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Inducible genetic suppression of neuronal excitability. (1/349)Graded, reversible suppression of neuronal excitability represents a logical goal of therapy for epilepsy and intractable pain. To achieve such suppression, we have developed the means to transfer "electrical silencing" genes into neurons with sensitive control of transgene expression. An ecdysone-inducible promoter drives the expression of inwardly rectifying potassium channels in polycistronic adenoviral vectors. Infection of superior cervical ganglion neurons did not affect normal electrical activity but suppressed excitability after the induction of gene expression. These experiments demonstrate the feasibility of controlled ion channel expression after somatic gene transfer into neurons and serve as the prototype for a novel generalizable approach to modulate excitability. (+info)
Depression of synaptic efficacy in high- and low-output Drosophila neuromuscular junctions by the molting hormone (20-HE). (2/349)The molt-related steroid hormone, 20-hydroxyecdysone (20-HE), was applied to muscles 6 and 7 of third instar larval of Drosophila melanogaster neuromuscular junction preparations to examine if rapid, nongenomic responses could be observed as was shown recently to occur in crustacean neuromuscular junctions. At a dose of 10 microM, the excitatory junction potentials were reduced in amplitude within minutes. To elucidate the site of action of the hormone, focal-macropatch recordings of synaptic currents were obtained over the neuromuscular junctions. The results showed that the high-output (Is) and the low-output (Ib) motor nerve terminals, which innervate muscles 6 and 7, released fewer synaptic vesicles for each stimulation while exposed to 20-HE. Because the size and shape of synaptic currents from spontaneous releases did not change, the effects of the 20-HE are presynaptic. The rapid effects of this hormone may account in part for the quiescent behavior associated with molts among insects and crustaceans. (+info)
Induction of Sarcophaga central nervous system remodeling by 20-hydroxyecdysone in vitro. (3/349)Proliferation and apoptosis of neural cells were found to be induced simultaneously when larval brains of Sarcophaga peregrina were cultured in the presence of 20-hydroxyecdysone (20-HE) for 24 h. The locations of proliferating cells and apoptotic cells in the brain hemispheres were different. The morphology of brains exposed to 20-HE for a short period proceeded to change sequentially when culture was continued for 2 days even in the absence of 20-HE. These changes mainly consisted of enlargement of the brain hemispheres and extension of the interval between two hemispheres, which closely paralleled the morphological changes of brains that occur in the early pupal stage, suggesting that ecdysteroid alone is sufficient to induce the remodeling of the central nervous system of holometabolous insects. Synthesis of a protein with a molecular mass of 66 kDa was shown to be selectively repressed when brains were cultured in the presence of 20-HE. (+info)
Transcript titers of ecdysteroid receptor components vary between tissues and stages during Drosophila development. (4/349)In Drosophila, the ecdysteroids trigger the key regulatory cascades controlling the coordinated changes in the developmental pathway of molting and metamorphosis. Ecdysone action is mediated by a heterodimer consisting of the three ecdysone receptor (EcR) isoforms and the ultraspiracle proteins (USP). Heterodimers of these proteins bind to the ecdysone response element and ecdysone to modulate gene transcription. In this study, we developed a competitive reverse transcription polymerase chain reaction (RT-PCR) method to quantify the transcripts of functional ecdysone receptor components in individual tissues and for the whole body. The relatively small amount of variation in usp transcripts of the different tissues indicates that this gene does not perform a spatially restricted function in the late third instar wandering larvae while EcR isoforms were expressed in a more tissue-restricted pattern in the same stage. EcR-B1 was expressed at higher levels in larval tissues that are fated for histolysis, whereas EcR-A predominates in the imaginal discs. This result supports the hypothesis that a particular metamorphic response requires particular EcR isoforms. The transcript levels of the functional ecdysone receptor components fluctuate dramatically during development, suggesting that the regulations of the transcriptional and posttranscriptional levels of these genes play some role in ecdysteroid response during Drosophila development. (+info)
