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Статті в журналах з теми "ARN activateur":
1
Antoniewski, C. "Le co-activateur du récepteur nucléaire était... un ARN !" médecine/sciences 15, no. 10 (1999): 1153. http://dx.doi.org/10.4267/10608/1230.
2
Martella, Christophe, Laetitia Waast, and Claudine Pique. "Tax, marionnettiste de la transcription du HTLV-1." médecine/sciences 38, no. 4 (April 2022): 359–65. http://dx.doi.org/10.1051/medsci/2022039.
Анотація:
Les rétrovirus sont des virus dont le génome est constitué d’un ARN rétrotranscrit en ADN dans la cellule, qui s’intègre alors dans le génome cellulaire. La transcription du génome rétroviral intégré est ensuite réalisée par la machinerie de transcription de l’ARN polymérase II. Dans le cas du virus T-lymphotrope humain de type 1 (HTLV-1, pour human T-lymphotropic virus type 1), rétrovirus responsable de la leucémie aiguë de l’adulte et de maladies inflammatoires, la transcription est contrôlée par la protéine virale Tax. Celle-ci agit selon un mode d’action original car le mécanisme activateur ne repose pas sur une interaction directe avec le promoteur viral, mais sur le recrutement de différents facteurs et cofacteurs cellulaires de la transcription. Les facteurs cellulaires recrutés par Tax sont impliqués dans l’activation initiale du promoteur, mais également dans les étapes ultérieures du processus de transcription lui-même. Cette revue décrit ce mécanisme particulier de transcription virale, de la levée de la répression transcriptionnelle jusqu’à l’élongation des transcrits viraux néosynthétisés.
3
Blake, Timo, Anne Barnard, Stephen J. W. Busby, and Jeffrey Green. "Transcription Activation by FNR: Evidence for a Functional Activating Region 2." Journal of Bacteriology 184, no. 21 (November 1, 2002): 5855–61. http://dx.doi.org/10.1128/jb.184.21.5855-5861.2002.
Анотація:
ABSTRACT The FNR protein of Escherichia coli controls the transcription of target genes in response to anoxia via the assembly-disassembly of oxygen-labile iron-sulfur clusters. Previous work identified patches of surface-exposed amino acids (designated activating regions 1 and 3 [AR1 and AR3, respectively]) of FNR which allow it to communicate with RNA polymerase (RNAP) and thereby activate transcription. Previously it was thought that FNR lacks a functional activating region 2 (AR2), although selecting for mutations that compensate for defective AR1 or a miscoordinated iron-sulfur cluster can reactivate AR2. Here we show that the substitution of two surface-exposed lysine residues (Lys49 and Lys50) of FNR impaired transcription from class II (FNR box centered at −41.5) but not class I (FNR box centered at −71.5) FNR-dependent promoters. The degree of impairment was greater when a negatively charged residue (Glu) replaced either Lys49 or Lys50 than when uncharged amino acid Ala was substituted. Oriented heterodimers were used to show that only the downstream subunit of the FNR dimer was affected by the Lys→Ala substitutions at a class II promoter. Site-directed mutagenesis of a negatively charged patch (162EEDE165) within the N-terminal domain of the RNAP α subunit that interacts with the positively charged AR2 of the cyclic AMP receptor protein suggested that Lys49 and Lys50 of FNR interact with this region of the α subunit of RNAP. Thus, it was suggested that Lys49 and Lys50 form part of a functional AR2 in FNR.
4
Liu, Xinhuai, and Allan Herbison. "Kisspeptin Regulation of Arcuate Neuron Excitability in Kisspeptin Receptor Knockout Mice." Endocrinology 156, no. 5 (March 10, 2015): 1815–27. http://dx.doi.org/10.1210/en.2014-1845.
Анотація:
The G protein-coupled receptor 54 (GPR54) is critical for kisspeptin to activate GnRH neurons to modulate fertility. However, the often mismatching distribution of kisspeptin and GPR54 in the brain suggests that kisspeptin may also act on other receptors. The arcuate nucleus (ARN) is one brain region with a very high density of kisspeptin fibers but only limited evidence for the expression of GPR54. Using acute brain slice electrophysiology in combination with Gpr54 knockout (GPR54KO) mouse models, we examined whether actions of kisspeptin in the ARN were dependent upon GPR54. Cell-attached recordings from unidentified ARN neurons in wild-type mice revealed that approximately one third of neurons were either excited or inhibited by kisspeptin in a dose-dependent manner. The responses of ARN neurons to kisspeptin were exactly the same in GPR54KO mice despite effects of kisspeptin on GnRH neurons being abolished. To evaluate whether kisspeptin may be acting through neuropeptide FF receptors, the effects of an agonist RFamide-related peptide 3 (RFRP-3) and antagonists RF9 and BIBP-3226 were evaluated. Both the excitatory and inhibitory effects of kisspeptin were mimicked by the agonist RFRP-3. RF9 itself activated ARN neurons and suppressed only the inhibitory actions of kisspeptin. BIBP-3226 suppressed kisspeptin actions in 50% of neurons. Whole-cell recordings in GPR54KO mice demonstrated that both kisspeptin and RFRP-3 acted directly on the same ARN neurons and activated the same ion channels. Together, these studies demonstrate that kisspeptin can act partly through neuropeptide FF receptors to modulate neuronal activity independent of GPR54 in the mouse brain.
5
Xu, Bo, Hong Zheng, Xuefei Liu, and Kaushik P. Patel. "Activation of afferent renal nerves modulates RVLM-projecting PVN neurons." American Journal of Physiology-Heart and Circulatory Physiology 308, no. 9 (May 1, 2015): H1103—H1111. http://dx.doi.org/10.1152/ajpheart.00862.2014.
Анотація:
Renal denervation for the treatment of hypertension has proven to be successful; however, the underlying mechanism/s are not entirely clear. To determine if preautonomic neurons in the paraventricular nucleus (PVN) respond to afferent renal nerve (ARN) stimulation, extracellular single-unit recording was used to investigate the contribution of the rostral ventrolateral medulla (RVLM)-projecting PVN (PVN-RVLM) neurons to the response elicited during stimulation of ARN. In 109 spontaneously active neurons recorded in the PVN of anesthetized rats, 25 units were antidromically activated from the RVLM. Among these PVN-RVLM neurons, 84% (21/25) were activated by ARN stimulation. The baseline discharge rate was significantly higher in these neurons than those PVN-RVLM neurons not activated by ARN stimulation (16%, 4/25). The responsiveness of these neurons to baroreflex activation induced by phenylephrine and activation of cardiac sympathetic afferent reflex (CSAR) was also examined. Almost all of the PVN neurons that responded to ARN stimulation were sensitive to baroreflex (95%) and CSAR (100%). The discharge characteristics for nonevoked neurons (not activated by RVLM antidromic stimulation) showed that 23% of these PVN neurons responded to ARN stimulation. All the PVN neurons that responded to ARN stimulation were activated by N-methyl-d-aspartate, and these responses were attenuated by the glutamate receptor blocker AP5. These experiments demonstrated that sensory information originating in the kidney is integrated at the level of preautonomic neurons within the PVN, providing a novel mechanistic insight for use of renal denervation in the modulation of sympathetic outflow in disease states such as hypertension and heart failure.
6
de Croft, Simon, Ulrich Boehm, and Allan E. Herbison. "Neurokinin B Activates Arcuate Kisspeptin Neurons Through Multiple Tachykinin Receptors in the Male Mouse." Endocrinology 154, no. 8 (August 1, 2013): 2750–60. http://dx.doi.org/10.1210/en.2013-1231.
Анотація:
Abstract Kisspeptin neurons located in the arcuate nucleus (ARN) coexpress dynorphin and neurokinin B (NKB) and may interact to influence gonadotropin secretion. Using a kisspeptin-green fluorescent protein mouse model, the present study examined whether the neuropeptides kisspeptin, dynorphin, and NKB modulate the electrical activity of ARN kisspeptin neurons in the adult male mouse. Cell-attached recordings showed that kisspeptin itself had no effect on kisspeptin neuron firing. Dynorphin and the κ-opioid receptor agonist U50-488 evoked a potent suppression of all ARN kisspeptin neuron firing that was blocked completely by the κ-opioid receptor antagonist nor-Binaltorphimine. Both NKB and Senktide, a neurokinin 3 receptor agonist, exerted a potent stimulatory action on ∼95% of ARN kisspeptin neurons. Although the selective neurokinin 3 receptor antagonists SB222200 and SR142801 blocked the effects of Senktide on kisspeptin neurons, they surprisingly had no effect on NKB activation of firing. Studies with selective neurokinin 1 receptor (SDZ-NKT343) and neurokinin 2 receptor (GR94800) antagonists revealed that the activation of kisspeptin neurons by NKB was only blocked completely by a cocktail of antagonists against all 3 tachykinin receptors. Whole-cell recordings revealed that individual kisspeptin neurons were activated directly by all 3 tachykinins substance, P, neurokinin A, and NKB. These experiments show that dynorphin and NKB have opposing actions on the electrical activity of kisspeptin neurons supporting the existence of an interconnected network of kisspeptin neurons in the ARN. However, the effects of NKB result from an unexpected activation of multiple tachykinin receptors.
7
Derrien, Thomas, and Roderic Guigó. "De longs ARN non codants activateurs de la transcription des gènes." médecine/sciences 27, no. 4 (April 2011): 359–61. http://dx.doi.org/10.1051/medsci/2011274009.
8
Qi, Guan-Ming, Li-Xin Jia, Yu-Lin Li, Hui-Hua Li, and Jie Du. "Adiponectin Suppresses Angiotensin II-Induced Inflammation and Cardiac Fibrosis through Activation of Macrophage Autophagy." Endocrinology 155, no. 6 (June 1, 2014): 2254–65. http://dx.doi.org/10.1210/en.2013-2011.
Анотація:
Previous studies have indicated that adiponectin (APN) protects against cardiac remodeling, but the underlying mechanism remains unclear. The present study aimed to elucidate how APN regulates inflammatory responses and cardiac fibrosis in response to angiotensin II (Ang II). Male APN knockout (APN KO) mice and wild-type (WT) C57BL/6 littermates were sc infused with Ang II at 750 ng/kg per minute. Seven days after Ang II infusion, both APN KO and WT mice developed equally high blood pressure levels. However, APN KO mice developed more severe cardiac fibrosis and inflammation compared with WT mice. This finding was demonstrated by the up-regulation of collagen I, α-smooth muscle actin, IL-1β, and TNF-α and increased macrophage infiltration in APN KO mice. Moreover, there were substantially fewer microtubule-associated protein 1 light chain 3-positive autophagosomes in macrophages in the hearts of Ang II-infused APN KO mice. Additional in vitro studies also revealed that globular APN treatment induced autophagy, inhibited Ang II-induced nuclear factor-κB activity, and enhanced the expression of antiinflammatory cytokines, including IL-10, macrophage galactose N-acetyl-galactosamine specific lectin 2, found in inflammatory zone 1, and type-1 arginase in macrophages. In contrast, APN-induced autophagy and antiinflammatory cytokine expression was diminished in Atg5-knockdown macrophages or by Compound C, an inhibitor of adenosine 5′-monophosphate-activated protein kinase. Our study indicates that APN activates macrophage autophagy through the adenosine 5′-monophosphate-activated protein kinase pathway and suppresses Ang II-induced inflammatory responses, thereby reducing the extent of cardiac fibrosis.
