Academic literature on the topic 'IRS-1'

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Journal articles on the topic "IRS-1"

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Ma, Zhefu, Shannon L. Gibson, Maura A. Byrne, Junran Zhang, Morris F. White, and Leslie M. Shaw. "Suppression of Insulin Receptor Substrate 1 (IRS-1) Promotes Mammary Tumor Metastasis." Molecular and Cellular Biology 26, no. 24 (October 9, 2006): 9338–51. http://dx.doi.org/10.1128/mcb.01032-06.

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ABSTRACT The insulin receptor substrate (IRS) proteins are cytoplasmic adaptors that organize signaling complexes downstream of activated cell surface receptors. Here, we show that IRS-1 and IRS-2, despite significant homology, play critical yet distinct functions in breast cancer, and we identify specific signaling pathways that are influenced by IRS-1 using the polyoma virus middle-T (PyV-MT) transgenic mouse model of mammary carcinoma and Irs-1 null (Irs1 −/−) mice. The absence of Irs-1 expression enhanced metastatic spread significantly without a significant effect on primary tumor growth. Orthotopic transplant studies revealed that the increased metastatic potential of Irs1-deficient tumor cells is cell autonomous. Mammary tumors that developed in PyV-MT::Irs1 −/− mice exhibited elevated Irs-2 function and enhanced phosphatidylinositol 3-kinase/Akt/mTor activity, suggesting that one mechanism by which Irs-1 impedes metastasis is to suppress Irs-2-dependent signaling. In support of this mechanism, reduction of Irs-2 expression in Irs1 −/− tumor cells restored mTor signaling to wild-type levels. PyV-MT::Irs1 −/− tumors also exhibited a significant increase in vascular endothelial growth factor expression and microvessel density, which could facilitate their dissemination. The significance of our findings for human breast cancer is heightened by our observation that Irs-1 is inactivated in wild-type, metastatic mammary tumors by serine phosphorylation. Collectively, our findings reveal that inactivation of IRS-1 enhances breast cancer metastasis and support the novel hypothesis that IRS-1 has metastasis suppressor functions for breast cancer.
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Negara, Dewa Ngakan Ketut Putra, Tjokorda Gde Tirta Nindhia, Lusiana, I. Made Widiyarta, I. Made Astika, and Cokorda Istri Putri Kusuma Kencanawati. "The Effect of Impregnation Ratio on the Surface Characteristics of Gigantochloa Verticillata Bamboo-Activated Carbon." Materials Science Forum 1045 (September 6, 2021): 59–66. http://dx.doi.org/10.4028/www.scientific.net/msf.1045.59.

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The activation process is the final stage in the manufacturing of activated carbon that can be carried out physically or chemically. This paper focuses on characterizing the surface properties of activated carbons from Gigantochloa verticillata bamboo that are chemically activated at 750°C under different impregnation ratios (IRs) of 1:1, 2:1, and 3:1. The activated carbons produced were denoted as IR1-AC, IR2-AC, and IR3-AC for impregnation ratios of 1:1, 2:1, and 3:1, respectively. Characterizations include TGA, SEM, and adsorption isotherm tests. The results of the research show that variation of the impregnation ratio yielded fluctuated content of proximate elements and surface properties of activated carbons. The highest fixed carbon of 75.69% and the lowest ash of 13.10% were obtained by IR2-AC. The highest surface area of 511.10 m2/g and pore volume of 0.561 cc/g was obtained by IR3-AC and IR2-AC, respectively. The activated carbon pores are distributed in micropores and mesopores areas with average pore diameters of 1.245, 2.494, and 1.984 nm for IR1-AC, IR2-AC, and IR3-AC, respectively. The existence of the pores can be found on the surface morphology of activated carbons.
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Hirashima, Y., K. Tsuruzoe, S. Kodama, M. Igata, T. Toyonaga, K. Ueki, CR Kahn, and E. Araki. "Insulin down-regulates insulin receptor substrate-2 expression through the phosphatidylinositol 3-kinase/Akt pathway." Journal of Endocrinology 179, no. 2 (November 1, 2003): 253–66. http://dx.doi.org/10.1677/joe.0.1790253.

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Insulin receptor substrate (IRS)-1 and IRS-2 are the major substrates that mediate insulin action. Insulin itself regulates the expression of the IRS protein in the liver, but the underlying mechanisms of IRS-1 and IRS-2 regulation are not fully understood. Here we report that insulin suppressed the expression of both IRS-1 and IRS-2 proteins in Fao hepatoma cells. The decrease in IRS-1 protein occurred via proteasomal degradation without any change in IRS-1 mRNA, whereas the insulin-induced suppression of IRS-2 protein was associated with a parallel decrease in IRS-2 mRNA without changing IRS-2 mRNA half-life. The insulin-induced suppression of IRS-2 mRNA and protein was blocked by the phosphatidylinositol (PI) 3-kinase inhibitor, LY294002, but not by the MAP kinase-ERK kinase (MEK) inhibitor, PD098059. Inhibition of Akt by overexpression of dominant-negative Akt also caused complete attenuation of the insulin-induced decrease in IRS-2 protein and partial attenuation of its mRNA down-regulation. Some nuclear proteins bound to the insulin response element (IRE) sequence on the IRS-2 gene in an insulin-dependent manner in vitro, and the binding was also blocked by the PI 3-kinase inhibitor. Reporter gene assay showed that insulin suppressed the activity of both human and rat IRS-2 gene promoters through the IRE in a PI 3-kinase-dependent manner. Our results indicate that insulin regulates IRS-1 and IRS-2 through different mechanisms and that insulin represses IRS-2 gene expression via a PI 3-kinase/Akt pathway.
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Hadsell, Darryl L., Walter Olea, Nicole Lawrence, Jessy George, Daniel Torres, Takahashi Kadowaki, and Adrian V. Lee. "Decreased lactation capacity and altered milk composition in insulin receptor substrate null mice is associated with decreased maternal body mass and reduced insulin-dependent phosphorylation of mammary Akt." Journal of Endocrinology 194, no. 2 (August 2007): 327–36. http://dx.doi.org/10.1677/joe-07-0160.

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Expression of insulin receptor substrates (IRS)-1 and -2 within the mammary gland was found to be high at mid-lactation and dramatically decreased with mammary involution. This observation supports the hypothesis that these proteins are induced in the mammary gland with lactogenesis and involved in normal milk synthesis. To test this hypothesis, lactation capacity, along with indices of mammary secretory cell glucose metabolism and cell signaling were compared in normal mice and mice carrying targeted mutations in either the Irs1 or Irs2 genes. Mammary IRS-1 and IRS-2 protein levels were increased within 1 day of parturition and reached maximal levels by 5 days post partum. Dams carrying germline mutations of Irs1 or Irs2 displayed reduced lactation capacity as assessed by weight gain of pup litters. The reduction was more dramatic in Irs1−/− versus Irs2−/− dams. Maternal body weight was also reduced in Irs1−/− dams as well as in Irs1+/− Irs2+/− dams. The loss of IRS-1 had little impact on mammary gland expression of milk protein mRNAs, glucose transport, or on the abundance and subcellular localization of hexokinases I and II. The loss of IRS-1 was associated with a compensatory increase in insulin-induced IRS-2 phosphorylation; however, the loss of IRS-1 did also cause a reduction in insulin-dependent mammary gland-specific activation of Akt phosphorylation. These results support the conclusion that IRS-1 is important for insulin-dependent activation of Akt signaling within the lactating mammary gland, but that loss of this protein has only modest impact on normal milk synthesis, since related signaling proteins such as IRS-2 may act in compensatory fashion.
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Lempke, Landon B., Rachel S. Johnson, Rachel K. Le, Melissa N. Anderson, Julianne D. Schmidt, and Robert C. Lynall. "Head Impact Biomechanics in Youth Flag Football: A Prospective Cohort Study." American Journal of Sports Medicine 49, no. 10 (July 15, 2021): 2817–26. http://dx.doi.org/10.1177/03635465211026643.