Control of oocyte maturation in sexually mature Drosophila females. (5/349)In many sexually mature insects egg production and oviposition are tightly coupled to copulation. Sex-Peptide is a 36-amino-acid peptide synthesized in the accessory glands of Drosophila melanogaster males and transferred to the female during copulation. Sex-Peptide stimulates vitellogenic oocyte progression through a putative control point at about stage 9 of oogenesis. Here we show that application of the juvenile hormone analogue methoprene mimics the Sex-Peptide-mediated stimulation of vitellogenic oocyte progression in sexually mature virgin females. Apoptosis is induced by 20-hydroxyecdysone in nurse cells of stage 9 egg chambers at physiological concentrations (10(-7) M). 20-Hydroxyecdysone thus acts as an antagonist of early vitellogenic oocyte development. Simultaneous application of juvenile hormone analogue, however, protects early vitellogenic oocytes from 20-hydroxyecdysone-induced resorption. These results suggest that the balance of these hormones in the hemolymph regulates whether oocytes will progress through the control point at stage 9 or undergo apoptosis. These data are further supported by a molecular analysis of the regulation of yolk protein synthesis and uptake into the ovary by the two hormones. We conclude that juvenile hormone is a downstream component in the Sex-Peptide response cascade and acts by stimulating vitellogenic oocyte progression and inhibiting apoptosis. Since juvenile hormone analogue does not elicit increased oviposition and reduced receptivity, Sex-Peptide must have an additional, separate effect on these two postmating responses. (+info)
Impairment of the proapoptotic activity of Bax by missense mutations found in gastrointestinal cancers. (6/349)We have reported previously that codon 169 of the proapoptotic gene BAX is a mutational hot spot in gastrointestinal cancer. Two different mutations were found in this codon, replacing the wild-type threonine by alanine or methionine. To compare the proapoptotic activity of these Bax mutants with wild-type Bax, we established an ecdysone (muristerone A)-inducible system in cultured human embryonal kidney 293 cells. Addition of muristerone A induced a dose-dependent decrease in the viability of cells transfected with wild-type BAX, but this loss of viability was inhibited in cells transfected with BAX mutants. Furthermore, muristerone A induced morphological changes characteristic of apoptosis, including cell shrinkage, rounding, formation of apoptotic bodies, detachment and nuclear condensation and fragmentation, in cells transfected with wild-type BAX. These hallmarks of apoptosis were clearly diminished in cells transfected with BAX mutants. Mutation of threonine 169 did not affect the binding of Bax to Bax, Bcl-2, or Bcl-X(L). These results demonstrate that missense mutations at codon 169 of BAX are functional because they inhibit its apoptotic activity. This is the first report of the functional significance of missense mutations in BAX, or any other proapoptotic member of the Bcl-2 family, in primary human tumors. (+info)
The interferon-inducible nucleolar p204 protein binds the ribosomal RNA-specific UBF1 transcription factor and inhibits ribosomal RNA transcription. (7/349)p204, a member of the interferon-inducible p200 family of murine proteins, is primarily nucleolar. We generated cell lines in which p204 was inducible by muristerone. This induction resulted in retardation of cell proliferation and inhibition of rRNA transcription in vivo. Interferon treatment, resulting in p204 induction and retardation of proliferation, also caused inhibition of rRNA transcription in vivo. p204 also inhibited rRNA transcription in vitro. This inhibition was overcome by addition of UBF1, the rRNA-specific transcription factor. A direct interaction between p204 and UBF1 was revealed in vitro in pull-down assays, and in vivo by co-immunoprecipitation from cell extracts. UBF1 bound strongly to at least two regions of p204: the N-terminal segment linked to the conserved 200 amino acid a segment, and the conserved 200 amino acid b segment. Cleavage of the a or b segments into two segments (encoded by single exons) resulted in a strong decrease or loss of binding. The inhibition of rRNA transcription by p204 may be due to the inhibition by p204 of the specific DNA binding of UBF1. This was revealed in electrophoretic mobility shift, magnetic bead and footprinting assays. Thus, p204 serves as a mediator of the inhibition of rRNA transcription by interferon. (+info)
