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Artykuły w czasopismach na temat "ITGAL"
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Sun, Chenyu, John Pocholo W. Tuason, Chandur Bhan, Arpana Paudel, Marwan K. Ahmed, Na Hyun Kim, Humaed Mohammed Abdul i in. "Association of ITGA 11 and ITGAV upregulation with outcomes in gastric cancer." Journal of Clinical Oncology 40, nr 4_suppl (1.02.2022): 332. http://dx.doi.org/10.1200/jco.2022.40.4_suppl.332.
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332 Background: Gastric cancer (GC) is a common cancer worldwide. The integrin α (ITGA) family members play essential roles in various cancers and variants of ITGA are involved in metastatic process in gastric cancer. Thus, this study was conducted to explore the roles of ITGA family members in stomach adenocarcinoma (STAD). Methods: RNA-sequencing FPKM data and corresponding clinical information of 375 STAD tumor tissues and 32 normal tissues were retrieved from The Cancer Genome Atlas (TCGA). The ‘limma’ package was used to compare the expression differences between the normal and cancer tissues using Wilcoxon rank-sum test. Analysis of overall survival (OS) was conducted by Kaplan–Meier (K–M) method via ‘survminer’ package. Univariate Cox hazard regression analysis was applied to seven clinicopathological variables from T stage, N stage, M stage, pathologic stage, histologic grade, gender, age, and expression level of selected ITGA family members, by using ‘survival’ package. Furthermore, a nomogram was also visualized by the R ‘rms’ package and ‘survival’ package to predict the 1-, 3-, and 5-year OS and individual predictors. Results: The expression of ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGA11, and ITGAV were upregulated in STAD tissues compared with normal tissues (P<0.05), whereas ITGA7, ITGA8, and ITGA9 were downregulated in tumor tissues (P<0.05). In addition, no statistically significant difference was found for TGA1 and ITGA10 between tumor and normal tissues ((P>0.05). Further survival analysis found that higher expression of ITGA 11 (HR=1.46, 95%CI 1.05-2.03, P<0.026) and ITGAV (HR=1.92, 95%CI 1.37-2.70, P<0.001) were associate with worse OS. Univariate Cox hazard regression analysis showed that T3, T4, N1, N3, M1, pathologic stage III and IV, age>65, and high expression level of ITGA11 and ITGAV were associated with worse OS (all P < 0.05). The nomogram based on six clinicopathological variables (T stage, N stage, M stage, pathologic stage, age, and expression levels of ITGA11 and ITGAV) and 1-, 3-, 5-year OS probabilities were developed. The concordance index (C-index) of the nomograms was 0.673(0.647-0.700), indicating that the potential predicting role and sufficient discrimination ability of the nomogram as C-index was more than 0.5. The calibration curves of 1-, 3-, and 5-year indicated the consistency of our results and the predictive values, indicating satisfactory performance for this nomogram. However, 1-, 3-, 5-year AUCs of ITGA11- and ITGAV-based nomogram were 0.687, 0.691, and 0.687, showing a relatively acceptable accuracy as they were great than 0.5. Conclusions: ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGA11, and ITGAV are upregulated, while ITGA7, ITGA8, and ITGA9 are down regulated in STAD tumor samples. High expression levels of ITGA11 and ITGAV are associated with worse OS. The ITGA11- and ITGAV-based monogram developed by this study might be useful in predicting the OS outcome for STAD patients.
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Park, Hye Jin, Ji Eun Park, Hyun Lee, Seong Jae Kim, Jung Im Yun, Minseok Kim, Kyu Hyun Park i Seung Tae Lee. "Integrins functioning in uterine endometrial stromal and epithelial cells in estrus". Reproduction 153, nr 3 (marzec 2017): 351–60. http://dx.doi.org/10.1530/rep-16-0516.
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Here, as a basic study in the construction of a non-cellular niche that supports artificial organization of three-dimensional endometrial tissue, we defined the types of integrin heterodimers that are expressed transcriptionally, translationally and functionally in endometrial stromal (ES) and endometrial epithelial (EE) cells isolated from the mouse uterus in estrus. Gene and protein expression of integrin subunits were analyzed at the transcriptional and translational level by real-time PCR and fluorescent immunoassay, respectively. Moreover, the functionality of integrin heterodimers was confirmed by attachment and antibody inhibition assays. Itga2, Itga5, Itga6, Itga9, Itgav, Itgb1, Itgb3 and Itgb5 in ES cells, and Itga2, Itga5, Itga6, Itga7, Itga9, Itgav, Itgb1, Itgb3, Itgb4, Itgb5 and Itga6 and in EE cells showed significantly higher transcriptional levels than the other integrin subunits. Furthermore, translational expression of the total integrin α and β subunit genes that showed increased transcription was determined in ES and EE cells. ES cells showed significantly increased adhesion to collagen I, fibronectin and vitronectin, and functional blocking of integrin α2, α5 or αV significantly inhibited adhesion to these molecules. Moreover, EE cells showed significantly increased adhesion to collagen I, fibronectin, laminin and vitronectin, and functional blocking of integrin α2, α5, α6 or αV significantly inhibited adhesion to these molecules. Accordingly, we confirmed that integrin α2β1, α5β1, αVβ1, αVβ3 and/or αVβ5, and integrin α2β1, α5β1, α6β1 and/or α6β4, αVβ1, αVβ3 and/or αVβ5, actively function on the surface of ES and EE cells from mouse uterus in estrus phase, respectively.
