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Artykuły w czasopismach na temat "PRR Signaling"
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Fujimori, Takeshi, Daisuke Ogawa, Kenta Suzuki, Masaaki Kochi, Yuki Shibayama, Masaki Okada, Keisuke Miyake, Akira Nishiyama i Takashi Tamiya. "ET-04 MOLECULAR TARGETED THERAPY AGAINST (PRO)RENIN RECEPTOR FOR GLIOBLASTOMA". Neuro-Oncology Advances 1, Supplement_2 (grudzień 2019): ii8—ii9. http://dx.doi.org/10.1093/noajnl/vdz039.038.
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Abstract INTRODUCTION (Pro)renin receptor(PRR) is part of the Wnt receptor complex. Wnt/β-catenin signaling pathway (Wnt signaling) plays important role in pathogenesis and self-renewal of glioblastoma (GBM), or differentiation of glioma stem cell. We previously reported that PRR activate Wnt signaling, PRR expression correlated with malignancy of glioma, and treatment with PRR siRNA reduced the proliferative capacity. This time, we have developed monoclonal antibodies against PRR and examined their effects in GBM. MATERIAL AND METHODS We used GBM cell line (U251MG and U87MG) and primary human glioma stem cell line (MGG23). Glioma stem-like cells were cultured and isolated by neurosphere method from U251MG and U87MG. PRR antibody was made targeting the extracellular domain of the PRR with rat lymph node method. WST-1 assay or MTT assay were performed to determine the cell proliferation. Apoptosis was examined by FITC labeled annexin V and propidium iodide with flow cytometry. We analyzed molecules of Wnt signaling and stem cell markers with qRT-PCR. RESULTS We observed that PRR antibody significantly reduced cell proliferation, decreased sphere formation. Antibody suppressed cell adherent in stem-like cell. Flow cytometry showed that antibody induced apoptosis. Antibody inhibited Wnt signaling and stem cell markers. CONCLUSIONS PRR antibody reduced cell proliferation and induced apoptosis through Wnt signaling. PRR antibody also suppressed stemness. Our results demonstrated that PRR was a potential target for future glioma therapy.
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Sellge, Gernot, i Thomas A. Kufer. "PRR-signaling pathways: Learning from microbial tactics". Seminars in Immunology 27, nr 2 (marzec 2015): 75–84. http://dx.doi.org/10.1016/j.smim.2015.03.009.
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Neerukonda, Sabari Nath, i Upendra Katneni. "Avian Pattern Recognition Receptor Sensing and Signaling". Veterinary Sciences 7, nr 1 (27.01.2020): 14. http://dx.doi.org/10.3390/vetsci7010014.
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Pattern recognition receptors (PRRs) are a class of immune sensors that play a critical role in detecting and responding to several conserved patterns of microorganisms. As such, they play a major role in the maintenance of immune homeostasis and anti-microbial defense. Fundamental knowledge pertaining to the discovery of PRR functions and their ligands continue to advance the understanding of immune system and disease resistance, which led to the rational design and/or application of various PRR ligands as vaccine adjuvants. In addition, the conserved nature of many PRRs throughout the animal kingdom has enabled the utilization of the comparative genomics approach in PRR identification and the study of evolution, structural features, and functions in many animal species including avian. In the present review, we focused on PRR sensing and signaling functions in the avian species, domestic chicken, mallard, and domestic goose. In addition to summarizing recent advances in the understanding of avian PRR functions, the present review utilized a comparative biology approach to identify additional PRRs, whose functions have been well studied in mammalians but await functional characterization in avian.
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Lahiri, Amit, Matija Hedl i Clara Abraham. "MTMR3 risk allele enhances innate receptor-induced signaling and cytokines by decreasing autophagy and increasing caspase-1 activation". Proceedings of the National Academy of Sciences 112, nr 33 (3.08.2015): 10461–66. http://dx.doi.org/10.1073/pnas.1501752112.
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Inflammatory bowel disease (IBD) is characterized by dysregulated host:microbial interactions and cytokine production. Host pattern recognition receptors (PRRs) are critical in regulating these interactions. Multiple genetic loci are associated with IBD, but altered functions for most, including in the rs713875 MTMR3/HORMAD2/LIF/OSM region, are unknown. We identified a previously undefined role for myotubularin-related protein 3 (MTMR3) in amplifying PRR-induced cytokine secretion in human macrophages and defined MTMR3-initiated mechanisms contributing to this amplification. MTMR3 decreased PRR-induced phosphatidylinositol 3-phosphate (PtdIns3P) and autophagy levels, thereby increasing PRR-induced caspase-1 activation, autocrine IL-1β secretion, NFκB signaling, and, ultimately, overall cytokine secretion. This MTMR3-mediated regulation required the N-terminal pleckstrin homology-GRAM domain and Cys413 within the phosphatase domain of MTMR3. In MTMR3-deficient macrophages, reducing the enhanced autophagy or restoring NFκB signaling rescued PRR-induced cytokines. Macrophages from rs713875 CC IBD risk carriers demonstrated increased MTMR3 expression and, in turn, decreased PRR-induced PtdIns3P and autophagy and increased PRR-induced caspase-1 activation, signaling, and cytokine secretion. Thus, the rs713875 IBD risk polymorphism increases MTMR3 expression, which modulates PRR-induced outcomes, ultimately leading to enhanced PRR-induced cytokines.
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Timmermans, Kim, Theo S. Plantinga, Matthijs Kox, Michiel Vaneker, Gert Jan Scheffer, Gosse J. Adema, Leo A. B. Joosten i Mihai G. Netea. "Blueprints of Signaling Interactions between Pattern Recognition Receptors: Implications for the Design of Vaccine Adjuvants". Clinical and Vaccine Immunology 20, nr 3 (23.01.2013): 427–32. http://dx.doi.org/10.1128/cvi.00703-12.
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ABSTRACTInnate immunity activation largely depends on recognition of microorganism structures by Pattern Recognition Receptors (PRRs). PRR downstream signaling results in production of pro- and anti-inflammatory cytokines and other mediators. Moreover, PRR engagement in antigen-presenting cells initiates the activation of adaptive immunity. Recent reports suggest that for the activation of innate immune responses and initiation of adaptive immunity, synergistic effects between two or more PRRs are necessary. No systematic analysis of the interaction between the major PRR pathways were performed to date. In this study, a systematical analysis of the interactions between PRR signaling pathways was performed. PBMCs derived from 10 healthy volunteers were stimulated with either a single PRR ligand or a combination of two PRR ligands. Known ligands for the major PRR families were used: Toll-like receptors (TLRs), C-type lectin receptors (CLRs), NOD-like receptors (NLRs), and RigI-helicases. After 24 h of incubation, production of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, and IL-10 was measured in supernatants by enzyme-linked immunosorbent assay (ELISA). The consistency of the PRR interactions (both inhibitory and synergistic) between the various individuals was assessed. A number of PRR-dependent signaling interactions were found to be consistent, both between individuals and with regard to multiple cytokines. The combinations of TLR2 and NOD2, TLR5 and NOD2, TLR5 and TLR3, and TLR5 and TLR9 acted as synergistic combinations. Surprisingly, inhibitory interactions between TLR4 and TLR2, TLR4 and Dectin-1, and TLR2 and TLR9 as well as TLR3 and TLR2 were observed. These consistent signaling interactions between PRR combinations may represent promising targets for immunomodulation and vaccine adjuvant development.
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Zhang, Zhongqin, Chika Tateda, Shang-Chuan Jiang, Jay Shrestha, Joanna Jelenska, DeQuantarius J. Speed i Jean T. Greenberg. "A Suite of Receptor-Like Kinases and a Putative Mechano-Sensitive Channel Are Involved in Autoimmunity and Plasma Membrane–Based Defenses in Arabidopsis". Molecular Plant-Microbe Interactions® 30, nr 2 (luty 2017): 150–60. http://dx.doi.org/10.1094/mpmi-09-16-0184-r.
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In plants, cell surface pattern recognition receptors (PRRs) provide a first line of defense against pathogens. Although each PRR recognizes a specific ligand, they share common signaling outputs, such as callose and other cell wall–based defenses. Several PRRs are also important for callose induction in response to the defense signal salicylic acid (SA). The extent to which common components are needed for PRR signaling outputs is not known. The gain-of-function Arabidopsis mutant of ACCELERATED CELL DEATH6 (ACD6) acd6-1 shows constitutive callose production that partially depends on PRRs. ACD6-1 (and ACD6) forms complexes with the PRR FLAGELLIN SENSING2, and ACD6 is needed for responses to several PRR ligands. Thus, ACD6-1 could serve as a probe to identify additional proteins important for PRR-mediated signaling. Candidate signaling proteins (CSPs), identified in our proteomic screen after immunoprecipitation of hemagglutinin (HA)-tagged ACD6-1, include several subfamilies of receptor-like kinase (RLK) proteins and a MECHANO-SENSITIVE CHANNEL OF SMALL CONDUCTANCE-LIKE 4 (MSL4). In acd6-1, CSPs contribute to autoimmunity. In wild type, CSPs are needed for defense against bacteria and callose responses to two or more microbial-derived patterns and an SA agonist. CSPs may function to either i) promote the assembly of signaling complexes, ii) regulate the output of known PRRs, or both.
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Buchholz, Kerry R., i Richard S. Stephens. "The Cytosolic Pattern Recognition Receptor NOD1 Induces Inflammatory Interleukin-8 during Chlamydia trachomatis Infection". Infection and Immunity 76, nr 7 (21.04.2008): 3150–55. http://dx.doi.org/10.1128/iai.00104-08.