Activation of the p38 mitogen-activated protein kinase pathway by Epstein-Barr virus-encoded latent membrane protein 1 coregulates interleukin-6 and interleukin-8 production. (8/349)The Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) is a pleiotropic protein the activities of which include effects on gene expression and cell transformation, growth, and death. LMP1 has been shown to induce nuclear factor (NF)-kappaB and c-Jun NH2-terminal kinase/AP-1 activities in target cells, and in this study we demonstrate that LMP1 also engages the p38 mitogen-activated protein kinase cascade, leading to activation of the transcription factor ATF2. Mutational analysis of the LMP1 cytoplasmic COOH terminus revealed that p38 activation occurs from both the tumor necrosis factor receptor-associated factor (TRAF)-interacting, membrane-proximal COOH-terminal activating region (CTAR)1 domain (amino acids 186-231) and the extreme tumor necrosis factor receptor-associated death domain (TRADD) binding CTAR2 region (amino acids 351-386). Because LMP1 also engages signaling on the NF-kappaB axis through CTAR1 and CTAR2, we have examined whether these two pathways are overlapping or independent. We have found that inhibition of p38 by the highly specific inhibitor SB203580 did not affect NF-kappaB binding activity. Conversely, although the metabolic inhibitor D609 blocked NF-kappaB activation, it did not impair the ability of LMP1 to signal on the p38 axis, suggesting that these two LMP1-mediated pathways are primarily independent. Divergence of signals must, however, occur downstream of TRAF2 as a dominant negative TRAF2 mutant that blocks LMP1-induced NF-kappaB activation also inhibited p38 signaling. In addition, we have found that p38 inhibition significantly impaired LMP1-mediated interleukin-6 and -8 expression. Thus, p38 may play a significant cooperative role in regulating at least some of the pleiotropic activities of LMP1. (+info)
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Hypnotic effect of ecdysterone isolated from pfaffia glomerata (spreng.) pedersen
In this study the depressant effect of fractions from P. glomerata was initially evaluated using the mice barbiturate sleeping time test as reference. The fractions tested were the CHCl3, the EtOAc, the n-BuOH and the aqueous fraction obtained from P. glomerata subterraneous parts. Only the pretreatment with the lipophilic fraction (CHCl3: EtOAc, 1:1, w/w) increased the barbiturate sleeping time (i.p 500 mg/kg; v.o. 1000 mg/kg). Ecdysterone, the main substance isolated from this lipophilic fraction, was identifi ed by spectroscopic methods and its content in the ethanol extract was determined as 1.4% (w/w) by HPLC. In order to investigate the hypothesis of ecdysterone displaying a depressant effect on nervous central system, an evaluation toward the hypnotic-sedative and anxiolytic effects of this drug was carried out. Ecdysterone 100 mg/kg, i.p, increased the barbiturate sleeping time without provoking hypothermia; when administered by oral route its minimal effective dose was 400 mg/kg. On the ...
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20-Hydroxyecdysone and other ecdysteroids are used in biochemistry research as inducers in transgenic animals, whereby a new gene is introduced into an animal so that its expression is under the control of an introduced ecdysone receptor. Adding or removing ecdysteroids from the animals diet then gives a convenient way to turn the inserted gene on or off (see ecdysone receptor). At usual doses, 20-hydroxyecdysone appears to have little or no effect on animals that do not have extra genes inserted; it also has high bioavailability when taken orally, so it is useful for determining whether the transgene has been taken up effectively. For uses in gene therapy, it may be necessary to investigate more thoroughly the natural sources of ecdysteroids in humans (which appear to include dietary phytoecdysteroids, gut flora, helminth infections, and other diseases). There is some in vitro evidence to show that 20-hydroxyecdysone has effects on some kinds of blood cells such as lymphocytes and ...
Ecdysone 20-monooxygenase activity in Drosophila virilis strains varying in ecdysteroid response to heat stress, Russian...
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Effect of Ecdysterone on Morphological and Physiological Processes in Plants, Russian Journal of Plant Physiology | 10.1023/B...
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Effects of methoxyisoflavone, ecdysterone, and sulfo-polysaccharide (CSP3) supplementation during training on body composition...