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Chidlow, John H., John D. Glawe, J. Steven Alexander i Christopher G. Kevil. "VEGF164 differentially regulates neutrophil and T cell adhesion through ItgaL- and ItgaM-dependent mechanisms". American Journal of Physiology-Gastrointestinal and Liver Physiology 299, nr 6 (grudzień 2010): G1361—G1367. http://dx.doi.org/10.1152/ajpgi.00202.2010.
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Leukocyte recruitment to inflamed tissues is the cornerstone of inflammatory responses and the driving force behind the establishment of inflammatory bowel disease, consisting of Crohn's disease and ulcerative colitis. It has been reported that angiogenic cytokines contribute to this inflammatory response that facilitates the chronic nature of disease. We have previously reported (Goebel S, Huang M, Davis WC, Jennings M, Siahaan TJ, Alexander JS, Kevil CG. Am J Physiol Gastrointest Liver Physiol 290: G648–G654, 2006) that vascular endothelial growth factor (VEGF)-A can stimulate neutrophil adhesion to colon microvascular endothelial cells in a β2-integrin (Itgb2)-dependent manner. However, it is not known which of the specific leukocyte integrins are critical for VEGF-A-dependent neutrophil and T cell recruitment. Here we examine the differential importance of either α-integrin (Itga)L or ItgaM in governing neutrophil and T cell adhesion to VEGF-A-activated colonic endothelium. Using an in vitro parallel-plate flow chamber model, we found that genetic deficiency of ItgaM completely blunted neutrophil adhesion to VEGF-A-stimulated endothelium, whereas ItgaL deficiency only partly blocked neutrophil adhesion. Deficiency of ItgaM did significantly decrease neutrophil rolling, whereas deficiency of ItgaL did not. We found that genetic deficiency of either ItgaL or ItgaM did significantly blunt T cell adhesion to VEGF-A-stimulated colon endothelium. We also found that genetic deficiency of these Itgas significantly attenuated T cell rolling behavior. Lastly, we examined whether VEGF-A-mediated leukocyte recruitment occurred through different VEGF receptor (VEGFR) pathways and found that VEGFR2 activation regulates neutrophil recruitment, whereas both VEGFR1 and VEGFR2 modulate T cell recruitment. Together, these data identify differential molecular mechanisms of VEGF-A-mediated leukocyte recruitment.
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Lin, Xiaozeng, Ying Dong, Yan Gu, Fengxiang Wei, Jingyi Peng, Yingying Su, Yanjun Wang i in. "Taxifolin Inhibits the Growth of Non-Small-Cell Lung Cancer via Downregulating Genes Displaying Novel and Robust Associations with Immune Evasion Factors". Cancers 15, nr 19 (30.09.2023): 4818. http://dx.doi.org/10.3390/cancers15194818.
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Using an LL2 cell-based syngeneic mouse LC model, taxifolin suppressed allografts along with the appearance of 578 differentially expressed genes (DEGs). These DEGs were associated with enhancement of processes related to the extracellular matrix and lymphocyte chemotaxis as well as the reduction in pathways relevant to cell proliferation. From these DEGs, we formulated 12-gene (TxflSig) and 7-gene (TxflSig1) panels; both predicted response to ICB (immune checkpoint blockade) therapy more effectively in non-small-cell lung cancer (NSCLC) than numerous well-established ICB biomarkers, including PD-L1. In both panels, the mouse counterparts of ITGAL, ITGAX, and TMEM119 genes were downregulated by taxifolin. They were strongly associated with immune suppression in LC, evidenced by their robust correlations with the major immunosuppressive cell types (MDSC, Treg, and macrophage) and multiple immune checkpoints in NSCLC and across multiple human cancer types. ITGAL, ITGAX, and IIT (ITGAL-ITGAX-TMEM119) effectively predicted NSCLC’s response to ICB therapy; IIT stratified the mortality risk of NSCLC. The stromal expressions of ITGAL and ITGAX, together with tumor expression of TMEM119 in NSCLC, were demonstrated. Collectively, we report multiple novel ICB biomarkers—TxflSig, TxflSig1, IIT, ITGAL, and ITGAX—and taxifolin-derived attenuation of immunosuppressive activities in NSCLC, suggesting the inclusion of taxifolin in ICB therapies for NSCLC.
