Increasing the spatial and temporal impact of ecological research: A roadmap for integrating a novel terrestrial process into an Earth system model.

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.

Proteomic profile of reversible protein oxidation using PROP, purification of reversibly oxidized proteins.

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.

Purification of reversibly oxidized proteins (PROP) reveals a redox switch controlling p38 MAP kinase activity.

Oxidation of cysteine residues of proteins is emerging as an important means of regulation of signal transduction, particularly of protein kinase function. Tools to detect and quantify cysteine oxidation of proteins have been a limiting factor in understanding the role of cysteine oxidation in signal transduction. As an example, the p38 MAP kinase is activated by several stress-related stimuli that are often accompanied by in vitro generation of hydrogen peroxide.

Nutrient isothiocyanates covalently modify and inhibit the inflammatory cytokine macrophage migration inhibitory factor (MIF).

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.

The isothiocyanate class of bioactive nutrients covalently inhibit the MEKK1 protein kinase.

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.

Methadone and heroin antinociception: predominant delta-opioid-receptor responses in methadone-tolerant mice.

Antinociceptive tail flick responses to heroin and 6-monoacetylmorphine mediated in the brain by mu-opioid receptor are switched by morphine pellet implantation to delta1- and delta2-opioid-receptors mediation, respectively. Present results showed that the mu-receptor response (inhibited by beta-funaltrexamine) to methadone was changed by morphine pellet implantation to delta1 (inhibited by 7-benzylidenenaltrexone)- and delta2 (inhibited by naltriben)-opioid-receptor responses. Methadone pellet implantation likewise changed mediation from mu- to delta-opioid receptors for heroin and methadone but not for morphine (beta-funaltrexamine continued to inhibit).

Nociceptin and dynorphin A(1-17) produce antianalgesia through independent systems in mice.

The administration of dynorphin A(1-17), Dyn, intrathecally (i.t.) or of nociceptin, intracerebroventricularly (i.

Confluence of antianalgesic action of diverse agents through brain interleukin(1beta) in mice.

Spinal dynorphin A(1-17) (Dyn) has been shown previously to produce an antianalgesic action against intrathecal morphine in the tail-flick test in CD-1 mice. This action is known to be mediated indirectly from the spinal cord through an afferent pathway that activates flumazenil-sensitive benzodiazepine receptors in the brain and a descending circuit back down to the spinal cord sequentially involving cholecystokinin, leu-enkephalin, and N-methyl-D-aspartate receptors to produce antianalgesia. Interleukin (IL)-1beta is also known to act on peripheral afferent nerves to the brain to activate a descending circuit to release spinal cholecystokinin.

Inverse agonist action of Leu-enkephalin at delta(2)-opioid receptors mediates spinal antianalgesia.

Dynorphin A(1-17) given intrathecally releases spinal cholecystokinin to produce an antianalgesic action against spinal morphine in the tail-flick test in CD-1 mice. The present study showed that following the cholecystokinin step, a delta(2)-opioid inverse agonist action of Leu-enkephalin (LE), was involved. Pretreatment with intrathecal LE antiserum eliminated dynorphin and cholecystokinin-8s antianalgesia.

Antianalgesic action of nociceptin originating in the brain is mediated by spinal prostaglandin E(2) in mice.

An antianalgesic action of intracerebroventricularly administered nociceptin was elicited against intrathecal morphine-induced antinociception in the tail-flick test in mice and investigated as a descending neuronal system for the spinal mediator involved. The nociceptin-induced antianalgesia originating in the brain was inhibited by intrathecally administered indomethacin and suggested the mediation of spinal prostaglandin. The antianalgesic action of intracerebroventricular nociceptin was closely matched by intrathecal prostaglandin (PG) E(2).

Acute cross-tolerance to opioids in heroin delta-opioid-responding Swiss Webster mice.

It is generally thought that the mu receptor actions of metabolites, 6-monoacetylmorphine (6MAM) and morphine, account for the pharmacological actions of heroin. However, upon intracerebroventricular (i.c.

Morphine tolerance in mice changes response of heroin from mu to delta opioid receptors.

Heroin produced antinociception in the tail flick test through mu receptors in the brain of ICR and CD-1 mice, a response inhibited by 3-O-methylnaltrexone. Tolerance to morphine was produced by subcutaneous morphine pellet implantation. By the third day, the heroin response was produced through delta opioid receptors.

Supraspinal neurotensin-induced antianalgesia in mice is mediated by spinal cholecystokinin.

Intracerebral injection of neurotensin into specific brain loci in rats produces hyperalgesia due to the release of cholecystokinin (CCK) in the spinal cord. The present purpose was to show in another species that neurotensin can antagonize the antinociceptive action of morphine through the spinal CCK mechanism in mice. Neurotensin given intracerebroventricularly (i.

Antianalgesic action of dynorphin A mediated by spinal cholecystokinin.

Previous work indicates that the antianalgesic action of pentobarbital and neurotensin administered intracerebroventricularly in mice arises from activation of a descending system to release cholecystokinin (CCK) in the spinal cord where CCK is known to antagonize morphine analgesia. Spinal dynorphin, like CCK, has an antianalgesic action against intrathecally administered morphine. This dynorphin action is indirect; even though it is initiated in the spinal cord, it requires the involvement of an ascending pathway to the brain and a descending pathway to the spinal cord where an antianalgesic mediator works.