9
Caverson, M. M., and J. Ciriello. "Contribution of paraventricular nucleus to afferent renal nerve pressor response." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 254, no. 3 (March 1, 1988): R531—R543. http://dx.doi.org/10.1152/ajpregu.1988.254.3.r531.
Анотація:
Experiments were done in alpha-chloralose-anesthetized, paralyzed, and artificially ventilated cats to determine the effect of afferent renal nerve (ARN) stimulation on the firing frequency of neurons in the paraventricular nucleus of the hypothalamus (PVH), whose axons project directly to the neurohypophysis (NH), and the contribution of these neurons to the pressor response elicited by ARN stimulation. In the first series of experiments, 474 single units were extracellularly recorded in the PVH region. Of these units 86 were antidromically excited by stimulation of the NH. Seventeen of the antidromic units (20%) responded orthodromically to ARN stimulation; 10 responded to ARN stimulation only, and 7 units responded to both ARN and buffer nerve stimulation. All PVH-NH-projecting neurons that responded to ARN stimulation were excited. In the second series the contribution of PVH neurons to the pressor response elicited by ARN stimulation was investigated in animals with the aortic depressor, carotid sinus, vagus, and cervical sympathetic nerves cut bilaterally. The ARN pressor response has previously been shown to be due to the activation of the sympathetic nervous system and to the release of arginine vasopressin (AVP). The primary and secondary (AVP component) components of the pressor response were attenuated by 51 and 69%, respectively, by bilateral injections of procaine hydrochloride into PVH or bilateral electrolytic lesions of PVH. Control injections of saline into PVH or electrolytic lesions of hypothalamic regions anterior, dorsal, or ventral to PVH did not alter the ARN pressor response. These experiments demonstrate that sensory information originating in renal receptors excites magnocellular neurosecretory neurons in PVH and suggest that this renal-paraventricular reflex loop may contribute to the elevated arterial pressure and AVP release during conditions when ARN are activated.
10
Li, Yuan, and Zong Jie Cui. "Photodynamic Activation of Cholecystokinin 1 Receptor with Different Genetically Encoded Protein Photosensitizers and from Varied Subcellular Sites." Biomolecules 10, no. 10 (October 8, 2020): 1423. http://dx.doi.org/10.3390/biom10101423.
Анотація:
Cholecystokinin 1 receptor (CCK1R) is activated by singlet oxygen (1O2) generated in photodynamic action with sulphonated aluminum phthalocyanine (SALPC) or genetically encoded protein photosensitizer (GEPP) KillerRed or mini singlet oxygen generator (miniSOG). A large number of GEPP with varied 1O2 quantum yields have appeared recently; therefore, in the present work, the efficacy of different GEPP to photodynamically activate CCK1R was examined, as monitored by Fura-2 calcium imaging. KillerRed, miniSOG, miniSOG2, singlet oxygen protein photosensitizer (SOPP), flavin-binding fluorescent protein from Methylobacterium radiotolerans with point mutation C71G (Mr4511C71G), and flavin-binding fluorescent protein from Dinoroseobacter shibae (DsFbFP) were expressed at the plasma membrane (PM) in AR4-2J cells, which express endogenous CCK1R. Light irradiation (KillerRed: white light 85.3 mW‧cm−2, 4’ and all others: LED 450 nm, 85 mW·cm−2, 1.5′) of GEPPPM-expressing AR4-2J was found to all trigger persistent calcium oscillations, a hallmark of permanent photodynamic CCK1R activation; DsFbFP was the least effective, due to poor expression. miniSOG was targeted to PM, mitochondria (MT) or lysosomes (LS) in AR4-2J in parallel experiments; LED light irradiation was found to all induce persistent calcium oscillations. In miniSOGPM-AR4-2J cells, light emitting diode (LED) light irradiation-induced calcium oscillations were readily inhibited by CCK1R antagonist devazepide 2 nM; miniSOGMT-AR4-2J cells were less susceptible, but miniSOGLS-AR4-2J cells were not inhibited. In conclusion, different GEPPPM could all photodynamically activate CCK1R. Intracellular GEPP photodynamic action may prove particularly suited to study intracellular GPCR.
Дисертації з теми "ARN activateur":
1
Sharov, Grigory. "Etude structurale du co-activateur transcriptionnel SAGA et de son module d'acétylation des histones." Thesis, Strasbourg, 2015. http://www.theses.fr/2015STRAJ040/document.
Анотація:
L’initiation de la transcription chez les eucaryotes nécessite le recrutement de l'ARN polymérase II (Pol II) et des facteurs de transcription généraux sur les promoteurs de gènes formant le complexe de préinitiation (PIC). Des activateurs se lient en amont du promoteur et stimulent l’ouverture de la chromatine et la formation du PIC en recrutant des complexes coactivateurs. SAGA est un tel coactivateur, conservé chez les eucaryotes, connu pour modifier les histones de tous les gènes et impliqué dans la transcription par Pol II. Dans ce travail, j’ai analysé l'organisation moléculaire de SAGA par microscopie électronique. J'ai (i) étudié l'architecture et les interactions des sous unités du module d’acétylation des histones et l’ai localisé dans SAGA; (ii) obtenu la première carte cryo-EM du complexe SAGA chez la levure et analysé sa flexibilité; (iii) défini le site d'interaction entre TBP et SAGA et montré que le complexe subit un changement conformationnel lors de cette liaisonTranscription initiation in eukaryotes requires the recruitment of RNA polymerase II (Pol II) and general transcription factors to the promoters of protein coding genes in order to form a PreInitiation Complex (PIC). Sequence specific activators bind up stream of the promoter, stimulating chromatin opening and PIC formation via recruitment of coactivator complexes. SAGA is such a coactivator, conserved in all eukaryotes, known to modify the histones on all expressed genes in yeast and human and involved in Pol II transcription. In this work I have analyzed SAGA’s molecular organization mostly by electron microscopy. I have (i) studied the architecture and sub unit interactions of SAGA histone acetylation (HAT) module and localized it in the full SAGA complex; (ii) obtained the first cryo-EM map of yeast SAGA and analyzed its flexibility; (iii) defined the interaction site of SAGA with TBP protein and shown that the complex under goes a large conformational change upon TBP binding
2
Yang, Qi. "Regulation of the yifK locus by multi-target small RNA GcvB in Salmonella." Phd thesis, Université Paris Sud - Paris XI, 2013. http://tel.archives-ouvertes.fr/tel-00954416.
Анотація:
GcvB is a conserved 200 nucleotide RNA that downregulates several genes involved in amino acid uptake or biosynthesis in bacteria. The physiological role of GcvB action is not entirely clear, but it is likely aimed at balancing of nutritional resources under fast growth conditions. GcvB inhibits translation of target messenger RNAs by pairing with sequences inside or upstream of ribosome binding sites. In the present study, characterization of a novel GcvB-regulated locus revealed some unique features in the mode of functioning of this regulatory RNA. We found that GcvB represses yifK - a highly conserved locus encoding a putative amino acid transporter - by targeting a translational enhancer element. Two ACA motifs within the target sequence are the main determinants of the enhancer activity. Replacing either of these motifs with random triplets caused up to a 10-fold decrease in yifK expression regardless of the GcvB allele (deleted or suitably modified to recognize the mutated target). It thus appears that GcvB effectiveness as a regulator results from countering the enhancer activity. When the enhancer is removed, GcvB action no longer constitutes a rate-limiting factor for yifK expression. Overall, this study is relevant not only to a better understanding of GcvB function but it also provides insight into an elusive aspect of the translation initiation process. Besides the GcvB control, the yifK locus is regulated at the transcriptional level by the leucine responsive regulator Lrp, and by HdfR (YifA) a poorly known transcriptional regulator, that appears to require the product of the adjacent, divergently oriented gene, yifE, for expression or activity. Transcription initiating at the yifK promoter extends into the adjacent argX-hisR-leuT-proM tRNA operon yielding an unusual primary transcript which both a messenger RNA and a tRNA precursor. This chimeric RNA si rapidly processed by RNAse E.
3
Hache, Antoine. "Molecular basis of transcriptional dysregulations in the spinocerebellar ataxia type 7, a neurodegenerative polyglutamine disorder." Thesis, Strasbourg, 2020. http://www.theses.fr/2020STRAJ083.
Анотація:
SCA7 est une maladie génétique dont l’un des principaux symptômes est une perte progressive d’acuité visuelle pouvant aller jusqu’à la cécité. La mutation responsible de cette pathologie est une expansion instable d’un triplet CAG au sein de l’ATXN7, gene codant une sous-unité du complexe SAGA, un co-activateur de l’ARN polymerase de type II. Des études réalisées sur modèles de souris transgéniques mirent en évidence une perte d’identité des photorécepteurs au niveau morphologique, fonctionnel, et moléculaire. Au cours de ma thèse la caractérisation d’un nouveau modèle knock-in de SCA7 fut réalisée. Ce modèle, qui exprime le gène muté à un niveau endogène récapitule les atteintes rétiniennes observées dans les modèles transgéniques et chez les patients. Une étude transcriptomique (RNA-seq) et épigénomique (ChIP-seq) de ce modèle fut réalisée et mis en évidence des défauts globaux de l’acétylation des lysines 9 et 27 de l’histone H3 (H3K9 et H3K27ac). De plus une étude plus poussée des ARNs non codants mit en évidence l’existance d’ARN enhancer (eRNA) encore non répertoriés au niveau des loci de gènes uniquement exprimés dans les photorécepteurs comme Rho, ces même eRNAs sont retrouvés dérégulés chez les animaux développant la rétinopathie SCA7SCA7 is a genetic disorder whose one of its main symptoms is a progressive loss of visual acuity which can ultimately lead to blindness. The mutation responsible for this disease is an unstable CAG expansion within ATXN7, a gene encoding a subunit of the SAGA complex, a co-activator of the RNA polymerase II. Previous studies performed on transgenic mouse models highlighted a neuronal identity loss of the photoreceptors at the morphological, functional and molecular levels. During my PhD a characterization of a new SCA7 knock-in mouse model was performed. This model, which expresses the mutated genes at endogenous level recapitulates the retinal impairments observed in transgenic models and in patients. A transcriptomic (RNA-seq) and epigenomic (ChIP-seq) analyses were performed on this model and highlight global acetylation defects on lysine 9 and 27 of histone H3 (H3K9ac and H3K27ac). Moreover, investigations on non-coding RNAs identified the presence of enhancer RNAs (eRNAs) on photoreceptor specific genes such as Rho. These eRNAs, which were never described before, undergo a downregulation in symptomatic SCA7 mice
4
Laustriat, Delphine. "Les cellules souches pluripotentes en modélisation pathologique pour l'identification de nouvelles cibles thérapeutiques : application à la Dystrophie Myotonique de type 1." Thesis, Evry-Val d'Essonne, 2010. http://www.theses.fr/2010EVRY0017.