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Takahashi, Toshiaki, Florian Friedmacher, Julia Zimmer i Prem Puri. "Decreased Expression of Integrin Subunits α3, α6, and α8 in the Branching Airway Mesenchyme of Nitrofen-Induced Hypoplastic Lungs". European Journal of Pediatric Surgery 28, nr 01 (12.07.2017): 109–14. http://dx.doi.org/10.1055/s-0037-1604022.
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Introduction Pulmonary hypoplasia (PH), characterized by smaller lung size and reduced airway branching, remains a major cause of neonatal mortality in newborns with congenital diaphragmatic hernia (CDH). Integrin-mediated cell–matrix interactions play an essential role in the fetal lung mesenchyme by stimulating branching morphogenesis. Mice lacking integrin subunits α3 (Itga3) and α6 (Itga6) exhibit severe PH. Furthermore, Itga8-knockout mice show defective airway branching, suggesting that Itga3, Itga6, and Itga8 are crucial for fetal lung development. We hypothesized that expression of Itga3, Itga6, and Itga8 is decreased in the branching airway mesenchyme of hypoplastic rat lungs in the nitrofen-induced CDH model. Materials and Methods Time-mated rats received nitrofen or vehicle on gestational day 9 (D9). Fetuses were sacrificed on D15, D18, and D21, and dissected lungs were divided into control and nitrofen-exposed specimens (n = 12 per time-point and group, respectively). Pulmonary gene expression of Itga3, Itga6, and Itga8 was analyzed by quantitative real-time polymerase chain reaction. Immunofluorescence double-staining for Itga3, Itga6, and Itga8 was combined with the mesenchymal marker Fgf10 to evaluate protein expression and localization in branching airway tissue. Results Relative mRNA expression of Itga3, Itga6, and Itga8 was significantly decreased in lungs of nitrofen-exposed fetuses on D15, D18, and D21 compared with controls. Confocal laser scanning microscopy showed markedly diminished immunofluorescence of Itga3, Itga6, and Itga8 mainly in mesenchymal cells surrounding branching airways of nitrofen-exposed fetuses on D15, D18, and D21 compared with controls. Conclusion Decreased expression of Itga3, Itga6, and Itga8 in the pulmonary mesenchyme may lead to disruptions in airway branching morphogenesis, thus contributing to PH in the nitrofen-induced CDH model.
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Xu, D., T. Li i R. Mu. "AB0095 EXPRESSION AND PATHOGENIC ROLES OF INTEGRIN FAMILY GENE IN SYSTEMIC SCLEROSIS". Annals of the Rheumatic Diseases 80, Suppl 1 (19.05.2021): 1076.2–1076. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3646.
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Background:Emerging evidence have shown that some integrin members are associated with inflammation and fibrosis in systemic sclerosis (SSc) patients[1-2]. However, the expression patterns and pathogenic significance of the whole integrin family in SSc are still unclear.Objectives:This study aimed at evaluating the integrin family gene expression in skin lesion from SSc patients and exploring its potential pathogenic mechanism.Methods:We utilized the public datasets of SSc skin tissue from Gene Expression Omnibus (GEO) database to analyze the expression and clinical significance of integrin family genes in SSc. In addition, functional enrichment and pathway analysis were also conducted.Results:Compared with healthy controls, ITGA5, ITGA7, ITGA8, ITGB2, ITGB5, ITGAE and ITGB3BP were abnormally overexpressed in the skin of SSc. Further analysis indicated that ITGA5, ITGA7, ITGA8, ITGB2 and ITGB5 were positively correlated with modified Rodnan skin thickness score (mRSS), while ITGAE and ITGB3BP were negatively correlated with mRSS in SSc. Increased ITGB5 expression was associated with positive of anti-centromere antibody (ACA). Functional enrichment and pathway analysis showed that integrin members had multiple functions in SSc. Among them, ITGA5, ITGB2 and ITGB5 might synergistically promote SSc through affecting extracellular matrix (ECM) turn over, ECM-receptor interaction, focal adhesion and leukocyte trans-endothelial migration. ITGA5 and ITGB5 also affected angiogenesis and endothelial cell function. In addition, ITGA5 was uniquely enriched for actin organization, ITGB5 was uniquely enriched for TGF-β signaling, and ITGB2 was uniquely associated with immune cells activation.Conclusion:Our results implied that integrins, especially ITGA5, ITGB5, ITGB2 participated in the process of inflammation, vasculopathy and fibrosis in SSc. Together, they might render important therapeutic targets for SSc.References:[1]Brown M, O’Reilly S. The immunopathogenesis of fibrosis in systemic sclerosis. Clin Exp Immunol. 2019;195(3):310-321.[2]Gerber, E.E., et al., Integrin-modulating therapy prevents fibrosis and autoimmunity in mouse models of scleroderma. Nature, 2013. 503(7474): p. 126-30.Disclosure of Interests:None declared
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Wang, Yizhe, Kezuo Hou, Yue Jin, Bowen Bao, Shiying Tang, Jianfei Qi, Yang Yang i in. "Lung adenocarcinoma-specific three-integrin signature contributes to poor outcomes by metastasis and immune escape pathways". Journal of Translational Internal Medicine 9, nr 4 (1.12.2021): 249–63. http://dx.doi.org/10.2478/jtim-2021-0046.