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Background: Youth flag football participation has rapidly grown and is a potentially safer alternative to tackle football. However, limited research has quantitatively assessed youth flag football head impact biomechanics. Purpose: To describe head impact biomechanics outcomes in youth flag football and explore factors associated with head impact magnitudes. Study Design: Cross-sectional study; Level of evidence, 3. Methods: We monitored 52 player-seasons among 48 male flag football players (mean ± SD; age, 9.4 ± 1.1 years; height, 138.6 ± 9.5 cm; mass, 34.7 ± 9.2 kg) across 3 seasons using head impact sensors during practices and games. Sensors recorded head impact frequencies, peak linear ( g) and rotational (rad/s2) acceleration, and estimated impact location. Impact rates (IRs) were calculated as 1 impact per 10 player-exposures; IR ratios (IRRs) were used to compare season, event type, and age group IRs; and 95% CIs were calculated for IRs and IRRs. Weekly and seasonal cumulative head impact frequencies and magnitudes were calculated. Mixed-model regression models examined the association between player characteristics, event type, and seasons and peak linear and rotational accelerations. Results: A total of 429 head impacts from 604 exposures occurred across the study period (IR, 7.10; 95% CI, 4.81-10.50). Weekly and seasonal cumulative median head impact frequencies were 1.00 (range, 0-2.63) and 7.50 (range, 0-21.00), respectively. The most frequent estimated head impact locations were the skull base (n = 96; 22.4%), top of the head (n = 74; 17.2%), and back of the head (n = 66; 15.4%). The combined event type IRs differed among the 3 seasons (IRR range, 1.45-2.68). Games produced greater IRs (IRR, 1.24; 95% CI, 1.01-1.53) and peak linear acceleration (mean difference, 5.69 g; P = .008) than did practices. Older players demonstrated greater combined event–type IRs (IRR, 1.46; 95% CI, 1.12-1.90) and increased head impact magnitudes than did younger players, with every 1-year age increase associated with a 3.78 g and 602.81-rad/s2 increase in peak linear and rotational acceleration magnitude, respectively ( P≤ .005). Conclusion: Head IRs and magnitudes varied across seasons, thus highlighting multiple season and cohort data are valuable when providing estimates. Head IRs were relatively low across seasons, while linear and rotational acceleration magnitudes were relatively high.
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Esposito, Diana L., Yunhua Li, Cinzia Vanni, Sandra Mammarella, Serena Veschi, Fulvio Della Loggia, Renato Mariani-Costantini, Pasquale Battista, Michael J. Quon, and Alessandro Cama. "A Novel T608R Missense Mutation in Insulin Receptor Substrate-1 Identified in a Subject with Type 2 Diabetes Impairs Metabolic Insulin Signaling." Journal of Clinical Endocrinology & Metabolism 88, no. 4 (April 1, 2003): 1468–75. http://dx.doi.org/10.1210/jc.2002-020933.

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Naturally occurring mutations in insulin receptor substrate-1 (IRS-1) have previously been implicated in impaired insulin action. We now report a novel mutation in IRS-1 with substitution of Arg for Thr608 that was identified in a patient with type 2 diabetes mellitus. We detected the T608R mutation in 1 of 136 chromosomes from diabetic patients and in 0 of 120 chromosomes from nondiabetic controls, suggesting that this is a rare IRS-1 variant. Conservation of Thr608 in human, monkey, rat, mouse, and chicken IRS-1 sequences is consistent with a crucial function for this residue. Moreover, Thr608 is located near the YMXM motif containing Tyr612 that is important for binding and activation of phosphoinositol 3-kinase (PI 3-kinase). To investigate whether the T608R mutation impairs insulin signaling, we transiently transfected NIH-3T3IR cells with hemagglutinin-tagged wild-type or T608R mutant IRS-1 constructs. Recombinant IRS-1 immunoprecipitated from transfected cells treated with or without insulin was subjected to immunoblotting for the p85 regulatory subunit of PI 3-kinase as well as a PI 3-kinase assay. As expected, in control cells transfected with wild-type IRS-1, insulin stimulation caused an increase in p85 coimmunoprecipitated with IRS-1 as well as a 10-fold increase in IRS-1-associated PI 3-kinase activity. Interestingly, when cells transfected with IRS1-T608R were stimulated with insulin, both the amount of p85 coimmunoprecipitated with IRS1-T608R as well as the associated PI 3-kinase activity were approximately 50% less than those observed with wild-type IRS-1. Moreover, in rat adipose cells, overexpression of IRS1-T608R resulted in significantly less translocation of GLUT4 to the cell surface than comparable overexpression of wild-type IRS-1. We conclude that a naturally occurring substitution of Arg for Thr608 in IRS-1 is a rare human mutation that may contribute to insulin resistance by impairing metabolic signaling through PI 3-kinase-dependent pathways.
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Delafontaine, P. "IRS-1 Variant." Arteriosclerosis, Thrombosis, and Vascular Biology 20, no. 2 (February 2000): 283–84. http://dx.doi.org/10.1161/01.atv.20.2.283.

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Brüning, J. C., J. Winnay, B. Cheatham, and C. R. Kahn. "Differential signaling by insulin receptor substrate 1 (IRS-1) and IRS-2 in IRS-1-deficient cells." Molecular and Cellular Biology 17, no. 3 (March 1997): 1513–21. http://dx.doi.org/10.1128/mcb.17.3.1513.

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Mice made insulin receptor substrate 1 (IRS-1) deficient by targeted gene knockout exhibit growth retardation and abnormal glucose metabolism due to resistance to the actions of insulin-like growth factor 1 (IGF-1) and insulin (E. Araki et al., Nature 372:186-190, 1994; H. Tamemoto et al., Nature 372:182-186, 1994). Embryonic fibroblasts and 3T3 cell lines derived from IRS-1-deficient embryos exhibit no IGF-1-stimulated IRS-1 phosphorylation or IRS-1-associated phosphatidylinositol 3-kinase (PI 3-kinase) activity but exhibit normal phosphorylation of IRS-2 and Shc and normal IRS-2-associated PI 3-kinase activity. IRS-1 deficiency results in a 70 to 80% reduction in IGF-1-stimulated cell growth and parallel decreases in IGF-1-stimulated S-phase entry, PI 3-kinase activity, and induction of the immediate-early genes c-fos and egr-1 but unaltered activation of the mitogen-activated protein kinases ERK 1 and ERK 2. Expression of IRS-1 in IRS-1-deficient cells by retroviral gene transduction restores IGF-1-stimulated mitogenesis, PI 3-kinase activation, and c-fos and egr-1 induction in proportion to the level of reconstitution. Increasing the level of IRS-2 in these cells by using a retrovirus reconstitutes IGF-1 activation of PI 3-kinase and immediate-early gene expression to the same degree as expression of IRS-1; however, IRS-2 overexpression has only a minor effect on IGF-1 stimulation of cell cycle progression. These results indicate that IRS-1 is not necessary for activation of ERK 1 and ERK 2 and that activation of ERK 1 and ERK 2 is not sufficient for IGF-1-stimulated activation of c-fos and egr-1. These data also provide evidence that IRS-1 and IRS-2 are not functionally interchangeable signaling intermediates for stimulation of mitogenesis despite their highly conserved structure and many common functions such as activating PI 3-kinase and early gene expression.
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Henry, Kevin A., Recinda L. Sherman, Kaila McDonald, Christopher J. Johnson, Ge Lin, Antoinette M. Stroup, and Francis P. Boscoe. "Associations of Census-Tract Poverty with Subsite-Specific Colorectal Cancer Incidence Rates and Stage of Disease at Diagnosis in the United States." Journal of Cancer Epidemiology 2014 (2014): 1–12. http://dx.doi.org/10.1155/2014/823484.

