Diverse roles of the Mediator complex in plants

Since its original discovery in yeast, the Mediator complex has been identified in a wide range of organisms across the eukaryotic kingdom. Despite being experimentally purified from a number of fungal and metazoan organisms, it was not until 2007, thirteen years after its initial discovery, that the Mediator complex was successfully isolated from plants. With a number of papers now beginning to emerge on the plant Mediator complex, this review aims to provide an overview of the diverse functions that have been identified for individual plant Mediator subunits. In addition to demonstrating roles in plant development, flowering, hormone signaling and biotic and abiotic stress tolerance; recent findings have revealed novel functions for plant Mediator subunits, including mRNA, miRNA and rRNA processing, as well as controlling DNA and protein stability. These diverse activities have expanded the known functions of the Mediator complex and demonstrate a variety of new insights that have been gained from investigations into the plant Mediator complex. Future directions for research into this multi-functional protein complex will be discussed.

A truncated fragment of Src protein kinase generated by calpain-mediated cleavage is a mediator of neuronal death in excitotoxicity

Excitotoxicity resulting from overstimulation of glutamate receptors is a major cause of neuronal death in cerebral ischemic stroke. The overstimulated ionotropic glutamate receptors exert their neurotoxic effects in part by overactivation of calpains, which induce neuronal death by catalyzing limited proteolysis of specific cellular proteins. Here, we report that in cultured cortical neurons and in vivo in a rat model of focal ischemic stroke, the tyrosine kinase Src is cleaved by calpains at a site in the N-terminal unique domain. This generates a truncated Src fragment of ?52 kDa, which we localized predominantly to the cytosol. A cell membrane-permeable fusion peptide derived from the unique domain of Src prevents calpain from cleaving Src in neurons and protects against excitotoxic neuronal death. To explore the role of the truncated Src fragment in neuronal death, we expressed a recombinant truncated Src fragment in cultured neurons and examined how it affects neuronal survival. Expression of this fragment, which lacks the myristoylation motif and unique domain, was sufficient to induce neuronal death. Furthermore, inactivation of the prosurvival kinase Akt is a key step in its neurotoxic signaling pathway. Because Src maintains neuronal survival, our results implicate calpain cleavage as a molecular switch converting Src from a promoter of cell survival to a mediator of neuronal death in excitotoxicity. Besides unveiling a new pathological action of Src, our discovery of the neurotoxic action of the truncated Src fragment suggests new therapeutic strategies with the potential to minimize brain damage in ischemic stroke.

Multipoint haptic mediator interface for robotic teleoperation

Despite recent advances in artificial intelligence and autonomous robotics, teleoperation can provide distinct benefits in applications requiring real-time human judgement and intuition. However, as robotic systems are increasingly becoming sophisticated and are performing more complex tasks, realizing these benefits requires new approaches to teleoperation. This paper introduces a novel haptic mediator interface for teleoperating mobile robotic platforms that have a variety of manipulators and functions. Identical master-slave bilateral teleoperation of the robotic manipulators is achieved by representing them in virtual reality and by allowing the operator to interact with them using a multipoint haptic device. The operator is also able to command motions to the mobile platform by using a novel haptic interaction metaphor rather than a separate dedicated input device. The presented interaction techniques enable the operator to perform a wide range of control functions and achieve functionality similar to that of conventional teleoperation schemes that use a single haptic interface. The mediator interface is presented, and important considerations such as workspace mapping and scaling are discussed. © 2015 IEEE.

Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment

Classical proinflammatory eicosanoids, and more recently discovered lipid mediators with anti-inflammatory and proresolving bioactivity, exert a complex role in the initiation, control, and resolution of inflammation. Using a targeted lipidomics approach, we investigated circulating lipid mediator responses to resistance exercise and treatment with the NSAID ibuprofen. Human subjects undertook a single bout of unaccustomed resistance exercise (80% of one repetition maximum) following oral ingestion of ibuprofen (400 mg) or placebo control. Venous blood was collected during early recovery (0–3 h and 24 h postexercise), and serum lipid mediator composition was analyzed by LC-MS-based targeted lipidomics. Postexercise recovery was characterized by elevated levels of cyclooxygenase (COX)-1 and 2-derived prostanoids (TXB2, PGE2, PGD2, PGF2α, and PGI2), lipooxygenase (5-LOX, 12-LOX, and 15-LOX)-derived hydroxyeicosatetraenoic acids (HETEs), and leukotrienes (e.g., LTB4), and epoxygenase (CYP)-derived epoxy/dihydroxy eicosatrienoic acids (EpETrEs/DiHETrEs). Additionally, we detected elevated levels of bioactive lipid mediators with anti-inflammatory and proresolving properties, including arachidonic acid-derived lipoxins (LXA4 and LXB4), and the EPA (E-series) and DHA (D-series)-derived resolvins (RvD1 and RvE1), and protectins (PD1 isomer 10S, 17S-diHDoHE). Ibuprofen treatment blocked exercise-induced increases in COX-1 and COX-2-derived prostanoids but also resulted in off-target reductions in leukotriene biosynthesis, and a diminished proresolving lipid mediator response. CYP pathway product metabolism was also altered by ibuprofen treatment, as indicated by elevated postexercise serum 5,6-DiHETrE and 8,9-DiHETrE only in those receiving ibuprofen. These findings characterize the blood inflammatory lipid mediator response to unaccustomed resistance exercise in humans and show that acute proinflammatory signals are mechanistically linked to the induction of a biological active inflammatory resolution program, regulated by proresolving lipid mediators during postexercise recovery.

Internalization as a mediator of the relationship between conformity to masculine norms and body image attitudes and behaviors among young men in Sweden, US, UK, and Australia

We examined whether internalization of sociocultural body ideals mediated the relationship between conformity to masculine norms and drive for muscularity, leanness, and thinness in a sample of males from Sweden, US, UK, and Australia. Over six hundred young men [n=142 (Sweden); n=192 (US); n=141 (UK); n=160 (Australia)] completed an online survey that included assessments of masculine role norms, body image, and internalization of sociocultural body ideals. Path analyses confirmed internalization as a mediator between greater conformity to masculine norms and body image measures (drive for thinness, desire for leanness, and desire for muscularity) across the sample. However, significant cross-country differences in the strength of these mediation effects were found. Mediation effects among US, Australian, and Swedish males were comparable, whereas these effects were weaker in the UK sample. Findings confirmed the importance of internalization of sociocultural body ideals in the tested models.

Role of protease-activated receptor-2 in inflammation, and its possible implications as a putative mediator of periodontitis

Proteinase-activated receptor-2 (PAR2) belongs to a novel subfamily of G-protein-coupled receptors with seven-transmembrane domains. This receptor is widely distributed throughout the body and seems to be importantly involved in inflammatory processes. PAR2 can be activated by serine proteases such as trypsin, mast cell tryptase, and bacterial proteases, such as gingipain produced by Porphyromonas gingivalis. This review describes the current stage of knowledge of the possible mechanisms that link PAR2 activation with periodontal disease, and proposes future therapeutic strategies to modulate the host response in the treatment of periodontitis.

Apoptosis as a mediator of hyperplastic recovery in human prostate lesions: cytochemical and immunocytochemical evaluation

The present study was carried out to investigate the occurrence of apoptosis in human prostatic lesions with emphasis on nodular hyperplasia and adenocarcinomas, using cytochemistry and immunocytochemistry. The results showed that apoptosis is a common event on nodular hyperplasia but not in adenocarcinomas. This led to the hypothesis that apoptosis may represent an important factor on the localized recovery response of the hyperplastic acini.

Recombinant disintegrin targets alpha(v) beta(3) integrin and leads to mediator production

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Citral and eugenol modulate DNA damage and pro-inflammatory mediator genes in murine peritoneal macrophages

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Pollination of Anemopaegma album (Bignoniaceae) with focus on floral nectar as the mediator of interactions with mutualistic and antagonistic bees

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)