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ABSTRACT Background: Inhibitors targeting integrins (ITGs) are applied as a novel strategy for cancers including lung cancer; however, the heterogeneity of ITG subunits might explain why ITG-targeted inhibitors only show limited efficacy for a small group of lung cancer patients. Materials and methods: RNA-Seq data of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients were obtained from the TCGA database. Cox regression analysis was performed to construct the prognostic signature and generate the nomogram combined with pathologic stages (pStage). GEO datasets were used for verification. The related biological functions were analyzed by Gene Set Enrichment Analysis (GSEA) software and the TIMER database. Results: By Cox regression analysis of 30 ITG subunits, ITG subunit alpha 5 (ITGA5), ITG subunit alpha 6 (ITGA6), and ITG subunit alpha L (ITGAL) were identified as the prognostic factors in LUAD, which were included in the construction of a LUAD-specific 3-ITG signature. Following the calculation of risk score (RS) of each patient based on 3-ITG signature, patients with high RS in LUAD were found to exhibit worse prognosis, especially in early stage. Nomogram combined with RS and pStage could predict the prognosis of LUAD patients accurately. Mechanism exploration by GSEA showed that metastasis-related microenvironmental pathways were significantly enriched in the high-RS group. An elevated expression of ITGA5 was mainly associated with the promotion of cell migration and invasion, while the high expression of ITGAL had a strong positive correlation with the capability of recognizing and killing cancer cells. Conclusions: Three-ITG signature could improve the prediction ability combined with pStage in LUAD and might contribute to poor prognosis by metastasis and immune escape-related pathways.
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Ząbek, Tomasz, Ewelina Semik, Agnieszka Fornal, Artur Gurgul i Monika Bugno-Poniewierska. "The Relevance of Methylation Profiles of Equine ITGAL Gene". Annals of Animal Science 16, nr 3 (1.07.2016): 711–20. http://dx.doi.org/10.1515/aoas-2015-0080.
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AbstractOne of epigenetic features of mammalian genomes is methylation of DNA. This nucleotide modification might exert suppressive effect on gene transcription. We have described putative relevance of methylation of one of immune cells related gene (ITGAL) observed in the set of 11 equine tissues. Comparison between qualitative RT-PCR results and DNA bisulfite sequencing of investigated set of tissues pointed to potential correlations between tissue specific methylation and tissue specific transcription in ITGAL locus. These findings might be important for studies on genetic and epigenetic background of autoimmune disorders in the horse.
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Esmaeili, Behnaz, Behnaz Bayat, Atefe Alirezaee, Mona Delkhah, Mohammad Reza Mehdizadeh i Zahra Pourpak. "Human Neutrophil Antigen Genotype and Allele Frequencies in Iranian Blood Donors". Journal of Immunology Research 2022 (7.02.2022): 1–11. http://dx.doi.org/10.1155/2022/4387555.
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Objective. Human neutrophil antigens (HNAs) can be targeted by HNA-allo antibodies and cause a variety of clinical conditions such as transfusion-related acute lung injury (TRALI) and neonatal alloimmune neutropenia (NAIN). The current study is aimed at identifying the genotype and allele frequencies of HNAs in Iranian blood donors. Methods. A total of 150 blood samples were obtained from healthy blood donors. HNA-1, HNA-3, HNA-4, and HNA-5 were genotyped, using the polymerase chain reaction sequence-specific primer (PCR-SSP) technique. The expression of the HNA-2 antigen on the neutrophil surface was evaluated by flow cytometry. Results. The allele frequencies of FCGR3B ∗ 1 (encoding HNA-1a), FCGR3B ∗ 2 (encoding HNA-1b), and FCGR3B ∗ 3 (encoding HNA-1c) were 0.34, 0.63, and 0.03, respectively. For HNA-3, the allele frequencies for SLC44A2 ∗ 1 (encoding HNA-3a) and SLC44A2 ∗ 2 (encoding HNA-3b) were 0.63 and 0.37, respectively. The frequencies of ITGAM ∗ 1 (encoding HNA-4a) and ITGAM ∗ 2 (encoding HNA-4b) alleles were 0.85 and 0.15, respectively. Furthermore, the frequencies of ITGAL ∗ 1 (encoding HNA-5a) and ITGAL ∗ 2 (encoding HNA-5b) alleles were 0.72 and 0.28, respectively. In the studied population, HNA-2 antigen was present on the neutrophil surface in 97.3% of the individuals, while no detectable HNA-2 expression was observed in 2.7% of the individuals. However, no significant difference in HNA-2 expression between different age groups was found. Conclusion. The present study provides the first report of the HNA allele and genotype frequencies among the Iranian population. All HNAs (HNA-1 to HNA-5) were typed using the PCR-SSP and flow cytometer. In the current cohort study, the determined HNA allele frequencies were similar to the previous reports from British, German, and Danish populations. Considering the presence of different Iranian ethnic groups, further studies with a larger sample size are needed to draw a total picture for HNA allele frequencies.
