability of relatively few analytical methods to examine protein oxidation compared to other signaling events such as protein phosphorylation. We report here the coupling of PROP, a method to purify reversibly oxidized proteins, with the proteomic identification of the purified mixture using mass spectrometry. A gene ontology (GO), KEGG enrichment and Wikipathways analysis of the identified proteins indicated a significant enrichment in proteins associated with both translation and mRNA splicing. This methodology also enabled the identification of some of the specific cysteine residue targets within identified proteins that are reversibly oxidized by hydrogen peroxide treatment of intact cells. From these identifications, we determined a potential consensus sequence motif associated with oxidized cysteine residues. Furthermore, because we identified proteins and specific sites of oxidation from both abundant proteins and from far less abundant signaling proteins (e.g. hepatoma derived growth factor, prostaglandin E synthase 3), the results suggest that the PROP procedure was efficient. Thus, this PROP-proteomics methodology offers a sensitive means to identify biologically relevant redox signaling events that occur within intact cells.

Proteínas/metabolismo , Proteómica/métodos , Células HeLa , Humanos , Espectrometría de Masas , Oxidación-Reducción , Proteínas/química
Biochem J ; 423(3): 315-21, 2009 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-19723024


Dietary ITCs (isothiocyanates) prevent cancer and show other bioactivities in vivo. As electrophiles, ITCs may covalently modify cellular proteins. Using a novel proteomics screen, we identified MIF (macrophage migration inhibitory factor) as the principal target of nutrient ITCs in intact cells. ITCs covalently modify the N-terminal proline residue of MIF and extinguish its catalytic tautomerase activity. MIF deficiency does not prevent induction of Phase 2 gene expression, a hallmark of many cancer chemopreventives, including ITCs. Due to the emerging role of MIF in the control of malignant cell growth and its clear involvement in inflammation, inhibition of MIF by nutrient ITCs suggests therapeutic strategies for inflammatory diseases and cancer.

Oxidorreductasas Intramoleculares/metabolismo , Isotiocianatos/metabolismo , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Procesamiento Proteico-Postraduccional , Células HeLa , Humanos , Inflamación/genética , Inflamación/metabolismo , Oxidorreductasas Intramoleculares/genética , Factores Inhibidores de la Migración de Macrófagos/genética , Neoplasias/genética , Neoplasias/metabolismo
BMC Cancer ; 7: 183, 2007 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-17894894


BACKGROUND: Dietary isothiocyanates (ITCs) are electrophilic compounds that have diverse biological activities including induction of apoptosis and effects on cell cycle. They protect against experimental carcinogenesis in animals, an activity believed to result from the transcriptional induction of "Phase 2" enzymes. The molecular mechanism of action of ITCs is unknown. Since ITCs are electrophiles capable of reacting with sulfhydryl groups on amino acids, we hypothesized that ITCs induce their biological effects through covalent modification of proteins, leading to changes in cell regulatory events. We previously demonstrated that stress-signaling kinase pathways are inhibited by other electrophilic compounds such as menadione. We therefore tested the effects of nutritional ITCs on MEKK1, an upstream regulator of the SAPK/JNK signal transduction pathway. METHODS: The activity of MEKK1 expressed in cells was monitored using in vitro kinase assays to measure changes in catalytic activity. The activity of endogenous MEKK1, immunopurified from ITC treated and untreated LnCAP cells was also measured by in vitro kinase assay. A novel labeling and affinity reagent for detection of protein modification by ITCs was synthesized and used in competition assays to monitor direct modification of MEKK1 by ITC. Finally, immunoblots with phospho-specific antibodies were used to measure the activity of MAPK protein kinases. RESULTS: ITCs inhibited the MEKK1 protein kinase in a manner dependent on a specific cysteine residue in the ATP binding pocket. Inhibition of MEKK1 catalytic activity was due to direct, covalent and irreversible modification of the MEKK1 protein itself. In addition, ITCs inhibited the catalytic activity of endogenous MEKK1. This correlated with inhibition of the downstream target of MEKK1 activity, i.e. the SAPK/JNK kinase. This inhibition was specific to SAPK, as parallel MAPK pathways were unaffected. CONCLUSION: These results demonstrate that MEKK1 is directly modified and inhibited by ITCs, and that this correlates with inhibition of downstream activation of SAPK. These results support the conclusion that ITCs may carry out many of their actions by directly targeting important cell regulatory proteins.

Alimentos , Isotiocianatos/farmacología , Quinasa 1 de Quinasa de Quinasa MAP/antagonistas & inhibidores , Quinasa 1 de Quinasa de Quinasa MAP/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Células HeLa , Humanos , Isotiocianatos/metabolismo , Inhibidores de Proteínas Quinasas/metabolismo