Search results for "agonism"
showing 10 items of 79 documents
Susceptibility of Grapholita molesta (Busck, 1916) to formulations of Bacillus thuringiensis, individual toxins and their mixtures.
2016
The Oriental fruit moth, Grapholita molesta (Lepidoptera: Tortricidae), is a major pest of fruit trees worldwide, such as peach and apple. Bacillus thuringiensis has been shown to be an efficient alternative to synthetic insecticides in the control of many agricultural pests. The objective of this study was to evaluate the effectiveness of B. thuringiensis individual toxins and their mixtures for the control of G. molesta. Bioassays were performed with Cry1Aa, Cry1Ac, Cry1Ca, Vip3Aa, Vip3Af and Vip3Ca, as well as with the commercial products DiPel® and XenTari®. The most active proteins were Vip3Aa and Cry1Aa, with LC50 values of 1.8 and 7.5ng/cm2, respectively. Vip3Ca was nontoxic to this …
Biased Agonism in Drug Discovery—Is It Too Soon to Choose a Path?
2018
A single receptor can activate multiple signaling pathways that have distinct or even opposite effects on cell function. Biased agonists stabilize receptor conformations preferentially stimulating one of these pathways, and therefore allow a more targeted modulation of cell function and treatment of disease. Dedicated development of biased agonists has led to promising drug candidates in clinical development, such as the G protein-biased µ opioid receptor agonist oliceridine. However, leveraging the theoretical potential of biased agonism for drug discovery faces several challenges. Some of these challenges are technical, such as techniques for quantitative analysis of bias and development …
Desensitization of cAMP Accumulation via Human β3-Adrenoceptors Expressed in Human Embryonic Kidney Cells by Full, Partial, and Biased Agonists
2019
β3-Adrenoceptors couple not only to cAMP formation but, at least in some cell types, also to alternative signaling pathways such as phosphorylation of extracellular signal-regulated kinase (ERK). β3-Adrenoceptor agonists are used in long-term symptomatic treatment of the overactive bladder syndrome; it is only poorly understood which signaling pathway mediates the clinical response and whether it undergoes agonist-induced desensitization. Therefore, we used human embryonic kidney cells stably transfected with human β3-adrenoceptors to compare coupling of ligands with various degrees of efficacy, including biased agonists, to cAMP formation and ERK phosphorylation, particularly regarding des…
Time-kill assays of amphotericin B plus anidulafungin against Candida tropicalis biofilms formed on two different biomaterials.
2017
Purpose: To determine the fungicidal activity by time-killing assays of amphotericin B (AMB) combined with anidulafungin (ANF) against biofilms of 2 clinical isolates of Candida tropicalis and the reference strain ATCC® 750, developed on polytetrafluoroethylene (PTFE) and titanium, using the CDC Biofilm Reactor (CBR) as an in vitro model. Methods: Biofilms were developed for 24 hours on the disk surfaces and then exposed to AMB (40 mg/L), ANF (8 mg/L), alone and combined. At predetermined time points after drug exposure, biofilms were removed from the disk surface by vortexing-sonication to quantify viable biofilm cells. Results: Drug activity was dependent on strain and time. After exposur…
Binary and tertiary combination of alternariol, 3-acetyl-deoxynivalenol and 15-acetyl-deoxynivalenol on HepG2 cells: Toxic effects and evaluation of …
2016
Fungi producers of mycotoxins are able to synthesize more than one toxin. Alternariol (AOH) is one of the mycotoxins produced by several Alternaria species, the most common one being Alternaria alternata. The toxins 3-Acetyl-deoxynivalenol (3-ADON) and 15-Acetyl-deoxynivalenol (15-ADON) are acetylated forms of deoxynivalenol (DON) produced by Fusarium graminearum. In the present work it is determined and evaluated the toxic effects of binary and tertiary combination treatment of HepG2 cells with AOH, 3-ADON and 15-ADON, by using the MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide), to subsequently apply the isobologram method and elucidate if the mixtures of these m…
miR-21 antagonism abrogates Th17 tumor promoting functions in multiple myeloma
2020
Multiple myeloma (MM) is tightly dependent on inflammatory bone marrow microenvironment. IL-17 producing CD4+ T cells (Th17) sustain MM cells growth and osteoclasts-dependent bone damage. In turn, Th17 differentiation relies on inflammatory stimuli. Here, we investigated the role of miR-21 in Th17-mediated MM tumor growth and bone disease. We found that early inhibition of miR-21 in naive T cells (miR-21i-T cells) impaired Th17 differentiation in vitro and abrogated Th17-mediated MM cell proliferation and osteoclasts activity. We validated these findings in NOD/SCID-g-NULL mice, intratibially injected with miR-21i-T cells and MM cells. A Pairwise RNAseq and proteome/phosphoproteome analysis…
Diversity of root-associated fluorescent pseudomonads as affected by ferritin overexpression in tobacco
2007
A transgenic tobacco overexpressing ferritin (P6) was recently shown to accumulate more iron than the wild type (WT), leading to a reduced availability of iron in the rhizosphere and shifts in the pseudomonad community. The impact of the transgenic line on the community of fluorescent pseudomonads was assessed. The diversity of 635 isolates from rhizosphere soils, rhizoplane + root tissues, and root tissues of WT and P6, and that of 98 isolates from uncultivated soil was characterized. Their ability to grow under iron stress conditions was assessed by identifying their minimal inhibitory concentrations of 8-hydroxyquinoline for each isolate, pyoverdine diversity by isoelectrofocusing and ge…
Lotman’s semiotic theory of culture or Laclau’s political ontology?
2018
AbstractThe present article concentrates on the main discrepancies that should arise in the discussion between Lotman’s semiotics of culture and Laclau’s discursive theory of hegemony. Some significant – but still abstract – commonalities conceal fundamental disagreements which I would group around four topics. Firstly, Lotman’s semiotic method is at odds with Laclau’s ontological way of thinking. Secondly, although both Lotman and Laclau subscribe to the openness of signification, it is impossible to incorporate their accounts of this openness without loose ends. In order to substantiate this claim, I examine Lotman’s concept of “boundary” and Laclau’s concept of the “limit.” Thirdly, we s…