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Skov, Vibe, Mads Thomassen, Lasse Kjær, Caroline Riley, Thomas Stauffer Larsen, Ole Weis Bjerrum, Torben A. Kruse i Hans Carl Hasselbalch. "Extracellular Matrix-Related Genes Are Deregulated in Peripheral Blood from Patients with Myelofibrosis and Related Neoplasms". Blood 132, Supplement 1 (29.11.2018): 5491. http://dx.doi.org/10.1182/blood-2018-99-117122.
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Abstract Introduction: The Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) which include essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) are characterized by varying degrees of bone marrow fibrosis and endothelial proliferation. We and others have previously reported that these stromal alterations are reflected by increased serum levels of matrix derived metabolites, striated collagens type I/III and basement membrane components. The existence of a prefibrotic seromarker profile in MPNs is further evidenced by reports on increased serum levels of matrix metalloproteinase-3 (MMP-3) and decreased tissue inhibitor of metalloproteinase- I (TIMP-I). Using whole blood gene expression profiling, we aimed to provide a comprehensive gene signature of extracellular matrix-related proteins in MPNs with particular focus on genes associated with the regulation of major stromal proteins and MMPs. Methods: Gene expression profiling was performed on whole blood from 21 control subjects, 19 patients with ET, 41 patients with PV, and 9 patients with PMF. RNA was converted to biotin labeled amplified RNA (aRNA) using the MessageAmpTM III RNA amplification kit, and fragmented aRNA was hybridized to Affymetrix HG-U133 Plus 2.0 microarray chips recognizing 54,675 probe sets (38,500 genes). The R statistical software was applied to perform data preprocessing and statistical analysis of microarray data. Results: We identified 20,439, 25,307, and 17,417 probe sets that were differentially expressed between controls and patients with ET, PV, and PMF, respectively (FDR£0.05). These genes included 116 genes encoding extracellular matrix and adhesion molecules (ECM) important for cell-cell and cell-matrix interactions. These genes are represented on the Qiagen Human ECM panel, and in addition, all remaining collagen genes have been included. In patients with ET, COL1A1, COL1A2, COL3A1, COL4A2, COL4A5, LAMA2, LAMB1, MMP1, MMP7, MMP11, MMP12, MMP14, AND TIMP3 were among the 42 upregulated ECM genes (FDR<0.05). In patients with PV, 53 ECM genes were upregulated including COL1A1, COL1A2, COL3A1, COL4A2, LAMA2, LAMB1, MMP1, MMP7, MMP8, MMP9, MMP11, MMP12, MMP14, and TIMP3 (FDR<0.05). In PMF, COL1A2, COL3A1, COL4A2, COL4A5, LAMA2, MMP1, MMP8, MMP9, MMP14, and TIMP3 were among the 26 upregulated genes (FDR<0.05) (Table 1). 17, 14, and 13 ECM genes were significantly downregulated in ET, PV, and PMF, respectively (FDR<0.05) (data not shown). ITGA7, ITGB3, and MMP1 were significantly upregulated from ET over PV to PMF, whereas ITGAL, SPG7, and TGFBI were significantly downregulated from ET over PV to PMF. ADAMTS8, ADAMTS13, COL10A1, COL14A1, COL1A2, COL29A1, COL3A1, COL4A2, COL6A1, ITGA7, ITGB3, ITGB5, LAMA2, MMP1, MMP14, NCAM1, THBS2, and TIMP3 were significantly upregulated in both ET, PV, and PMF (FDR<0.05). COL4A3BP, COL6A2, ITGA4, ITGA5, ITGAL, ITGB1, PECAM1, SPG7, and TGFBI were significantly downregulated in both ET, PV, and PMF (FDR<0.05). In table 2a-b are shown the 10 most significantly up- and downregulated genes. Discussion and conclusions: Bone marrow fibrosis and endothelial proliferation in MPNs are elicited due to the release of fibrogenic and angiogenic growth factors primarily from hyperproliferating megakaryocytes. The connective tissue components of the bone marrow in MPNs include type III collagen, which is deposited in the early disease stages (ET/PV) as "reticulin fibrosis" being accompanied and substituted by mature Van Giesson positive collagen (type I collagen) in the advanced myelofibrosis stage. Increased endothelial cell proliferation is followed by the development of continuous sheets of basement membrane material beneath endothelial cells as assessed by increased deposition of type IV collagen and laminin. Using whole blood gene expression profiling, we provide evidence that abnormal extracellular matrix metabolism is reflected in the gene signature of peripheral blood cells from patients with MPNs. Further studies are needed to determine whether these changes represent local bone marrow fibrogenesis and/or systemic disease manifestations. Disclosures Hasselbalch: Novartis: Research Funding.