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ABSTRACT Inflammation is a hallmark of chlamydial infections, but how inflammatory cytokines are induced is not well understood. Pattern recognition receptors (PRR) of the host innate immune system recognize pathogen molecules and activate intracellular signaling pathways that modulate immune responses. The role of PRR such as Toll-like receptors (TLR) and nucleotide-binding oligomerization domain (NOD) proteins in the endogenous interleukin-8 (IL-8) response induced during Chlamydia trachomatis infection is not known. We hypothesized that a PRR is essential for the IL-8 response induced by C. trachomatis infection. RNA interference was used to knock down the TLR signaling partner MyD88 as well as NOD1 and its signaling molecule receptor-interacting protein 2 (RIP2). IL-8 induced at 30 h postinfection by C. trachomatis was dependent on NOD1 signaling through RIP2; however, the IL-8 response was independent of MyD88-dependent TLR signaling. Activation of the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase cellular signaling pathway, which is essential for up-regulation of IL-8 in response to C. trachomatis infection, was independent of NOD1 or RIP2. We conclude that the endogenous IL-8 response induced by C. trachomatis infection is dependent upon NOD1 PRR signaling through RIP2 as part of a signal system requiring multiple inputs for optimal IL-8 induction. Since ERK is not activated through this pathway, a concomitant interaction between the host and bacteria is additionally required for full activation of the endogenous IL-8 response.
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Beitia, Maider, Jon Danel Solano-Iturri, Peio Errarte, Julio Calvete-Candenas, Alberto Loizate, Mari Carmen Etxezarraga, Begoña Sanz i Gorka Larrinaga. "(Pro)renin Receptor Expression Increases throughout the Colorectal Adenoma—Adenocarcinoma Sequence and It Is Associated with Worse Colorectal Cancer Prognosis". Cancers 11, nr 6 (24.06.2019): 881. http://dx.doi.org/10.3390/cancers11060881.
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(Pro)renin receptor (PRR) is a protein that takes part in several signaling pathways such as Renin Angiotensin System and Wnt signalling. Its biological role has recently been related to cancer progression and in this study, we investigated its relevance in colorectal cancer (CRC). To that end, we analysed the immunohistochemical expression of PRR in adenomatous polyps and CRCs from the same patients (n = 42), and in primary tumours and nodal and liver metastases from advanced CRC patients (n = 294). In addition, the soluble fraction of PRR was measured by ELISA in plasma samples from 161 CRC patients. The results showed that PRR expression was gradually augmented along the uninvolved mucosa–adenoma–adenocarcinoma sequence. Besides, the stronger expression of PRR in primary tumours was markedly associated with local tumour extent and the onset of metastases. Moreover, PRR expression in both primary and distant metastases was associated with worse 5- and 10-year survival of CRC patients. Plasmatic PRR levels did not change with respect to controls and were not associated with CRC aggressiveness. These results suggest a key role of PRR in the development and progression of CRC and a potential use of this protein as a new prognostic biomarker and/or therapeutic target for this disease.
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Kouchi, Masaaki, Yuki Shibayama, Daisuke Ogawa, Keisuke Miyake, Akira Nishiyama i Takashi Tamiya. "(Pro)renin receptor is crucial for glioma development via the Wnt/β-catenin signaling pathway". Journal of Neurosurgery 127, nr 4 (październik 2017): 819–28. http://dx.doi.org/10.3171/2016.9.jns16431.
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OBJECTIVEThe (pro)renin receptor (PRR) plays an essential role in the early development of the central nervous system by activating the Wnt/β-catenin signaling pathway. The authors investigated the potential role of the PRR in the pathogenesis of glioma.METHODSThe authors performed immunohistochemical analysis to detect both the PRR and isocitrate dehydrogenase 1 with mutations involving arginine 132 (IDH1R132H) in paraffin sections of 31 gliomas. Expression of the PRR and Wnt pathway components in cultured human glioma cell lines (U251MG, U87MG, and T98G) was measured using Western blotting. The effects of PRR short interfering RNA (siRNA) on glioma cell proliferation (WST-1 assay and direct cell counting) and apoptosis (flow cytometry and the caspase-3 assay) were also examined.RESULTSPRR expression was significantly higher in glioblastoma than in normal tissue or in lower grade glioma, regardless of IDH1R132H mutation. PRR expression was also higher in human glioblastoma cell lines than in human astrocytes. PRR expression showed a significant positive correlation with the Ki-67 labeling index, while it had a significant negative correlation with the survival time of glioma patients. Treatment with PRR siRNA significantly reduced expression of Wnt2, activated β-catenin, and cyclin D1 by human glioblastoma cell lines, and it reduced the proliferative capacity of these cell lines and induced apoptosis.CONCLUSIONSThis is the first evidence that the PRR has an important role in development of glioma by aberrant activation of the Wnt/β-catenin signaling pathway. This receptor may be both a prognostic marker and a therapeutic target for glioma.
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Fujimori, Takeshi, Daisuke Oagawa, Takahiro Kanda, Kenta Suzuki, Saki Shibayama, Keisuke Miyake, Akira Nishiyama i Takashi Tamiya. "CBMS-12 Pro renin receptor antibody regulates glioblastoma stemness". Neuro-Oncology Advances 2, Supplement_3 (1.11.2020): ii5. http://dx.doi.org/10.1093/noajnl/vdaa143.019.
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Abstract Objective: Glioblastoma multiforme (GBM) is characterized by a strong self-renewal potential and poor differentiated state. We previously reported that (pro)renin receptor (PRR) was a potential target for glioma therapy by silencing the gene of PRR. Here, we have developed the monoclonal antibody of PRR and examined their effects on GBM. Materials and methods: We performed immunohistochemical analysis to detect the protein expression of PRR and SOX-2 in human sample of 56 gliomas. We used human glioma cell lines (U251MG and U87MG) and glioma stem cell line (MGG23) in vitro study. PRR antibody was designed to target the extracellular domain of the PRR with the rat lymph node method. Expression of the Wnt signaling components and stem marker (SOX-2, Oct3/4) in human glioma cell lines and glioma stem cell line treated with PRR antibody were measured using Western blotting. The effects of PRR antibody on cell proliferation, sphere formation, apoptosis, invasion were also examined. Subcutaneous xenografts with U87MG were induced in nude mice. Results: PRR expression showed a positive correlation with SOX-2 expression in glioma samples. Treatment with PRR antibody significantly reduced expression of Wnt signaling components and stem marker. We observed that PRR antibody significantly reduced cell proliferation and decreased sphere formation. Furthermore, PRR antibody suppressed invasion and induced apoptosis. In a subcutaneous U87MG xenograft model, systemic administration of the PRR antibody significantly reduced the size of the tumor volume. Conclusion: PRR has important role for the maintenance of stem cells and contribute to stem cell proliferation. PRR antibody inhibits cell proliferation and cell invasion and induces apoptosis. Treatment with PRR antibody could be an attractive therapeutic strategy for GBM.
Rozprawy doktorskie na temat "PRR Signaling"
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Claverie, Justine. "Identification du xyloglucane comme nouvel éliciteur oligosaccharidique stimulant l’immunité de Vitis vinifera et d’Arabidopsis thaliana et caractérisation de deux récepteurs aux chito-oligosaccharides chez la vigne (VvLYK1-1 et VvLYK1-2)". Thesis, Bourgogne Franche-Comté, 2018. http://www.theses.fr/2018UBFCK076/document.
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L’activation des réponses immunitaires des plantes repose sur la reconnaissance de motifs moléculaires associés aux pathogènes (aussi appelés PAMP) par des récepteurs de l’immunité, également nommés PRR (pattern recognition receptors). La chitine, principal composant de la paroi des champignons, est un PAMP bien caractérisé qui induit des réponses de défense aussi bien chez les mammifères que chez les plantes.La première partie de cette étude met en évidence que deux chito-oligosaccharides, la chitine et le chitosan, agissent comme des PAMP chez la vigne (Vitis vinifera) puisqu’ils induisent des évènements précoces de signalisation, l’expression de gènes de défense et une résistance contre des agents pathogènes. Ces résultats suggèrent que des systèmes de perception existent chez la vigne. Une analyse phylogénétique a permis d’identifier trois récepteurs kinases à domaine LysM (LysM-RK ou LYK) chez V. vinifera (VvLYK1-1, -2, -3) appartenant au même clade que le récepteur à la chitine chez Arabidopsis et nommé AtCERK1 (Arabidopsis thaliana Chitin Elicitor Receptor Kinase 1). Leur analyse fonctionnelle a été réalisée par complémentation du mutant d’Arabidopsis Atcerk1, affecté dans la perception de la chitine. Nos résultats montrent que VvLYK1-1 et VvLYK1-2, mais pas VvLYK1-3, complémentent fonctionnellement le mutant Atcerk1 en restaurant l’activation des MAPK (Mitogen-Activated Protein Kinases) et l’expression de gènes de défense induits par les chito-oligosaccharides. De plus, l’expression de VvLYK1-1 chez Atcerk1 restaure la résistance basale à l’agent de l’oïdium de la vigne (Erysiphe necator).La seconde partie du projet s’est focalisée sur les éliciteurs oligosaccharidiques de type « damage-associated molecular patterns (DAMP) ». Ces molécules endogènes peuvent provenir de la dégradation de la paroi lors d’une attaque et sont capables d’activer les réponses immunitaires de la plante. Les DAMP les mieux caractérisés actuellement sont les oligogalacturonates (OG), des fragments de pectine qui induisent des réponses immunitaires chez de nombreuses espèces végétales dont l’activation de MAPK, la production d’H2O2, l’expression de gènes de défense et le dépôt de callose. Nous avons montré dans cette étude que les xyloglucanes (Xh), des fragments d’hémicellulose pariétale purifiés, induisaient l’activation de MAPK et l’expression de gènes de défense chez la vigne et Arabidopsis, afin d’induire une résistance contre le champignon nécrotrophe Botrytis cinerea. Les Xh induisent également la production de resvératrol, une phytoalexine majoritaire chez la vigne, et un dépôt de callose chez Arabidopsis. Par une approche génétique, nous avons identifié certains composants de la signalisation induite par les Xh chez Arabidopsis. L’utilisation de mutants suggère que la résistance induite par les Xh contre B. cinerea est dépendante des voies de la camalexine, de l’acide salicylique, de l’acide jasmonique et de l’éthylène chez Arabidopsis. De manière globale, nos résultats mettent en lumière que les xyloglucanes peuvent être considérés comme de nouveaux éliciteurs de l’immunité chez la vigne et ArabidopsisActivation of the plant immune responses requires recognition of common pathogen-associated molecular pattern (PAMP) by their cognate pattern recognition receptors (PRR). Chitin, a major component of fungal cell walls, is a well-known PAMP that triggers defense responses in several mammal and plant species.In the first part of this study, we show that two chitooligosaccharides, chitin and chitosan, act as PAMPs in grapevine (Vitis vinifera) as they elicit immune signaling events, defense gene expression, and resistance against pathogens. These two PAMPs are active in grapevine suggesting that at least one perception system exists. Phylogenetic analysis clearly distinguished three V. vinifera LysM Receptor Kinases (VvLYK1-1, -2, -3) located in the same clade as the Arabidopsis Chitin Elicitor Receptor Kinase 1 (AtCERK1), which mediates chitin-induced immune responses. Their functional characterization was achieved by complementation assays in the Atcerk1 mutant, impaired in chitin perception. Our results provide evidence that VvLYK1-1 and VvLYK1-2, but not VvLYK1-3, functionally complement the loss of AtCERK1 function by restoring chitooligosaccharide-induced MAPK activation and immune gene expression. Moreover, expression of VvLYK1-1 in Atcerk1 restored penetration resistance to the non-adapted grapevine powdery mildew (Erysiphe necator).The second part of this study focused on damaged-associated molecular patterns (DAMP), endogenous molecules that can be released from the plant cell wall during an attack and activate the plant innate immunity. Until now, the best characterized DAMPs are oligogalacturonides (OG) coming from pectin fragments that induce innate immune responses in various plant species, including MAPK activation, H2O2 production, defense gene expression and callose deposition. In this study, we showed that purified xyloglucans (Xh), derived from the plant cell wall hemicellulose, elicit MAPK activation and immune gene expression in grapevine (V. vinifera) and Arabidopsis to trigger induced resistance against the necrotrophic fungus Botrytis cinerea. Xh also elicit the production of resveratrol, the main grapevine phytoalexin, and callose deposition in Arabidopsis. Using a genetic approach, we identified some signaling components of Xh-induced immunity. The use of Arabidopsis mutants suggests that Xh-induced resistance against B. cinerea is dependent on the camalexin, salicylate, jasmonate and ethylene pathways. Taken together, our data highlight that Xh can be considered as new elicitors of grapevine and Arabidopsis immunity
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Czechowski, Tomasz. "Nitrogen signalling in Arabidopsis thaliana". Phd thesis, [S.l. : s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=975976095.
