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Littérature scientifique sur le sujet « GPC1 »

Auteur : Grafiati
Publié le 1 avril 2023

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Articles de revues sur le sujet "GPC1"

1

Mucientes, A., E. Herranz, P. Lois, F. J. Blanco, L. Abasolo, L. Rodriguez Rodriguez, J. R. Lamas et B. Fernandez. « AB0077 CONTRIBUTION OF NOTUM TO THE DEVELOPMENT OF OSTEOARTHRITIS ». Annals of the Rheumatic Diseases 79, Suppl 1 (juin 2020) : 1338.1–1339. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4569.

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Background:Osteoarthritis (OA) is a degenerative disease characterized by altered homeostasis of joint cartilage and bone, the functionality of which relies on chondrocytes and osteoblasts, that leads to the formation of a defective extracellular matrix (ECM). The ECM plays an essential role in bone biology as it provides the structure of cartilage which serves as a template for bone formation. Collagen X, main component of the ECM, has been described by our group as down-regulated in OA [1]. Our data also points to an important role of the Wnt pathway in OA [1,2]. Furthermore, Wnt proteins have been reported to inhibit chondrogenesis [3], and the Wnt pathway and its modulators have gained attention [4]. Glypicans (GPC1 to GPC6) and NOTUM, among others, have been identified as modulators of this pathway [5,6]. Notably, due to its highly specific inhibition of the Wnt pathway, NOTUM has been proposed as a therapeutic target in conditions with a high activity of the Wnt pathway is involved, such as OA [7].Objectives:We hypothesize that modulators of the Wnt pathway are involved in the development of OA. The aim of this study is to evaluate the presence of Glypicans and NOTUM in the serum of OA patients and healthy individuals in order to determine whether significant differences exist and could clarify their likely involvement in OA.Methods:Peripheral blood samples were obtained from OA patients during routine rheumatologist hospital visits. OA diagnosis was established according to the ACR criteria. Samples from healthy individuals were obtained from the local Blood Bank. In both cases, blood samples were centrifugated (2000g, 15 minutes, 10°C) and serum was obtained.Quantitative ELISA assays for GPC1-6 and NOTUM were carried out using commercial kits (Human GPC1 ELISA Kit, #E-EL-H1710, Elabscience; Human GPC2 ELISA Kit, #E-EL-H1711, Elabscience; Human GPC3 ELISA Kit, #E-EL-H1712, Elabscience; Human GPC4 ELISA Kit, #E-EL-H1713, Elabscience; Human GPC5 ELISA Kit, #ELH-GPC5, RayBiotech; Human GPC6 ELISA Kit, #CSB-EL009708HU, Cusabio; Human Protein NOTUM homolog ELISA Kit, #EK3787, Sab Biotech) and measured in a plate reader (Heales MB-580,Shenzhen Heales Technology Development Co. Ltd.). Protein concentration in serum was calculated using GraphPad Prism 7 software. Differences between samples were analysed with Mann-Withney U test. Significance level set wasp<0.05.Results:Serum from 40 OA patients and 40 healthy donors were included in the study. There were no differences between groups (Table 1).Table 1.Cohort descriptionControl group (n=40)OA group (n=40)Age66,82±5,7569,59±11,24Women (%)32 (80%)30 (75%)Out of 7 proteins analyzed, only NOTUM showed a significant difference between healthy and OA groups (MedianOA=0.4451ng/mL, MedianCONTROL=0.8263ng/mL,p=0.0013). Besides, GPC4 showed an approaching formal significance (MedianOA=0.1254ng/mL, MedianCONTROL=0.1596ng/mL,p=0.0767). The rest of Glypicans analyzed showed no significance differences between groups (GPC1, MedianOA=0.1346ng/mL, MedianCONTROL=0.1190ng/mL,p=0.2379; GPC2, MedianOA=2.593ng/mL, MedianCONTROL=2.955ng/mL,p=0.7489; GPC3, MedianOA=2.024ng/mL, MedianCONTROL=1.422ng/mL,p=0.3574; GPC5, MedianOA=3.663ng/mL, MedianCONTROL=5.529ng/mL,p=0.8829; GPC6, MedianOA=0.3922ng/mL, MedianCONTROL=0.3558ng/mL,p=0.3212).Conclusion:Our results suggest that low levels of NOTUM may contribute to the development of OA. The lack of this inhibitor promotes the activation of the Wnt pathway, high activity of which has been related with OA.References:[1]Lamas JRet al.Ann Rheum Dis, 2010. 69(10):1880-5.[2]Tornero-Esteban Pet al. PLoS One, 2015. 10(9): p. e0137170.[3]Dayet al. Dev Cell. 2005. 8(5):739-50.[4]Monteagudo S and Lories RJ. Nat Rev Rheumatol, 2017. 13(11): p. 670-681.[6]Li Net al. Trends Cancer. 2018 Nov;4(11):741-754.[7]De Robertis Met al. Oncotarget, 2015. 6(38): p. 41237-57.[8]Nusse R. Nature, 2015. 519(7542): p. 163-4.Disclosure of Interests:Arkaitz Mucientes: None declared, Eva Herranz: None declared, Pia Lois: None declared, Francisco J. Blanco Grant/research support from: Sanofi-Aventis, Lilly, Bristol MS, Amgen, Pfizer, Abbvie, TRB Chemedica International, Glaxo SmithKline, Archigen Biotech Limited, Novartis, Nichi-iko pharmaceutical Co, Genentech, Jannsen Research & Development, UCB Biopharma, Centrexion Theurapeutics, Celgene, Roche, Regeneron Pharmaceuticals Inc, Biohope, Corbus Pharmaceutical, Tedec Meiji Pharma, Kiniksa Pharmaceuticals, Ltd, Gilead Sciences Inc, Consultant of: Lilly, Bristol MS, Pfizer, Lydia Abasolo: None declared, Luis Rodriguez Rodriguez: None declared, José Ramón Lamas: None declared, Benjamin Fernandez: None declared
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Wang, Shiqing, Zhenzhen Wu, Minyu Zhou et Wangjun Liao. « Effect of GPC1 on epithelial-to-mesenchymal transition and stemness and interaction with ITGB1 in gastric cancer. » Journal of Clinical Oncology 35, no 15_suppl (20 mai 2017) : e15580-e15580. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e15580.