Анотація:
La Dystrophie Myotonique de type 1 (DM1) ou maladie de Steinert est une des atteintes neuromusculaires parmi les plus fréquentes chez l’adulte et pour laquelle il n’existe de solution thérapeutique autre que symptomatique à l’heure actuelle. La mutation, une expansion instable d’un triplet CTG dans la région 3’ transcrite non traduite du gène codant la DMPK, conduit notamment à la dérégulation de protéines de liaison à l’ARN, ce qui engendre différents défauts d’épissage alternatif qui sont associés aux atteintes multisystémiques observées dans la maladie. La disponibilité d’un diagnostic préimplantatoire a permis la dérivation de lignées de cellules souches embryonnaires humaines (CSEh) à partir d’embryons portant la mutation causale. Ces lignées, et désormais les cellules souches induites à la pluripotence issues de patients, constituent des sources prometteuses de modèles pour l’étude des maladies génétiques. Outre la possibilité d’étudier la pathologie dans un contexte naturel, ces cellules offrent l’accès à tous les phénotypes cellulaires sans limite quantitative. Ceci en fait un outil de choix pour les approches de criblage à grande échelle, et notamment celles de génomique fonctionnelle, qui visent à explorer de manière systématique l’implication de gènes dans une maladie. L’objectif de mes travaux de doctorat a été de démontrer l’intérêt de tels cribles en développant une approche par perte de fonction, via le mécanisme d’interférence par l’ARN (ARNi), pour identifier de nouvelles cibles thérapeutiques pour la DM1 en utilisant une lignée de CSEh exprimant la mutation causale. Après avoir identifié une population de progéniteurs mésenchymateux issus de cette lignée qui exprime deux biomarqueurs de la DM1 - les foci et le défaut d’épissage de l’INSR - et qui est adaptée à une approche de crible par transfection, mes travaux ont consisté à développer, miniaturiser puis automatiser les étapes de transfection et de détection des phénotypes pathologiques. Le crible de collections de siRNAs a permis d’identifier plusieurs gènes candidats, parmi lesquels ELAVL1 qui apparaît comme une nouvelle cible thérapeutique pour la DM1. En effet, l’extinction de son expression permet d’améliorer plusieurs défauts d’épissages et de normaliser l’anomalie de capture du glucose. Nous avons montré que l’enrichissement de sa fraction nucléaire par l’utilisation d’activateurs de l’AMPK, composés classiquement indiqués pour la prise en charge du diabète de type 2, permettait de reproduire cet effet restaurateur. Mes travaux ont ainsi montré l’intérêt d’associer, et particulièrement dans le cas des maladies rares, les approches de crible par ARNi aux cellules souches pluripotentes modèles de maladies pour l’identification de nouvelles cibles moléculaires afin d’accélérer le développement de thérapeutiquesMyotonic Dystrophy type 1 (DM1), or Steinert disease, is one of the most common neuromuscular disorders in adults for whom no therapeutic solution other than symptomatic is available at present. The mutation, which consists in an unstable CTG expansion located in the 3' transcribed but untranslated region of the DMPK gene, leads in particular to the deregulation of several RNA-binding proteins. This engenders various splicing defects that are associated to the multisystemic symptoms. The availability of a preimplantation genetic diagnosis enabled the derivation of human embryonic stem cell lines (hESC) from embryos carrying the causative mutation. These cell lines, and now the induced pluripotent stem cells established from patients, constitute promising models for genetic disease’s exploration. Besides the possibility to investigate the pathology in a natural context, these cells open the way to every cell phenotypes without any quantitative restriction and thus appear as a valuable tool for large scale screening, and particularly for functional genomics approaches that systematically explore the involvement of genes in a given phenotype. The aim of my work was to explore the potential of such an approach by developing a loss of function RNA interference screen in order to identify new therapeutic targets by using a hESC line expressing the DM1 mutation. To that purpose we first identified a disease relevant cell population, i.e. hESC derived-mesenchymal progenitors expressing two DM1 biomarkers – foci and INSR splicing defects, suitable for large scale siRNA transfection. Then we developed, miniaturized and automated the transfection’s and phenotype detection’s steps. Finally, once all the conditions determined, we conducted a screening of a siRNA library targeting RNA-binding proteins that led to the identification of several candidate genes, including ELAVL1 which appears as a new DM1 therapeutic target. Indeed, its knockdown resulted in the improvement of several pathological splicing defects and normalized the glucose uptake impairment. We also showed that the enrichment of its nuclear fraction through the use of AMPK activators, some of which being widely prescribed anti-diabetic drug, was able to mimic this corrective effect. My work thus underlies the interest of coupling RNAi screening to pathological pluripotent stem cells for the identification of new therapeutic targets with the view to accelerate drug discovery, and particularly in the case of rare diseases
5
Saguy, Matthieu. "Activateurs précoces du processus de trans-traduction : rôle de la protéine ribosomique S1 et recherche d’une activité ribonucléase liée au ribosome." Rennes 1, 2008. http://www.theses.fr/2008REN1S001.
Анотація:
Lorsque la traduction bactérienne est bloquée sur un ARN messager (ARNm) incomplet, les ribosomes sont libérés grâce à un mécanisme appelé trans-traduction. Ce système requiert le concours de l?ARN transfert-message (ARNtm) qui agit en présence de plusieurs protéines dont la protéine ribosomique S1. Des études in vitro ont permis d?établir que S1 est essentielle à la traduction du cadre interne de lecture de l?ARNtm et des études in vitro d'observer qu'une variation de son expression était néfaste à ce processus. Dans le cas d'ARNm en cours de traduction, un site de décodage libre est nécessaire au recrutement de la trans-traduction. Le facteur responsable du clivage de l'ARNm dans ce site est encore inconnu. Afin de l'identifier, un système de purification des ribosomes bloqués a été mis au point au laboratoire. Le facteur responsable de cette activité n'a pu être identifié cependant une activité exonucléase a été observée. Un modèle d'intervention de la trans-traduction a été proposéWhen bacterial translation stalls on a truncated messenger RNA (mRNA), ribosomes are released by process called trans-translation. This system requires a particular ribonucleic acid: transfer-messenger RNA (tmRNA), acting in concert with several protein partners including ribosomal protein S1. In vitro studies showed that S1 is essential to the resume of translation on the internal open reading frame of tmRNA. Accordingly, any variation of the expression level of S1 in vivo is harmful to the process. Trans-translation occurs sometimes on non truncated mRNAs, which are subsequently cleaved into the ribosomal A site to trigger the process. The factor responsible of the cleavage is still unknown. In order to find out the way these mRNA are cleaved, an in vivo system allowing purification of stalled ribosomes on non truncated mRNAs was set up. No endoribonuclease could be identified, nevertheless an exonucleotytic activity was observed. A new model of trans-translation intervention was established
6
Kieffer, Kyong-Rim. "Stimulation de la réparation de l'ADN par des activateurs de la transcription." Université Louis Pasteur (Strasbourg) (1971-2008), 2002. http://www.theses.fr/2002STR13085.
Анотація:
Les gènes eucaryotes sont organisés, grâce aux protéines d'histones, en une structure appelée la chromatine. La compaction de l'ADN au sein de la chromatine permet non seulement à l'ensemble du génome d'être contenu dans un noyau cellulaire mais également de restreindre l'accès de cette ADN à une multitude de protéines de régulation impliquées dans des processus essentiels tel que la réplication, la transcription ou la recombinaison. La chromatine adopte une structure dynamique capable localement de se condenser ou de se décondenser, c'est-à-dire capable de se remodeler en réponse à des signaux spécifiques. Le remodelage de la chromatine nécessite un ensemble d'enzymes spécifiques qui agit au niveau du nucléosome, unité de base de la chromatine. Ce travail montre d'une part que les processus de réparation de l'ADN sont également entravés par une structure condensée de la chromatine et d'autre part, que les enzymes de remodelage de la chromatine sont nécessaires pour permettre une fonctionnalité optimale des processus de réparation de l'ADN. L'action des enzymes de remodelage est gérée par des activateurs de la transcription, qui facilitent et stimule la réparation dans les régions promotrices des gènes. Cette stimulation est totalement indépendante des machineries d'initiation et d'élongation de la transcription et ce malgré le fait que tous ces processus coexistent. En effet des activateurs inactifs sur la transcription sont tout de même aptes à stimuler les processus de réparation de l'ADN. Il est probable que la fonction des activateurs soit double. Ils permettent une décondensation locale de la chromatine, phénomène commun à tous processus génomiques et en parallèle ou séquentiellement voir de manière coopérative recrutent les facteurs spécifiques impliqués dans la transcription, la réparation de l'ADN ou la réplicationEukaryotic genes are contained within a higher order complex of DNA and histones called chromatin. Although packaging of DNA into chromatin provides the means for compaction of the entire genome to fit in the nucleus, it restricts the access of the many regulatory proteins required for essential biological processes such as DNA replication, transcription, and recombination. The chromatin, however, is not a static structure, but rather a dynamic assembly that condenses and decondenses (remodeling) in response to specific signals during cell life. Chromatin remodeling requires a specific set of enzymes that modify the nucleosome, the building block of chromatin. These enzymes fall into two classes: the first includes ATP-dependent chromatin remodeling activities that use energy derived from ATP hydrolysis to alter nucleosomal structure and/or arrangement, whereas the second class includes enzymes that add acetyl groups to the histone N termini. This thesis has described that DNA repair is also hindered by chromatin structure and requires a subset of chromatin remodeling enzymes from each class to optimally occur. In the promoter region, chromatin remodeling enzymes are dictated by sequence-specific activators, resulting in facilitated damage removal in the proximity of transcription initiation site. The mechanism of this preferential repair is independent of transcription machinery and transcription per se, although two events pass on the same template. Furthermore, transcriptionally inactive activator accomplishes the stimulation of repair by binding to its cognate sequences. It is likely that the function of activators is dual : (i) they help to derepress chromatin, a step common to DNA processes, (ii) in parallel or subsequently, and possibly in a cooperative manner according to activities demanded by the surrounding DNA, they recruit specific factors involved in transcription, DNA repair or replication
7
Diouf, Sarah. "Le co-activateur transcriptionnel CREB-binding protein (CBP) : un nouvel acteur de la fonction mitochondriale." Thesis, Toulouse 3, 2018. http://www.theses.fr/2018TOU30050.