Rozprawy doktorskie na temat "ITGAL"
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Idani, Aida. "A multiomics approach to primary immunodeficiencies in human". Electronic Thesis or Diss., Strasbourg, 2024. http://www.theses.fr/2024STRAJ061.
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Les déficits immunitaires primitifs sont un groupe de troubles causés par des mutations monogéniques dans des gènes jouant un rôle clé dans le développement et la fonction du système immunitaire. Dans cette thèse, une approche multiomique a été adoptée pour étudier deux gènes associés à ces conditions, afin d'élucider davantage les mécanismes par lesquels les variants pathogènes nuisent au système immunitaire. Le premier sujet était HYOU1, défini comme un gène dont les défauts causent un déficit immunitaire primitif. Nous avons observé une hypogranularité dans les neutrophiles du patient et révélé un arrêt de maturation dans la lignée des cellules B avant le stade des cellules B pro. Le deuxième sujet était ITGAL, un gène candidat potentiel non précédemment décrit en relation avec les déficits immunitaires primitifs. Nous avons démontré que le variant étudié est hérité selon un mode autosomique récessif, et les analyses de voies ont révélé un dysfonctionnement de plusieurs voies liées à l'adhésion et à la motilité. De plus, nous avons montré une élévation de l'expression d'autres intégrines, suggérant une réponse compensatoire visant à contrebalancer les intégrines défectueusesPrimary immunodeficiencies, or inborn errors of immunity, are a group of disorders caused by monogenic mutations in genes playing a key role in the development and function of the immune system. In this thesis, a multiomics approach was taken to study two genes associated with these conditions, further elucidating the mechanisms by which pathogenic variants impair the immune system. The first subject was HYOU1, defined as a gene whose defects cause primary immunodeficiency. We observed hypogranularity in the patient's neutrophils and revealed a maturation arrest in the B cell lineage before the pro-B cell stage. The second subject was ITGAL, a potential candidate gene not previously described in relation to primary immunodeficiencies. We demonstrated that the studied variant is inherited in an autosomal recessive pattern, and pathway analyses revealed impairment of multiple adhesion and motility-related pathways. Moreover, we showed an elevation in the expression of other integrins, suggesting a compensatory response to counterbalance the defective integrins
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Heller, Kristin Noreen. "Alternative to Gene Replacement for Duchenne Muscular Dystrophy using Human Alpha7 Integrin (ITGA7)". The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1388401639.
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GAMBELLI, ALICE. "ITGA6 is a key molecule in driving metastatization of platinum resistant epithelial ovarian cancer". Doctoral thesis, Università degli Studi di Trieste, 2022. http://hdl.handle.net/11368/3014977.
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Epithelial ovarian cancer (EOC) is a relatively rare disease usually diagnosed in advanced stages (III and IV stage). Standard of care includes radical surgery followed by platinum-based chemotherapy. Yet, 15% to 30% of EOC patients have a primary platinum-resistant or refractory disease and more than 70% of originally platinum-sensitive advanced stages patients will develop a resistant disease disseminated in the abdomen and pelvis. For these reasons, the net five-year survival by stage is only of 26% and 13% for stage III and IV, respectively. The resistance to chemotherapy is one of the major challenges cancer research faces nowadays. In our lab, we have established several Platinum (PT) resistant (PT-res) cellular models to better understand the molecular pathways that could guide PT-resistance in ovarian cancer. We observed that one of the common features of these PT-res cells was the higher ability to adhere on the mesothelial cells respect to their sensitive counterpart, a fundamental capacity for driving cell dissemination into the peritoneal cavity.