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McDonald, Sarah E. "Steroid pre-receptor signalling in human endometrium". Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/24938.
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This work has shown that 11βHSD-1 mRNA is present at highest levels in the menstrual phase of the cycle and in first trimester deciduas, the times when an inflammatory response is evident. 11βHSD-2 mRNA and protein are present at all stages of the cycle, and also in first trimester deciduas. GR mRNA and protein are highly expressed throughout the cycle. MR mRNA expression varies across the cycle in a pattern similar to progesterone expression. 11βHSD-1 mRNA expression is increased in response to IL-1α and cortisol, and GR mRNA shows a similar trend. 11βHSD-1 and MR expression are not altered by IL-1α or cortisol.3βHSD-1 mRNA has been shown to be present only in first trimester deciduas; 3βHSD-1 is not detectable by these methods. Immunohistochemistry using an antibody which detects both 3βHSD-1 and -2 has shown low levels of protein in the tissues studied. AKR1C1-3 mRNAs are expressed throughout the menstrual cycle; all three enzymes are predominantly expressed in the secretory phase. AKR1C3 is localised to the glandular and surface epithelial cells, and vascular endothelium. AKR1C4 mRNA is not detectable in the endometrium at any stage of the menstrual cycle. Expression of steroid-metabolising enzymes is perturbed in the endometrium of users of a Levonorgestrel intra-uterine system, and also the following GnRH antagonist treatment for sub-fertility. These studies have shown that the endometrium has the ability to precisely regulate its balance of steroid hormone availability at a local level, and that this balance may be altered following administration of exogenous steroids. Further functional studies such as knockout or knockdown of these enzymes would expand this knowledge and fully elucidate steroid hormone metabolism and pre-receptor signalling.
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McKenzie, Maxine. "Akt signalling in the human parasite 'Schistosoma mansoni'". Thesis, Kingston University, 2017. http://eprints.kingston.ac.uk/41116/.
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The study of cell signalling in schistosomes is crucial in deepening our knowledge of the biology of these blood flukes, which affect hundreds of millions of people worldwide. Here, Akt/protein kinase B (PKB) signalling has been functionally characterised and mapped in Schistosoma mansoni; an Akt variant of approximately 52 kDa has been characterised and RNA interference of the S. mansoni Akt gene, resulted in an 84% reduction in Akt expression. The phosphorylation (activation) status of the characterised Akt protein was increased by host molecules, including insulin and L-arginine in somules and adult worms, and L-arginine and linoleic acid in cercariae. Akt phosphorylation (activation) was also attenuated by Akt Inhibitor X and herbimycin A treatment. Immunohistochemistry/confocal laser scanning microscopy revealed phosphorylated Akt in all S. mansoni human infective/resident life stages. Somules and adult worms displayed activated Akt primarily in the tegument, particularly the tubercles and gynaecophoric canal of adult males. Cercariae exhibited activated Akt in the nervous system and punctate regions along the length of the tail prompting investigation into the role of Akt in cercarial motility. Behavioural studies demonstrated a significant increase in cercarial swimming in response to host factors, which was attenuated following exposure to Akt inhibitor X. The striking activation of Akt observed in the tegument of adult worms stimulated research into its possible role in glucose uptake in this host-interactive layer. RNAi of Akt resulted in a 59% and 47% reduction in SGTP4 glucose transporter expression in male and female adult worms respectively with a concomitant reduction in glucose uptake by the parasite. In somules, the expression of SGTP4 and its evolution at the apical tegument membrane during transformation were significantly attenuated by Akt Inhibitor X; a 74% reduction in glucose uptake was also demonstrated following Akt inhibition. Bioinformatic analysis of S. mansoni Akt interacting proteins uncovered a putative connection between Akt and Rab vesicle trafficking proteins and a mechanistic model illuminating the possible role of Akt in the translocation of SGTP4 to the parasite surface was proposed. Collectively, this research highlights the significance of Akt in schistosome homeostasis and host-parasite interactions and thus demonstrates that Akt may be a suitable target for anti-schistosome drug development strategies.
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Groves, Tim C. "Pre-TCR and TCR-Ãß signaling during T cell development". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/NQ27657.pdf.
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Wang, Fang. "The Role of Acinus in Retinoic Acid Signaling Pathway". Diss., Temple University Libraries, 2014. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/277479.
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BiochemistryPh.D.
Retinoic acid receptor (RAR), a member of the steroid/thyroid hormone nuclear receptor superfamily, functions as a RA-dependent transcription activator bound to the RA response element (RARE) within the promoter or enhancer region of target genes. The transcriptional activity of RAR is modulated by a large number of coregulators including coactivators and corepressors. Acinus is a nuclear protein with three isoforms (Acinus-L, Acinus-S and Acinus-S'). Acinus-S' interacts with the A/B domain of RAR and represses RAR-regulated genes expression. Acinus (without isoform definition) has been identified as a component of nuclear speckles, the spliceosome and the exon junction complex (EJC), suggesting its localization in nuclear speckles and involvement in RNA processing. Acinus-S has been shown to localize in nuclear speckles. However, it is unclear whether the other two isoforms also localize in nuclear speckles. In addition, the role of Acinus in regulating pre-mRNA splicing is unclear. The goal of these studies was to examine the nuclear localization of Acinus-L and Acinus-S' and to determine the role of Acinus isoforms in RAR-dependent splicing. The sub-nuclear localization of Acinus-L and Acinus-S' was determined using fluorescence microscopy. Acinus-S' colocalizes with SC35 in nuclear speckles while Acinus-L localizes diffusely throughout the nucleoplasm. RA treatment has little effect on the sub-nuclear localization of Acinus-L and Acinus-S'. The domains/regions necessary for the distinct sub-nuclear localization of Acinus-L and Acinus-S' were identified. The speckled sub-nuclear localization of Acinus-S' is dependent on its C-terminal RS- and RD/E-rich region but is independent of the phosphorylation status of Ser-453 and Ser-604 within this region. The unique N-terminal SAP-motif of Acinus-L is responsible for its diffuse localization in the nucleus. Moreover, the sub-nuclear localization of Acinus isoforms is affected by each other, which is determined by the combinatorial effect of the more potent SAP motif of Acinus-L and the C-terminal RS- and RD/E-rich region in all Acinus isoforms. The C-terminal RS- and RD/E-rich region of Acinus mediates the colocalization of Acinus isoforms as well as with its interacting protein RNPS1. The role of Acinus isoforms in regulating pre-mRNA splicing was explored using in vivo splicing assays. Both Acinus-L and Acinus-S', with the activity of Acinus-L higher than that of Acinus-S', increase the splicing of a RA-responsive minigene containing a weak 5' splice site but not a RA-responsive minigene containing a strong 5' splice site. RA treatment further enhances the splicing activity of Acinus in a dose- and time-dependent manner, suggesting a RA-dependent activity in addition to a RA-independent activity of Acinus. The RA-independent effect of Acinus on the splicing of pre-mRNAs containing the weak 5' splice site occurs to varying degrees using minigene constructs containing several different promoters while the RA-dependent splicing activity of Acinus is specific for transcripts derived from the minigene driven by the RARE-containing promoter. This suggests that the ligand-dependent splicing activity of Acinus is related to the RA-activated RAR bound to the RARE. The ligand-dependent splicing activity of Acinus was further shown to be promoter-specific, depending on the ligand-dependent transcription activator. The RRM domain was identified to be necessary for the RA-dependent splicing activity of Acinus. The RA-independent splicing activity of Acinus is repressed by RNPS1. Unexpectedly, the C-terminal RS- and RD/E rich region is dispensable for the splicing activity of Acinus in regulating the minigene containing a weak 5' splice site. Importantly, measurement of the splicing of endogenous human RARâ and Bcl-x in vivo demonstrates that Acinus stimulates the use of the weaker alternative 5' splice site of these two genes in a RA-dependent manner for RARâ and in a RA-independent manner for Bcl-x. Taken together, these studies demonstrate the distinct sub-nuclear localization of Acinus-L and Acinus-S', and identified the domains that are responsible for their sub-nuclear localization, which shed light on possible distinct functions between Acinus isoforms. In addition, both Acinus-L and Acinus-S' have been shown to be splicing cofactors (with the activity of Acinus-L higher than that of Acinus-S') that facilitate constitutive splicing of pre-mRNAs containing a weak 5' splice site and regulate alternative splicing in favor of the isoform generated from the weaker alternative 5' splice site. Both Acinus-L and Acinus-S' have a RA-dependent splicing activity specific for RA-responsive genes, which suggests that Acinus functions in RAR-dependent splicing.