Анотація:
De par son activité acétyltransférase et sa capacité à interagir avec un très grand nombre de facteurs de transcription, CBP (CREB Binding Protein également appelé KAT3A) co-active la transcription de nombreux gènes. De ce fait, CBP est impliqué dans des processus physiologiques variés tels que la prolifération, la différentiation ou l'apoptose, mais également dans certaines pathologies (cancers, syndrome de Rubinstein-Taybi, ...). Il a notamment été montré que CBP régulait la myogenèse, processus conduisant à la formation des muscles au cours de l'embryogenèse et chez l'adulte au cours de la régénération. L'étude du rôle de CBP au cours de ce processus a été réalisée en utilisant des myoblastes primaires humains comme modèle. L'analyse de l'expression et de la localisation subcellulaire de CBP dans ces cellules a permis d'observer qu'une fraction de la protéine se relocalisait dans les mitochondries au cours de la différenciation myogénique. Mes travaux de thèse ont consisté à étudier ce rôle inédit de CBP hors du noyau et en particulier dans les mitochondries. Les mitochondries possèdent leur propre génome et une de leurs fonctions principales est de produire l'énergie nécessaire au fonctionnement cellulaire. Nous avons pu montrer que l'adressage de CBP aux mitochondries est dépendant de l'état métabolique des cellules. Nous avons également montré que CBP, ainsi que son activité acétyltransférase, étaient impliqués dans la régulation de la réplication et de la transcription de l'ADN mitochondrial. Nos résultats indiquent aussi que CBP participe au contrôle de la respiration mitochondriale et ainsi à la production d'énergie via la phosphorylation oxydative. Pour finir, nous avons montré que CBP est présent dans les mitochondries d'autres types cellulaires et d'autres espèces, suggérant que CBP aurait un rôle important et conservé dans le contrôle de la fonction mitochondrialeCBP (CREB Binding Protein also called KAT3A) is a nuclear co-activator with an acetyltransferase activity. It interacts with a large number of transcription factors and thus regulates the transcription of many genes thereby being involved in a wide range of processes (proliferation, differentiation, apoptosis ...). CBP expression is also deregulated in several pathologies such as Rubinstein-Taybi Syndrome or cancers. For instance, CBP has been shown to regulate myogenesis, i.e. the formation of muscles during embryogenesis and during regeneration in adults. In this work, we studied the role of CBP in this process using human primary myoblasts as a model. The analysis of CBP expression and sub-cellular localization in these cells showed that a fraction of the protein is found inside mitochondria. This finding suggests for the first time a role of this well-known nuclear co-activator outside of the nucleus. Hence, my Ph.D. project focused on deciphering the functions of CBP in this organelle. Mitochondria have their own genome and one of their main functions is to produce the energy required for the cell functions. We have shown that the cellular metabolic state controls the import of CBP into mitochondria. We also found that CBP and its acetyltransferase activity regulate the mitochondrial DNA replication and transcription. Furthermore, our results indicate that CBP is involved in the regulation of mitochondrial oxidative phosphorylation and therefore in the energy production. Finally, we show that CBP is also in mitochondria in other cell types and in other species, strongly suggesting that CBP functions in mitochondria are important and conserved
8
Jomrich, Gerd, Florian Maroske, Jasmin Stieger, Matthias Preusser, Aysegül Ilhan-Mutlu, Daniel Winkler, Ivan Kristo, Matthias Paireder, and Sebastian Friedrich Schoppmann. "MK2 and ETV1 Are Prognostic Factors in Esophageal Adenocarcinomas." IVyspring International Publisher, 2018. http://dx.doi.org/10.7150/jca.22310.
Анотація:
Background. Esophageal cancer is ranked in the top ten of diagnosed tumors worldwide. Even though
improvements in survival could be noticed over the last years, prognosis remains poor. ETS
translocation variant 1 (ETV1) is a member of a family of transcription factors and is phosphorylated
by mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2). Aim of this study was
to evaluate the prognostic role of MK2 and ETV1 in esophageal cancer.
Methods. Consecutive patients that underwent surgical resection at the department of surgery at the
Medical University of Vienna between 1991 and 2012 were included into this study. After
microscopic analysis, tissue micro arrays (TMAs) were created and immunohistochemistry was
performed with antibodies against MK2 and ETV1.
Results. 323 patients were included in this study. Clinical data was achieved from a prospective
patient data base. Nuclear overexpression of MK2 was observed in 143 (44.3%) cases for nuclear
staining and in 142 (44.0%) cases a cytoplasmic overexpression of MK2 was observed. Nuclear and
cytoplasmic ETV1 overexpression was detected in 20 cases (6.2%) and 30 cases (9.3%), respectively.
In univariate survival analysis, cMK2 and nETV1 were found to be significantly associated with
patients' overall survival. Whereas overexpression of cMK2 was associated with shorter, nETV1
was associated with longer overall survival. In multivariate survival analysis, both cMK2 and nETV1
were found to be independent prognostic factors for the subgroup of EAC as well.
Discussion. Expression of MK2 and ETV1 are prognostic factors in patients, with esophageal
adenocarcinoma.
9
Mikaelian, Ivan. "Identification des domaines fonctionnels de la protéine EB1, activateur des gènes précoces du virus d'Epstein-Barr." Lyon 1, 1992. http://www.theses.fr/1992LYO1T178.
10
Gruffat, Henri. "Caractérisation fonctionnelle des éléments géniques transmettant l'effet activateur du facteur de transcription R codé par le virus d'Epstein-Barr." Lyon 1, 1991. http://www.theses.fr/1991LYO1T128.
Книги з теми "ARN activateur":
1
Martorell, Francisco. How do earnings change when reservists are activated?: A reconciliation of estimates derived from survey and administrative data. Santa Monica, CA: RAND Corp., 2008.
2
Trambakoulos, Dimitra Mimi. Cardiovascular effects of activated coagulation FXII, "new pressor protein" (NPP), are associated with potent adrenal medullary catecholamine release. Ottawa: National Library of Canada, 1999.
3
Bashin, Yuriy, Gennadiy Grinev, and Yuliya Dremova. Economics of the information society. ru: INFRA-M Academic Publishing LLC., 2020. http://dx.doi.org/10.12737/1039916.
Анотація:
The textbook presents modern ideas about the development and formation of the economy of the information society. Scientific concepts of transformation of the modern post-industrial society into an information society based on information and communication technologies and knowledge are highlighted. The basic concepts of technological processes of the information society, as well as definitions and dynamics of development of information resources, products and services in the economy of the information society, and a number of other topical issues are presented. The structure of the manual helps to identify the main aspects of the studied socio-economic processes, organize and specify the educational process. Questions for self-control and tasks are offered to activate the assimilation of the material. Meets the requirements of the Federal state educational standards of higher education of the latest generation. It is intended for students of higher educational institutions studying in the field of training 38.03.05 "Business Informatics".
4
Beninger, Richard J. Dopamine as the dependent variable. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198824091.003.0005.
Анотація:
Dopamine as the dependent variable discusses how postmortem biochemistry, intracerebral microdialysis, electrophysiological recording, in vivo electrochemistry, and positron emission tomography studies provide compelling evidence that dopaminergic neurons are activated by primary rewarding stimuli including food and water and by numerous conditioned incentives, including money. Early in training, primary rewarding stimuli activate dopaminergic neurons. When a cue is reliably paired with a primary rewarding stimulus over trials, the dopamine response begins to be seen upon presentation of the cue and eventually is not seen upon presentation of the primary rewarding stimulus when it follows the cue. These conditioned cues acquire the ability to act as rewarding stimuli that can produce incentive learning. If conditioned incentive stimuli are repeatedly presented in the absence of primary incentive stimuli, they gradually lose their ability to elicit approach and other responses and to act as rewarding stimuli by producing incentive learning in their own right.
5
Sullivan, Mark D. Advancing from Activated Patient to Autonomous Patient. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780195386585.003.0008.
Анотація:
Patient action in chronic disease care may not be best understood as “behavior.” Healthy patients do not just emit healthy behaviors but act as agents in their own lives. Bandura revolutionized health psychology through his “agentic” approach that emphasized patient confidence or self-efficacy. Now, the personal importance of behavior change is elicited using techniques like motivational interviewing. These and other approaches that include personal goals and identity shift our focus from behavior to action. Health action includes not just management of a disease separate from the self, but self-transformation. Achieving lasting change in health actions requires attention to the autonomous quality of patient motivation. Self-determination theory offers a useful theory of intrinsic motivation and an understanding of the process of internalization of motivation. This helps us understand the promise of shared decision-making and its difference from informed consent. Ultimately, patient empowerment must be understood as fostering patient autonomy.
6
Beninger, Richard J. Dopamine and the elements of incentive learning. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198824091.003.0003.
Анотація:
Dopamine and the elements of incentive learning explains how, in lever pressing for food tasks, incentive learning produces a gradient of attractiveness of environment stimuli: during magazine training, food activates dopaminergic neurons and the click and food cup become conditioned incentive stimuli, acquiring the ability to elicit approach and other responses; during lever-press training, the click activates dopaminergic neurons and the lever and lever-related stimuli become conditioned incentive stimuli. In conditioned place preference, amphetamine enhances dopaminergic neurotransmission and stimuli paired with amphetamine become conditioned incentive stimuli. In conditioned activity experiments, test-box stimuli paired with a dopamine-enhancer, e.g., cocaine, produce greater activity revealing incentive learning. In conditioned avoidance, the offset of an aversive warning stimulus putatively activates dopaminergic neurons leading safety-related stimuli to become conditioned incentive stimuli. If trained animals are treated with a dopamine receptor blocker, the initially intact ability of conditioned incentive stimuli to control responding declines over trials.
7
De Souza, Jonathan. Sounding Actions. Oxford University Press, 2017. http://dx.doi.org/10.1093/acprof:oso/9780190271114.003.0003.
Анотація:
When a musical instrument converts energy into sound, it makes aspects of the player’s action audible. This chapter analyzes this action-sound coupling in various instruments, drawing on ecological acoustics, organology, and cybernetics. It introduces a distinction between two aspects of sound production—“activation” and “control”—either of which may come from the player or the instrument. Pipe organs, for example, are activated by nonhuman power sources, though the pitches are controlled by the organist. Barrel organs, by contrast, are activated by human energy, but the pitches are preprogrammed. Instrumental sound production also involves distinctive combinations of sonic, visual, and tactile feedback. Moreover, by adapting Merleau-Ponty’s work on the body schema, this theory of action-sound coupling accounts for the feeling, often reported by performers, that an instrument is an extension of the body.