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Background. It remains unclear whether neighborhood poverty contributes to differences in subsite-specific colorectal cancer (CRC) incidence. We examined associations between census-tract poverty and CRC incidence and stage by anatomic subsite and race/ethnicity.Methods. CRC cases diagnosed between 2005 and 2009 from 15 states and Los Angeles County (N=278,097) were assigned to 1 of 4 groups based on census-tract poverty. Age-adjusted and stage-specific CRC incidence rates (IRs) and incidence rate ratios (IRRs) were calculated. Analyses were stratified by subsite (proximal, distal, and rectum), sex, race/ethnicity, and poverty.Results. Compared to the lowest poverty areas, CRC IRs were significantly higher in the most impoverished areas for men (IRR = 1.14 95% CI 1.12–1.17) and women (IRR = 1.06 95% CI 1.05–1.08). Rate differences between high and low poverty were strongest for distal colon (male IRR = 1.24 95% CI 1.20–1.28; female IRR = 1.14 95% CI 1.10–1.18) and weakest for proximal colon. These rate differences were significant for non-Hispanic whites and blacks and for Asian/Pacific Islander men. Inverse associations between poverty and IRs of all CRC and proximal colon were found for Hispanics. Late-to-early stage CRC IRRs increased monotonically with increasing poverty for all race/ethnicity groups.Conclusion. There are differences in subsite-specific CRC incidence by poverty, but associations were moderated by race/ethnicity.
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Kappel, Camila Ripoll, Nélson A. Kretzmann, and Mário Reis Álvares-da-Silva. "IRS1 Expression in Hepatic Tissue and Leukocytes in Chronic Hepatitis C Virus Infected Patients: A Comparative Study." International Journal of Hepatology 2012 (2012): 1–6. http://dx.doi.org/10.1155/2012/698905.

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Aims.To determine lymphocyte IRS (IRS1 cells) in HCV patients, correlating it to liver IRS (IRS 1liver) and HOMA-IR. This study tested the hypothesis that IRS1 cells expression can be used as insulin resistance (IR) marker in HCV-infected patients. IRS1 cells were not studied before in HCV infection.Materials and Methods.HCV chronically infected patients, naïve, nonobese, noncirrhotic, and nondiabetic were prospectively included and compared to controls (blood donors). Blood was taken, and leukocytes were separated. IRS1 was determined by real-time PCR. Liver tissue was obtained from transplant donors as controls.Results.41 HCV-positive patients were included, 26 males (60.5%); mean age of 45 (); 33 (80.5%) from genotype 1. 6 out of 12 controls were males (50%); mean age was 26.7 (). There was expression of IRS1 in leukocytes. The median IRS1 cells (HCV) were 0.061 (0.004 to 0.469); the median IRS 1liver (HCV) was 0.0003 (0.00002 to 0.0186)—lower than in controls (resp., and ). HOMA-IR had an inverse correlation with IRS 1liver (). There was no correlation between IRS1 liver and IRS1 cells ().Conclusions.There was expression of IRS1 in leukocytes. IRS1 cells and IRS1 liver were lower in HCV patients than in controls.
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Dissertations / Theses on the topic "IRS-1"

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Nawaratne, Ranmali. "Serine phosphorylation of the IRS-1 PH domain." Thesis, University of Cambridge, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.615121.

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Oliveira, Josenilson Campos de. "Papel do IRS-1 no desenvolvimento do cancer de prostata." [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/309951.

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Orientador: Jose Barreto Campello Carvalheira
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: A regulação adequada da via de sinalização PI 3-quinase-Akt é essencial para a prevenção da carcinogênese. Dados recentes caracterizaram uma alça de retroalimentação negativa na qual a mammalian target of rapamycin (mTOR), bloqueia a ativação adicional da via Akt/mTOR por meio da inibição da função do substrato 1 do receptor de insulina (IRS-1). Entretanto, a inibição potencial do IRS-1 durante o tratamento com rapamicina não foi estudado. No presente estudo, demonstramos que um oligonucleotídeo anti-sense direcionado ao IRS-1 e a rapamicina antagonizam sinergicamente a ativação da mTOR in vivo e induzem supressão tumoral, por meio de inibição da proliferação e indução de apoptose, em enxertos de células de câncer de próstata. Estes dados demonstram que a inclusão de agentes que bloqueiam o IRS-1 potencializam o efeito da inibição da mTOR no crescimento de enxertos de células de câncer de próstata.
Abstract: Proper activation of phosphoinositide 3-kinase-Akt pathway is critical for the prevention of tumorigenesis. Recent data have characterized a negative feedback loop where in mammalian target of rapamycin (mTOR), blocks additional activation of the Akt/mTOR pathway through inhibition insulin receptor substrate 1 (IRS-1) function. However, the potential of IRS-1 inhibition during rapamycin treatment has not been examined. Herein, we show that IRS-1 antisense oligonucleotide and rapamycin synergistically antagonize the activation of mTOR in vivo and induced tumor suppression, through inhibition of proliferation and induction of apoptosis, in prostate cancer cell xenografts. These data demonstrate that the addition of agents that blocks IRS-1 potentiate the effect of mTOR inhibition in the growth of prostate cancer cell xenografts.
Doutorado
Clinica Medica
Doutor em Clínica Médica
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Fakler, Hariolf Eugen. "Expression und Funktion von Insulinrezeptor-Substrat (IRS) /-1 und /-2." [S.l. : s.n.], 2006. http://nbn-resolving.de/urn:nbn:de:bsz:289-vts-55718.

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Landis, Justine M. "Mechanistic Analysis of Differential Signal Transduction Mediated by the Insulin Receptor Substrate Proteins IRS-1 and IRS-2: A Dissertation." eScholarship@UMMS, 2014. https://escholarship.umassmed.edu/gsbs_diss/735.

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The Insulin Receptor Substrate (IRS) proteins IRS-1 and IRS-2 are cytoplasmic adaptor proteins that organize and propagate intracellular signaling downstream of specific growth factor receptors, including the Insulin and Insulin-Like Growth Factor-1 Receptors (IR and IGF-1R, respectively). Despite sharing a high level of homology and the ability to stimulate Phosphotidylinositol-3-Kinase (PI3K) and Mitogen-Activated Protein Kinase (MAPK) signaling, IRS-1 and IRS-2 play distinct roles in mammary tumor progression. Specifically, IRS-1 promotes growth and proliferation, whereas IRS- 2 promotes motility, invasion, survival, aerobic glycolyis, and metastasis. To further understand the differences between IRS-1 and IRS-2, I investigated the mechanistic basis of IRS-2-mediated PI3K activation. I identified tyrosines in IRS-2 that mediate its recruitment and activation of PI3K in response to insulin and IGF-1 stimulation. Using a PI3K-binding deficient IRS-2 mutant, I demonstrated that IRS-2-dependent PI3K signaling promotes aerobic glycolysis through its ability to selectively regulate the phosphorylation of the Akt effector Glycogen Synthase Kinase-3β (Gsk-3β). I also performed a rigorous comparison of IRS-1 and IRS-2 signal transduction and their ability to regulate functions associated with tumor progression. These studies required the generation of a novel model system where IRS-1 and IRS-2 function could be compared in a genetically identical background. Using this model, I confirmed a role for IRS-1 in growth regulation and IRS-2 in tumor cell invasion, as well as expanded the understanding of differential IRS protein function by showing that IRS-2 more vi effectively promotes Akt activation. The model system I have established can be used for further characterization of IRS-1 and IRS-2-specific functions.
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Landis, Justine M. "Mechanistic Analysis of Differential Signal Transduction Mediated by the Insulin Receptor Substrate Proteins IRS-1 and IRS-2: A Dissertation." eScholarship@UMMS, 2008. http://escholarship.umassmed.edu/gsbs_diss/735.

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The Insulin Receptor Substrate (IRS) proteins IRS-1 and IRS-2 are cytoplasmic adaptor proteins that organize and propagate intracellular signaling downstream of specific growth factor receptors, including the Insulin and Insulin-Like Growth Factor-1 Receptors (IR and IGF-1R, respectively). Despite sharing a high level of homology and the ability to stimulate Phosphotidylinositol-3-Kinase (PI3K) and Mitogen-Activated Protein Kinase (MAPK) signaling, IRS-1 and IRS-2 play distinct roles in mammary tumor progression. Specifically, IRS-1 promotes growth and proliferation, whereas IRS- 2 promotes motility, invasion, survival, aerobic glycolyis, and metastasis. To further understand the differences between IRS-1 and IRS-2, I investigated the mechanistic basis of IRS-2-mediated PI3K activation. I identified tyrosines in IRS-2 that mediate its recruitment and activation of PI3K in response to insulin and IGF-1 stimulation. Using a PI3K-binding deficient IRS-2 mutant, I demonstrated that IRS-2-dependent PI3K signaling promotes aerobic glycolysis through its ability to selectively regulate the phosphorylation of the Akt effector Glycogen Synthase Kinase-3β (Gsk-3β). I also performed a rigorous comparison of IRS-1 and IRS-2 signal transduction and their ability to regulate functions associated with tumor progression. These studies required the generation of a novel model system where IRS-1 and IRS-2 function could be compared in a genetically identical background. Using this model, I confirmed a role for IRS-1 in growth regulation and IRS-2 in tumor cell invasion, as well as expanded the understanding of differential IRS protein function by showing that IRS-2 more vi effectively promotes Akt activation. The model system I have established can be used for further characterization of IRS-1 and IRS-2-specific functions.
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Bellinazzi, Vera Regina 1972. "Prevalencia do polimorfismo GLY972ARG do substrato 1 do receptor de insulina (IRS-1) em idosos brasileiros." [s.n.], 2006. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311209.