Temple University--Theses
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Bhangu, P. S. "Vesicular 'pre-synaptic' glutamatergic signalling mechanisms in bone". Thesis, University of York, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.288814.
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Krjukova, Jelena. "Investigation on Pre- and Postsynaptic Ca2+ Signaling in Neuronal Model Systems". Doctoral thesis, Uppsala universitet, Institutionen för neurovetenskap, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4300.
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Communication between neuronal and non-neuronal is called volume transmission when the released neurotransmitter (NT) acts via diffusion and affects several target cells. Both the neurosecretory and postsynaptic cell responses are linked to [Ca2+]i elevations. In the present thesis the role of pre-and postsynaptic Ca2+ elevations has been investigated in the reconstituted "synapse" model comprised of NGF-differentiated PC12 and HEL cells as well as in SH-SY5Y neuroblastoma cells. In PC12 cells, both 70mM K+ and nicotine triggered NT release, which could be detected as a secondary [Ca2+]i increase in surrounding HEL cells. Both secretagogues shared the same voltage-dependent Ca2+ influx pathway as judged from the pharmacological profile blockers of voltage-gated Ca2+ channels. The coupling of electrical responses to the activation of Ca2+ signaling via muscarinic receptors in SH-SY5Y cells was also studied. These data revealed that depolarization caused a considerable potentiation of the muscarinic Ca2+ response. The potentiated Ca2+ increase was mainly dependent on the enhanced Ca2+ influx and to a lesser extent on [Ca2+]i release from intracellular stores. A phospholipase C (PLC) activator, m-3M3FBS was used to further study the role of G-protein coupled receptor (GPCR)-coupled Ca2+ signaling. However, it was found that m-3M3FBS instead triggered [Ca2+]i elevations independently of PLC activation. In conclusion, the results indicate that the magnitude of NT release from PC12 cells is sufficient to cause a robust activation of neighboring target cells. Postsynaptic muscarinic signaling is amplified due to integration of electrical excitation and GPCR signaling. The PLC activator, m-3M3FBS is not suitable for studies of PLC-mediated signals in intact cells.
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Simón, Moya Miguel. "Unveiling the role of Phytochrome Interacting Factor 1 (PIF1) homologs in tomato". Doctoral thesis, Universitat Autònoma de Barcelona, 2020. http://hdl.handle.net/10803/670860.
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La llum és un dels senyals ambientals més importants que influeixen en el cicle de vida de la planta. Les plantes han desenvolupat un conjunt de complexos mecanismes moleculars que detecten canvis en la qualitat i quantitat de la llum. Els PHYTOCHROME INTERACTING FACTORS (PIFs) són factors de transcripció que interactuen amb els fotoreceptors fitocroms (phy) i intervenen les respostes a llum vermella / vermella llunyana. Els PIF estan involucrats en la regulació d'una àmplia gamma de processos de desenvolupament. S'han estudiat àmpliament en Arabidopsis thaliana, però se sap molt poc sobre el seu paper en altres espècies. En aquesta tesi, vam investigar el paper dels dos homòlegs de PIF1 presents en tomàquet (Solanum lycopersicum): PIF1a i PIF1b.
L'anàlisi de l'expressió de PIF1a i PIF1b va mostrar patrons molt diferents, el que indica una possible divergència evolutiva en els seus rols. Els experiments d'estabilitat de les corresponents proteïnes en llum vermella i vermella llunyana van revelar que PIF1b ha perdut la seva capacitat d'interactuar amb PhyB, mentre que PIF1a encara pot fer-ho, confirmant la hipòtesi de divergència evolutiva.
D'altra banda, l'edició del genoma de plantes de tomàquet per CRISPR-CAS9 va generar línies de pèrdua de funció pif1a i pif1b, així com mutants dobles pif1a pif1b. La caracterització fenotípica d'aquests mutants va mostrar que tots dos factors de transcripció estan involucrats en la regulació de la germinació de les llavors, la síntesi de pigments en les fulles durant la des-etiolació i la producció de fruits. Altres processos estan regulats només per PIF1a, com l'allargament de pèls radiculars, la síntesi de glicoalcaloides esteroides en fulles, el temps de floració i el creixement i estovament del fruit. No identifiquem cap procés que estigui regulat específicament per PIF1b.
A causa del paper central de PIF1a, vam decidir realitzar experiments de RNA-seq en línies induïbles. Els resultats van mostrar que la inducció de PIF1a té un impacte relativament menor en el perfil transcriptòmic, i que els possibles gens diana de PIF1a en tomàquet són diferents dels identificats prèviament en Arabidopsis.
Totes aquestes dades en conjunt suggereixen que PIF1a i, en molt menor grau, PIF1b comparteixen algunes funcions amb el seu homòleg PIF1 d'Arabidopsis, però també il·lustren que s'han produït esdeveniments de neofuncionalització en tomàquet. Al fer això, l'evolució ha pogut utilitzar el potencial d'aquests factors de transcripció per regular nous processos específics en aquest cultiu d'interès agronòmic.La luz es una de las señales ambientales más importantes que influyen en el ciclo de vida de la planta. Las plantas han desarrollado un conjunto de complejos mecanismos moleculares que detectan cambios en la calidad y cantidad de la luz. Los PHYTOCHROME INTERACTING FACTORs (PIFs) son factores de transcripción que interactúan con los fotorreceptores fitocromos (phy) y median las respuestas a luz roja/roja lejana. Los PIF están involucrados en la regulación de una amplia gama de procesos del desarrollo. Se han estudiado ampliamente en Arabidopsis thaliana, pero se sabe muy poco sobre su papel en otras especies. En esta tesis, investigamos el papel de los dos homólogos de PIF1 presentes en tomate (Solanum lycopersicum): PIF1a y PIF1b. El análisis de la expresión de PIF1a y PIF1b mostró patrones muy diferentes, lo que indica una posible divergencia evolutiva en sus roles. Los experimentos de estabilidad de las correspondientes proteínas en luz roja y roja lejana revelaron que PIF1b ha perdido su capacidad de interactuar con PhyB, mientras que PIF1a todavía puede hacerlo, confirmando la hipótesis de divergencia evolutiva. Por otro lado, la edición del genoma de plantas de tomate por CRISPR-Cas9 generó líneas de pérdida de función pif1a y pif1b, así como mutantes dobles pif1a pif1b. La caracterización fenotípica de estos mutantes mostró que ambos factores de transcripción están involucrados en la regulación de la germinación de las semillas, la síntesis de pigmentos en las hojas durante la des-etiolación y la producción de frutos. Otros procesos están regulados solo por PIF1a, como el alargamiento de pelos radiculares, la síntesis de glicoalcaloides esteroideos en hojas, el tiempo de floración y el crecimiento y ablandamiento del fruto. No identificamos ningún proceso que esté regulado específicamente por PIF1b. Debido al papel central de PIF1a, decidimos realizar experimentos de RNA-seq en líneas inducibles. Los resultados mostraron que la inducción de PIF1a tiene un impacto relativamente menor en el perfil transcriptómico, y que los posibles genes diana de PIF1a en tomate son distintos a los identificados previamente en Arabidopsis. Todos estos datos en conjunto sugieren que PIF1a y, en mucho menor grado, PIF1b comparten algunas funciones con su homólogo PIF1 de Arabidopsis, pero también ilustran que se han producido eventos de neofuncionalización en tomate. Al hacer esto, la evolución ha podido utilizar el potencial de estos factores de transcripción para regular nuevos procesos específicos en este cultivo de interés agronómico.
Light is one of the most important environmental cues influencing the plant life cycle. Plants have developed a set of complex molecular mechanisms that sense changes in light quality and quantity. PHYTOCHROME INTERACTING FACTORs (PIFs) are transcription factors that interact with the photoreceptors phytochromes (phy) and mediate the responses to red/far-red light. PIFs are involved in the regulation of a broad range of developmental processes. They have been extensively studied in Arabidopsis thaliana, but very little is known about their roles in other species. In this thesis, we investigate the role of the two homologs of PIF1 found in tomato (Solanum lycopersicum): PIF1a and PIF1b. The analysis of PIF1a and PIF1b expression showed very different patterns, indicating a potential evolutionary divergence in their roles. Protein stability experiments in red and far-red light unveiled that PIF1b has lost its ability to interact with PhyB, while PIF1a is still able to do it, confirming the evolutionary divergence hypothesis. On the other hand, tomato genome editing by CRISPR-Cas9 generated pif1a and pif1b loss-of-function lines, as well as double mutants pif1a pif1b. The phenotypic characterization of these mutants showed that both transcription factors are involved in the regulation of seed germination, synthesis of leaf pigments during de-etiolation and fruit production. Other processes are regulated just by PIF1a, such as root hair elongation, synthesis of steroidal glycoalkaloids in leaves, flowering time and fruit growth and softening. We did not identify any process regulated specifically by PIF1b alone. Due to the central role of PIF1a, we decided to perform RNA-seq experiments in PIF1a-inducible lines. The results showed that the induction of PIF1a had a relatively minor impact in the transcriptomic profile, and that the putative gene targets of PIF1a in tomato were different from those previously identified in Arabidopsis. All this data together suggests that PIF1a and, to a much lower extent, PIF1b share some roles with Arabidopsis PIF1, but also illustrate that neofunctionalization has taken place in tomato. Doing this, evolution managed to use the potential of these transcription factors to regulate new specific processes in this crop of agronomic interest.
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Macfarlane, Scott Robert. "Proteinase-activated receptor-2 mediated signalling in a human keratinocyte cell line". Thesis, University of Strathclyde, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366849.