8
Kleihues, Paul, Elisabeth Rushing, and Hiroko Ohgaki. The 2016 revision of the WHO classification of tumours of the central nervous system. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199651870.003.0001.
Анотація:
The revised fourth edition of the WHO classification of Tumours of the Central Nervous System, published in 2016, comprises several newly recognized tumour entities, and a significant restructuring of the classification, mainly based on genetic profiling. Glioblastomas are now classified into two major types. Isocitrate dehydrogenase (IDH)-wildtype glioblastoma (primary glioblastoma IDH-wildtype) develops rapidly de novo without a recognizable precursor lesion. IDH-mutant glioblastoma (secondary glioblastoma IDH-mutant) develops more slowly through malignant progression from diffuse or anaplastic astrocytoma. Medulloblastomas are now defined by combining histological patterns (classic, desmoplastic/nodular, extensive nodularity, anaplastic) and genetic hallmarks (WNT-activated; SHH-activated, TP53-mutant; SHH-activated, TP53-wildtype; non-WNT/non-SHH). Other newly recognized tumour entities include diffuse midline glioma, H3 K27M-mutant; ependymoma, RELA fusion-positive; and embryonal tumour with multilayered rosettes. The new classification is a significant step forward and will facilitate the development of novel targeted therapies of brain tumours.
9
Grom, Alexei A., and Athimalaipet V. Ramanan. Macrophage activation syndrome. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0168.
Анотація:
Macrophage activation syndrome (MAS) is a life-threatening condition caused by excessive activation and proliferation of T lymphocytes and haemophagocytic macrophages. Although MAS has been reported in association with almost any rheumatic disease, it is by far most common in systemic juvenile idiopathic arthritis. Flares of the underlying disease or infection are most common triggers of MAS. The pathognomonic feature of MAS is typically found in bone marrow: numerous, well-differentiated macrophagic histiocytes phagocytosing normal haematopoietic elements. The expansion of these histiocytes leads to a massive systemic inflammatory reaction associated with three cardinal clinical features: severe cytopenias, liver dysfunction, and coagulopathy consistent with disseminated intravascular coagulation. Clinically, MAS is strikingly similar to the autosomal recessive disorders collectively known as familial haemophagocytic lymphohistiocytosis (FHLH). FHLH has been associated with various genetic defects affecting the cytolytic pathway. Cytolytic function is profoundly depressed in MAS patients as well, and this abnormality is caused by both genetic and acquired factors. Studies in animals suggest that uncontrolled expansion of activated CD8+ T lymphocytes secreting cytokines that activate macrophages is central to the pathophysiology of haemophagocytic syndromes. Consistent with this view, the combination of steroids and ciclosporin, an immunosuppressant that preferentially inhibits T lymphocytes, is an effective treatment for the majority of MAS patients. Patients in whom MAS remains active despite this treatment present a serious challenge and require more aggressive immunosuppression. However, in MAS triggered by infection, the optimal level of immunosuppression is difficult to determine. As a result, reported mortality rates reach 20%.
10
Beninger, Richard J. Life's rewards. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198824091.001.0001.
Анотація:
Life’s Rewards: Linking Dopamine, Incentive Learning, Schizophrenia, and the Mind explains how increased brain dopamine produces reward-related incentive learning, the acquisition by neutral stimuli of increased ability to elicit approach and other responses. Dopamine decreases may produce inverse incentive learning, the loss by stimuli of the ability to elicit approach and other responses. Incentive learning is gradually lost when dopamine receptors are blocked. The brain has multiple memory systems defined as “declarative” and “non-declarative;” incentive learning produces one form of non-declarative memory. People with schizophrenia have hyperdopaminergia, possibly producing excessive incentive learning. Delusions may rely on declarative memory to interpret the world as it appears with excessive incentive learning. Parkinson’s disease, associated with dopamine loss, may involve a loss of incentive learning and increased inverse incentive learning. Drugs of abuse activate dopaminergic neurotransmission, leading to incentive learning about drug-associated stimuli. After withdrawal symptoms have been alleviated by detoxification treatment, drug-associated conditioned incentive stimuli will retain their ability to elicit responses until they are repeatedly experienced in the absence of primary drug rewards. Incentive learning may involve the action of dopamine at dendritic spines of striatal medium spiny neurons that have recently had glutamatergic input from assemblies of cortical neurons activated by environmental and proprioceptive stimuli. Glutamate initiates a wave of phosphorylation normally followed by a wave of phosphatase activity. If dopaminergic neurons fire, stimulation of D1 receptors prolongs the wave of phosphorylation, allowing glutamate synaptic strengthening. Activity in dopaminergic neurons in humans appears to affect mental experience.
Частини книг з теми "ARN activateur":
1
Klapars, Artis. "Glucokinase Activator." In The Art of Process Chemistry, 223–39. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 2010. http://dx.doi.org/10.1002/9783527633562.ch8.
2
Duesberg, P. H., M. Nunn, Nancy Kan, D. Watson, P. H. Seeburg, and T. Papas. "Are Activated Proto-onc Genes Cancer Genes?" In Modern Trends in Human Leukemia VI New Results in Clinical and Biological Research Including Pediatric Oncology, 9–27. Berlin, Heidelberg: Springer Berlin Heidelberg, 1985. http://dx.doi.org/10.1007/978-3-642-70385-0_4.
3
Duesberg, Peter H., Michael Nunn, Nancy Kan, Dennis Watson, Peter H. Seeburg, and Takis Papas. "Are Activated Proto-ONC Genes Cancer Genes?" In Cell Transformation, 21–63. Boston, MA: Springer US, 1985. http://dx.doi.org/10.1007/978-1-4684-5009-5_2.
4
Waller, Michael, and Ulrich Kohnert. "Reteplase, a recombinant plasminogen activator." In Biopharmaceuticals, an Industrial Perspective, 185–216. Dordrecht: Springer Netherlands, 1999. http://dx.doi.org/10.1007/978-94-017-0926-2_8.
5
Dirican, Enver Kerem. "Magnetic-Activated Cell Sorting of Human Spermatozoa." In Gamete Assessment, Selection and Micromanipulation in ART, 131–44. New York, NY: Springer New York, 2013. http://dx.doi.org/10.1007/978-1-4614-8360-1_9.
6
Duesberg, Peter H., Michael Nunn, Nancy Kan, Dennis Watson, Peter H. Seeburg, and Takis Papas. "Which Cancers are Caused by Activated Proto-Onc Genes?" In RNA Tumor Viruses, Oncogenes, Human Cancer and AIDS: On the Frontiers of Understanding, 168–90. Boston, MA: Springer US, 1985. http://dx.doi.org/10.1007/978-1-4613-2583-3_14.
7
Newton, Peter W., Peter W. G. Newman, Stephen Glackin, and Giles Thomson. "The Global Greyfields Transition: Why Urban Redevelopment in Low-Density, Car-Based Middle Suburbs Needs a New Model." In Greening the Greyfields, 1–48. Singapore: Springer Singapore, 2021. http://dx.doi.org/10.1007/978-981-16-6238-6_1.
Анотація:
AbstractThis chapter provides the framework and rationale for Greening the Greyfields and its two new models for greyfield precinct regeneration (GPR): place-activated and transit-activated GPR. They provide a basis for regenerative urban redevelopment in the middle-ring greyfield suburbs of fast-growing, low-density cities. Place-activated GPR advances a new development model for the ‘missing middle’ in cities: new medium-density housing at precinct scale. Transit-activated GPR extends new sustainable modes of mobility into car-dependent suburbs. Both processes are required for retrofitting suburbia to fix the shortcomings of mid- to late-twentieth-century urban planning and development.
8
Cooper, Jonathan A., Nathaniel S. Allen, and Libing Feng. "Protein Kinases and Signaling Pathways that Are Activated by Reelin." In Reelin Glycoprotein, 193–216. New York, NY: Springer New York, 2008. http://dx.doi.org/10.1007/978-0-387-76761-1_13.
9
Ilg, U. J., and P. Thier. "MST Neurons are Activated by Smooth Pursuit of Imaginary Targets." In Parietal Lobe Contributions to Orientation in 3D Space, 173–84. Berlin, Heidelberg: Springer Berlin Heidelberg, 1997. http://dx.doi.org/10.1007/978-3-642-60661-8_10.
10
Ilg, U. J., J. A. Rommel, and P. Thier. "Parietal Neurons are Activated by Smooth Pursuit of Imaginary Targets." In Current Oculomotor Research, 37–44. Boston, MA: Springer US, 1999. http://dx.doi.org/10.1007/978-1-4757-3054-8_5.
Тези доповідей конференцій з теми "ARN activateur":
1
Govers-Riemslag, J. W. P., M. H. J. Knapen, G. Tans, R. F. A. Zwaal, and J. Rosing. "STRUCTURAL AND FUNCTIONAL PROPERTIES OF A PROTHROMBIN ACTIVATOR FROM THE VENOM OF BOTHROPS NEUWIDI." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644321.
Анотація:
The prothrombin activator from the venom of Bothrops neuwidi has been purified to homogeniety by gelfiltration on Sephadex G-100, ion-exchange chromatography on DEAE-Sephacel and metal-chelate affinity chromatography on an Epoxy-activated Sepharose 6B column loaded with ZnCl . The overall purification was about 200-fold, which indicates that the crude venom contains about 0.5 weight % of the prothrombin activator. The venom activator is a single chain protein with an apparent molecular weight of 60,000 dalton. It readily activated bovine prothrombin with a Km of 37.7 uM and a Vmax of 120 umoles prothrombin activated per min/mg of purified venom activator. Venom-catalyzed prothrombin activation was not accelerated by the accessory components of the prothrombinase complex i.e. phospholipids plus calcium-ions and Factor Va. The venom activator does not require added calcium-ions for the expression of its prothrombin-converting activity. Calcium ions do, however, affect the catalytic activity of the venom activator. At 2 mM CaCl there is a 2-fold increase of the rate of venom-catalyzed prothrombin activation. However, at higher CaCl concentrations there is a gradual decrease of the activity of the venom activator. Gelelectro-phoretic analysis of prothrombin activation indicated that the venom activator only cleaved the Arg 323-Ile 324 bond of bovine prothrombin since meizothrombin was the only product of prothrombin activation. The activator did not hydrolyze the chromogenic substrates S2222, S2337, S2238, S2366, S2302 or chromozym TH and its prothrombin converting activity was not inhibited by benza-midine, phenylmethylsulfonylfluoride, dansyl-glu-gly-arg-chloro-methylketone and soybean trypsin inhibitor. However, chelating agents such as EDTA, EGTA and o-phenanthroline strongly inhibited the enzymatic activity of the venom activator. The activity of chelator-treated venom activator could, however, be restored by the addition of an excess CaCl . These results indicate that the enzyme from Bothrops neuwidi does not belong to the serine proteases but has the properties of a metal proteinase. Thus, the activator differs remarkably from Factor Xa, but strongly resembles the prothrombin activator from the venom of Echis carinatus, both structurally and functionally.