TY - CONF. T1 - Effects of methoxyisoflavone, ecdysterone, and sulfo-polysaccharide (CSP3) supplementation during training on body composition and training adaptations. AU - Wilborn, C.. AU - Campbell, B.. AU - Thomas, A.. AU - Slonaker, B.. AU - Vacanti, T.. AU - Marcello, B.. AU - Baer, J.. AU - Kerksick, C.. AU - Rasmussen, C.. AU - Greenwood, M.. AU - Ounpraseuth, S.. AU - Casey, P.. AU - Wilson, R.. AU - Kreider, R.. AU - Earnest, C.P.. PY - 2004. Y1 - 2004. UR - http://www.aspet.org/Page.aspx?id=425. M3 - Abstract. T2 - Experimental Biology, 2004. Y2 - 16 April 2004 through 21 April 2004. ER - ...
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Prediction of the ligand-binding modes of various molecules to the molting hormone receptor using docking simulation at JCUP IV...
Insect molting is initiated by interaction of the molting hormone (20-hydroxyecdysone: 20E) with the ecdysone receptor (EcR). Thus, compounds that modulate the 20E-EcR interaction are able to interrupt insect molting and therefore may have useful insecticidal activity. Diacylhydrazines (DAHs) have been found to disrupt the 20E-EcR interaction and five DAHs, including tebufenozide and chromafenozide, are currently in use as insecticides. Most of them are very toxic to Lepidoptera but inactive or very weakly active against other insect orders such as Diptera and Coleoptera. This order-specific toxicity of DAHs is caused by differences in their binding affinity to the EcRs in the different insect species. The three dimensional structures of the ligand binding domains (LBDs) of EcR of Heliothis virescens (HvEcR) complexed with ponasterone A (PonA) and 20E have been solved crystallographically. Furthermore, EcR bound to a DAH (BYI06830, a chromafenozide analog) has also been solved, and comparison of ...
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The insect ecdysteroid receptor consists of a heterodimer between EcR and the RXR-orthologue, USP. We addressed the question of whether this heterodimer, like all other RXR heterodimers, may be formed in the absence of ligand and whether ligand promotes dimerization. We found that C-terminal protein fragments that comprised the ligand binding, but not the DNA binding domain of EcR and USP and which were equipped with the activation or DNA binding region of GAL4, respectively, exhibit a weak ability to interact spontaneously with each other. ...
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Ecdysteroids are a class of hormones that are the androgens of insects; they are involved with reproduction and molting, but human ingestion might be healthy or increase muscle mass. Human interventions are lacking and problems with ecdysteroid ingestion exist.
Ecdysone receptors: from the Ashburner model to structural biology
In 1974, Ashburner and colleagues postulated a model to explain the control of the puffing sequence on Drosophila polytene chromosomes initiated by the molting hormone 20-hydroxyecdysone. This model inspired a generation of molecular biologists to clone and characterize elements of the model, thereb …
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Regulation of the transcription factor E75 by 20-hydroxyecdysone and juvenile hormone in the epidermis of the tobacco hornworm,...
TY - JOUR. T1 - Regulation of the transcription factor E75 by 20-hydroxyecdysone and juvenile hormone in the epidermis of the tobacco hornworm, Manduca sexta, during larval molting and metamorphosis. AU - Zhou, Baohua. AU - Hiruma, Kiyoshi. AU - Jindra, Marek. AU - Shinoda, Tetsuro. AU - Segraves, William A.. AU - Malone, Fae. AU - Riddiford, Lynn M.. PY - 1998/1/15. Y1 - 1998/1/15. N2 - The homolog of the ecdysteroid-induced transcription factor E75A in Drosophila melanogaster was cloned from the tobacco hornworm, Manduca sexta, and its developmental expression and hormonal regulation were analyzed. Both E75A and E75B mRNAs were found in the abdominal epidermis during both the larval and the pupal molts, with E75A appearing before E75B, coincident with the rise of ecdysteroid. Exposure of either fourth or fifth instar epidermis to 20E in vitro caused the rapid, transient induction of E75A RNA with a peak at 6 and 3 h, respectively, followed by maintenance at low levels until 24 h. Epidermis ...
Frontiers | The GPCR membrane receptor, DopEcR, mediates the actions of both dopamine and ecdysone to control sex pheromone...