My PhD project focused the attention on the dissection of the molecular basis of the higher adhesion capability of PT-res cells to possibly identify new therapeutic targets to overcome EOC peritoneal dissemination. We found all tested PT-res cells over-expressed the integrin alpha 6 (ITGA6) protein that in turn mediated their higher ability to adhere and migrate on the specific substrate laminin (LM) and on mesothelial cells. Using pharmacological and genetic tools, we showed that ITGA6 expression was linked to a higher capacity of PT-res cells to form ovaryspheres in vitro and to grow and disseminate in vivo. Molecular analyses next demonstrated that under PT treatment positively regulated ITGA6 gene promoter activity by via the SP1 transcription factor, possibly explaining the higher ITGA6 expression in PT-res cells. Moreover, PT-treatment also induced an active secretion of ITGA6. Once secreted, ITGA6 on one side primed mesothelial cells to form a pro-metastatic niche and, on the other, favoured the spreading of neighbour tumour cells. Mechanistically, the engagement of ITGA6 with LM positively regulated Snail expression favouring cell adhesion and spreading. These in vitro data were recapitulated in the human pathology since we found higher ITGA6 levels in the ascitic fluids of EOC patients with a PT-resistant disease and also demonstrated that higher levels of circulating ITGA6 could be found in the plasma of EOC after PT-based chemotherapy. Altogether, our collected data suggested that ITGA6 could be a reasonable druggable target to prevent EOC metastatization and dissemination in the peritoneal cavity, for instance by the use of specific blocking antibodies. Moreover, since ITGA6 is easily quantifiable in the circulation of EOC patients it could be used as predictive biomarkers to identify patients that could not respond to the standard PT-based chemotherapyEpithelial ovarian cancer (EOC) is a relatively rare disease usually diagnosed in advanced stages (III and IV stage). Standard of care includes radical surgery followed by platinum-based chemotherapy. Yet, 15% to 30% of EOC patients have a primary platinum-resistant or refractory disease and more than 70% of originally platinum-sensitive advanced stages patients will develop a resistant disease disseminated in the abdomen and pelvis. For these reasons, the net five-year survival by stage is only of 26% and 13% for stage III and IV, respectively. The resistance to chemotherapy is one of the major challenges cancer research faces nowadays. In our lab, we have established several Platinum (PT) resistant (PT-res) cellular models to better understand the molecular pathways that could guide PT-resistance in ovarian cancer. We observed that one of the common features of these PT-res cells was the higher ability to adhere on the mesothelial cells respect to their sensitive counterpart, a fundamental capacity for driving cell dissemination into the peritoneal cavity. My PhD project focused the attention on the dissection of the molecular basis of the higher adhesion capability of PT-res cells to possibly identify new therapeutic targets to overcome EOC peritoneal dissemination. We found all tested PT-res cells over-expressed the integrin alpha 6 (ITGA6) protein that in turn mediated their higher ability to adhere and migrate on the specific substrate laminin (LM) and on mesothelial cells. Using pharmacological and genetic tools, we showed that ITGA6 expression was linked to a higher capacity of PT-res cells to form ovaryspheres in vitro and to grow and disseminate in vivo. Molecular analyses next demonstrated that under PT treatment positively regulated ITGA6 gene promoter activity by via the SP1 transcription factor, possibly explaining the higher ITGA6 expression in PT-res cells. Moreover, PT-treatment also induced an active secretion of ITGA6. Once secreted, ITGA6 on one side primed mesothelial cells to form a pro-metastatic niche and, on the other, favoured the spreading of neighbour tumour cells. Mechanistically, the engagement of ITGA6 with LM positively regulated Snail expression favouring cell adhesion and spreading. These in vitro data were recapitulated in the human pathology since we found higher ITGA6 levels in the ascitic fluids of EOC patients with a PT-resistant disease and also demonstrated that higher levels of circulating ITGA6 could be found in the plasma of EOC after PT-based chemotherapy. Altogether, our collected data suggested that ITGA6 could be a reasonable druggable target to prevent EOC metastatization and dissemination in the peritoneal cavity, for instance by the use of specific blocking antibodies. Moreover, since ITGA6 is easily quantifiable in the circulation of EOC patients it could be used as predictive biomarkers to identify patients that could not respond to the standard PT-based chemotherapy
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Hsieh, Jenny [Verfasser], Rolf [Akademischer Betreuer] Marschalek i Theodor [Akademischer Betreuer] Dingermann. "Funktionelle Analyse des MLH1·ITGA9-Fusionsproteins einer Lynch-Syndrom-Familie / Jenny Hsieh. Gutachter: Rolf Marschalek ; Theodor Dingermann. Betreuer: Rolf Marschalek". Frankfurt am Main : Univ.-Bibliothek Frankfurt am Main, 2012. http://d-nb.info/1044093447/34.
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Mokrani, M'barka. "CD103 : du gène à la protéine : Etude de la régulation et de la signalisation de l’intégrine αE(CD103)β7 exprimée par les lymphocytes T CD8+ intratumoraux". Thesis, Paris 11, 2013. http://www.theses.fr/2013PA11T071.