2
Hariman, H., J. R. Hughes, P. J. Grant, and J. A. Davies. "THE EFFECTS OF PHYSIOLOGICAL CONCENTRATIONS OF VASOPRESSIN ON COMPONENTS OF THE FIBRINOLYTIC PATHWAY." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643121.
Анотація:
Evidence from studies in man suggests that vasopressin (aVP) at physiological concentrations activates the coagulation pathway, increases plasminogen activator activity and may have a role in the regulation of haemostasis under conditions of physical stress. Infusion of aVP in normal subjects increases plasma factor VIII concentrations and shortens the euglobulin clot lysis time (ECLT), but the mechanisms involved in these changes and their haemostatic significance are unclear. The aims of this study were to investigate the effects of aVP on the fibrinolytic pathway and to evaluate whether thrombin or plasmin are generated in vivo by aVP. After 30 min 0.9% saline infusion, vasopressin (20iu in 250ml 0.9% saline) was infused at 2.0 u/h for 1h in 9 normal subjects to achieve plasma aVP concentrations comparable to those attained during stress. Venous blood samples were taken before saline infusion (time 0) and every 30 min for 2h for assay of aVP, activated partial thromboplastin time (APTT), fibrinopeptide A (FPA), FPA generation time, FPBB15-42 ECLT, tissue-type plasminogen activator (t-PA) and t-PA inhibition. Plasma aVP rose frcm 0.5 pg/ml at time 0 to (median) 70.7 pg/ml at 90 min. The APTT shortened from 43.8 ± 1.9 to 34.4 ± 1.6 (SEM) seconds (p < 0.001) at 90 min. Plasma FPA and the FPA generation time remained unchanged (p > 0.05). Plasminogen activator activity rose from 36.4 ± 15.2 to 587.5 ± 206.6 units (p < 0.005), t-PA increased frcm 229.8 ± 20.4 to 1107.4 ± 224.1 ml.U/ml (p < 0.005) and t-PA inhibition fell frcm 7.9 ± 1.1 to 3.9 ± 0.9 I.U/ml (p < 0.05) in response to the aVP infusion. FPB815-42 increased frcm a baseline value of 1.7 ± 0.4 to 2.2 ± 0.7 pmol/ml after 90 min (p < 0.05). The results suggest the effects of aVP on fibrinolysis are due to an increase in t-PA and decrease in t-PA inhibition. The increase in FPBB 15-42 with no change in FPA supports the hypothesis that plasmin was generated by non-fibrin dependent pathways.
3
Rose, Jr., C. E., Marie D. Burdick, Brett A. Strieter, Ling Liu, and Robert M. Strieter. "Increased Circulating Activated Fibrocytes Are Associated With Severe Asthma." In American Thoracic Society 2011 International Conference, May 13-18, 2011 • Denver Colorado. American Thoracic Society, 2011. http://dx.doi.org/10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a3722.
4
Taylor-Clark, Tom, Lika Nesuashvili, Stephen Hadley, and Parmvir Bahia. "Airway Sensory Nerves Are Activated By Acute Mitochondrial Modulation." In American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California. American Thoracic Society, 2012. http://dx.doi.org/10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a2158.
5
Roberts, NJ, and S. McNarry. "P107 Non completers in pulmonary rehabilitation – are they activated?" In British Thoracic Society Winter Meeting 2018, QEII Centre, Broad Sanctuary, Westminster, London SW1P 3EE, 5 to 7 December 2018, Programme and Abstracts. BMJ Publishing Group Ltd and British Thoracic Society, 2018. http://dx.doi.org/10.1136/thorax-2018-212555.265.
6
Lambers, J. W. J., M. Cammenga, B. Konig, H. Pannekoek, and J. A. van Mourik. "ACTIVATION OF HUMAN ENDOTHELIAL TYPE PLASMINOGEN ACTIVATOR INHIBITOR (PAI-1) BY NEGATIVELY CHARGED PHOSPHOLIPIDS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642807.
Анотація:
The endothelial cell type plasminogen activator inhibitor (PAI-1) may exist in an active, latent form that can be converted into an active form upon exposure to denaturants such as sodium dodecyl sulphate (SDS), guanidine-HCl or urea. Here we show that latent PAI-1 can be activated with lipid vesicles, consisting of the negatively charged phospholipids phosphatidylserine (PS) or phosphatidylinositol (PI). The presence of a net negative charge on the phospholipid headgroup is essential for activation. Incubation with lipid vesicles, consisting of the zwitterionic phospholipids phosphatidylcholine (PC) and phosphatidylethanol-amine (PE), does not result in activation of the inhibitor. In the presence of PS vesicles, the capacity of PAI-1 to inhibit tissue type plasminogen activator (t-PA) is 50-fold higher than that of the untreated protein. For comparison, the activity of PAI-1 was enhanced 25-fold by treatment of the protein with SDS. PS induces activation of the inhibitor at much lower concentrations than SDS. For example, to achieve 50% inhibition of t-PA with a more than 100-fold excess of PAI-1, 0.25 nmoles of PS are required, whereas L.60 nmoles of SDS are necessary to reach half maximal inactivation of t-PA. Activation of PAI-1 by PS can be reversed by the addition of Ca2+-ions, suggesting that Ca2+-ions interfere with the interaction of PAI-1 with the negatively charged lipid surface, thus preventing its activation. The lipid-induced activation of PAI-1 points to a possibly important role of phospholipids in fibrinolysis; regulation of the fibrinolytic activity in blood plasma may ultimately be determined by the extent to which these phospholipids activate the inhibitor of t-PA.This study was supported by the Netherlands Thrombosis Foundation.
7
Comp, P. C., and C. T. Esmon. "Defects in the protein C pathway." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643715.
Анотація:
Activated protein C functions as an anticoagulant by enzymatically degrading factors Va and Villa in the clotting cascade. Protein C may be converted to its enzymatically active form bythrombin. The rate at which thrombin cleavage of the zymogen occurs is greatly enhanced when thrombin is bound to an endothelial cell receptor protein, thrombomodulin. Activated proteinC has a relatively long half-life in vivo and the formation of activated protein C in response to low level thrombin infusion suggests that the protein C system may provide a feedback mechanism to limit blood clotting. Clinical support for such a physiologic role for activated protein C includes an increased incidence of thrombophlebitis and pulmonary emboli in heterozygous deficient individuals, and severe, often fatal, cutaneous thrombosis in homozygous deficient newborns. A third thrombotic condition associated with protein C deficiency is coumarin induced skin (tissue) necrosis. This localized skin necrosis occurs shortly after the initiation of coumarin therapy and is hypothesized to bedue to the rapid disappearance of protein C activity in the plasma beforean adequate intensity of anticoagulation is achieved. Recent estimates of heterozygous protein C deficiency range as high as 1 in 300 individuals in the general population. Since coumarin compounds are in routine clinical use throughout the world and skin necrosis remains a relatively rare clinical finding, this suggests that factors other than protein C deficiency alone may be involved in the pathogenesis of the skin necrosis.The anticoagulant properties of activated protein C are greatly enhanced by another vitamin K-dependent plasma protein, protein S. Protein S functions by increasing the affinity of activated protein C for cell surfaces.Protein S is found in two forms in plasma: free and in complex with C4b-binding protein, "an inhibitor of the complement system. Free protein S is functionally active and the complexed protein S is not active. Individuals congenitally deficient in protein S ae subject to recurrent thromboembolicevents. At least two classes of protin S deficiency occur.Some patienshavedecreased levels of protein S antigen and reduced protein S functional activity. A second group of deficient individuals have normal levels of protein S antigen but most or all their protein S is complexed to C4b-binding protein and they have little or no functional protein S activity. Such a protein S distribution could result from abnormal forms of protein S or C4b-binding protein or some other abnormal plasma or cellular component. Patients with functionally inactive forms of protein S have yet to be identified. Identification of protein S deficient individuals is complicated by thepossible effect of sex hormones on plasma protein S levels. Total protein S antigen is reduced during pregnancyand during oral contraceptive administration. This finding is of practicalclinical importance since the decrease in protein S which occurs during pregnancy may be an added risk factor for congenitally protein S deficient women and may explain why some proteinS deficient women experience their first episode of thrombosis during pregnancy.In addition to having anticoagulant properties, activated protein C enhances fibrinolysis, at least in part,by inhibiting the inhibitor of tissueplasminogen activator. This profibrinolytic effect is enhanced by protein S and cell surfaces. This protection of plasminogen activator activity suggests that the combination of tissue plasminogen activator and activated protein C may be useful in the treatment of coronary artery thrombi. Tissueplasminogen activator would promote clot lysis while activated protein C protected the plasminogen activatorfrom inhibition and also prevented further clot deposition. There is no evidence at present that fibrinolytic activity is reduced in protein C deficient individuals. The possible clinical relevance of this aspect of protein Cfunction in the predisposition of protein C deficient individuals to thrombosis remains to be defined.
8
Hiraga, F., N. Nakamura, and I. Miki. "Remote Dismantling of Activated Reactor Internals with Plasma Arc Torch." In 6th International Symposium on Automation and Robotics in Construction. International Association for Automation and Robotics in Construction (IAARC), 1989. http://dx.doi.org/10.22260/isarc1989/0037.
9
Ganguly, Sourik S., Leann S. Fiore, Jonathan T. Sims, J. Woodrow Friend, DivyaMani Srinivasan, Matthew Thacker, Michael L. Cibull, Wang Chi, and Rina Plattner. "Abstract C51: c-Abl and Arg are activated in human primary melanomas, promote melanoma cell invasion, proliferation, survival, and drive metastatic progression." In Abstracts: AACR Special Conference on Tumor Invasion and Metastasis - January 20-23, 2013; San Diego, CA. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.tim2013-c51.
10
Matsuyama, H., T. Isshiki, A. Chiba, T. Yamaguchi, G. Murayama, Y. Akasaka, Y. Eishi, S. Miyake, and S. Homma. "Mucosal-Associated Invariant T Cells Are Activated in Lungs of Sarcoidosis." In American Thoracic Society 2019 International Conference, May 17-22, 2019 - Dallas, TX. American Thoracic Society, 2019. http://dx.doi.org/10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a2427.