Heroin antinociception changed from mu to delta receptor in streptozotocin-treated mice.

CD-1 mice were treated intravenously with streptozotocin, 200 mg/kg, and tested 2 weeks later or treated with 60 mg/kg and tested 3 days later. Both treatments changed the tail flick response of heroin and 6-monoacetylmorphine (6 MAM) given intracerebroventricularly from a mu- to delta-opioid receptor-mediated action as determined by differential effects of opioid receptor antagonists. The response to morphine remained mu.

Opioid receptor selectivity of heroin given intracerebroventricularly differs in six strains of inbred mice.

Heroin administered i.c.v.

Heroin acts on delta opioid receptors in the brain of streptozocin-induced diabetic rats.

Heroin, like morphine, given intracerebroventricularly produces analgesia by acting on mu opioid receptors in most mice. In contrast, in Swiss Webster mice, heroin has the unusual property of acting on brain delta opioid receptors whereas morphine still acts on mu receptors. The literature indicates that in diabetic mice and rats, the mu agonist potency of morphine is diminished while that to a delta receptor agonist is enhanced.

Supraspinal flumazenil inhibits the antianalgesic action of spinal dynorphin A (1-17).

DynorphinA (Dyn) administered intrathecally or released spinally in mice produces antianalgesia, that is, antagonizes morphine analgesia (tail-flick test). Spinal transection eliminates this Dyn antianalgesia. Present results in mice show that intracerebroventricular administration of flumazenil, a benzodiazepine receptor antagonist, also eliminated the antianalgesic action of Dyn; flumazenil in the brain eliminated the suppressant effect of intrathecal Dyn on intrathecal and intracerebroventricular morphine-induced antinociception.

Pentobarbital antagonism of morphine analgesia mediated by spinal cholecystokinin.

Pentobarbital administered intracerebroventricularly to mice has been shown previously to inhibit the analgesic action of morphine given intrathecally. The purpose of the present study was to examine the proposal that this antianalgesic action was mediated spinally by cholecystokinin. First, intrathecal coadministration of cholecystokinin-B sulfate (CCK8s) with morphine inhibited the analgesic action of morphine in the mouse tail-flick test.

Cloning and analysis of an actin-encoding cDNA from the dimorphic pathogenic fungus Histoplasma capsulatum.

We have cloned an actin-encoding cDNA from the dimorphic fungus Histoplasma capsulatum, an important pathogen of humans. The predicted amino acid sequence as well as the general codon pattern of Histoplasma actin revealed the highest degree of similarity to the actin of the filamentous ascomycete Aspergillus nidulans. Southern blot analysis determined that actin was encoded by a single copy in the Histoplasma genome.

Spinal delta opioid receptor subtype activity of 6-monoacetylmorphine in Swiss Webster mice.

Heroin and 6-monoacetylmorphine (6MAM) given intracerebroventricularly in Swiss Webster mice, act on supraspinal delta (delta) opioid receptors to produce antinociception in the tail flick test. More specifically, this action of heroin involves delta 1 and 6MAM involves delta 2 opioid receptors. Even though 6MAM given intrathecally (IT) in Swiss Webster mice also activates delta receptors to produce antinociception, the subtype of delta receptor in the spinal cord is not known.

Isolation and characterization of a calmodulin-encoding cDNA from the pathogenic fungus Histoplasma capsulatum.

We describe in this paper the isolation and complete sequence of a calmodulin (CaM) encoding cDNA from the dimorphic pathogenic fungus Histoplasma capsulatum (GenBank accession U12505). The deduced amino acid sequence was identical to the CaM of Aspergillus nidulans and had only one amino acid difference from the CaM of Neurospora crassa. Saccharomyces cerevisiae CaM, however, has only about 60% amino acid identity compared with H.

Supraspinal delta 2 opioid agonist analgesia in Swiss-Webster mice involves spinal GABAA receptors.

The tail-flick response is a spinal reflex that can be modulated by administration of antinociceptive agents supraspinally through activation of descending systems and involvement of the action of neurotransmitters in the spinal cord. Descending noradrenergic and serotonergic systems are involved in morphine (and other mu opioid receptor agonists)-induced antinociception. These descending systems, however, are not involved in supraspinal delta opioid receptor agonist-induced antinociception.

Spinal GABA receptors mediate brain delta opioid analgesia in Swiss Webster mice.

Morphine and heroin act on supraspinal mu-opioid receptors in ICR mice to activate descending noradrenergic and serotonergic systems to inhibit the tail flick response. Antinociception induced by supraspinal [D-Pen2,5]-enkephalin (DPDPE, delta agonist) involves a descending system mediated by spinal gamma-aminobutyric acid, GABAA and GABAB, receptors. Because in Swiss Webster mice the receptor selectivity of heroin changes to delta whereas morphine remains mu, the purpose of the present study was to determine whether this delta action of heroin was mediated spinally by GABAA and GABAB receptors.