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e15580 Background: Gastric cancer is the fourth frequently diagnosed cancer worldwide and tumor metastasis plays an important role in its poor prognosis. EMT, which occurs during embryonic development and carcinoma progression, contributes to metastasis and regulates stemness. GPC1, a member of the heparan sulfate proteoglycans family, is overexpressed in many types of cancer, and associates with metastasis and tumor progression. However, it is unknown that the functions of GPC1 and its underlying mechanism in gastric cancer. Methods: Immunohistochemistry analysis was performed in 245 GC tissues to explore the relationship between GPC1 and tumor metastasis. Transwell migration and wound-healing assay were conducted to evaluate the effects of GPC1 on migration and invasiveness. Epithelial marker and mesenchymal markers expression in GC cells were detected by Western blot and immunofluorescence. GPC1 expression induced by TGF-β was detected by Western Blot. After GPC1 was knock downed, the metastatic effect and EMT markers induced by TGF-β were detected. Co-Immunoprecipitation was used to detect the interaction between ITGB1 and GPC1. Results: The expression of GPC1 was higher in GC tissues than in adjacent normal tissues and associated with poor prognosis. Knocking down GPC1 suppressed EMT and stemness which reduced metastasis in vivo and vitro by inhibiting Erk1/2 MAPK and FAK/Akt pathways. TGF-β stimulation significantly upregulated the expression of GPC1 whereas knocking down of GPC1 reversed TGF-β-mediated EMT and stemness. Moreover, we found that knocking down GPC1 could downregulate ITGB1 which was known to promote EMT in gastric cancer. Overexpression of ITGB1 counteracted the influence of knocking down GPC1 on EMT and stemness. Furthermore, GPC1 formed a complex with ITGB1, which indicated that the ability of GPC1 to stimulate EMT is ITGB1-dependent. Conclusions: We conclude that GPC1, through its interaction with ITGB1, plays an important role in regulating TGF-β-mediated EMT and stemness, and could be a potential future therapeutic target to prevent progression of gastric cancer.
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Lu, Fei, Shuran Chen, Weijun Shi, Xu Su, Huazhang Wu et Mulin Liu. « GPC1 promotes the growth and migration of colorectal cancer cells through regulating the TGF-β1/SMAD2 signaling pathway ». PLOS ONE 17, no 6 (7 juin 2022) : e0269094. http://dx.doi.org/10.1371/journal.pone.0269094.

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In this study, we analyzed GPC family genes in colorectal cancer (CRC) and the possible mechanism of action of GPC1 in CRC. CRC patient data were extracted from The Cancer Genome Atlas, and the prognostic significance of GPC1 expression and its association with clinicopathological features were identified by Kolmogorov–Smirnov test. CRC patients with high GPC1 expression had poor overall survival compared with patients with low GPC1 expression. In vitro experiments demonstrated that knockdown of GPC1 significantly inhibited the proliferation and migration and promoted cell apoptosis in CRC cell lines. Gene Ontology analysis of differential genes indicated that GPC1 may influence the TGF-β1 signaling pathway. Additional experiments revealed that silencing GPC1 suppressed the levels of TGF-β1 and p-SMAD2 but increased the expression of SMAD2. Taken together, these findings suggest that GPC1 may function as a tumor promoter in CRC cells through promoting TGF-β signaling pathway. Our results also indicate that GPC1 may serve as a critical effector in CRC progression and a new potential target for CRC therapy.
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Qiao, Dianhua, Xinhai Yang, Kristy Meyer et Andreas Friedl. « Glypican-1 Regulates Anaphase Promoting Complex/Cyclosome Substrates and Cell Cycle Progression in Endothelial Cells ». Molecular Biology of the Cell 19, no 7 (juillet 2008) : 2789–801. http://dx.doi.org/10.1091/mbc.e07-10-1025.

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Glypican-1 (GPC1), a member of the mammalian glypican family of heparan sulfate proteoglycans, is highly expressed in glioma blood vessel endothelial cells (ECs). In this study, we investigated the role of GPC1 in EC replication by manipulating GPC1 expression in cultured mouse brain ECs. Moderate GPC1 overexpression stimulates EC growth, but proliferation is significantly suppressed when GPC1 expression is either knocked down or the molecule is highly overexpressed. Flow cytometric and biochemical analyses show that high or low expression of GPC1 causes cell cycle arrest at mitosis or the G2 phase of the cell cycle, accompanied by endoreduplication and consequently polyploidization. We further show that GPC1 inhibits the anaphase-promoting complex/cyclosome (APC/C)–mediated degradation of mitotic cyclins and securin. High levels of GPC1 induce metaphase arrest and centrosome overproduction, alterations that are mimicked by overexpression of cyclin B1 and cyclin A, respectively. These observations suggest that GPC1 regulates EC cell cycle progression at least partially by modulating APC/C-mediated degradation of mitotic cyclins and securin.
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Qiao, Dianhua, Kristy Meyer et Andreas Friedl. « Glypican 1 Stimulates S Phase Entry and DNA Replication in Human Glioma Cells and Normal Astrocytes ». Molecular and Cellular Biology 33, no 22 (9 septembre 2013) : 4408–21. http://dx.doi.org/10.1128/mcb.00238-13.

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Malignant gliomas are highly lethal neoplasms with limited treatment options. We previously found that the heparan sulfate proteoglycan glypican 1 (GPC1) is universally and highly expressed in human gliomas. In this study, we investigated the biological activity of GPC1 expression in both human glioma cells and normal astrocytesin vitro. Expression of GPC1 inactivates the G1/S checkpoint and strongly stimulates DNA replication. Constitutive expression of GPC1 causes DNA rereplication and DNA damage, suggesting a mutagenic activity for GPC1. GPC1 expression leads to a significant downregulation of the tumor suppressors pRb, Cip/Kip cyclin-dependent kinase inhibitors (CKIs), and CDH1, and upregulation of the pro-oncogenic proteins cyclin E, cyclin-dependent kinase 2 (CDK2), Skp2, and Cdt1. These GPC1-induced changes are accompanied by a significant reduction in all types of D cyclins, which is independent of serum supplementation. It is likely that GPC1 stimulates the so-called Skp2 autoinduction loop, independent of cyclin D-CDK4/6. Knockdown of Skp2, CDK2, or cyclin E, three key elements within the network modulated by GPC1, results in a reduction of the S phase and aneuploid fractions, implying a functional role for these regulators in GPC1-induced S phase entry and DNA rereplication. In addition, a significant activation of both the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways by GPC1 is seen in normal human astrocytes even in the presence of growth factor supplement. Both pathways are constitutively activated in human gliomas. The surprising magnitude and the mitogenic and mutagenic nature of the effect exerted by GPC1 on the cell cycle imply that GPC1 may play an important role in both glioma tumorigenesis and growth.
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Liu, Ying, Hui Ren, Mu-qing Yang et Ji-yu Li. « GPC1 Is Associated with Poor Prognosis and Treg Infiltration in Colon Adenocarcinoma ». Computational and Mathematical Methods in Medicine 2022 (14 septembre 2022) : 1–15. http://dx.doi.org/10.1155/2022/8209700.

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Glypican-1 (GPC1) is a glycosylated protein recognized as a promising biomarker for cancer. Nonetheless, there have been few systematic studies on GPC1 in colon adenocarcinoma (COAD). We conducted bioinformatic analysis based on The Cancer Genome Atlas (TCGA) and used clinical samples to verify that GPC1 is overexpressed in colon adenocarcinoma. Kaplan-Meier analysis showed that higher GPC1 expression was associated with poor overall survival (OS). The Cox regression model further showed that GPC1 expression is an independent negative prognostic factor for COAD. Gene set enrichment analysis demonstrated that multiple oncogenic signaling pathways were differentially enriched in GPC1 high- versus low-expressing COAD tumors, including DNA methylation, G2/M damage checkpoint, and telomere dysfunction. We observed a positive correlation between GPC1 expression and immune cell infiltration, such as regulatory T cells (Tregs), macrophages, and mast cells, and immunohistochemistry of 50 COAD tissues revealed that GPC1 expression was positively associated with Treg enrichment. Our results provide a promising candidate gene to predict the prognosis of COAD and new insights into tumor immunity. Further research is required to validate these results.
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Schlaepfer Sales, Caroline B., Vanessa S. N. Guimarães, Ludmila F. Valverde, Rosane B. Dias, Raíza D. Freitas, Leonardo de Oliveira Siquara da Rocha, Malu Coelho de Miranda et al. « Glypican-1, -3, -5 (GPC1, GPC3, GPC5) and Hedgehog Pathway Expression in Oral Squamous Cell Carcinoma ». Applied Immunohistochemistry & ; Molecular Morphology 29, no 5 (27 janvier 2021) : 345–51. http://dx.doi.org/10.1097/pai.0000000000000907.