Olfactory information mediating sexual behavior is crucial for reproduction in many animals, including insects. In male moths, the macroglomerular complex of the primary olfactory center, the antennal lobe (AL) is specialized in the treatment of information on the female-emitted sex pheromone. Evidence is accumulating that modulation of behavioral pheromone responses occurs through neuronal plasticity via the action of hormones and/or catecholamines. We recently showed that a G-protein-coupled receptor (GPCR), AipsDopEcR, with its homologue known in Drosophila for its double affinity to the main insect steroid hormone 20-hydroxyecdysone (20E), and dopamine (DA), present in the ALs, is involved in the behavioral response to pheromone in the moth, Agrotis ipsilon. Here we tested the role of AipsDopEcR as compared to nuclear 20E receptors in central pheromone processing combining receptor inhibition with intracellular recordings of AL neurons. We show that the sensitivity of AL neurons for the pheromone in
An analysis of an ecdysterone response element from the Drosophila hsp27 gene. :: Dartmouth Dissertations
In Copyright. This material is protected by copyright and/or related rights. You are free to use this material in any way that is permitted by copyright law that applies to your use. For other uses, you need to obtain permission from the rights-holder(s). http://rightsstatements.org/page/InC/1.0/ ...
Drosophila metamorphosis: The only way is USP?<...
TY - JOUR. T1 - Drosophila metamorphosis. T2 - The only way is USP?. AU - Buszczak, Michael. AU - Segraves, William A.. PY - 1998/12/3. Y1 - 1998/12/3. N2 - The steroid insect molting hormone 20-hydroxyecdysone is believed to control critical aspects of development and reproduction through a heterodimeric receptor comprising the Ecdysone Receptor and the Ultraspiracle proteins. Recent findings suggest that other hormones and receptors might also be involved.. AB - The steroid insect molting hormone 20-hydroxyecdysone is believed to control critical aspects of development and reproduction through a heterodimeric receptor comprising the Ecdysone Receptor and the Ultraspiracle proteins. Recent findings suggest that other hormones and receptors might also be involved.. UR - http://www.scopus.com/inward/record.url?scp=0032481121&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0032481121&partnerID=8YFLogxK. M3 - Article. C2 - 9843674. AN - SCOPUS:0032481121. VL - 8. SP - ...
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Are Ecdysteroids insect hormones? - Atlas of Science
The polyhydroxylated derivatives of 7-dehydro, 6-ketocholesterol (Ecdysone, Ecdysteroids, Ecd) were accidentally discovered in the search for an insect moulting hormone in 1965. The first Ecd compound, named ecdysone (ecdysis = shedding off the cuticle), was isolated from silkworm pupae.
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... ecdysterone, turkesterone and 2-deoxyecdysone. These compounds are synthesized in arthropods from dietary cholesterol upon ...
The seed contain insect moulting hormones including rubrosterone, ecdysterone, and inokosterone. The root contains ...
... (ecdysterone or 20E) is a naturally occurring ecdysteroid hormone which controls the ecdysis (moulting) and ... July 2019). "Ecdysteroids as non-conventional anabolic agent: performance enhancement by ecdysterone supplementation in humans ... July 2019). "Ecdysteroids as non-conventional anabolic agent: performance enhancement by ecdysterone supplementation in humans ... ecdysterone, and sulfo-polysaccharide supplementation on training adaptations in resistance-trained males". Journal of the ...
The root contains phytochemicals including saponins (pfaffosides), pfaffic acid, beta-ecdysterone, glycosides, and ...
Ecdysterone, an insect moulting hormone, and long chain alcohols are also found in Achyranthes aspera. BSBI List 2007 (xls). ...
Ecdysterone, and Sulfo-Polysaccharide Supplementation on Training Adaptations in Resistance-Trained Males". Journal of the ...
Gao XY, Wang DW, Li FM (2000). "Determination of ecdysterone in Achyranthes bidentata Bl and its activity promoting ...
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List of MeSH codes (D06)
... ecdysterone MeSH D06.472.445.573.666 - juvenile hormones MeSH D06.472.445.573.666.170 - diflubenzuron MeSH D06.472.445.573. ...
The skeleton is rich in histidine and contains the unusual ecdysterone, ajugasterone-C. The growth rate of the colony is slow ...
List of MeSH codes (D04)
... ecdysterone MeSH D04.808.247.222.265.450 - ketocholesterols MeSH D04.808.247.222.284 - cholesterol MeSH D04.808.247.222.284.070 ...
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