Pełny tekst źródłaKsiążki na temat "PRR Signaling"
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Groves, Tim C. Pre-TCR and TCRab signaling during T cell development. Ottawa: National Library of Canada = Bibliothèque nationale du Canada, 1997.
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Zhu, Wei-Min. Signalling through the pre-B cell receptor on late pre-B cell lines. Ottawa: National Library of Canada, 1994.
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Kung, Shu hung. The role that bacterial DNA and RNA play in PKR and JNK signalling in cardiac myocyte and 2FTGH cells. Sudbury, Ont: Laurentian University, 2005.
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Vidhyasekaran, P. Switching on Plant Innate Immunity Signaling Systems: Bioengineering and Molecular Manipulation of PAMP-PIMP-PRR Signaling Complex. Springer, 2018.
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Vidhyasekaran, P. Switching on Plant Innate Immunity Signaling Systems: Bioengineering and Molecular Manipulation of PAMP-PIMP-PRR Signaling Complex. Springer International Publishing AG, 2016.
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Vidhyasekaran, P. Switching on Plant Innate Immunity Signaling Systems: Bioengineering and Molecular Manipulation of PAMP-PIMP-PRR Signaling Complex. Springer, 2016.
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Geri, Guillaume, i Jean-Paul Mira. Host–pathogen interactions in the critically ill. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0306.
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Infection by a pathogenic micro-organism triggers a coordinated activation of both innate and adaptive immune responses. The innate immune response quickly triggers an antimicrobial response that will initiate development of a pathogen-specific, long-lasting adaptive immune response. Accurate recognition of microbial-associated molecular patterns by pattern-recognition receptors (PRRs) is the cornerstone of this immediate response. Most studied PRRs are Toll-like receptors (TLRs) and their kinase signalling cascades that activate nuclear transcription factors, and induce gene expression and cytokine production. Deficiencies or genetic variability in these different signalling pathways may lead to recurrent pyogenic infections and severe invasive diseases. After initial contact between the host and pathogen, numerous factors mediate the inflammatory response, as pro-inflammatory cytokines and chemokines. Apart from host genetic variability, pathogen diversity also influences the phenotypic features of various infectious diseases. Genomic analysis may assist in the development of targeted therapies or new therapeutic strategies based on both patient and microorganism genotype.
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Carmeliet, Peter, Guy Eelen i Joanna Kalucka. Arteriogenesis versus angiogenesis. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780198755777.003.0008.
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Higher organisms have a cardiovascular circulatory system with blood vessels to supply vital nutrients and oxygen to distant tissues. It is therefore not surprising that vascular disorders are leading causes of mortality. Understanding how new blood vessels form, creates opportunities to cure these life-threatening diseases. After birth, growth of blood vessels mainly occurs via two distinct mechanisms depending on the initial trigger: angiogenesis (referred here as capillary sprouting) is induced primarily by hypoxia, whereas arteriogenesis (referred here as the rapid enlargement of pre-existing collateral arteries, induced by vascular occlusion) is mainly driven by fluid shear stress. Arteriogenesis allows conductance of much larger volumes of blood per unit of time than does the increase in capillary density during angiogenesis. Notwithstanding these major differences, angiogenesis and arteriogenesis share a number of underlying mechanisms, e.g. the involvement of growth factor signalling. This chapter highlights the cellular and molecular events driving the two processes and discusses the therapeutic potential of targeting angiogenesis in cancer and arteriogenesis in cardiovascular diseases.
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Endlich, Karlhans, i Rodger Loutzenhiser. Regulation of vasomotor tone in the afferent and efferent arterioles. Redaktor Neil Turner. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0208.
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Pre-glomerular vessels are regulated by membrane potential alterations affecting the activity of L-type voltage-activated Ca2+ channels; whereas voltage-independent mechanisms regulate the efferent arteriole, notably influenced by angiotensin II and therefore by angiotensin converting enzyme inhibitors, and by non-steroidal anti-inflammatory drugs.These properties underlie the physiologic control of glomerular capillary pressure, for example, by prostaglandin E2, during conditions of reduced renal perfusion and the stabilization of glomerular capillary pressure when the kidney is exposed to pressure fluctuations. A wealth of hormones affects the tone of renal vessels. The chapter focuses on basic regulatory and signalling mechanisms, emphasizing the unique aspects of the renal vasculature and the underlying features that facilitate the independent regulation of pre-glomerular and post-glomerular tone.
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Mira, Helena, Aixa Victoria Morales i Ruth Diez Del Corral, red. Generation of Neurons and Their Integration in Pre-Existing Circuits in the Postnatal Brain: Signalling in Physiological and Regenerative Contexts. Frontiers Media SA, 2020. http://dx.doi.org/10.3389/978-2-88963-988-5.
Pełny tekst źródłaCzęści książek na temat "PRR Signaling"
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Seybold, Heike, Marie Boudsocq i Tina Romeis. "CDPK Activation in PRR Signaling". W Methods in Molecular Biology, 173–83. New York, NY: Springer New York, 2017. http://dx.doi.org/10.1007/978-1-4939-6859-6_14.
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Sadler, Anthony John. "PKR". W Encyclopedia of Signaling Molecules, 4038–46. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-67199-4_51.
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Sadler, Anthony John. "PKR". W Encyclopedia of Signaling Molecules, 1–9. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4614-6438-9_51-1.
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Donato, Dominique M., Steven K. Hanks, Kenneth A. Jacobson, M. P. Suresh Jayasekara, Zhan-Guo Gao, Francesca Deflorian, John Papaconstantinou i in. "PKR". W Encyclopedia of Signaling Molecules, 1435–39. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4419-0461-4_51.
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Weik, Martin H. "gigabit per second signaling rate". W Computer Science and Communications Dictionary, 681. Boston, MA: Springer US, 2000. http://dx.doi.org/10.1007/1-4020-0613-6_7956.
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Weik, Martin H. "megabit-per-second signaling rate". W Computer Science and Communications Dictionary, 998. Boston, MA: Springer US, 2000. http://dx.doi.org/10.1007/1-4020-0613-6_11306.
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Donato, Dominique M., Steven K. Hanks, Kenneth A. Jacobson, M. P. Suresh Jayasekara, Zhan-Guo Gao, Francesca Deflorian, John Papaconstantinou i in. "Protein Kinase RNA-Activated (PKR)". W Encyclopedia of Signaling Molecules, 1482. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4419-0461-4_101100.
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Millican, Daniel S., i Ian M. Bird. "Preparation of Single-Stranded Antisense cDNA Probes by Asymmetric PCR". W Phospholipid Signaling Protocols, 337–50. Totowa, NJ: Humana Press, 1998. http://dx.doi.org/10.1385/0-89603-491-7:337.
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Michniewicz, Marta, Samantha K. Powers i Lucia C. Strader. "IBA Transport by PDR Proteins". W Signaling and Communication in Plants, 313–31. Cham: Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-06511-3_17.
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Donato, Dominique M., Steven K. Hanks, Kenneth A. Jacobson, M. P. Suresh Jayasekara, Zhan-Guo Gao, Francesca Deflorian, John Papaconstantinou i in. "Protein Kinase Interferon-Induced Double-Stranded RNA-Activated (PRKR)". W Encyclopedia of Signaling Molecules, 1482. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4419-0461-4_101099.
Pełny tekst źródłaStreszczenia konferencji na temat "PRR Signaling"
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Alkoby, Shani, David Sarne i Igal Milchtaich. "Strategic Signaling for Selling Information Goods". W Twenty-Eighth International Joint Conference on Artificial Intelligence {IJCAI-19}. California: International Joint Conferences on Artificial Intelligence Organization, 2019. http://dx.doi.org/10.24963/ijcai.2019/4.
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This paper studies the benefit in using signaling by an information seller holding information that can completely disambiguate some uncertainty concerning the state of the world for the information buyer. We show that a necessary condition for having the information seller benefit from signaling in this model is having some ``seed of truth" in the signaling scheme used. We then introduce two natural signaling mechanisms that adhere to this condition, one where the seller pre-commits to the signaling scheme to be used and the other where she commits to use a signaling scheme that contains a ``seed of truth". Finally, we analyze the equilibrium resulting from each and show that, somehow counter-intuitively, despite the inherent differences between the two mechanisms, they are equivalent in the sense that for any equilibrium associated with the maximum revenue in one there is an equilibrium offering the seller the same revenue in the other.
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Martins, João Batista Silva, i Jéferson Campos Nobre. "Análise da Sinalização na Arquitetura Proposta no IETF ANIMA: o GRASP". W V Workshop Pré-IETF. Sociedade Brasileira de Computação - SBC, 2018. http://dx.doi.org/10.5753/wpietf.2018.3211.
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O avanço da tecnologia e complexidade de redes de computadores cria a necessidade de novos mecanismos de gerenciamento para tais redes. A intervenção humana não será mais efetiva, sendo necessário automatizar determinados processos. As redes autonômicas se apresentam para atuar em redes complexas e tomar decisões sem necessitar de um administrador de rede e repassando a responsabilidade de resolver problemas para os nós da rede autonõmica. O Autonomic Networking Integrated Model and Approach ANIMA Working Group (WG) tem por objetivo propor uma arquitetura para redes autonômicas. Nessa arquitetura, a sinalização é realizada pelo GeneRic Autonomic Signaling Protocol, protocolo responsável por habilitar nós de uma rede para atuar autonomicamente. Este trabalho apresenta um estudo sobre o ANIMA, com foco na utilização do GRASP.
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Colino, Mark P., i Elena B. Rosenstein. "One Train per Ventilation Zone: Application and Innovation". W ASME 2010 International Mechanical Engineering Congress and Exposition. ASMEDC, 2010. http://dx.doi.org/10.1115/imece2010-37176.