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Whipple, Chery A., Arthur D. Lander et Murray Korc. « Discovery of a Novel Molecule that Regulates Tumor Growth and Metastasis ». Scientific World JOURNAL 8 (2008) : 1250–53. http://dx.doi.org/10.1100/tsw.2008.152.

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The heparan sulfate proteoglycan, Glypican-1 (GPC1), significantly impacts the growth of pancreatic cancer cellsin vivoand markedly attenuates tumor angiogenesis and metastasis in athymic mice. Interestingly, both cancer cell–derived and host-derived GPC1 play an important role in tumor development and spread. These data suggest that GPC1 may be a valid therapeutic target for pancreatic cancer.
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Khurana, Satish, Chacko Joseph, Lia Margamuljana, Shannon Buckley, Sarah Scouteden et Catherine M. Verfaillie. « Tissue Factor Pathway Inhibitor Increases Hematopoietic Stem Cell Homing and Engraftment by Glypican-3 Mediated Inhibition of CD26 Activity ». Blood 118, no 21 (18 novembre 2011) : 725. http://dx.doi.org/10.1182/blood.v118.21.725.725.

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Abstract Abstract 725 Directional migration is an important factor that determines homing of transplanted hematopoietic stem cells (HSC). The SDF-1α-CXCR4 axis is one of the most important determinants of this process. CD26, expressed on various cell types, leads to proteolytic cleavage of SDF-1α, which leads to the inactivation of its chemokine activity. We identified tissue factor pathway inhibitor (TFPI) as an inhibitor of CD26. Culture of murine bone marrow derived c-kit+Lin−Sca-1+ (KLS) cells or human umbilical cord blood derived Lin−CD34+ cells with TFPI significantly inhibited CD26 activity, which resulted in significantly increased migration towards SDF-1α. Moreover, TFPI treatment of murine KLS cells led to significant improvement in homing following intravenous injection and long-term reconstitution upon transplantation in competitive repopulation assays. We found that the effects of TFPI were mediated by the heparan sulphate proteoglycan, Glypican-3 (Gpc3). TFPI directly bound Gpc3; TFPI did not affect CD26 activity, migration or homing of Gpc3−/− KLS cells, but affected Gpc1−/− KLS cells similar to the wild type. Finally, KLS cells from Gpc3−/− but not Gpc1−/− mice homed significantly less following IV injection. Hence, we present a novel molecule that can be used in an HSC specific manner to enhance HSC migration, homing and engraftment. Disclosures: No relevant conflicts of interest to declare.
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Qiu, Wenli, Huifeng Zhang, Xiao Chen, Lina Song, Wenjing Cui, Shuai Ren, Yajie Wang et al. « A GPC1-targeted and gemcitabine-loaded biocompatible nanoplatform for pancreatic cancer multimodal imaging and therapy ». Nanomedicine 14, no 17 (septembre 2019) : 2339–53. http://dx.doi.org/10.2217/nnm-2019-0063.

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Aim: Biomarker-targeted nanocarrier holds promise for early diagnosis and effective therapy of cancer. Materials & methods: This work successfully designs and evaluates GPC1-targeted, gemcitabine (GEM)-loaded multifunctional gold nanocarrier for near-infrared fluorescence (NIRF)/MRI and targeted chemotherapy against pancreatic cancer in vitro and in vivo. Results: Blood biochemical and histological analyses show that the in vivo toxicity of GPC1-GEM-nanoparticles (NPs) was negligible. Both in vitro and in vivo studies demonstrate that GPC1-GEM-NPs can be used as NIRF/MR contrast agent for pancreatic cancer detection. Treatment of xenografted mice with GPC1-GEM-NPs shows a higher tumor inhibitory effect compared with controls. Conclusion: This novel theranostic nanoplatform provides early diagnostic and effective therapeutic potential for pancreatic cancer.
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Thèses sur le sujet "GPC1"

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Blankenship, Elise. « Conserved solvent networks in GPCR activation ». Case Western Reserve University School of Graduate Studies / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=case1458221506.

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Poudel, Sagar. « GPCR-Directed Libraries for High Throughput Screening ». Thesis, University of Skövde, School of Humanities and Informatics, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-29.

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Guanine nucleotide binding protein (G-protein) coupled receptors (GPCRs), the largest receptor family, is enormously important for the pharmaceutical industry as they are the target of 50-60% of all existing medicines. Discovery of many new GPCR receptors by the “human genome project”, open up new opportunities for developing novel therapeutics. High throughput screening (HTS) of chemical libraries is a well established method for finding new lead compounds in drug discovery. Despite some success this approach has suffered from the near absence of more focused and specific targeted libraries. To improve the hit rates and to maximally exploit the full potential of current corporate screening collections, in this thesis work, identification and analysis of the critical drug-binding positions within the GPCRs were done, based on their overall sequence, their transmembrane regions and their drug binding fingerprints. A proper classification based on drug binding fingerprints on the basis for a successful pharmacophore modelling and virtual screening were done, which facilities in the development of more specific and focused targeted libraries for HTS.

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Majin, Wodu. « Mathematical modelling of GPCR-mediated calcium signalling ». Thesis, University of Nottingham, 2012. http://eprints.nottingham.ac.uk/12451/.

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Ca2+ is an important messenger which mediates several physiological functions, including muscle contraction, fertilisation, heart regulation and gene transcription. One major way its cytosolic level is raised is via a G-protein coupled receptor (GPCR)- mediated release from intracellular stores. GPCR’s are the target of approximately 50% of all drugs in clinical use. Hence, understanding the underlying mechanisms of signalling in this pathway could lead to improved therapy in disease conditions associated with abnornmal Ca2+ signalling, and to the identification of new drug targets. To gain such insight, this thesis builds and analyses a detailed mathematical model of key processes leading to Ca2+ mobilisation. Ca2+ signalling is considered in the particular context of the M3 muscarinic receptor system. Guided by available data, the Ca2+ mobilisation model is assembled, first by analysing a base G-protein activation model, and subsequently extending it with downstream details. Computationally efficient designs of a global parameter sensitivity analysis method are used to identify the key controlling parameters with respect to the main features of the Ca2+ data. The underlying mechanism behind the experimentally observed, rapid, amplified Ca2+ response is shown to be a rapid rate of inositol trisphosphate (IP3) formation from Phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis. Using the same results, potential drug targets (apart fromthe GPCR) are identified, including the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) and PIP2. Moreover, possible explanations for therapeutic failures were found when some parameters exerted a biphasic effect on the relative Ca2+ increase. The sensitivity analysis results are used to simplify the process of parameter estimation by a significant reduction of the parameter space of interest. An evolutionary algorithm is used to successfully fit the model to a significant portion of the Ca2+ data. Subsequent sensitivity analyses of the best-fitting parameter sets suggest that mechanistic modelling of kinase-mediated GPCR desensitisation, and SERCA dynamics may be required for a comprehensive representation of the data.
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Tang, Lisa Sarah. « GPCR expressions in Saccharomyces cerevisiae : engineering transductions ». Thesis, University of Leeds, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.423190.