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Orientador: Mario Jose Abdalla Saad
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Apesar dos mecanismos da longevidade não serem totalmente conhecidos, sabe-se que mutações em genes que reduzem a sinalização intracelular de insulina/IGF-1 são capazes de aumentar a sobrevida de animais invertebrados e mamíferos Na mosca Drosophila Melanogaster, mutações no receptor de insulina (similar ao gene do receptor de insulina humano) e no gene chico (similar ao gene do IRS-1 humano) levam ao aumento da sobrevida do animal. Em roedores, estudos sobre restrição calórica e diversas mutações tem relacionado a via de sinalização insulina/IGF-1 com longevidade. Em humanos, a sensibilidade à insulina normalmente declina com o envelhecimento, porém existem evidências que idosos longevos apresentam ação da insulina preservada e nível de IGF-1 sérico reduzido, o que sugere que a resposta à insulina tem impacto na longevidade humana. Evidências recentes que reforçam esta teoria demonstram que polimorfismos de genes da via de sinalização de insulina/IGF-1( IGF-1R e PI3K), afetam o IGF-1 sérico e a longevidade humana, sugerindo que este mecanismo esteja conservado através da evolução das espécies. Baseada nestas evidências, nosso estudo investigou a prevalência do polimorfismo mais comum do IRS-1, a substituição de glicina por arginina no códon 972 (Gly972Arg), numa amostra da população longeva brasileira, e a sua associação com diversos fenótipos e com a longevidade. Foram incluídos no estudo 94 idosos, de ambos os sexos, com idades entre 80 e 100 anos. Como grupo controle foram incluídos 194 recém-nascidos da mesma região brasileira. A freqüência genotípica encontrada nos idosos foi: Gly/GIy 80,85%, Gly/Arg 19,15%, e Arg/Arg 0%. Não foi encontrada diferença estatística entre a prevalência do polimorfismo em longevos e em neonatos brasileiros. Também não houve associação deste polimorfismo com resistência à insulina, hipertensão, diabetes, ou com alterações no IMC, circunferência da cintura, e lípides nessa população. Nossos achados indicam que não há associação do polimorfismo Gly972Arg do IRS-1 com longevidade em humanos. E possível que esta falta de relação esteja relacionada ao seu efeito neutro tanto na sensibilidade à insulina quanto no nível de IGF-1.
Abstract: Although the underlying mechanisms of longevity are not fully understood, it is known that mutations in genes that decrease the insulin/IGF-1 signal response pathway are capable of extending life span in a variety of model systems from invertebrates to mammals. In Drosophila Melanogaster, mutations of either the insulin receptor gene (similar of human insulin receptor gene) or the Chico (similar of human IRS-1 gene) led to enhanced longevity. In humans, insulin sensitivity normally declines during aging. Although there are evidences that long-lived subjects have decreased plasma IGF-1 levels and preserved insulin action, thus indicating that insulin responsiveness impacts on human longevity. Recent findings also provide novel and intriguing indications for the involvement of insulin and IGF-1 in the control of aging and longevity in humans. In particular, it has been demonstrated that polymorphic variants of IGF-1 receptor (IGF-IR) and phosphatidylinositol 3-kinase (PI3K) genes affect IGF-1 plasma levels and human longevity, indicating that the impact of these genes on species longevity is an evolutionary conserved property. On the basis of the above-mentioned literature, we investigate the prevalence of a most common IRS-1 variant, a Gly --> Arg substitution at codon 972 (GIy972Arg) in a population-based sample of Brazilian elderly, its association with phenotypes and longevity. Ninety-four Brazilian subjects (men and women), from 80-100 yr. of age, volunteered for this study. As a control population we studied 194 newborn children from our University Hospital. Genotype frequencies were Gly/Gly 80,85%, Gly/Arg 19,15%, and Arg/Arg 0%, which are in Hardy-Weinberg equilibrium In addition, no significant differences among allele and genotype distribution were found between Brazilian elderly and Brazilian newborns Also, the Arg variant was not associated with insulin resistance, hypertension, diabetes, detrimental values for body mass index, waist circumference, and lipids in the Brazilian elderly. Our findings indicate that the IRS-1 Gly972Arg variant is not related with longevity. It is possible that the lack of this association might be related to its neutral effect on insulin sensitivity and on IGF-1 levels.
Mestrado
Clinica Medica
Mestre em Clinica Medica
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Lima, Maria Helena de Melo 1966. "Regulação da interação IRS-1/SHP2 em modelos de resistencia a insulina." [s.n.], 2000. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314544.