Звіти організацій з теми "ARN activateur":
1
Trowbridge, L. Isotopic selectivity of surface diffusion: An activated diffusion model. Office of Scientific and Technical Information (OSTI), November 1989. http://dx.doi.org/10.2172/5462238.
2
Prusky, Dov, Nancy P. Keller, and Amir Sherman. global regulation of mycotoxin accumulation during pathogenicity of Penicillium expansum in postharvest fruits. United States Department of Agriculture, January 2014. http://dx.doi.org/10.32747/2014.7600012.bard.
Анотація:
Background to the topic- Penicilliumas a postharvest pathogen and producer of the mycotoxin PAT. Penicilliumspp. are destructive phytopathogens, capable of causing decay in many deciduous fruits, during postharvest handling and storage; and the resulting losses can amount to 10% of the stored produce and the accumulation of large amounts of the mycotoxinpatulin. The overall goal of this proposal is to identify critical host and pathogen factors that modulate P. expansummycotoxin genes and pathways which are required for PAT production and virulence. Our preliminary results indicated that gluconic acid are strongly affecting patulin accumulation during colonization. P. expansumacidifies apple fruit tissue during colonization in part through secretion of gluconic acid (GLA). Several publications suggested that GLA accumulation is an essential factor in P. expansumpathogenicity. Furthermore, down regulation of GOX2 significantly reduced PAT accumulation and pathogenicity. PAT is a polyketide and its biosynthesis pathway includes a 15-gene cluster. LaeA is a global regulator of mycotoxin synthesis. It is now known that patulin synthesis might be subjected to LaeA and sometimes by environmental sensing global regulatory factors including the carbon catabolite repressor CreA as well as the pH regulator factor PacC and nitrogen regulator AreA. The mechanisms by which LaeA regulates patulin synthesis was not fully known and was part of our work. Furthermore, the regulatory system that controls gene expression in accordance with ambient pH was also included in our work. PacC protein is in an inactive conformation and is unable to bind to the promoter sites of the target genes; however, under alkaline growth conditions activated PacC acts as both an activator of alkaline-expressed genes and a repressor of acid-expressed genes. The aims of the project- This project aims to provide new insights on the roles of LaeA and PacC and their signaling pathways that lead to GLA and PAT biosynthesis and pathogenicity on the host. Specifically, our specific aims were: i) To elucidate the mechanism of pH-controlled regulation of GLA and PAT, and their contribution to pathogenesis of P. expansum. We are interested to understanding how pH and/or GLA impact/s under PacC regulation affect PAT production and pathogenesis. ii) To characterize the role of LaeA, the global regulator of mycotoxin production, and its effect on PAT and PacC activity. iii) To identify the signaling pathways leading to GLA and PAT synthesis. Using state- of-the-art RNAseq technologies, we will interrogate the transcriptomes of laeAand pacCmutants, to identify the common signaling pathways regulating synthesis of both GLA and PAT. Major conclusions, solutions, achievements- In our first Aim our results demonstrated that ammonia secreted at the leading edge of the fungal colony induced transcript activation of the global pH modulator PacC and PAT accumulation in the presence of GLA. We assessed these parameters by: (i) direct exogenous treatment of P. expansumgrowing on solid medium; (ii) direct exogenous treatment on colonized apple tissue; (iii) growth under self-ammonia production conditions with limited carbon; and (iv) analysis of the transcriptional response to ammonia of the PAT biosynthesis cluster. Ammonia induced PAT accumulation concurrently with the transcript activation of pacCand PAT biosynthesis cluster genes, indicating the regulatory effect of ammonia on pacCtranscript expression under acidic conditions. Transcriptomic analysis of pH regulated processes showed that important genes and BARD Report - Project 4773 Page 2 of 10 functionalities of P. expansumwere controlled by environmental pH. The differential expression patterns of genes belonging to the same gene family suggest that genes were selectively activated according to their optimal environmental conditions to enable the fungus to cope with varying conditions and to make optimal use of available enzymes. Concerning the second and third Aims, we demonstrated that LaeA regulates several secondary metabolite genes, including the PAT gene cluster and concomitant PAT synthesis invitro. Virulence studies of ΔlaeAmutants of two geographically distant P. expansumisolates (Pe-21 from Israel and Pe-T01 from China) showed differential reduction in disease severity in freshly harvested fruit ranging from no reduction for Ch-Pe-T01 strains in immature fruit to 15–25% reduction for both strains in mature fruit, with the ΔlaeAstrains of Is-Pe-21 always showing a greater loss in virulence. Results suggest the importance of LaeA regulation of PAT and other secondary metabolites on pathogenicity. Our work also characterized for the first time the role of sucrose, a key nutritional factor present in apple fruit, as a negative regulator of laeAexpression and consequent PAT production in vitro. This is the first report of sugar regulation of laeAexpression, suggesting that its expression may be subject to catabolite repression by CreA. Some, but not all of the 54 secondary metabolite backbone genes in the P. expansumgenome, including the PAT polyketide backbone gene, were found to be regulated by LaeA. Together, these findings enable for the first time a straight analysis of a host factor that potentially activates laeAand subsequent PAT synthesis.
3
Wall, M. A., T. W. Jr Barbee, and T. P. Weihs. An in situ electron microscopy technique for the study of thermally activated reactions in multilayered materials. Office of Scientific and Technical Information (OSTI), April 1995. http://dx.doi.org/10.2172/132651.
4
Daniel J. Stepan, Thomas A. Moe, Melanie D. Hetland, and Margaret L. Laumb. POWDERED ACTIVATED CARBON FROM NORTH DAKOTA LIGNITE: AN OPTION FOR DISINFECTION BY-PRODUCT CONTROL IN WATER TREATMENT PLANTS. Office of Scientific and Technical Information (OSTI), June 2001. http://dx.doi.org/10.2172/825585.
5
Sessa, Guido, та Gregory Martin. MAP kinase cascades activated by SlMAPKKKε and their involvement in tomato resistance to bacterial pathogens. United States Department of Agriculture, січень 2012. http://dx.doi.org/10.32747/2012.7699834.bard.
Анотація:
The research problem: Pseudomonas syringae pv. tomato (Pst) and Xanthomonas campestrispv. vesicatoria (Xcv) are the causal agents of tomato bacterial speck and spot diseases, respectively. These pathogens colonize the aerial parts of the plant and cause economically important losses to tomato yield worldwide. Control of speck and spot diseases by cultural practices or chemicals is not effective and genetic sources of resistance are very limited. In previous research supported by BARD, by gene expression profiling we identified signaling components involved in resistance to Xcvstrains. Follow up experiments revealed that a tomato gene encoding a MAP kinase kinase kinase (MAPKKKe) is required for resistance to Xcvand Pststrains. Goals: Central goal of this research was to investigate the molecular mechanisms by which MAPKKKεand associated MAP kinase cascades regulate host resistance. Specific objectives were to: 1. Determine whether MAPKKKεplays a broad role in defense signaling in plants; 2. Identify components of MAP kinase cascades acting downstream of MAPKKKε; 3. Determine the role of phosphorylation-related events in the function of MAPKKKε; 4. Isolate proteins directly activated by MAPKKKε-associatedMAPK modules. Our main achievements during this research program are in the following major areas: 1. Characterization of MAPKKKεas a positive regulator of cell death and dissection of downstream MAP kinase cascades (Melech-Bonfil et al., 2010; Melech-Bonfil and Sessa, 2011). The MAPKKKεgene was found to be required for tomato resistance to Xcvand Pstbacterial strains and for hypersensitive response cell death triggered by different R gene/effector gene pairs. In addition, overexpression analysis demonstrated that MAPKKKεis a positive regulator of cell death, whose activity depends on an intact kinase catalytic domain. Epistatic experiments delineated a signaling cascade downstream of MAPKKKεand identified SIPKK as a negative regulator of MAPKKKε-mediated cell death. Finally, genes encoding MAP kinase components downstream of MAPKKKεwere shown to contribute to tomato resistance to Xcv. 2. Identification of tomato proteins that interact with MAPKKKεand play a role in plant immunity (Oh et al., 2011). We identified proteins that interact with MAPKKKε. Among them, the 14-3-3 protein TFT7 was required for cell death mediated by several R proteins. In addition, TFT7 interacted with the MAPKK SlMKK2 and formed homodimersin vivo. Thus, TFT7 is proposed to recruit SlMKK2 and MAPKKK client proteins for efficient signal transfer. 3. Development of a chemical genetic approach to identify substrates of MAPKKKε-activated MAP kinase cascades (Salomon et al., 2009, 2011). This approach is based on engineering the kinase of interest to accept unnatural ATP analogs. For its implementation to identify substrates of MAPKKKε-activated MAP kinase modules, we sensitized the tomato MAP kinase SlMPK3 to ATP analogs and verified its ability to use them as phosphodonors. By using the sensitized SlMPK3 and radiolabeled N6(benzyl)ATP it should be possible to tag direct substrates of this kinase. 4. Development of methods to study immunity triggered by pathogen-associated molecular patterns (PAMPs) in tomato and N. benthamiana plants (Kim et al., 2009; Nguyen et al. 2010). We developed protocols for measuring various PTI-associatedphenotypes, including bacterial populations after pretreatment of leaves with PAMPs, induction of reporter genes, callose deposition at the cell wall, activation of MAP kinases, and a luciferase-based reporter system for use in protoplasts. Scientific and agricultural significance: Our research activities discovered and characterized a signal transduction pathway mediating plant immunity to bacterial pathogens. Increased understanding of molecular mechanisms of immunity will allow them to be manipulated by both molecular breeding and genetic engineering to produce plants with enhanced natural defense against disease. In addition, we successfully developed new biochemical and molecular methods that can be implemented in the study of plant immunity and other aspects of plant biology.
6
Moran, Nava, Richard Crain, and Wolf-Dieter Reiter. Regulation by Light of Plant Potassium Uptake through K Channels: Biochemical, Physiological and Biophysical Study. United States Department of Agriculture, September 1995. http://dx.doi.org/10.32747/1995.7571356.bard.