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Mishra, Satyakam. « Frequent Subgraph Mining Analysis of GPCR Activation ». Case Western Reserve University School of Graduate Studies / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1613575702373053.

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Sladek, Barbara. « Structural studies of integral membrane GPCR accessory proteins ». Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:09bf7ada-8e58-49f4-a979-bcd0cec95e8b.

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GPCR accessory proteins regulate the strength, efficiency and specificity of signal transfer upon receptor activation. Due to the inherent difficulties of studying membrane proteins in vitro and in vivo, little is known about the structure and topology of these small accessory proteins. Two examples of GPCR accessory proteins are the Melanocortin-2 receptor accessory protein (MRAP) and the Receptor-activity-modifying protein (RAMP) family. MRAP and RAMP1 are the main focus of this thesis in which they are thoroughly characterised by solution-state NMR and further biophysical techniques. The single-pass transmembrane domain protein MRAP regulates the class A GPCR melanocortin receptors. It is specifically required for trafficking the melanocortin-2-receptor from the endoplasmic reticulum to the cell surface and subsequent receptor activation. A remarkable characteristic of MRAP is its proposed native dual-topology, which leads to an antiparallel homodimeric conformation. Investigation of the biochemical and biophysical properties of MRAP revealed an α-helical transmembrane domain, and an α-helical N-terminal LD(Y/I)L-motif. Further efforts concentrated on establishing the homodimeric conformation of MRAP in vitro. RAMP1 facilitates receptor trafficking and alters the ligand specificity of the GPCR Class B receptors calcitonin receptors and calcitonin receptor-like receptors. Moreover, RAMP1 is required to act as a Calcitonin-gene-related peptide (CGRP) receptor (RAMP1). RAMP1 has been shown to form stable parallel homodimers in the absence of its cognate receptor. Its dimerisation and the possible dimerisation motif PxxxxP-motif were studied extensively. With the goal of understanding the mechanism of dimerisation and the role of GPCR accessory proteins I have used solution-state NMR in detergent micelles as my main technique. NMR provides unique possibilities for understanding the structure and dynamics of such small membrane proteins.
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Richardson, Kathryn. « Mechanisms of GPCR signal regulation in fission yeast ». Thesis, University of Warwick, 2014. http://wrap.warwick.ac.uk/63554/.

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Cells communicate with each other and respond to environmental cues by sending and receiving signals. Many external signals (ligands) are detected through G protein-coupled receptors (GPCRs), a major class of transmembrane proteins. GPCRs transduce these external signals into appropriate intracellular responses, enabling the cell to adapt to its environment. Malfunctions in these signalling pathways can lead to a range of human diseases and hence GPCRs have become attractive candidates for pharmacological design. The activation of a single receptor has the ability to induce numerous intracellular responses. Coupling this with the great number of different GPCR-types expressed in human cells means that understanding the basic principles of signal transduction and termination in humans is complicated. This study utilises the more simplistic eukaryotic yeast Schizosaccharomyces pombe (S. pombe) to overcome this complexity, as it contains only two GPCR types and hence the cross-talk between pathways is greatly reduced, whilst the structure and signalling functions of GPCRs are often evolutionarily conserved between yeast and humans. Mathematical modelling was used to aid the understanding of GPCR signalling in S. pombe and to inform experimental design. Speci�cally, an ordinary differential equation model �rst developed by Croft et al. (2013) was extended to include all known downstream signal transduction, regulation and termination events. This model is the �rst of its kind to describe a whole GPCR signalling pathway within S. pombe. Although it accurately predicts the cellular response to GPCR signalling it could only reproduce the biological plateau in temporal response with the addition of a 'yet unknown mechanism' GPCR degradation term. This motivated the investigation of how GPCRs in S. pombe are internalised from the plasma membrane in response to ligand stimulation. The primary mechanism for signal termination is via internalisation of the GPCR. This study identi�ed three potential casein kinases (Cki1, Cki2 and Cki3) that promote internalisation of the S. pombe GPCR Mam2. Microscopy analyses in combination with quantitative transcriptional, cell growth and cell cycle position assays uncovered a novel role for these kinases: that Cki2 regulates cell size during vegetative growth, Cki1 and Cki3 regulate the GPCR-response pathway and that Cki3 is essential for completing cytokinesis in S. pombe that have already undergone formation of a conjugation tube in response to ligand. Confocal microscopy of uorescent labelled Mam2 indicated a role for Cki2 in the internalisation and hence termination of the GPCR-response pathway. These findings add to the growing body of evidence that casein kinases are implicated in GPCR desensitisation.
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Goddard, Alan David. « Functional analysis of GPCR signalling cascades in Schizosaccharomyces pombe ». Thesis, University of Warwick, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437696.

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Koyama, Hiroyuki. « Comprehensive Profiling of GPCR Expression in Ghrelin-producing Cells ». Kyoto University, 2016. http://hdl.handle.net/2433/215953.

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Kiess, Alexandra. « Funktionelle Relevanz intrazellulärer Splicevarianten des Brain-specific Angiogenesis Inhibitor 2 (BAI2) ». Doctoral thesis, Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-156171.

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BAI2 gehört zu den Adhesion-G-Protein-gekoppelten Rezeptoren (aGPCR). Diese bisher wenig untersuchte Klasse von ca. 30 GPCR ist charakterisiert durch eine komplexe genomische Struktur, sehr große extrazelluläre Domänen und eine Vielzahl von Splicevarianten. Bisher ist bei den meisten aGPCR, wie auch bei BAI2, wenig über ihre Signaltransduktion und Funktion bekannt. Zum Verständnis der physiologischen Relevanz und zur Suche nach dem endogenen Agonist sind Kenntnisse über Proteinstruktur, Splicevarianten und Signaltransduktion essentiell. Ziel dieser Arbeit war es, mittels verschiedener in vitro-Methoden die Proteinstruktur des BAI2 in den transmembranären und intrazellulären Domänen näher zu untersuchen, sowie die natürlichen Splicevarianten in diesem Bereich, deren evolutionäre Konservierung, Gewebespezifität und Quantität zu erfassen. Für beide gefundenen Splicevarianten, eine im dritten intrazellulären Loop (ICL3) und eine im C-Terminus, konnte eine evolutionäre Konservierung auf Aminosäure- und genomischer Organisationsebene, sowie ihre Entstehung durch Exonskipping nachgewiesen werden. Nachfolgend wurden die Splicevarianten auf mögliche Interaktionen mit intrazellulären Komponenten untersucht. In dieser Arbeit konnte gezeigt werden, dass beide ICL3-Splicevarianten natürlicherweise in einem definierten Verhältnis auftreten. Außerdem konnte gezeigt werden, dass die lange ICL3-Variante des BAI2 nicht zu einer Änderung der Membrantopologie des Rezeptors, einer Homodimerisierung über die zusätzliche Aminosäuresequenz oder zu einer Interaktion mit dem C-Terminus führt. Die Splicevariante im humanen C-Terminus des BAI2 konnte als eine variable, durch Exonskipping entstandene Calcium-unabhängige Calmodulin-Bindungsstelle identifiziert werden. Diese Arbeit belegt die Existenz mehrerer BAI2-Isoformen in vivo. Die Struktur dieser Isoformen lässt unterschiedliche Funktionalitäten vermuten. Auch wenn erste Untersuchungen zwischen den beiden ICL3-Varianten keinen Unterschied ergaben, sind diese Erkenntnisse für die weitere Analyse der Signaltransduktion und Ligandensuche bedeutend. Es ist z.B. denkbar, dass sich die beiden ICL3-Varianten in der G-Protein-Kopplung oder bei der Rekrutierung von intrazellulären Interaktionspartnern unterscheiden oder dass die Splicevariante im C-Terminus zu einer Scaffold- Funktion des Calmodulins führt und/oder die Signaltransduktion durch eine permanente Bindung des Calmodulins an einer Isoform moduliert wird.
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Livres sur le sujet "GPC1"