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Orientador: Mario Jose Abdalla Saad
Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: A insulina, ao se ligar à subunidade a de seu receptor heterotetramérico, dá início a uma série de ações imediatas e tardias, metabólicas e promotoras de crescimento. Tais eventos ocorrem através da estimulação da subunidade 13 transmembrana do receptor, que se autofosforila e ativa a fosforilação de substratos endógenos intracelulares, dos quais o mais estudado é o IRS-l. Esta proteína de peso molecular _160 kDa pode ser bem caracterizada como um substrato direto do receptor de insulina e quando se fosforila associa-se a proteínas com porção SH2, PI-3 quinase e SHP2 ativando-as. Uma etapa distal a estas associações/ativações é a fosforilação em serina da AKT/PKB. Utilizando-se técnicas de "immunoblotting" com anticorpos anti-IRS-l, antifosfotirosina, anti-SHP2 e antiAKT/PKB é possível analisar o grau de fosforilação do IRS-l e AKT/PKB, a concentração protéica da SHP2 e a associação do IRS-l com SHP2, ou seja, as ações iniciais da insulina. Neste estudo investigamos a quantidade protéica da SHP2, o grau de fosforilação do IRS-l e associação com SHP2 e a fosforilação do AKT /PKB no tecido muscular e hepático de ratos normais e em cinco modelos de resistência à insulina: o jejum prolongado, o envelhecimento, o uso agudo de adrenalina, o uso crônico de dexametasona e ratos com diabetes induzido por STZ. Em experimentos com ratos normais para avaliação do efeito tempo após infusão de insulina no grau de fosforilação do IRS-l e associação com SHP2, verificou-se que o pico de fosforilação do IRS-l e associação IRS-l/SHP2 foi aos 30" para o tecido hepático e aos 90" para o tecido muscular, após a infusão de insulina, na veia porta. Nos animais que receberam estreptozotocina, em tecido hepático não houve alteração no nível protéico da SHP2. Observamos um aumento significativo no grau de fosforilação do IRS-l para 141 :!: 12%, p < 0,05, quando comparados aos animais controle. Não houve alteração na associação IRS-l/SHP2 quando comparados com o controle. Houve uma redução para 65 :!: 6%, p< 0,035, no grau de fosforilação do AKT/PKB. Em tecido muscular destes animais tratados com estreptozotocina, não houve alteração no nível protéico da SHP2, ocorrendo um aumento para 191 :!: 14%, p< 0,036 no grau de fosforilação do IRS-l quando comparados com o controle, sem alteração na associação IRS-l/SHP2 quando comparados com o controle. O grau de fosforilação do AKT IPKB foi reduzido para 70 :t 7%, p< 0,04, nos animais tratados com STZ quando comparados com o controle. Animais submetidos ao tratamento agudo de adrenalina não apresentaram alteração no nível protéico da SHP2 tanto para o tecido hepático como para o muscular. Houve uma redução significativa no grau de fosforilação do IRS-l para 37 :t 3%, (p< 0,019), e para 37 :t 7%, (p< 0,003) em tecido hepático e muscular respectivamente, acompanhado de uma diminuição da associação IRS/SHP2 para 52 :t 3%, (p< 0,002), e para 20 :t 7%, (p< 0,041), em tecido hepático e muscular, respectivamente. A fosforilação do AKTIPKB foi reduzida para 60 :t 5%, (p< 0,045), e para 70 :t 6%, (p< 0,030), em tecido hepático e muscular, respectivamente O envelhecimento não alterou o nível protéico da SHP2 em tecido hepático. A fosforilação do IRS-l foi reduzida para 64 :t 7%, (p< 0,029), ocorrendo um aumento na associação IRS-lISHP2 para 155 :t 9%, (p< 0,012) em tecido hepático dos animais senis. O grau de fosforilação do AKTIPKB dos animais senis não apresentou alteração. Em tecido muscular dos animais com 20 meses de idade observamos que não houve alteração do nível protéico da SHP2. O grau de fosforilacão do IRS-l foi reduzido para 50 :t 7%, (p<0,007), acompanhado de uma redução na associação do IRS-lISHP2 para 48 :t 12%, (p< 0,034), como também uma redução no grau de fosforilação do AKTIPKB para 70 :t 6%, (p< 0,05), em tecido muscular do animais senis quando comparados com o controle. Os animais mantidos em jejum prolongado não apresentaram alteração no nível protéico da SHP2 tanto para tecido hepático como muscular. Houve um aumento no grau de fosforilação do IRS-l para 152 :t 13%, (p< 0,007), e para 155 :t 2%, (p< 0,004), em tecido hepático e muscular, respectivamente, em relação aos animais alimentados. Observamos um aumento na associação do IRS-lISHP2 para 136 :t 7%, (p< 0,035), e para 162 :t 7%, (p< 0,019), em tecido hepático e muscular, respectivamente, quando comparados com os animais alimentados. Os animais submetidos ao tratamento crônico com dexametasona tanto para o tecido hepático como para o muscular não apresentaram alteração no nível protéico da SHP2. Houve uma redução significativa no grau de fosforilação do IRS-l para 48 :t 5%, (p< 0,040), e para 36 :t 5%, (p< 0,035), em tecido hepático e muscular, respectivamente, quando comparados com os controles. Não houve alteração na associação IRS-lISHP2 em tecido hepático e muscular do animais que receberam tratamento crônico com dexametasona quando comparados com o controle. A análise in_egrada dos 5 modelos animais sugere que a regulação do grau de fosforilação do IRS-l, bem como da interação deste com a PI 3-quinase depende dos níveis insulinêmicos do animal: animais hiperinsulinêmicos apresentam menor fosforilação e menor interação IRS-l/PI 3-quinase, e animais hipoinsulinêmicos mostram o oposto. Por outro lado, a regulação da interação IRS-lISHP2 não parece manter nenhuma relação com níveis insulinêmicos. Parece que a interação IRS-lISHP2 contribui para a modulação da transmissão do sinal insulínico, influenciando a fosforilação/ativação da AKT/PKB. Em situações com aumento da fosforilação do IRS-I sem aumento na associação IRS-l/SHP2, o efeito final do AKT/PKB é atenuado, como demonstrado em figado e músculo de animais tratados com STZ. Por outro lado, a diminuição da fosforilação do IRS1, sem uma diminuição da associação IRS-lISHP2, protege a fosforilação do AKT /PKB, como demonstrado em figado dos animais senis
Abstract: Insulin stimulates the tyrosine kinase activity of insulin receptor resulting in the phosphorylation of its cytosolic substrate, insulin receptor substrate 1 (IRS-l). After activation on by insulin, IRS-l associates with several proteins, including phosphatidylinositol (PI) 3-Kinase, phosphotyrosine phosphatase Syp, and adapter molecules like Nck, Grb2 and Fyn. U sing antipeptide antibodies to SHP2, to IRS-l, to antiphosphotyrosine and to AKT /PKB it is possible to study insulin-stimulated IRS-l phosphorylation and the association between IRS-l and SHP2; and the of phosphorylation AKT/PKB. It's also possible to quantify the leveI of SHP2. In the present study we have examined early steps of insulin action in muscle and liver in tive animal models of insulin resistance: 72 hours fasting and diabetes (STZ) (hypoinsulinemia), aging and effect of chronic treatment with dexametasone (hyperinsulinemia) and the effect of acute epinephrine treatment (normoinsulinemia). We used immunoprecipitation and immunoblotting technices with specitic antibodies. ln liver of diabetic rats (STZ) there was an increased IRS-1 phosphorylation o 141 :t 12% compared to the control value (p <0.05). The IRS-l/SHP2 association did not change, but the phosphorylation leveI of AKT/PKB was decreased in the liver of rats treated with STZ. In muscle samples there was an increase in IRS-l phosphorylation to 191:t 14% (p< 0.036), without change in the association ofIRS-l with SHP2. There was also no change in SHP2 protein levei, and the AKT/PKB phosphorylation was reduced to 70:t 7%(p< 0.04) of in muscle of diabetic rats compared to contrais. In fasting there was an increase to 152 :t 13% (p< 0.007) in IRS-l phosphorylation. There was also an increase of IRS-lISHP2 association to 136 :t 7% (p< 0.035) in liver tissue of fasting rats, after insulin stimulation compared to contraIs. In muscle samples from fasting rats the results were similar to that in liver. There was an increase to 155 :t 2% (p<0.019) IRS-l in phosphorylation in tissue of diabetic rats compared to contrais after insulin-stimulation. There was an increase of IRS-lISHP2 association of 162:t 7% (p< 0.019) in tissue of diabetic rats compared to contrais. In rats treated acutely with epinephrine there was a decrease in insulin stimulated IRS-1 phosphorylation to 37 :t 3% of control value (p< 0.019), accompained by reduced to 52 :t 3% (p< 0.002) in IRS-l/SHP2 association in liver. The leveI of SHP2 protein was found be unchanged and the AKT!PKB phosphorylation induced by insulin was reduced to 60 :t 5% (p< 0.045) in the liver of rats treated acutely with epinephrine. In muscle of epinephrine treated rats, there was a marked reduction to 57 :t 9% (p< 0.003) in insulin-stimulated IRS-1 phosphorylation compared to controI. The association of IRS-l/SHP2 was reduced to 20 :t 7% (p< 0.041) in muscle of epinephrine treated rats. There was no change in the SHP2 protein leveI, and the phosphorylation of AKT!PKB was reduced to 70:t 6% (p<0.030) in muscle ofrats treated with epinephrine. There was a decrease in IRS-1 phosphorylation to 64 :t 7% in liver of 20-month-old rats compared to 2-month-old rats. When the same blots were subsequently incubated with anti-SHP2 antibody there was an increase to 155 :t 9% (p<0.012) in insulin-induced IRS-l/SHP2 association in liver of 20-month-old rats compared to 2-months-old rats. Aging did not change the leveI of SHP2 protein and the phosphorylation leveI of AKT!PKB in liver. In muscle there was a decrease in insulin-stimulated IRS-1 phosphorylation to 50 :t 7% (p< 0.007) in 20-months-old rats. There was a simultaneous decrease to 48 :t 6% (p< 0.034) in insulin-induced IRS-l/SHP2 association in muscle of 20-months-old rats. The AKT!PKB phosphorylation was reduced to 70 :t 6% (p< 0.05) in muscle of the 20-month-old rats when compared 2-month-old rats. Finaly, dexamethasone treatment for 5 days induced a decrease in insulin-stimulated IRS-1 phosphorylation levels to 48:t 5% (p< 0.040), without changes in insulin-induced IRS-l/SHP2 association in liver of rats. Immunoprecipitation and immunoblotting with anti-SHP2 antibody showed that the leveI of this protein did not change in liver of rats treated with dexamethasone. In muscle tissue the results were similar to that in liver. There was a reduced in insulin-induced IRS-1 phosphorylation to 36 :t 5% (p< 0.035), and there was no change in the association of IRS-1 with SHP2 in muscle of rats treated with dexametasone afier stimulation with insulin. There was also no change in SHP2 protein leveI in muscle oftreated rats compared to controls. In summary, the results demonstrated that in hiperinsulinemia animaIs (i.e.; aging and dexamethasone treatment) there is a increased IRS-I phosphorylation induced by insulin compared to controls and in hipoinsulinemia models (i.e.; fasting and STZ treatment) the IRS-l phosphorylation induced by insulin is reduced. This phenomenon influence the downstream signal transduction through the IRS-l pathway as indicated by reduced insulin-induced AKT/PKB phosphorylation in liver and muscle of diabetic rats; increased insulin-induced IRS-l/SHP2 association in liver and muscle of fasting rats and liver of aging animaIs. Our results suggest that modulation in insulin signal transduction through IRS-I may occur in response to insulin circulatory levels and for metabolic changes
Doutorado
Fisiologia
Doutor em Biologia Funcional e Molecular
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GRIMOLIZZI, FRANCO. "Neutrophils alter placental glucose metabolism in gestational diabetes mellitus via neutrophil elastase mediated IRS1 degradation." Doctoral thesis, Università Politecnica delle Marche, 2017. http://hdl.handle.net/11566/245194.