Анотація:
The swelling of plant motor cells is regulated by various signals with almost unknown mediators. One of the obligatory steps in the signaling cascade is the activation of K+-influx channels -K+ channels activated by hyperpolarization (KH channels). We thus explored the regulation of these channels in our model system, motor cell protoplasts from Samanea saman, using patch-clamp in the "whole cell" configuration. (a) The most novel finding was that the activity of KH channels in situ varied with the time of the day, in positive correlation with cell swelling: in Extensor cells KH channels were active in the earlier part of the day, while in Flexor cells only during the later part of the day; (b) High internal pH promoted the activity of these channels in Extensor cells, opposite to the behavior of the equivalent channels in guard cells, but in conformity with the predicted behavior of the putative KH channel, cloned from S. saman recently; (c) HIgh external K+ concentration increased (KH channel currents in Flexor cells. BL depolarized the Flexor cells, as detected in cell-attached patch-clamp recording, using KD channels (the K+-efflux channels) as "voltage-sensing devices". Subsequent Red-Light (RL) pulse followed by Darkness, hyperpolarized the cell. We attribute these changes to the inhibition of the H+-pump by BL and its reactivation by RL, as they were abolished by an H+-pump inhibitor. BL increased also the activity KD channels, in a voltage-independent manner - in all probability by an independent signaling pathway. Blue-Light (BL), which stimulates shrinking of Flexor cells, evoked the IP3 signaling cascade (detected directly by IP3 binding assay), known to mobilize cytosolic Ca2+. Nevertheless, cytosolic Ca2+ . did not activate the KD channel in excised, inside-out patches. In this study we established a close functional similarity of the KD channels between Flexor and Extensior cells. Thus the differences in their responses must stem from different links to signaling in both cell types.
7
Gu, B., and K. E. Dowlen. An investigation of groundwater organics, soil minerals, and activated carbon on the complexation, adsorption, and separation of technetium-99. Office of Scientific and Technical Information (OSTI), January 1996. http://dx.doi.org/10.2172/219315.
8
Prusky, Dov, Noel T. Keen, and Stanley Freeman. Elicitation of Preformed Antifungal Compounds by Non-Pathogenic Fungus Mutants and their Use for the Prevention of Postharvest Decay in Avocado Fruits. United States Department of Agriculture, January 1996. http://dx.doi.org/10.32747/1996.7570573.bard.
Анотація:
C. gloeosporioides attacks unripe avocado fruits in the orchard. Germinated spores produce appressoria that germinate and breach the cuticle, but the resultant subcuticular hyphae become quiescent and do not develop further until fruit is harvested and ripens. Resistance of unripe avocado to attach by C. gloeosporioides is correlated with the presence of fungitoxic concentrations of the preformed antifungal compound, 1-acetoxy-2-hydroxy-4-oxoheneicosa-12, 15 diene in the pericarp of unripe fruits. The objective of this proposal was to study the signal transduction process by which elicitors induce resistance in avocado. It was found that abiotic elicitors, infection of avocado fruit with C. gloeosporioides or treatment of avocado cell suspension with cell-wall elicitor induced a significant production of reactive oxygen species (ROS). Ripe and unripe fruit tissue differ with regard to the ROS production. The unripe, resistant fruit are physiologically able to react and to produce high levels of ROS and increased activity of H+ATPase that can enhance the phenylpropanoid pathway ad regulate the levels of the antifungal compound-diene, inhibit fungal development, resulting in its quiescence. Interestingly, it was also found that growth regulators like cytokinin could do activation of the mechanism of resistance. Postharvest treatments of cytokinins strongly activated the phenylpropanoid pathway and induce resistance. We have developed non-pathogenic strains of C. gloeosporioides by Random Enzyme Mediated Integration and selected a hygromycin resistance, non-pathogenic strain Cg-142 out of 3500 transformants. This non-pathogenic isolate activates H+ATPase and induces resistance against Colletotrichum attack. As a basis for studying the importance of PL in pathogenicity, we have carried out heterologous expression of pel from C. gloeosporioides in the non-pathogenic C. magna and determine the significant increase in pathogenicity of the non-pathogenic strain. Based on these results we can state that pectate lyase is an important pathogenicity factor of C. gloeosporioides and found that fungal pathogenicity is affected not by pel but by PL secretion. Our results suggest that PH regulates the secretion of pectate lyase, and support its importance as a pathogenicity factor during the attack of avocado fruit by C. gloeosporioides . This implicates that if these findings are of universal importance in fungi, control of disease development could be done by regulation of secretion of pathogenicity factors.
9
Splitter, Gary, Zeev Trainin, and Yacov Brenner. Lymphocyte Response to Genetically Engineered Bovine Leukemia Virus Proteins in Persistently Lymphocytic Cattle from Israel and the U.S. United States Department of Agriculture, July 1995. http://dx.doi.org/10.32747/1995.7570556.bard.
Анотація:
The goal of this proposal was to identify proteins of BLV recognized by lymphocyte subpopulations and determine the contribution of these proteins to viral pathogenesis. Our hypothesis was that BLV pathogenesis is governed by the T-cell response and that the immune system likely plays an important role in controlling the utcome of infection. Our studies presented in ths final report demonstrate that T cell competency declines with advancing stages of infection. Dramatic differences were observed in lymphocyte proliferation to recombinant proteins encoded by BLV gag (p12, p15, and p24) and env (gp30 and gp15) genes in different disease stages. Because retroviruses are known to mutate frequently, examinatin of infected cattle from both Israel and the United States will likely detect variability in the immune response. This combined research approach provides the first opportunity to selectively address the importance of T-cell proliferation to BLV proteins and cytokines produced during different stages of BLV infection. Lack of this information regarding BLV infection has hindered understanding lympocyte regulation of BLV pathogenesis. We have developed the essential reagents necessary to determine the prominence of different lymphocyte subpopulations and cytokines produced during the different disease stages within the natural host. We found that type 1 cytokines (IL-2 and IFN-g) increased in PBMCs from animals in early disease, and decreasd in PBMCs from animals in late disease stages of BLV infection, while IL-10, increased with disease progression. Recently, a dichotomy between IL-12 and IL-10 has emerged in regards to progression of a variety of diseases. IL-12 activates type 1 cytokine production and has an antagonistic effect on type 2 cytokines. Here, using quantitative competitive PCR, we show that peripheral blood mononuclear cells from bovine leukemia virus infected animals in the alymphocytotic disease stage express increased amount of IL-12 p40 mRNA. In contrast, IL-12 p40 mRNA expression by PL animals was significantly decreased compared to normal and alymphocytotic animals. To examine the functions of these cytokines on BLV expression, BLV tax and pol mRNA expression and p24 protein production were quantified by competitive PCR, and by immunoblotting, respectively. IL-10 inhibited BLV tax and pol mRNA expression by BLV-infected PBMCs. In addition, we determined that macrophages secret soluble factor(s) that activate BLV expression, and that secretion of the soluble factor(s) could be inhibited by IL-10. In contrast, IL-2 increased BLV tax and pol mRNA, and p24 protein production. These findings suggest that macrophages have a key role in regulating BLV expression, and IL-10 produced by BLV-infected animals in late disease stages may serve to control BLV expression, while IL-2 in the early stage of disease may activate BLV expression. PGE2 is an important immune regulator produced only by macrophages, and is known to facilitate HIV replication. We hypothesized that PGE2 may regulate BLV expression. Here, we show that cyclooxygenase-2 (COX-2) mRNA expression was decreased in PBMCs treated with IL-10, while IL-2 enhanced COX-2 mRNA expression. In contrast, addition of PGE2 stimulated BLV tax and pol mRNA expression. In addition, the specific COX-2 inhibitor, NS-398, inhibited BLV expression, while addition of PGE2 increased BLV tax expression regardless of NS-398. These findings suggest that macrophage derived cyclooxygenase -2 products, such as PGE2, may regulate virus expression and disease rogression in BLV infection, and that cytokines (IL-2 and IL-10) may regulate BLV expression through PGE2 production.
10
Rafaeli, Ada, and Russell Jurenka. Molecular Characterization of PBAN G-protein Coupled Receptors in Moth Pest Species: Design of Antagonists. United States Department of Agriculture, December 2012. http://dx.doi.org/10.32747/2012.7593390.bard.
Анотація:
The proposed research was directed at determining the activation/binding domains and gene regulation of the PBAN-R’s thereby providing information for the design and screening of potential PBAN-R-blockers and to indicate possible ways of preventing the process from proceeding to its completion. Our specific aims included: (1) The identification of the PBAN-R binding domain by a combination of: (a) in silico modeling studies for identifying specific amino-acid side chains that are likely to be involved in binding PBAN with the receptor and; (b) bioassays to verify the modeling studies using mutant receptors, cell lines and pheromone glands (at tissue and organism levels) against selected, designed compounds to confirm if compounds are agonists or antagonists. (2) The elucidation ofthemolecular regulationmechanisms of PBAN-R by:(a) age-dependence of gene expression; (b) the effect of hormones and; (c) PBAN-R characterization in male hair-pencil complexes. Background to the topic Insects have several closely related G protein-coupled receptors (GPCRs) belonging to the pyrokinin/PBAN family, one with the ligand pheromone biosynthesis activating neuropeptide or pyrokinin-2 and another with diapause hormone or pyrokinin-1 as a ligand. We were unable to identify the diapause hormone receptor from Helicoverpa zea despite considerable effort. A third, related receptor is activated by a product of the capa gene, periviscerokinins. The pyrokinin/PBAN family of GPCRs and their ligands has been identified in various insects, such as Drosophila, several moth species, mosquitoes, Triboliumcastaneum, Apis mellifera, Nasoniavitripennis, and Acyrthosiphon pisum. Physiological functions of pyrokinin peptides include muscle contraction, whereas PBAN regulates pheromone production in moths plus other functions indicating the pleiotropic nature of these ligands. Based on the alignment of annotated genomic sequences, the primary and secondary structures of the pyrokinin/PBAN family of receptors have similarity with the corresponding structures of the capa or periviscerokinin receptors of insects and the neuromedin U receptors found in vertebrates. Major conclusions, solutions, achievements Evolutionary trace analysisof receptor extracellular domains exhibited several class-specific amino acid residues, which could indicate putative domains for activation of these receptors by ligand recognition and binding. Through site-directed point mutations, the 3rd extracellular domain of PBAN-R was shown to be critical for ligand selection. We identified three receptors that belong to the PBAN family of GPCRs and a partial sequence for the periviscerokinin receptor from the European corn borer, Ostrinianubilalis. Functional expression studies confirmed that only the C-variant of the PBAN-R is active. We identified a non-peptide agonist that will activate the PBAN-receptor from H. zea. We determined that there is transcriptional control of the PBAN-R in two moth species during the development of the pupa to adult, and we demonstrated that this transcriptional regulation is independent of juvenile hormone biosynthesis. This transcriptional control also occurs in male hair-pencil gland complexes of both moth species indicating a regulatory role for PBAN in males. Ultimate confirmation for PBAN's function in the male tissue was revealed through knockdown of the PBAN-R using RNAi-mediated gene-silencing. Implications, both scientific and agricultural The identification of a non-peptide agonist can be exploited in the future for the design of additional compounds that will activate the receptor and to elucidate the binding properties of this receptor. The increase in expression levels of the PBAN-R transcript was delineated to occur at a critical period of 5 hours post-eclosion and its regulation can now be studied. The mysterious role of PBAN in the males was elucidated by using a combination of physiological, biochemical and molecular genetics techniques.