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Gilchrist, Annette, dir. GPCR Molecular Pharmacology and Drug Targeting. Hoboken, NJ, USA : John Wiley & Sons, Inc., 2010. http://dx.doi.org/10.1002/9780470627327.

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Heifetz, Alexander, dir. Computational Methods for GPCR Drug Discovery. New York, NY : Springer New York, 2018. http://dx.doi.org/10.1007/978-1-4939-7465-8.

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Dupré, Denis J., Terence E. Hébert et Ralf Jockers, dir. GPCR Signalling Complexes – Synthesis, Assembly, Trafficking and Specificity. Dordrecht : Springer Netherlands, 2012. http://dx.doi.org/10.1007/978-94-007-4765-4.

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J, Huffman George, et United States. National Aeronautics and Space Administration., dir. The Global Precipitation Climatology Project (GPCP) combined precipitation dataset. [Washington, D.C : National Aeronautics and Space Administration, 1997.

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Zuckerman, Stephen. Updating the geographic practice cost index : The malpractice GPCI. Washington, DC : Urban Institute, 1994.

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Bitmead, Robert R. Adaptive optimal control : The thinking man's GPC. New York : Prentice Hall, 1990.

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Wang, Jiangtao, Longbiao Chen, Lei Tang et Yunji Liang, dir. Green, Pervasive, and Cloud Computing – GPC 2020 Workshops. Singapore : Springer Singapore, 2020. http://dx.doi.org/10.1007/978-981-33-4532-4.

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Annette, Gilchrist, dir. GPCR molecular pharmacology and drug targeting : Shifting paradigms and new directions. Hoboken, N.J : Wiley, 2010.

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Edwards, D. A. Some uses of GPC in a marine surveying laboratory. London : Institute of Petroleum, 1985.

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Pope, Gregory. Updating the geographic practice cost index : The practice expense GPCI : final report. Waltham, Mass : Health Economics Research, Inc., 1994.

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Chapitres de livres sur le sujet "GPC1"

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Manji, Husseini K., Jorge Quiroz, R. Andrew Chambers, Anthony Absalom, David Menon, Patrizia Porcu, A. Leslie Morrow et al. « GPCR ». Dans Encyclopedia of Psychopharmacology, 561. Berlin, Heidelberg : Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-540-68706-1_1464.

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Filmus, Jorge. « Glypicans (GPCs) ». Dans Encyclopedia of Signaling Molecules, 2169–73. Cham : Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-67199-4_101637.

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Filmus, Jorge. « Glypicans (GPCs) ». Dans Encyclopedia of Signaling Molecules, 1–5. New York, NY : Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4614-6438-9_101637-1.

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Gooch, Jan W. « GPC ». Dans Encyclopedic Dictionary of Polymers, 346. New York, NY : Springer New York, 2011. http://dx.doi.org/10.1007/978-1-4419-6247-8_5588.

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Fernandez-Camacho, Eduardo, et Carlos Bordons-Alba. « Multivariable GPC ». Dans Model Predictive Control in the Process Industry, 105–28. London : Springer London, 1995. http://dx.doi.org/10.1007/978-1-4471-3008-6_5.

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Wu, Yiran, Jiahui Tong, Kang Ding, Qingtong Zhou et Suwen Zhao. « GPCR Allosteric Modulator Discovery ». Dans Advances in Experimental Medicine and Biology, 225–51. Singapore : Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-8719-7_10.

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Kenakin, Terry. « The Evolution of Receptors : From On-Off Switches to Microprocessors ». Dans GPCR Molecular Pharmacology and Drug Targeting, 1–26. Hoboken, NJ, USA : John Wiley & Sons, Inc., 2010. http://dx.doi.org/10.1002/9780470627327.ch1.

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Hoffmann, Carsten, et Moritz Bünemann. « Fluorescence and Resonance Energy Transfer Shine New Light on GPCR Function ». Dans GPCR Molecular Pharmacology and Drug Targeting, 226–51. Hoboken, NJ, USA : John Wiley & Sons, Inc., 2010. http://dx.doi.org/10.1002/9780470627327.ch10.

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Nayler, Oliver, Magdalena Birker-Robaczewska et John Gatfield. « Integration of Label-Free Detection Methods in GPCR Drug Discovery ». Dans GPCR Molecular Pharmacology and Drug Targeting, 252–75. Hoboken, NJ, USA : John Wiley & Sons, Inc., 2010. http://dx.doi.org/10.1002/9780470627327.ch11.

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Langmead, Christopher. « Screening for Allosteric Modulators of G Protein-Coupled Receptors ». Dans GPCR Molecular Pharmacology and Drug Targeting, 276–99. Hoboken, NJ, USA : John Wiley & Sons, Inc., 2010. http://dx.doi.org/10.1002/9780470627327.ch12.

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Actes de conférences sur le sujet "GPC1"

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Ebong, E. E., D. C. Spray et J. M. Tarbell. « The Roles of HS and Its Glypican-1 Core Protein in Flow-Induced Endothelial NOS Activation and Cell Remodeling ». Dans ASME 2011 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2011. http://dx.doi.org/10.1115/sbc2011-53294.