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La gravidanza è da considerarsi una condizione pro-inflammatoria dove si osserva un’attivazione dei neutrofili circolanti. Con l'avanzare della gravidanza la concentrazione nel sangue di nucleosomi e mieloperossidasi aumenta e riflette la produzione delle trappole extracellulari dei neutrofili (NETs). Abbiamo dimostrato che in corso di diabete mellito gestazionale (GDM) tale produzione è aumentata in confronto ad una gravidanza fisiologica. Elevati livelli di glucosio e TNF-a, segni tipici presenti in corso di GDM, in vitro agiscono in modo sinergico e sono in grado di pre-attivare i neutrofili ed indurre il rilascio delle NETs. Abbiamo ipotizzato che, lo stato di iperattivazione osservato a livello sistemico possa essere associato ad una aumentata attività leucocitaria a livello placentare. A sostegno della nostra ipotesi, si osserva nei villi coriali isolati da placente GDM un’aumentata infiltrazione di PMNs pro-NETotici in associazione ad un accumulo della neutrofili elastasi (NE). Per valutare un possibile effetto pro-infiammatorio del glucosio a livello placentare, abbiamo incubato cellule di trofoblasto (BeWo) in presenza di un’elevata concentrazione di glucosio e successivamente valutato la produzione di TNF-a. È stato interessante rilevare un aumento nel rilascio di TNF- a tale da indurre un effetto pro-NETotico sui PMN con consequente rilascio della NE. Da recenti ricerche è emerso come in corso di diabete e tumore la NE possa essere internalizzata dalle cellule ed alterare la trasduzione del segnale insulinico attraverso la degradazione del substrato 1 del recettore insulinico (IRS1). Esperimenti in vitro hanno dimostrato che in presenza della NE si osserva una riduzione di IRS1 nelle cellule BeWo ed una diminuzione dell’internalizzazione del glucosio. Poichè l’espressione di IRS1 risulta ridotta nelle placente GDM é verosimile ipotizzare che la massiva presenza di NE ne può essere la causa. In conclusione, i nostri dati suggeriscono che in corso di GDM si verifica un’elevata produzione di NETs ed una massiva infiltrazione di pro-NETotici PMN nella placenta. Queste scoperte dimostrano come la NETosi abbia una significativa utilità diagnostica in corso di GDM e la NE un nuovo potenziale bersaglio terapeutico.
Human pregnancy is associated with a mild pro-inflammatory state characterized by activation of circulatory neutrophils (PMNs). Skewing of PMNs responses toward to neutrophil extracellular traps generation (NETs) is reflected in an increased of circulating nucleosomes and myeloperoxidase with advancing gestational age. Our data indicated that this pro-NETotic profile is enhanced in women with gestational diabetes mellitus (GDM). Maternal hyperglycemia and increased levels of TNF-a are a hallmark of GDM and we show a synergistic effect of both factors on the priming and release of NETs. Moreover, we hypothesized that systemic activation was associated with activated PMN in placenta. Indeed, we observed a massive infiltration of pro-NETotic PMNs and neutrophil elastase (NE) accumulation along chorionic villi of GDM placentas. To further explore whether hyperglycemia predisposes to exaggerated inflammatory response in placenta we incubated trophoblast BeWo cells in high glucose conditions and we next tested the TNF-a production capacity. Interestingly, TNF-a level was incresed and exert a pro-NETotic effect on PMN with consequent NE release. Recent studies in cancer tissues and diabetes models have described that released NE induce profound changes in the surrounding cells, altering the signal transducing cascade and promoting insulin resistance via degradation of insulin receptor substrate 1 (IRS1). Our in-vitro data indicate that addition of NE to trophoblast cell line BeWo causes degradation of IRS1 with consequent glucose uptake impairment. IRS1 is reduced in GDM placentas when compared to control placentas, suggesting that the presence of NE might be the causal factor. Taken together, our data showed that GDM is characterized by excessive NET formation and by a massive influx of pro-NETotic PMN into placentas. These findings underline the competence of NETs as a highly relevant diagnostic biomarker for GDM and NE as a new potential therapeutic target.
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Kamontum, Siripon. "Fusion of Landsat-7, IRS-1D and Radarsat-1 data for flood delineation." [Gainesville, Fla.] : University of Florida, 2009. http://purl.fcla.edu/fcla/etd/UFE0024237.

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Псарьова, Валентина Григорівна, Валентина Григорьевна Псарева, and Valentyna Hryhorivna Psarova. "Ассоциации генетического полиморфизма irs-1 c выраженностью различных компонентов метаболического синдрома у гипертензивных пациентов." Thesis, ГУ “Национальный институт терапии имени Л. Т. Малой НАМН Украины”, 2019. http://essuir.sumdu.edu.ua/handle/123456789/74658.

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Books on the topic "IRS-1"

1

United States. Government Accountability Office. Tax administration: IRS should take steps to improve the accuracy of schedule K-1 data : report to the Committee on Finance, U.S. Senate. Washington, D.C: GAO, 2004.

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IRS oversight: Hearings before the Committee on Finance, United States Senate, One Hundred Fifth Congress, second session, April 28, 29, 30, and May 1, 1998. Washington: U.S. G.P.O., 1998.

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United States. Congress. House. Committee on Small Business. IRS compliance with the Regulatory Flexibility Act: Hearing before the Committee on Small Business, House of Representatives, One Hundred Eighth Congress, first session, Washington, DC, May 1, 2003. Washington: U.S. G.P.O., 2003.

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United States. Congress. Senate. Committee on Governmental Affairs. Collecting unpaid taxes: Why can't the IRS do better? : hearing before the Committee on Governmental Affairs, United States Senate, One Hundred First Congress, second session, August 1, 1990. Washington: U.S. G.P.O., 1991.

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Miller, Kate. Thef irst book of PS/1. Carmel, Ind., USA: SAMS, 1991.

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Sánchez, Sergio López. Esperanza Iris, la tiple de hierro: Escritos 1. [México]: Instituto Nacional de Bellas Artes, 2002.

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Consultants, GEI. IRA status report no. 1: 50 Tufts Street, Somerville, MA. Winchester, MA: GEI Consultants, 2006.

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Eriksson, Kenneth. Applied Mathematics: Body and Soul: Volume 1: Derivatives and Geometry in IR3. Berlin, Heidelberg: Springer Berlin Heidelberg, 2004.

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Fellowship, Family Guardian. Great IRS Hoax, Volume 1, Form #11. 302. Independently Published, 2014.

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Bennington, Robert, and Cort W. Christie. 1, 800, Away, IRS: The Answer to a Nation's Plea. Griffin Pub Group, 1998.

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Book chapters on the topic "IRS-1"

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Salajegheh, Ali. "Insulin Receptor Substrate (IRS-1)." In Angiogenesis in Health, Disease and Malignancy, 189–92. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-28140-7_28.

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Schilke, Peter, and Malcolm Walmsley. "15NH3 Millimasers Toward NGC7538-Irs 1." In Fragmentation of Molecular Clouds and Star Formation, 489–90. Dordrecht: Springer Netherlands, 1991. http://dx.doi.org/10.1007/978-94-011-3384-5_81.