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In recognition of paragraph 7.2.5 of the National Fire Protection Association (NFPA) Standard 130 for Fixed Guideway and Passenger Rail Systems, a major commuter railroad project design team has undertaken detailed coordination of its train signaling, traction power and tunnel ventilation systems. Per the writing of the Standard, the coordination effort was aimed at designing the systems to match the total number of trains that could be between ventilation shafts during an emergency, but also recognized that, the best protection to passengers is to allow no more than one train in a ventilation zone. The coordination of the train signaling, traction power and tunnel ventilation system designs per NFPA 130 paragraphs 7.2.5 and A.7.2.5 has permitted the project to achieve a reasonable degree of safety from fire and its related hazards, while at the same time: preserving the commuter railroad’s throughput requirements; reducing overall construction costs; and, minimizing civic/environmental impacts. In particular, the design coordination has permitted the project to forego tunnel fan installations within existing structures in one portion of the project, and an innovative fan plant design between two tunnels has precluded the need for an additional tunnel ventilation shaft in another portion of the project.
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Joiner, Danese M., Ethan L. H. Daley i Steven A. Goldstein. "The Effects of the Inhibition of Connexin 43 on Pre-Osteoblasts and Their Response to Mechanical Stimulation". W ASME 2008 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2008. http://dx.doi.org/10.1115/sbc2008-192700.
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It is well established that bone can adapt to the demands of daily mechanical usage. Mechanical loading can result in bone formation depending on the magnitude, duration, and frequency. Unloading, which can occur during bed rest, micro-gravity exposure and a variety of clinical conditions, can result in bone resorption. In vitro studies have demonstrated that osteoblasts and osteocytes respond to mechanical stimulation, especially oscillatory fluid shear stress. Mechano-responses have included increases in inter- and intra-cellular communication through gap junctions and soluble factors such as nitric oxide and prostaglandin E2 [1]. Bone cell gap junctions are primarily comprised of connexin 43 (Cx43). Mice lacking Cx43 have an osteopenic phenotype and when subjected to cyclic 4 pt. bending loads have an increased tibia bone marrow area [2, 3]. These observations may represent altered cell signaling. To investigate the role of Cx43 in cell signaling and bone mechanotransduction the Cx43 gene was silenced in MC3T3-E1 pre-osteoblast cells subjected to oscillatory fluid shear stress.
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Erickson, J. R., R. A. Nordin, W. A. Payne i M. T. Ratajack. "A 1.5 Gigabit-per-Second, Time-Multiplexed Photonic Switching Experiment". W Photonic Switching. Washington, D.C.: Optica Publishing Group, 1987. http://dx.doi.org/10.1364/phs.1987.fd2.
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Current experimental Ti:LiNbO3 switching systems need electronics for control, regeneration, and compensation for the imperfections of the photonic switching fabric. These early photonic switches do, however, have advantages over their electronic counterparts: 1) Their switching fabric can carry 100 Mb/s or 10 Gb/s with little modification, 2) Their switching fabric is synergistic with fiber transmission, especially when optical amplifiers can be used, 3) They provide valuable experience in optics and photonic switching, 4) They give insight into the future of optical switching and how the signaling and protocols of the network need to evolve to accommodate this emerging technology[1].
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Obernikhin, Sergey Stanislavovich, Nataliya Valentinovna Yaglova, Valentin Vasilyevich Yaglov i Svetlana Vladimirovna Nazimova. "TRANSCRIPTIONAL REGULATION OF RAT ADRENAL ZONA GLOMERULOSA POSTNATAL DEVELOPMENT EXPOSED TO LOW DOSES OF DDT". W International conference New technologies in medicine, biology, pharmacology and ecology (NT +M&Ec ' 2020). Institute of information technology, 2020. http://dx.doi.org/10.47501/978-5-6044060-0-7.09.
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The role of the transcription factor Oct4 and canonical Wnt signaling in the postnatal morphogenesis of the
glomerular zone of the adrenal glands of rats under the conditions of pre- and postnatal exposure to low
doses of DDT endocrine disruptor was determined.
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Barbee, Kenneth A., Gulyeter Serbest i Joel Horwitz. "Membrane Integrity as a Therapeutic Target in Neural Cell Injury". W ASME 2004 International Mechanical Engineering Congress and Exposition. ASMEDC, 2004. http://dx.doi.org/10.1115/imece2004-61566.
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The importance of cell membrane integrity for normal cell function and indeed survival is well established, yet the role of membrane disruption in cellular pathology is seldom considered except as a prelude to, or indication of, cell death. However, evidence from diverse fields strongly implicates membrane disruption as a key precipitating event in the pathological responses to various stimuli. Dynamic mechanical loading of neural cells produces an acute disruption of the plasma membrane as indicated by a rapid and transient release of LDH from the cytoplasm of injured cells. In this report, we show that this cellular level injury is not immediately fatal, but rather gives rise to a cascade of signaling events that lead to cell death in the long term. In our model, over 50% of the cells were dead at 24 hours post injury, the majority of which were apoptotic as assessed by the TUNEL assay using flow cytometry. Though many of the signaling pathways involved in this response to injury have been studied, the link between the initial membrane damage and the subsequent signaling is poorly understood. We report for the first time that treating injured neurons with an agent that promotes resealing of membrane pores can rescue the cells from both necrotic cell death and apoptosis at 24 hours post injury. Treatment with the nonionic surfactant, poloxamer 188 (P188), at 15 minutes post injury restored cell viability at 24 hours to control values. The role of the pro-apoptosis MAP kinase, p38, in cell death following injury was investigated using Western blot analysis. Activation of p38 was increased over 2-fold at 15 minutes post injury. P188 treatment at 10 minutes inhibited p38 activation. However, treatment with a specific inhibitor of p38 activation produced only a partial reduction in apoptosis and had no effect on necrotic cell death. These data suggest multiple signaling pathways are involved in the long term response of neurons to mechanical injury. Furthermore, the putative mechanism of action of P188 to promote membrane resealing suggests that the acute membrane damage due to trauma is a critical precipitating event lying upstream of the many signaling cascades that contribute to the subsequent pathology.
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Baek, Hyeonguk, Seunghyeon Kim, Changjun Lee, Hojun Kim, Yulong Shang i Taejin Jung. "Orthogonal Faster-Than-Nyquist Signaling using Cholesky Pre-whitening Filter". W 2020 International Conference on Electronics, Information, and Communication (ICEIC). IEEE, 2020. http://dx.doi.org/10.1109/iceic49074.2020.9051088.
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Kim, Yong Jin Daniel, i Jan Bajcsy. "On Spectrum Broadening of Pre-Coded Faster-Than-Nyquist Signaling". W 2010 IEEE Vehicular Technology Conference (VTC 2010-Fall). IEEE, 2010. http://dx.doi.org/10.1109/vetecf.2010.5594451.
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Pan, Jie, Pierre Isautier, Jerrod S. Langston i Stephen E. Ralph. "DAC Enabled Frequency Domain Pre-shaper Design for Nyquist Signaling". W Signal Processing in Photonic Communications. Washington, D.C.: OSA, 2014. http://dx.doi.org/10.1364/sppcom.2014.sm3e.2.
Pełny tekst źródłaRaporty organizacyjne na temat "PRR Signaling"
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Sessa, Guido, i Gregory B. Martin. molecular link from PAMP perception to a MAPK cascade associated with tomato disease resistance. United States Department of Agriculture, styczeń 2012. http://dx.doi.org/10.32747/2012.7597918.bard.
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The research problem: The detection of pathogen-associated molecular patterns (PAMPs) by plant pattern recognition receptors (PRRs) is a key mechanism by which plants activate an effective immune response against pathogen attack. MAPK cascades are important signaling components downstream of PRRs that transduce the PAMP signal to activate various defense responses. Preliminary experiments suggested that the receptor-like cytoplasmickinase (RLCK) Mai5 plays a positive role in pattern-triggered immunity (PTI) and interacts with the MAPKKK M3Kε. We thus hypothesized that Mai5, as other RLCKs, functions as a component PRR complexes and acts as a molecular link between PAMP perception and activation of MAPK cascades. Original goals: The central goal of this research was to investigate the molecular mechanisms by which Mai5 and M3Kε regulate plant immunity. Specific objectives were to: 1. Determine the spectrum of PAMPs whose perception is transmitted by M3Kε; 2. Identify plant proteins that act downstream of M3Kε to mediate PTI; 3. Investigate how and where Mai5 interacts with M3Kε in the plant cell; 4. Examine the mechanism by which Mai5 contributes to PTI. Changes in research directions: We did not find convincing evidence for the involvement of M3Kε in PTI signaling and substituted objectives 1 and 3 with research activities aimed at the analysis of transcriptomic profiles of tomato plants during the onset of plant immunity, isolation of the novel tomato PRR FLS3, and investigation of the involvement of the RLCKBSKs in PTI. Main achievements during this research program are in the following major areas: 1. Functional characterization of Mai5. The function of Mai5 in PTI signaling was demonstrated by testing the effect of silencing the Mai5 gene by virus-induced gene silencing (VIGS) experiments and in cell death assays. Domains of Mai5 that interact with MAPKKKs and subcellular localization of Mai5 were analyzed in detail. 2. Analysis of transcriptional profiles during the tomato immune responses to Pseudomonas syringae (Pombo et al., 2014). We identified tomato genes whose expression is induced specifically in PTI or in effector-triggered immunity (ETI). Thirty ETI-specific genes were examined by VIGS for their involvement in immunity and the MAPKKK EPK1, was found to be required for ETI. 3. Dissection of MAP kinase cascades downstream of M3Kε (Oh et al., 2013; Teper et al., 2015). We identified genes that encode positive (SGT and EDS1) and negative (WRKY1 and WRKY2) regulators of the ETI-associated cell death mediated by M3Kε. In addition, the MKK2 MAPKK, which acts downstream of M3Kε, was found to interact with the MPK3 MAPK and specific MPK3 amino acids involved interaction were identified and found to be required for induction of cell death. We also identified 5 type III effectors of the bacterial pathogen Xanthomonaseuvesicatoria that inhibited cell death induced by components of ETI-associated MAP kinase cascades. 4. Isolation of the tomato PRR FLS3 (Hind et al., submitted). FLS3, a novel PRR of the LRR-RLK family that specifically recognizes the flagellinepitope flgII-28 was isolated. FLS3 was shown to bind flgII-28, to require kinase activity for function, to act in concert with BAK1, and to enhance disease resistance to Pseudomonas syringae. 5. Functional analysis of RLCKs of the brassinosteroid signaling kinase (BSK) family.Arabidopsis and tomato BSKs were found to interact with PRRs. In addition, certain ArabidospsisBSK mutants were found to be impaired in PAMP-induced resistance to Pseudomonas syringae. Scientific and agricultural significance: Our research activities discovered and characterized new molecular components of signaling pathways mediating recognition of invading pathogens and activation of immune responses against them. 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.