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Endothelial cell (EC) glycocalyx (GCX) is an endovascular protective coat that is degraded in disease. GCX heparan sulfate (HS) proteoglycan is essential for flow-induced nitric oxide (NO) release and cell remodeling, but the HS core proteins involved in these mechanotransduction events are unknown. We hypothesize that the glypican-1 (GPC1) HS core protein mediates flow-induced EC NO synthase (eNOS) activation and is less important for flow-induced cell remodeling, because GPC1 is located in the caveolae where eNOS resides but, to our knowledge, GPC1 has no direct association with the cytoskeleton. We tested our hypotheses by exposing monolayers of bovine aortic EC (BAEC) with intact GCX, heparinase III (HepIII) enzymatically degraded HS, and RNA-silenced GPC1 to 12–15 dyne/cm2 average shear stress for 3 and 24 hours. HS removal by HepIII and GPC1 inhibition by shRNA equally blocked shear-induced eNOS activation that occurs in shear-conditioned BAEC with fully intact GCX. EC remodeling in response to flow was attenuated by HS degradation, but preserved with GPC1 knockdown. These results suggest that while HS is involved in both centralized and decentralized GCX-mediated mechanotransduction mechanisms, GPC1 plays a role in only centralized GCX-mediated mechanotransduction.
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Saito, Yurina, Tsuyoshi Takahashi, Kosuke Hiramatsu, Satoshi Serada, Minoru Fujimoto, Koji Tanaka, Yasuhiro Miyazaki et al. « Abstract B034 : CpG oligodeoxynucleotides potentiate the antitumor activity of anti-GPC1 antibody ». Dans Abstracts : AACR-NCI-EORTC International Conference : Molecular Targets and Cancer Therapeutics ; October 26-30, 2017 ; Philadelphia, PA. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1535-7163.targ-17-b034.

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Onaka, P., C. Rae, S. Isani, J. L. Tonry, A. Lee, R. Uyeshiro, L. Robertson et G. Ching. « GPC1 and GPC2 : the Pan-STARRS 1.4 gigapixel mosaic focal plane CCD cameras with an on-sky on-CCD tip-tilt image compensation ». Dans SPIE Astronomical Telescopes + Instrumentation, sous la direction de Andrew D. Holland et James W. Beletic. SPIE, 2012. http://dx.doi.org/10.1117/12.925830.

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Qiao, Dianhua, Kristy Meyer et Andreas Friedl. « Abstract 3042 : Glypican-1 (GPC1) promotes S-phase entry and DNA replication in human glioma cells ». Dans Proceedings : AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012 ; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-3042.

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Whipple, Chery A., et Murray Korc. « Abstract 2811 : GPC1 promotes tumor growth and angiogenesis in a KrasG12D- Driven mouse model of pancreatic cancer ». Dans Proceedings : AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011 ; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-2811.

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Qiao, Dianhua, Kristy Meyer et Andreas Friedl. « Abstract 1307 : c-Myc is a key mediator of glypican-1 (GPC1)-dependent deregulation of the cell cycle ». Dans Proceedings : AACR Annual Meeting 2014 ; April 5-9, 2014 ; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-1307.

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Kuksis, Arnis. « Hydrolysis of hydroxy PUFA GPC of plasma lipoproteins by group IIA, V and X sPLA2s ». Dans 2022 AOCS Annual Meeting & Expo. American Oil Chemists' Society (AOCS), 2022. http://dx.doi.org/10.21748/jxxc8749.

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This study describes the isolation and identification of mono-, di- and tri-hydroxy AA, EPA and DHA in plasma LDL, HDL, HDL3 and acute phase HDL using normal phase LC/ESI/MS as previously reported for plasma lipoprotein GPC epoxides and isoprostanes. The lipoproteins contained variable amounts of the hydroxy PUFA GPC (1 to 10 nanomoles/mg protein), likely the product of lipid peroxidation and the action of various lipoxygenases and cytochrome P450 enzymes on both free fatty acids and the parent GPCs, although transesterification by preformed hydroxy fatty acids was not excluded. The hydroxy PUFA GPC was hydrolyzed to variable extent (20-90%) by the different-PLA2s, with group IIA sPLA2 showing the lowest and group X sPLA2 the highest activity. Although standards were not available and detailed identification of the structure was not performed, there was general agreement between the masses determined for the identified structures and masses calculated for the GPC equivalents of the resolvins, protectins and maresins, as reported in the literature. There has been no biological testing of the GPC esters of the specialized pro-resolving mediators.
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Aung, Tint Htoo, Romain Djenani, Aaron Byrd, Matt Beavers, Cedric Manzoleloua, Sarah Green et Balkrishna Gadiyar. « Novel Approach in Deploying Filter Cake Breaker Post Open Hole Gravel Pack with Non-Aqueous Gravel Pack Carrier Fluid in Reservoir with Reactive Shales ». Dans SPE International Conference and Exhibition on Formation Damage Control. SPE, 2022. http://dx.doi.org/10.2118/208827-ms.

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Abstract Non-aqueous gravel pack carrier fluids (GPCF) have been introduced into the industry to eliminate the risks associated with the water-based carrier fluids in the presence of reactive shale interbeds in the reservoir. However, non-aqueous GPCF pose a significant barrier to the effective deployment of post-gravel pack filter cake breaker (FCB) application because all FCB systems are water-based. Therefore, a novel approach was developed for FCB application in non-aqueous GPCF environment to improve the efficiency of the FCB and the overall well performance. The non-aqueous GPCF was redesigned from ground up to promote the better diffusion of the FCB. This was accomplished by introducing a reversible emulsifier package into the non-aqueous GPCF design which allows the gravel to change wettability from an oil-wet state to a water-wet state when a low pH solution i.e., breaker is spotted inside the sand screens after the open hoel gravel pack (OHGP). To complement this, the FCB design was deconstructed, and the in-situ breaker component was blended with the gravel. The concept was to incorporate the in-situ breaker component into the gravel pore space which would promote better diffusion of FCB through the reversible non-aqueous GPCP. The in-situ breaker component is inert to the carrier fluid until it is activated by the temperature and water posing no threat to the stability of the carrier fluid while pumping. The innovative approach was tested in the laboratory setting using ceramic disks and return to flow method to prove the concept before conducting an elaborate return permeability testing with the reservoir core plugs for the final validation. Return to flow method indicated that the novel approach could improve the results by at least 10% compared to the baseline test with no breaker application. In the return permeability tests with reservoir core plugs, the novel approach resulted in 76% of the initial permeability whereas the baseline test was only 50%. Both the tests with ceramic disks and full-sequence formation damage tests with actual reservoir cores highlighted the benefits of the novel approach for gravel packing with non-aqueous GPCF and post-gravel pack FCB scenario. Non-aqueous GPCFs are relatively new to the industry and no record of the filter cake breaker application in such environment exists. This novel approach makes the filter cake breaker application possible in non-aqueous environment and pushes the existing boundaries of filter cake breaker chemistries.
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Ye, Jieping, Ravi Janardan et Qi Li. « GPCA ». Dans the 2004 ACM SIGKDD international conference. New York, New York, USA : ACM Press, 2004. http://dx.doi.org/10.1145/1014052.1014092.

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Andrews, Mark, Gavin Jones, Brian Leyde, Lie Xiong, Max Xu et Peter Chien. « A Statistical Imputation Method for Handling Missing Values in Generalized Polynomial Chaos Expansions ». Dans ASME Turbo Expo 2019 : Turbomachinery Technical Conference and Exposition. American Society of Mechanical Engineers, 2019. http://dx.doi.org/10.1115/gt2019-91035.