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Mendez, Raul, Gavin Welsh, Miranda Kleijn, Martin G. Myers, Morris F. White, Christopher G. Proud, and Robert E. Rhoads. "Regulation of Protein Synthesis by Insulin Through IRS-1." In Signaling Pathways for Translation, 49–93. Berlin, Heidelberg: Springer Berlin Heidelberg, 2001. http://dx.doi.org/10.1007/978-3-642-56688-2_3.

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Ogawa, Wataru, Takashi Matozaki, and Masato Kasuga. "Role of binding proteins to IRS-1 in insulin signalling." In Insulin Action, 13–22. Boston, MA: Springer US, 1998. http://dx.doi.org/10.1007/978-1-4615-5647-3_2.

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Pratap, Preethi, Lewis E. Snyder, and Wolfgang Batrla. "A Model for the Maser Source NGC 7538 IRS 1." In Astrochemistry of Cosmic Phenomena, 347–48. Dordrecht: Springer Netherlands, 1992. http://dx.doi.org/10.1007/978-94-011-2761-5_78.

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Boardman, Marty. "IRS Form W-9." In Fixing and Flipping Real Estate, 219–20. Berkeley, CA: Apress, 2012. http://dx.doi.org/10.1007/978-1-4302-4645-9_29.

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Dubin, Jeffrey A. "Recent Patterns in IRS Enforcement." In The Causes and Consequences of Income Tax Noncompliance, 13–22. New York, NY: Springer New York, 2011. http://dx.doi.org/10.1007/978-1-4419-0907-7_3.

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McDaniel, Tim. "IRS Revenue Ruling 59–60." In Know and Grow the Value of Your Business, 177–86. Berkeley, CA: Apress, 2013. http://dx.doi.org/10.1007/978-1-4302-4786-9_12.

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Dubin, Jeffrey A. "IRS Criminal Enforcement Activities and Taxpayer Noncompliance." In The Causes and Consequences of Income Tax Noncompliance, 81–109. New York, NY: Springer New York, 2011. http://dx.doi.org/10.1007/978-1-4419-0907-7_7.

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Fox, Russell. "Dear Valued Taxpayer: When You Hear from the IRS." In Tax Strategies for the Small Business Owner, 217–33. Berkeley, CA: Apress, 2013. http://dx.doi.org/10.1007/978-1-4302-4843-9_17.

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Conference papers on the topic "IRS-1"

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Coppens, Dorothee, Bertrand Theodore, Bernard Tournier, and Carsten Standfuss. "MTG-IRS level 1 operational processing status (Conference Presentation)." In Sensors, Systems, and Next-Generation Satellites, edited by Steven P. Neeck, Toshiyoshi Kimura, and Philippe Martimort. SPIE, 2018. http://dx.doi.org/10.1117/12.2326274.

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Lassak, Adam, Dorota Wyczechowska, Anna Wilk, Adriana Zapata, Mathew Dean, Luis DelValle, Jann N. Sarkaria, Augusto Ochoas, Francesca Peruzzi, and Krzysztof Reiss. "Abstract 2520: IRS-1/LC3 nuclear structures and glioblastoma drug resistance." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-2520.

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Tarable, Alberto, and Alessandro Nordio. "On the optimality of IRS-user association for rank-1 channel conditions." In 2022 3rd URSI Atlantic and Asia Pacific Radio Science Meeting (AT-AP-RASC). IEEE, 2022. http://dx.doi.org/10.23919/at-ap-rasc54737.2022.9814332.

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Giraud, J., R. L. Leshan, Y. H. Lee, and M. F. White. "Insulin-Stimulated Phosphorylation of IRS-1 on Ser302 Correlates with Enhanced Insulin Signaling." In Minority Trainee Research Forum, 2004. TheScientificWorld Ltd, 2004. http://dx.doi.org/10.1100/tsw.2004.157.

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Wang, Lei, Yan Cui, and Wenbo Li. "The application of forest and grassland fires monitoring based on HJ-1 CCD/IRS images." In Seventh International Symposium on Multispectral Image Processing and Pattern Recognition (MIPPR2011), edited by Jianguo Liu, Jinwen Tian, Hongshi Sang, and Jie Ma. SPIE, 2011. http://dx.doi.org/10.1117/12.902744.

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Liu, Sanchao, and Siquan Yang. "Australian fire monitoring and assessment using CCD and IRS data of HJ-1-A/B." In International Conference on Space Information Technology 2009, edited by Xingrui Ma, Baohua Yang, and Ming Li. SPIE, 2009. http://dx.doi.org/10.1117/12.855769.

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Wang, Zifeng, Liangfu Chen, Baohua He, Qing Li, Lin Su, and Jinhua Tao. "Introduction to infrared spectrometer (IRS) aboard HJ-1-B satellite: characteristics and potentials of fire detection." In Remote Sensing System Engineering II. SPIE, 2009. http://dx.doi.org/10.1117/12.825195.

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Shchurov, M. A., I. E. Valtts, and N. N. Shakhvorostova. "Vlbi research in the ”Radioastron” project: structure of the H2O maser in NGC 2071 IRS 1." In Всероссийская с международным участием научная конференция студентов и молодых ученых, посвященная памяти Полины Евгеньевны Захаровой «Астрономия и исследование космического пространства». Ural University Press, 2021. http://dx.doi.org/10.15826/b978-5-7996-3229-8.54.

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Within the Radioastron interferometer scientific program, observational data of the H2O maser at a frequency of 22.2280 GHz in the NGC 2071 nebula were processed. A space radio telescope (SRT — 10 m) and three radio telescopes of the ground network: RT — 32 m (Medicina, Italy), RT — 32 m (Torun, Poland) and RT —64 m (Kalyazin, RF) took part in the observations. A map of the maser spot distribution has been obtained, where there are 13 spatial components with VLSR in the range 4.7 — 20.5 km/s. Correlation is observed on ground-space baselines for the component on VLSR = 14.3 km/s. Based on the visibility function dependence analysis from the baseline projection values, there was proposed a twocomponent model of this component spatial structure with the dimensions of the extended and compact constituent of 4 and 0.06 msec, i.e. 1.56 and 0.023 au, respectively.
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Cory’ah, Fitra Arsy Nur, Vanda Primaditya, Linda Ika Puspita Ariati, Zakiah, Dyah Woro Kartiko Kusumo Wardani, Dianita Primihastuti, Yuningsih, Husnul Khotimah, Mohammad Muljohadi Ali, and Nurdiana. "Ethanolic extract of Centella asiatica increased IGF-1 and IRS expression in zebrafish (Danio rerio) rotenone-induced." In PROCEEDINGS OF THE 3RD INTERNATIONAL SEMINAR ON METALLURGY AND MATERIALS (ISMM2019): Exploring New Innovation in Metallurgy and Materials. AIP Publishing, 2020. http://dx.doi.org/10.1063/5.0002606.

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McCampbell, Adrienne, Heather Harris, Judy Crabtree, Richard Winneker, Cheryl Walker, and Russell Broaddus. "Abstract A28: Loss of inhibitory IRS-1 phosphorylation is an early event in mTOR-dependent endometrial hyperplasia and carcinoma." In Abstracts: Frontiers in Cancer Prevention Research 2008. American Association for Cancer Research, 2008. http://dx.doi.org/10.1158/1940-6207.prev-08-a28.

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Reports on the topic "IRS-1"

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Byron, Sara A. Differential Roles of Insulin Receptor Substrate-1 and -2 (IRS-1, IRS-2) in Insulin-Like Growth Factor Signaling in Breast Cancer Cells. Fort Belvoir, VA: Defense Technical Information Center, June 2003. http://dx.doi.org/10.21236/ada418361.

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Sachdev, Deepali. Role of IRS-1 Phosphorylation in IGF-1 and IL-4 Signaling in Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, June 2001. http://dx.doi.org/10.21236/ada396609.

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Sachdev, Deepali. Role of IRS-1 Phosphorylation in IGF-1 and IL-4 Signaling in Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, June 2002. http://dx.doi.org/10.21236/ada407504.