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Sessa, Guido, i Gregory Martin. role of FLS3 and BSK830 in pattern-triggered immunity in tomato. United States Department of Agriculture, styczeń 2016. http://dx.doi.org/10.32747/2016.7604270.bard.
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Pattern-recognition receptors (PRRs) located on the plant cell surface initiate immune responses by perceiving conserved pathogen molecules known as pathogen-associated molecular patterns (PAMPs). PRRs typically function in multiprotein complexes that include transmembrane and cytoplasmickinases and contribute to the initiation and signaling of pattern-triggered immunity (PTI). An important challenge is to identify molecular components of PRR complexes and downstream signaling pathways, and to understand the molecular mechanisms that mediate their function. In research activities supported by BARD-4931, we studied the role of the FLAGELLIN SENSING 3 (FLS3) PRR in the response of tomato leaves to flagellin-derivedPAMPs and PTI. In addition, we investigated molecular properties of the tomato brassinosteroid signaling kinase 830 (BSK830) that physically interacts with FLS3 and is a candidate for acting in the FLS3 signaling pathway. Our investigation refers to the proposal original objectives that were to: 1) Investigate the role of FLS3 and its interacting proteins in PTI; 2) Investigate the role of BSK830 in PTI; 3) Examine molecular and phosphorylation dynamics of the FLS3-BSK830 interaction; 4) Examine the possible interaction of FLS3 and BSK830 with Pstand Xcveffectors. We used CRISPR/Cas9 techniques to develop plants carrying single or combined mutations in the FLS3 gene and in the paralogsFLS2.1 and FLS2.2 genes, which encode the receptor FLAGELLIN SENSING2 (FLS2), and analyzed their function in PTI. Domain swapping analysis of the FLS2 and FLS3 receptors revealed domains of the proteins responsible for PAMP detection and for the different ROS response initiated by flgII-28/FLS3 as compared to flg22/FLS2. In addition, in vitro kinase assays and point mutations analysis identified FLS2 and FLS3 domains required for kinase activity and ATP binding. In research activities on tomato BSK830, we found that it interacts with PRRs and with the co-receptor SERK3A and PAMP treatment affects part of these interactions. CRISPR/Cas9 bsk830 mutant plants displayed enhanced pathogen susceptibility and reduced ROS production upon PAMP treatment. In addition, BSK830 interacted with 8 Xanthomonastype III secreted effectors. Follow up analysis revealed that among these effectors XopAE is part of an operon, is translocated into plant cells, and displays E3 ubiquitinligase activity. Our investigation was also extended to other Arabidopsis and tomato BSK family members. Arabidopsis BSK5 localized to the plant cell periphery, interacted with receptor-like kinases, and it was phosphorylatedin vitro by the PEPR1 and EFRPRRs. bsk5 mutant plants displayed enhanced susceptibility to pathogens and were impaired in several, but not all, PAMP-induced responses. Conversely, BSK5 overexpression conferred enhanced disease resistance and caused stronger PTI responses. Genetic complementation suggested that proper localization, kinase activity, and phosphorylation by PRRs are critical for BSK5 function. BSK7 and BSK8 specifically interacted with the FLS2 PRR, their respective mutant plants were more susceptible to B. cinereaand displayed reduced flg22-induced responses. The tomato BSK Mai1 was found to interact with the M3KMAPKKK, which is involved in activation of cell death associated with effector-triggered immunity. Silencing of Mai1 in N. benthamianaplants compromised cell death induced by a specific class of immune receptors. In addition, co-expression of Mai1 and M3Kin leaves enhanced MAPKphosphorylation and cell death, suggesting that Mai1 acts as a molecular link between pathogen recognition and MAPK signaling. Finally, We identified the PP2C phosphatase Pic1 that acts as a negative regulator of PTI by interacting with and dephosphorylating the receptor-like cytoplasmickinase Pti1, which is a positive regulator of plant immunity. The results of this investigation shed new light on the molecular characteristics and interactions of components of the immune system of crop plants providing new knowledge and tools for development of novel strategies for disease control.
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Avni, Adi, i Gitta L. Coaker. Proteomic investigation of a tomato receptor like protein recognizing fungal pathogens. United States Department of Agriculture, styczeń 2015. http://dx.doi.org/10.32747/2015.7600030.bard.
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Maximizing food production with minimal negative effects on the environment remains a long-term challenge for sustainable food production. Microbial pathogens cause devastating diseases, minimizing crop losses by controlling plant diseases can contribute significantly to this goal. All plants possess an innate immune system that is activated after recognition of microbial-derived molecules. The fungal protein Eix induces defense responses in tomato and tobacco. Plants recognize Eix through a leucine-rich-repeat receptor- like-protein (LRR-RLP) termed LeEix. Despite the knowledge obtained from studies on tomato, relatively little is known about signaling initiated by RLP-type immune receptors. The focus of this grant proposal is to generate a foundational understanding of how the tomato xylanase receptor LeEix2 signals to confer defense responses. LeEix2 recognition results in pattern triggered immunity (PTI). The grant has two main aims: (1) Isolate the LeEix2 protein complex in an active and resting state; (2) Examine the biological function of the identified proteins in relation to LeEix2 signaling upon perception of the xylanase elicitor Eix. We used two separate approaches to isolate receptor interacting proteins. Transgenic tomato plants expressing LeEix2 fused to the GFP tag were used to identify complex components at a resting and activated state. LeEix2 complexes were purified by mass spectrometry and associated proteins identified by mass spectrometry. We identified novel proteins that interact with LeEix receptor by proteomics analysis. We identified two dynamin related proteins (DRPs), a coiled coil – nucleotide binding site leucine rich repeat (SlNRC4a) protein. In the second approach we used the split ubiquitin yeast two hybrid (Y2H) screen system to identified receptor-like protein kinase At5g24010-like (SlRLK-like) (Solyc01g094920.2.1) as an interactor of LeEIX2. We examined the role of SlNRC4a in plant immunity. Co-immunoprecipitation demonstrates that SlNRC4a is able to associate with different PRRs. Physiological assays with specific elicitors revealed that SlNRC4a generally alters PRR-mediated responses. SlNRC4a overexpression enhances defense responses while silencing SlNRC4 reduces plant immunity. We propose that SlNRC4a acts as a non-canonical positive regulator of immunity mediated by diverse PRRs. Thus, SlNRC4a could link both intracellular and extracellular immune perception. SlDRP2A localizes at the plasma membrane. Overexpression of SlDRP2A increases the sub-population of LeEIX2 inVHAa1 endosomes, and enhances LeEIX2- and FLS2-mediated defense. The effect of SlDRP2A on induction of plant immunity highlights the importance of endomembrane components and endocytosis in signal propagation during plant immune . The interaction of LeEIX2 with SlRLK-like was verified using co- immunoprecipitation and a bimolecular fluorescence complementation assay. The defence responses induced by EIX were markedly reduced when SlRLK-like was over-expressed, and mutation of slrlk-likeusing CRISPR/Cas9 increased EIX- induced ethylene production and SlACSgene expression in tomato. Co-expression of SlRLK-like with different RLPs and RLKs led to their degradation, apparently through an endoplasmic reticulum-associated degradation process. We provided new knowledge and expertise relevant to expression of specific be exploited to enhance immunity in crops enabling the development of novel environmentally friendly disease control strategies.
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Karagiannis, G., T. Taylor, K. Chan, M. Menth i P. Eardley. Requirements for Signaling of Pre-Congestion Information in a Diffserv Domain. RFC Editor, lipiec 2012. http://dx.doi.org/10.17487/rfc6663.
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Bruno, Francesco, Domenico Arcuri, Francesca Vozzo, Antonio Malvaso, Alberto Montensanto i Raffaele Maletta. Expression and signaling pathways of Nerve Growth Factor (NGF) and pro-NGF in breast cancer: a systematic review. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, październik 2022. http://dx.doi.org/10.37766/inplasy2022.10.0017.
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Review question / Objective: This study aims to systematically review and comprehensively summarize the current experimental evidence about the involvement of Nerve Growth Factor (NGF) and pro-NGF signaling pathways in breast cancer. Therefore, the questions are as follows: (1) What is the expression level of NGF, pro-NGF and their receptors in breast cancer? (2) What is the role played by NGF, pro-NGF and their receptors in the pathophysiological mechanisms (i.e., proliferation, apoptosis, angiogenesis, invasion, metastasis) of breast cancer? (3) What is the diagnostic, prognostic and therapeutic potential of NGF, pro-NGF and their receptors in breast cancer? Condition being studied: Breast cancer is a neoplasm of epithelial origin that generally develops in the parts of the breast tissue made up of the glands involved in milk production or in the ducts that connect the glands to the nipple. In women it represents the most frequent cancer as well as the leading cause of cancer death. The incidence of breast cancer is estimated to increase over the years and to reach 3.2 million in 2050, thus representing a health emergency both from a medical and a psychological point of view. Therefore, prevention and early diagnosis of breast cancer appears to be of primary urgency as well as the development of new treatments able to improve its prognosis.
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Yuval, Boaz, i Todd E. Shelly. Lek Behavior of Mediterranean Fruit Flies: An Experimental Analysis. United States Department of Agriculture, lipiec 2000. http://dx.doi.org/10.32747/2000.7575272.bard.