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Abstract Generalized Polynomial Chaos Expansion (gPCE) is widely used in uncertainty quantification and sensitivity analysis for applications in the aerospace industry. gPCE uses the spectrum projection to fit a polynomial model, the gPCE model, to a sparse grid Design of Experiments (DOEs). The gPCE model can be used to make predictions, analytically determine uncertainties, and calculate sensitivity indices. However, the model’s accuracy is very dependent on having complete DOEs. When a sampling point is missing from the sparse grid DOE, this severely impacts the accuracy of the gPCE analysis and often necessitates running a new DOE. Missing data points are a common occurrence in engineering testing and simulation. This problem complicates the use of the gPCE analysis. In this paper, we present a statistical imputation method for addressing this missing data problem. This methodology allows gPCE modeling to handle missing values in the sparse grid DOE. Using a series of numerical results, the study demonstrates the convergence characteristics of the methodology with respect to reaching steady state values for the missing points. The article concludes with a discussion of the convergence rate, advantages, and feasibility of using the proposed methodology.
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Rapports d'organisations sur le sujet "GPC1"

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Dubcovsky, Jorge, Tzion Fahima et Ann Blechl. Positional cloning of a gene responsible for high grain protein content in tetraploid wheat. United States Department of Agriculture, septembre 2003. http://dx.doi.org/10.32747/2003.7695875.bard.

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High Grain Protein Content (GPC) is a desirable trait in breadmaking and pasta wheat varieties because of its positive effects on quality and nutritional value. However, selection for GPC is limited by our poor understanding of the genes involved in the accumulation of protein in the grain. The long-term goal of this project is to provide a better understanding of the genes controlling GPC in wheat. The specific objectives of this project were: a) to develop a high-density genetic map of the GPC gene in tetraploid wheat, b) to construct a T. turgidum Bacterial Artificial Chromosome (BAC) library, c) to construct a physical map of the GPC gene and identify a candidate for the GPC gene. A gene with a large effect on GPC was detected in Triticum turgidum var. dicoccoides and was previously mapped in the short arm of chromosome 6B. To define better the position of the Gpc-B1 locus we developed homozygous recombinant lines with recombination events within the QTL region. Except for the 30-cM region of the QTL these RSLs were isogenic for the rest of the genome minimizing the genetic variability. To minimize the environmental variability the RSLs were characterized using 10 replications in field experiments organized in a Randomized Complete Block Design, which were repeated three times. Using this strategy, we were able to map this QTL as a single Mendelian locus (Gpc-B1) on a 2.6-cM region flanked by RFLP markers Xcdo365 and Xucw67. All three experiments showed that the lines carrying the DIC allele had an average absolute increase in GPC of 14 g/kg. Using the RFLP flanking markers, we established the microcolinearity between a 2.l-cM region including the Gpc-B1 gene in wheat chromosome 6BS and a 350-kb region on rice chromosome 2. Rice genes from this region were used to screen the Triticeae EST collection, and these ESTs were used to saturate the Gpc-B1 region with molecular markers. With these new markers we were able to map the Gpc-B1 locus within a 0.3-cM region flanked by PCR markers Xucw83 and Xucw71. These flanking markers defined a 36-kb colinear region with rice, including one gene that is a potential candidate for the Gpc-B1 gene. To develop a physical map of the Gpc-B1 region in wheat we first constructed a BAC library of tetraploid wheat, from RSL#65 including the high Gpc-B1 allele. We generated half- million clones with an average size of l3l-kb (5.1 X genome equivalents for each of the two genomes). This coverage provides a 99.4% probability of recovering any gene from durum wheat. We used the Gpc-BI flanking markers to screen this BAC library and then completed the physical map by chromosome walking. The physical map included two overlapping BACs covering a region of approximately 250-kb, including two flanking markers and the Gpc-B1 gene. Efforts are underway to sequence these two BACs to determine if additional wheat genes are present in this region. Weare also developing new RSLs to further dissect this region. We developed PCR markers for flanking loci Xucw79andXucw71 to facilitate the introgression of this gene in commercial varieties by marker assisted selection (httQ://maswheat.ucdavis.edu/ orotocols/HGPC/index.hlm). Using these markers we introgressed the Gpc-B1 gene in numerous pasta and common wheat breeding lines.
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Reynolds, R. Michael, et Ernie Lewis. Marine ARM GPCI Investigation of Clouds Psychrometer Field Campaign Report. Office of Scientific and Technical Information (OSTI), septembre 2016. http://dx.doi.org/10.2172/1324981.

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Lewis, Ernie R. Marine ARM GPCI Investigation of Clouds (MAGIC) Field Campaign Report. Office of Scientific and Technical Information (OSTI), décembre 2016. http://dx.doi.org/10.2172/1343577.

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Dubcovsky, Jorge, Tzion Fahima, Ann Blechl et Phillip San Miguel. Validation of a candidate gene for increased grain protein content in wheat. United States Department of Agriculture, janvier 2007. http://dx.doi.org/10.32747/2007.7695857.bard.

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High Grain Protein Content (GPC) of wheat is important for improved nutritional value and industrial quality. However, selection for this trait is limited by our poor understanding of the genes involved in the accumulation of protein in the grain. A gene with a large effect on GPC was detected on the short arm of chromosome 6B in a Triticum turgidum ssp. dicoccoides accession from Israel (DIC, hereafter). During the previous BARD project we constructed a half-million clones Bacterial Artificial Chromosome (BAC) library of tetraploid wheat including the high GPC allele from DIC and mapped the GPC-B1 locus within a 0.3-cM interval. Our long-term goal is to provide a better understanding of the genes controlling grain protein content in wheat. The specific objectives of the current project were to: (1) complete the positional cloning of the GPC-B1 candidate gene; (2) characterize the allelic variation and (3) expression profile of the candidate gene; and (4) validate this gene by using a transgenic RNAi approach to reduce the GPC transcript levels. To achieve these goals we constructed a 245-kb physical map of the GPC-B1 region. Tetraploid and hexaploid wheat lines carrying this 245-kb DIC segment showed delayed senescence and increased GPC and grain micronutrients. The complete sequencing of this region revealed five genes. A high-resolution genetic map, based on approximately 9,000 gametes and new molecular markers enabled us to delimit the GPC-B1 locus to a 7.4-kb region. Complete linkage of the 7.4-kb region with earlier senescence and increase in GPC, Zn, and Fe concentrations in the grain suggested that GPC-B1 is a single gene with multiple pleiotropic effects. The annotation of this 7.4-kb region identified a single gene, encoding a NAC transcription factor, designated as NAM-B1. Allelic variation studies demonstrated that the ancestral wild wheat allele encodes a functional NAC transcription factor whereas modern wheat varieties carry a non-functional NAM-B1 allele. Quantitative PCR showed that transcript levels for the multiple NAMhomologues were low in flag leaves prior to anthesis, after which their levels increased significantly towards grain maturity. Reduction in RNA levels of the multiple NAMhomologues by RNA interference delayed senescence by over three weeks and reduced wheat grain protein, Zn, and Fe content by over 30%. In the transgenic RNAi plants, residual N, Zn and Fe in the dry leaves was significantly higher than in the control plants, confirming a more efficient nutrient remobilization in the presence of higher levels of GPC. The multiple pleiotropic effects of NAM genes suggest a central role for these genes as transcriptional regulators of multiple processes during leaf senescence, including nutrient remobilization to the developing grain. The cloning of GPC-B1 provides a direct link between the regulation of senescence and nutrient remobilization and an entry point to characterize the genes regulating these two processes. This may contribute to their more efficient manipulation in crops and translate into food with enhanced nutritional value. The characterization of the GPC-B1 gene will have a significant impact on wheat production in many regions of the world and will open the door for the identification of additional genes involved in the accumulation of protein in the grain.
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Reynolds, R. Michael, et Ernie Lewis. Marine ARM GPCI Investigation of Clouds Bridge Display Field Campaign Report. Office of Scientific and Technical Information (OSTI), septembre 2016. http://dx.doi.org/10.2172/1324980.