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Sachdev, Deepali. Role of IRS-1 Phosphorylation in IGF-1 and IL-4 Signaling in Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, June 2003. http://dx.doi.org/10.21236/ada418308.

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Garrick, Cynthia J. Strategy for Advancement of IRP in Public Power -- Volume 1: IRP Advancement Strategy. Office of Scientific and Technical Information (OSTI), October 1995. http://dx.doi.org/10.2172/135055.

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Elroy-Stein, Orna, and Dmitry Belostotsky. Mechanism of Internal Initiation of Translation in Plants. United States Department of Agriculture, December 2010. http://dx.doi.org/10.32747/2010.7696518.bard.

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Original objectives Elucidation of PABP's role in crTMV148 IRES function in-vitro using wheat germ extract and krebs-2 cells extract. Fully achieved. Elucidation of PABP's role in crTMV148 IRES function in-vivo in Arabidopsis. Characterization of the physical interactions of PABP and other potential ITAFs with crTMV148 IRES. Partly achieved. To conduct search for additional ITAFs using different approaches and evaluate the candidates. Partly achieved. Background of the topic The power of internal translation via the activity of internal ribosomal entry site (IRES) elements allow coordinated synthesis of multiple gene products from a single transcription unit, and thereby enables to bypass the need for sequential transformation with multiple independent transgenes. The key goal of this project was to identify and analyze the IRES-trans-acting factors (ITAFs) that mediate the activity of a crucifer-infecting tobamovirus (crTMV148) IRES. The remarkable conservation of the IRES activity across the phylogenetic spectrum (yeast, plants and animals) strongly suggests that key ITAFs that mediate its activity are themselves highly conserved. Thus, crTMV148 IRES offers opportunity for elucidation of the fundamental mechanisms underlying internal translation in higher plants in order to enable its rational manipulation for the purpose of agricultural biotechnology. Major conclusions and achievements. - CrTMV IRES requires PABP for maximal activity. This conclusion was achieved by PABP depletion and reconstitution of wheat germ- and Krebs2-derived in-vitro translation assays using Arabidopsis-derived PABP2, 3, 5, 8 and yeast Pab1p. - Mutations in the internal polypurine tract of the IRES decrease the high-affinity binding of all phylogenetically divergent PABPs derived from Arabidopsis and yeast in electro mobility gel shift assays. - Mutations in the internal polypurine tract decrease IRES activity in-vivo. - The 3'-poly(A) tail enhances crTMV148 IRES activity more efficiently in the absence of 5'-methylated cap. - In-vivo assembled RNPs containing proteins specifically associated with the IRES were purified from HEK293 cells using the RNA Affinity in Tandem (RAT) approach followed by their identification by mass spectroscopy. - This study yielded a list of potential protein candidates that may serve as ITAFs of crTMV148 IRES activity, among them are a/b tubulin, a/g actin, GAPDH, enolase 1, ribonuclease/angiogenin inhibitor 1, 26S proteasome subunit p45, rpSA, eEF1Bδ, and proteasome b5 subunit. Implications, both scientific and agriculture. The fact that the 3'-poly(A) tail enhances crTMV148 IRES activity more efficiently in the absence of 5'-methylated cap suggests a potential joint interaction between PABP, the IRES sequence and the 3'-poly(A). This has an important scientific implication related to IRES function in general.
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Hanan, N. A., and J. E. Matos. Criticality calculations for the VR-1 reactor with IRT-3M-HEU fuel and IRT-4MLEU fuel. Office of Scientific and Technical Information (OSTI), January 2007. http://dx.doi.org/10.2172/898523.

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Quinn, George W., Patrick Grother, and Mei Ngan. IREX IV part 1 : evaluation of iris identification algorithms. National Institute of Standards and Technology, July 2013. http://dx.doi.org/10.6028/nist.ir.7949.

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Irudayaraj, Joseph, Ze'ev Schmilovitch, Amos Mizrach, Giora Kritzman, and Chitrita DebRoy. Rapid detection of food borne pathogens and non-pathogens in fresh produce using FT-IRS and raman spectroscopy. United States Department of Agriculture, October 2004. http://dx.doi.org/10.32747/2004.7587221.bard.

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Rapid detection of pathogens and hazardous elements in fresh fruits and vegetables after harvest requires the use of advanced sensor technology at each step in the farm-to-consumer or farm-to-processing sequence. Fourier-transform infrared (FTIR) spectroscopy and the complementary Raman spectroscopy, an advanced optical technique based on light scattering will be investigated for rapid and on-site assessment of produce safety. Paving the way toward the development of this innovative methodology, specific original objectives were to (1) identify and distinguish different serotypes of Escherichia coli, Listeria monocytogenes, Salmonella typhimurium, and Bacillus cereus by FTIR and Raman spectroscopy, (2) develop spectroscopic fingerprint patterns and detection methodology for fungi such as Aspergillus, Rhizopus, Fusarium, and Penicillium (3) to validate a universal spectroscopic procedure to detect foodborne pathogens and non-pathogens in food systems. The original objectives proposed were very ambitious hence modifications were necessary to fit with the funding. Elaborate experiments were conducted for sensitivity, additionally, testing a wide range of pathogens (more than selected list proposed) was also necessary to demonstrate the robustness of the instruments, most crucially, algorithms for differentiating a specific organism of interest in mixed cultures was conceptualized and validated, and finally neural network and chemometric models were tested on a variety of applications. Food systems tested were apple juice and buffer systems. Pathogens tested include Enterococcus faecium, Salmonella enteritidis, Salmonella typhimurium, Bacillus cereus, Yersinia enterocolitis, Shigella boydii, Staphylococus aureus, Serratiamarcescens, Pseudomonas vulgaris, Vibrio cholerae, Hafniaalvei, Enterobacter cloacae, Enterobacter aerogenes, E. coli (O103, O55, O121, O30 and O26), Aspergillus niger (NRRL 326) and Fusarium verticilliodes (NRRL 13586), Saccharomyces cerevisiae (ATCC 24859), Lactobacillus casei (ATCC 11443), Erwinia carotovora pv. carotovora and Clavibacter michiganense. Sensitivity of the FTIR detection was 103CFU/ml and a clear differentiation was obtained between the different organisms both at the species as well as at the strain level for the tested pathogens. A very crucial step in the direction of analyzing mixed cultures was taken. The vector based algorithm was able to identify a target pathogen of interest in a mixture of up to three organisms. Efforts will be made to extend this to 10-12 key pathogens. The experience gained was very helpful in laying the foundations for extracting the true fingerprint of a specific pathogen irrespective of the background substrate. This is very crucial especially when experimenting with solid samples as well as complex food matrices. Spectroscopic techniques, especially FTIR and Raman methods are being pursued by agencies such as DARPA and Department of Defense to combat homeland security. Through the BARD US-3296-02 feasibility grant, the foundations for detection, sample handling, and the needed algorithms and models were developed. Successive efforts will be made in transferring the methodology to fruit surfaces and to other complex food matrices which can be accomplished with creative sampling methods and experimentation. Even a marginal success in this direction will result in a very significant breakthrough because FTIR and Raman methods, in spite of their limitations are still one of most rapid and nondestructive methods available. Continued interest and efforts in improving the components as well as the refinement of the procedures is bound to result in a significant breakthrough in sensor technology for food safety and biosecurity.
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Zhao, Qing, and Lili Zhou. Culture, sex, and their combined impact on self-report empathy—Meta-analyses. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, April 2022. http://dx.doi.org/10.37766/inplasy2022.4.0172.

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Condition being studied: The current meta-analysis covers empirical investigations of self-report empathy (evaluated using the EQ and the IRI scales) based on different populations. Studies with general populations and physical/mental clinical populations were included. Both cross-cultural and non-cross-cultural studies (studies based on a single cultural background) were considered. Eligibility criteria: We restricted our current meta-analysis to studies that satisfied all of the following criteria: (1) studies evaluated participants’ self-report empathy using the EQ or the IRI; (2) studies reported the EQ and IRI version (i.e., scale item number and language); (3) studies reported the EQ and IRI total or subscale scores (e.g., mean and SD) based on the overall sample or both sex groups separately. (4) studies reported participants’ cultural backgrounds (e.g., country of origin, nationality, ethnicity, and language).
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