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The Mediterranean fruit fly, Ceratitis capitata (Diptera: Tephritidae), is a ubiquitous pest of fruit trees, causing significant economic damage both in the U.S. and in Israel. Control efforts in the future will rely heavily on the sterile insect technique (SIT). Success of such operations hinges on the competitive ability of released males. The mating system of the medfly is based on leks. These are aggregations of sexually signaling males that attract females (who then select and copulate a courting male). A major component of male competitiveness is their ability to join existing leks or establish leks that are attractive to wild females. Accordingly, we identified leks and the behaviors associated with them as critical for the success of SIT operations. The objectives of this proposal were to determine 1. what makes a good lek site, 2. what are the energetic costs of lekking, 3. how females choose leks, and finally 4. whether the copulatory success of sterile males may be manipulated by particular pre-release diets and judicious spatial dispersal. We established that males choose lek sites according to their spatial location and penological status, that they avoid predators, and within the lek tree choose the perch that affords a compromise between optimal signalling, micro-climatic conditions and predation risk (Kaspi & Yuval 1999 a&b; Field et al 2000; Kaspi & Yuval submitted). We were able to show that leks are exclusive, and that only males with adequate protein and carbohydrate reserves can participate (Yuval et al 1998; Kaspi et al 2000; Shelly et al 2000). We determined that females prefer leks formed by protein fed, sexually experienced males (Shelly 2000). Finally, we demonstrated that adding protein to the diet of sterile males significantly enhances their probability of participating in leks and copulating wild females (Kaspi & Yuval 2000).
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Martinho, Diogo, Hugo Sarmento, Ana Faria, Hadi Nobari i Adam Field. Oral branched chain amino acids supplementation in trained participants: a systematic review. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, kwiecień 2022. http://dx.doi.org/10.37766/inplasy2022.4.0014.
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Review question / Objective: The present review following PICO criteria: (1) population – athletes or participants described with experience in sport; (2) intervention – oral branched chain amino acids (BCAAs) supplementation; (3) outcomes – indicators of performance, body composition, recovery, hormonal response or cellular signalling; (4) comparator – control group or placebo, and; (5) output – pre-and post-test changes. Exclusion criteria were: (1) studies that described participants as healthy or active; (2) articles classified as letter to editor or review, and; (3) BCAAs supplementation by infusion or combined with other substances. Condition being studied: The condition to be studied is the ingestion of branched chain amino acids in participants with training experience (participants involved in organized sports or with training experience). Note, the participants classified as active or healthy were not included in this review.
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Hambur, Jonathan, i Qazi Haque. Can We Use High-frequency Yield Data to Better Understand the Effects of Monetary Policy and Its Communication? Yes and No! Reserve Bank of Australia, maj 2023. http://dx.doi.org/10.47688/rdp2023-04.
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Understanding the effects of monetary policy and its communication is crucial for a central bank. This paper explores a new approach to identifying the effects of monetary policy using high-frequency data around monetary policy decisions and other announcements that allows us to explore different facets of monetary policy, specifically: current policy action; signalling or forward guidance about future rates; and the effect on uncertainty and term premia. The approach provides an intuitive lens through which to understand how policy and its communication affected expectations for rates and risks during certain historical periods, and more generally. For example, it suggests that: (i) signalling/forward guidance shocks tended to raise expected future policy rates in the mid-2010s as the RBA highlighted rising risks in housing markets; (ii) COVID-19-era monetary policy worked mainly through affecting term premia rather than expectations for future policy rates, unlike pre-COVID-19 policy; and (iii) shocks to the expected path of rates are predictable based on data available at the time, which suggests that markets systematically misunderstand how the RBA reacts to data, highlighting the importance of clear communication. We also explore the macroeconomic effects of these different shocks. The effects of shocks to current policy are similar to those estimated in previous papers, and existing issues such as the 'price puzzle' remain, while the effects of other shocks are imprecisely estimated. Although the approach provides little new information on the macroeconomic effects of monetary policy, it does highlight the importance of these other facets of policy in moving interest rates and suggests additional work in this space could be valuable.
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Savaldi-Goldstein, Sigal, i Todd C. Mockler. Precise Mapping of Growth Hormone Effects by Cell-Specific Gene Activation Response. United States Department of Agriculture, grudzień 2012. http://dx.doi.org/10.32747/2012.7699849.bard.
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Plant yield largely depends on a complex interplay and feedback mechanisms of distinct hormonal pathways. Over the past decade great progress has been made in elucidating the global molecular mechanisms by which each hormone is produced and perceived. However, our knowledge of how interactions between hormonal pathways are spatially and temporally regulated remains rudimentary. For example, we have demonstrated that although the BR receptor BRI1 is widely expressed, the perception of BRs in epidermal cells is sufficient to control whole-organ growth. Supported by additional recent works, it is apparent that hormones are acting in selected cells of the plant body to regulate organ growth, and furthermore, that local cell-cell communication is an important mechanism. In this proposal our goals were to identify the global profile of translated genes in response to BR stimulation and depletion in specific tissues in Arabidopsis; determine the spatio-temporal dependency of BR response on auxin transport and signaling and construct an interactive public website that will provide an integrated analysis of the data set. Our technology incorporated cell-specific polysome isolation and sequencing using the Solexa technology. In the first aim, we generated and confirmed the specificity of novel transgenic lines expressing tagged ribosomal protein in various cell types in the Arabidopsis primary root. We next crossed these lines to lines with targeted expression of BRI1 in the bri1 background. All lines were treated with BRs for two time points. The RNA-seq of their corresponding immunopurified polysomal RNA is nearly completed and the bioinformatic analysis of the data set will be completed this year. Followed, we will construct an interactive public website (our third aim). In the second aim we started revealing how spatio-temporalBR activity impinges on auxin transport in the Arabidopsis primary root. We discovered the unexpected role of BRs in controlling the expression of specific auxin efflux carriers, post-transcriptionally (Hacham et al, 2012). We also showed that this regulation depends on the specific expression of BRI1 in the epidermis. This complex and long term effect of BRs on auxin transport led us to focus on high resolution analysis of the BR signaling per se. Taking together, our ongoing collaboration and synergistic expertise (hormone action and plant development (IL) and whole-genome scale data analysis (US)) enabled the establishment of a powerful system that will tell us how distinct cell types respond to local and systemic BR signal. BR research is of special agriculture importance since BR application and BR genetic modification have been shown to significantly increase crop yield and to play an important role in plant thermotolerance. Hence, our integrated dataset is valuable for improving crop traits without unwanted impairment of unrelated pathways, for example, establishing semi-dwarf stature to allow increased yield in high planting density, inducing erect leaves for better light capture and consequent biomass increase and plant resistance to abiotic stresses.
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Or, Etti, David Galbraith i Anne Fennell. Exploring mechanisms involved in grape bud dormancy: Large-scale analysis of expression reprogramming following controlled dormancy induction and dormancy release. United States Department of Agriculture, grudzień 2002. http://dx.doi.org/10.32747/2002.7587232.bard.
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The timing of dormancy induction and release is very important to the economic production of table grape. Advances in manipulation of dormancy induction and dormancy release are dependent on the establishment of a comprehensive understanding of biological mechanisms involved in bud dormancy. To gain insight into these mechanisms we initiated the research that had two main objectives: A. Analyzing the expression profiles of large subsets of genes, following controlled dormancy induction and dormancy release, and assessing the role of known metabolic pathways, known regulatory genes and novel sequences involved in these processes B. Comparing expression profiles following the perception of various artificial as well as natural signals known to induce dormancy release, and searching for gene showing similar expression patterns, as candidates for further study of pathways having potential to play a central role in dormancy release. We first created targeted EST collections from V. vinifera and V. riparia mature buds. Clones were randomly selected from cDNA libraries prepared following controlled dormancy release and controlled dormancy induction and from respective controls. The entire collection (7920 vinifera and 1194 riparia clones) was sequenced and subjected to bioinformatics analysis, including clustering, annotations and GO classifications. PCR products from the entire collection were used for printing of cDNA microarrays. Bud tissue in general, and the dormant bud in particular, are under-represented within the grape EST database. Accordingly, 59% of the our vinifera EST collection, composed of 5516 unigenes, are not included within the current Vitis TIGR collection and about 22% of these transcripts bear no resemblance to any known plant transcript, corroborating the current need for our targeted EST collection and the bud specific cDNA array. Analysis of the V. riparia sequences yielded 814 unigenes, of which 140 are unique (keilin et al., manuscript, Appendix B). Results from computational expression profiling of the vinifera collection suggest that oxidative stress, calcium signaling, intracellular vesicle trafficking and anaerobic mode of carbohydrate metabolism play a role in the regulation and execution of grape-bud dormancy release. A comprehensive analysis confirmed the induction of transcription from several calcium–signaling related genes following HC treatment, and detected an inhibiting effect of calcium channel blocker and calcium chelator on HC-induced and chilling-induced bud break. It also detected the existence of HC-induced and calcium dependent protein phosphorylation activity. These data suggest, for the first time, that calcium signaling is involved in the mechanism of dormancy release (Pang et al., in preparation). We compared the effects of heat shock (HS) to those detected in buds following HC application and found that HS lead to earlier and higher bud break. We also demonstrated similar temporary reduction in catalase expression and temporary induction of ascorbate peroxidase, glutathione reductase, thioredoxin and glutathione S transferase expression following both treatments. These findings further support the assumption that temporary oxidative stress is part of the mechanism leading to bud break. The temporary induction of sucrose syntase, pyruvate decarboxylase and alcohol dehydrogenase indicate that temporary respiratory stress is developed and suggest that mitochondrial function may be of central importance for that mechanism. These finding, suggesting triggering of identical mechanisms by HS and HC, justified the comparison of expression profiles of HC and HS treated buds, as a tool for the identification of pathways with a central role in dormancy release (Halaly et al., in preparation). RNA samples from buds treated with HS, HC and water were hybridized with the cDNA arrays in an interconnected loop design. Differentially expressed genes from the were selected using R-language package from Bioconductor project called LIMMA and clones showing a significant change following both HS and HC treatments, compared to control, were selected for further analysis. A total of 1541 clones show significant induction, of which 37% have no hit or unknown function and the rest represent 661 genes with identified function. Similarly, out of 1452 clones showing significant reduction, only 53% of the clones have identified function and they represent 573 genes. The 661 induced genes are involved in 445 different molecular functions. About 90% of those functions were classified to 20 categories based on careful survey of the literature. Among other things, it appears that carbohydrate metabolism and mitochondrial function may be of central importance in the mechanism of dormancy release and studies in this direction are ongoing. Analysis of the reduced function is ongoing (Appendix A). A second set of hybridizations was carried out with RNA samples from buds exposed to short photoperiod, leading to induction of bud dormancy, and long photoperiod treatment, as control. Analysis indicated that 42 genes were significant difference between LD and SD and 11 of these were unique.