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Reynolds, R. Michael, et Charles N. Long. Marine ARM GPCI Investigation of Clouds Sunshine Pyranometer (SPN1) Field Campaign Report. Office of Scientific and Technical Information (OSTI), janvier 2016. http://dx.doi.org/10.2172/1328011.

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Rafaeli, Ada, Russell Jurenka et Daniel Segal. Isolation, Purification and Sequence Determination of Pheromonotropic-Receptors. United States Department of Agriculture, juillet 2003. http://dx.doi.org/10.32747/2003.7695850.bard.

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Moths constitute a major group of pest insects in agriculture. Pheromone blends are utilised by a variety of moth species to attract conspecific mates, which is under circadian control by the neurohormone, PBAN (pheromone-biosynthesis-activating neuropeptide). Our working hypothesis was that, since the emission of sex-pheromone is necessary to attract a mate, then failure to produce and emit pheromone is a potential strategy for manipulating adult moth behavior. The project aimed at identifying, characterising and determining the sequence of specific receptors responsible for the interaction with pheromonotropic neuropeptide/s using two related moth species: Helicoverpa armigera and H. lea as model insects. We established specific binding to a membrane protein estimated at 50 kDa in mature adult females using a photoaffinity-biotin probe for PBAN. We showed that JH is required for the up-regulation of this putative receptor protein. In vitro studies established that the binding initiates a cascade of second messengers including channel opening for calcium ions and intracellular cAMP production. Pharmacological studies (using sodium fluoride) established that the receptor is coupled to a G-protein, that is, the pheromone-biosynthesis-activating neuropeptide receptor (PBAN-R) belongs to the family of G protein-coupled receptor (GPCR)'s. We showed that PBAN-like peptides are present in Drosophila melanogaster based on bioassay and immunocytochemical data. Using the annotated genome of D. melanogaster to search for a GPCR, we found that some were similar to neuromedin U- receptors of vertebrates, which contain a similar C-terminal ending as PBAN. We established that neuromedin U does indeed induce pheromone biosynthesis and cAMP production. Using a PCR based cloning strategy and mRNA isolated from pheromone glands of H. zea, we successfully identified a gene encoding a GPCR from pheromone glands. The full-length PBAN-R was subsequently cloned and expressed in Sf9 insect cells and was shown to mobilize calcium in response to PBAN in a dose-dependent manner. The successful progress in the identification of a gene, encoding a GPCR for the neurohormone, PBAN, provides a basis for the design of a novel battery of compounds that will specifically antagonize pheromone production. Furthermore, since PBAN belongs to a family of insect neuropeptides with more than one function in different life stages, this rationale may be extended to other physiological key-regulatory processes in different insects.
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Reynolds, R. Michael, et Charles N. Long. Marine ARM GPCI Investigation of Clouds Infrared Sea Surface Temperature Autonomous Radiometer (ISAR) Field Campaign Report. Office of Scientific and Technical Information (OSTI), janvier 2016. http://dx.doi.org/10.2172/1328010.

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Bonfil, David J., Daniel S. Long et Yafit Cohen. Remote Sensing of Crop Physiological Parameters for Improved Nitrogen Management in Semi-Arid Wheat Production Systems. United States Department of Agriculture, janvier 2008. http://dx.doi.org/10.32747/2008.7696531.bard.

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To reduce financial risk and N losses to the environment, fertilization methods are needed that improve NUE and increase the quality of wheat. In the literature, ample attention is given to grid-based and zone-based soil testing to determine the soil N available early in the growing season. Plus, information is available on in-season N topdressing applications as a means of improving GPC. However, the vast majority of research has focused on wheat that is grown under N limiting conditions in sub-humid regions and irrigated fields. Less attention has been given to wheat in dryland that is water limited. The objectives of this study were to: (1) determine accuracy in determining GPC of HRSW in Israel and SWWW in Oregon using on-combine optical sensors under field conditions; (2) develop a quantitative relationship between image spectral reflectance and effective crop physiological parameters; (3) develop an operational precision N management procedure that combines variable-rate N recommendations at planting as derived from maps of grain yield, GPC, and test weight; and at mid-season as derived from quantitative relationships, remote sensing, and the DSS; and (4) address the economic and technology-transfer aspects of producers’ needs. Results from the research suggest that optical sensing and the DSS can be used for estimating the N status of dryland wheat and deciding whether additional N is needed to improve GPC. Significant findings include: 1. In-line NIR reflectance spectroscopy can be used to rapidly and accurately (SEP <5.0 mg g⁻¹) measure GPC of a grain stream conveyed by an auger. 2. On-combine NIR spectroscopy can be used to accurately estimate (R² < 0.88) grain test weight across fields. 3. Precision N management based on N removal increases GPC, grain yield, and profitability in rainfed wheat. 4. Hyperspectral SI and partial least squares (PLS) models have excellent potential for estimation of biomass, and water and N contents of wheat. 5. A novel heading index can be used to monitor spike emergence of wheat with classification accuracy between 53 and 83%. 6. Index MCARI/MTVI2 promises to improve remote sensing of wheat N status where water- not soil N fertility, is the main driver of plant growth. Important features include: (a) computable from commercial aerospace imagery that include the red edge waveband, (b) sensitive to Chl and resistant to variation in crop biomass, and (c) accommodates variation in soil reflectance. Findings #1 and #2 above enable growers to further implement an efficient, low cost PNM approach using commercially available on-combine optical sensors. Finding #3 suggests that profit opportunities may exist from PNM based on information from on-combine sensing and aerospace remote sensing. Finding #4, with its emphasis on data retrieval and accuracy, enhances the potential usefulness of a DSS as a tool for field crop management. Finding #5 enables land managers to use a DSS to ascertain at mid-season whether a wheat crop should be harvested for grain or forage. Finding #6a expands potential commercial opportunities of MS imagery and thus has special importance to a majority of aerospace imaging firms specializing in the acquisition and utilization of these data. Finding #6b on index MCARI/MVTI2 has great potential to expand use of ground-based sensing and in-season N management to millions of hectares of land in semiarid environments where water- not N, is the main determinant of grain yield. Finding #6c demonstrates that MCARI/MTVI2 may alleviate the requirement of multiple N-rich reference strips to account for soil differences within farm fields. This simplicity will be less demanding of grower resources, promising substantially greater acceptance of sensing technologies for in-season N management.
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Heitman, Joseph. Novel Gbeta Mimic Kelch Proteins (Gpb1 and Gpb2 Connect G-Protein Signaling to Ras via Yeast Neurofibromin Homologs Ira1 and Ira2 : A Model for Human NF1. Fort Belvoir, VA : Defense Technical Information Center, mars 2008. http://dx.doi.org/10.21236/ada483900.

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