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L’élucidation des mécanismes permettant l’optimisation de la réponse immunitaire antitumorale correspond à un enjeu majeur pour le développement de stratégies d’immunothérapie efficace. En effet, les réponses immunitaires antitumorales se traduisent rarement par l’éradication de la tumeur. Dans ce contexte, les travaux antérieurs de mon équipe ont démontré que l’interaction de l’intégrine αE(CD103)β7, souvent exprimée par les lymphocytes infiltrant la tumeur (TIL), avec son ligand E-cadhérine, à la surface des cellules tumorales épithéliales, joue un rôle majeur dans la potentialisation de l’activité lytique des cellules T en induisant la polarisation et l’exocytose des granules cytotoxiques. Nos résultats ont indiqué aussi que le TGF-β1, souvent abondant dans les tumeurs, joue un rôle déterminant dans cette induction suite à l’engagement du récepteur des cellules T. Dans ce contexte, nous avons cherché à comprendre les mécanismes de régulation du gène ITGAE qui codent la sous-unité alphaE de l’intégrine CD103. Nos résultats ont montré que les facteurs transcriptionnels Smad2, Smad3 et NFAT-1 sont impliqués dans la régulation de l’expression de la sous-unité αE(CD103). En effet, une costimulation avec du TGF-β1 recombinant et un anticorps anti-CD3 d’un clone T CD103- induit l’expression de cette intégrine qui est accompagnée d’une translocation dans le noyau de Smad2, Smad3 et NFAT-1 qui sont cytoplasmiques à l’état basal. L’inhibition spécifique de ces facteurs transcriptionnels inhibe l’expression de CD103 et abroge le potentiel lytique du clone T vis à vis de sa cible tumorale autologue. De plus, nous avons identifié deux séquences régulatrices du gène ITGAE humain, un promoteur proximal et un enhancer. Par ailleurs, mon équipe a récemment montré que l’interaction de CD103 à la surface des TIL avec une molécule E-cadhérine recombinante est suffisante pour induire la polarisation des granules cytolytiques par un mécanisme dépendant de la PLC-g1 et ERK et que cette intégrine possède non seulement une fonction d’adhérence, mais aussi une fonction de costimulation du signal TCR des TIL antitumoraux. Nous avons cherché à mieux comprendre la signalisation de l’intégrine CD103, en identifiant les domaines intracytoplasmiques de la sous-unité αE impliqués dans son activation. Nous avons ainsi construit une protéine de fusion CD103-GFP et plusieurs mutants du domaine intracytoplasmique de la sous-unité αE qui ont été ensuite transfectés dans la lignée Jurkat Tag CD103-/beta7+. Nos résultats ont montré que le domaine intracytoplasmique de la chaîne alphaE n’est pas nécessaire à la reconnaissance du ligand, la E-cadhérine. Par contre, nous avons montré que ce domaine est impliqué dans le phénomène de clustering de l’intégrine et dans sa polarisation à la zone de contact avec des billes couvertes avec la E-cadhérine-Fc. Nous avons identifié un domaine de 8 acides aminés (ESIRKAQL), contenant une sérine en position 1163 potentiellement phosphorylable, et qui est indispensable pour la signalisation de l’intégrine. De plus, nos travaux ont montré que ce domaine ESIRKAQL, est nécessaire pour la phosphorylation de la ERK1/2 et PLC-g1. Ainsi, une meilleure compréhension des mécanismes moléculaires régulant les fonctions de CD103 pourrait contribuer au développement et à l’amélioration de la réponse antitumorale exercée par les CTLThe elucidation of mechanisms for optimizing the antitumor immune response is a major challenge for the development of strategies for effective immunotherapy. Indeed, the anti-tumor immune responses rarely result in the eradication of the tumor. In this context, the previous work of my team have shown that the interaction of integrin αE(CD103)β7, often expressed by tumor infiltrating lymphocytes (TIL) with its ligand E-cadherin at the cell surface tumor epithelial cells, plays a major role in the potentiation of the lytic activity of T cells by inducing polarization and exocytosis of cytotoxic granules. Our results also indicated that TGF-β1, often abundant in tumors, plays a key role in the induction due to the commitment of the T cell receptor. In this context, we sought to understand the mechanisms regulating ITGAE gene encoding the subunit αE of integrin. Our results showed that the transcription factors Smad2, Smad3 and NFAT-1 are involved in regulating the expression of subunit αE(CD103)β7. Indeed, costimulation with recombinant TGF-β1 and anti-CD3 antibody induces on T cell clone CD103- the expression of this integrin ant the translocation into the nucleus of Smad2, Smad3 and NFAT-1 that are cytoplasmic at baseline. Specific inhibition of these transcription factors inhibits the expression of CD103 and repeals the lytic potential of cloned T with respect to the autologous tumor target. In addition, we identified two regulatory sequences of human ITGAE gene, proximal promoter and enhancer. In addition, my team has recently shown that the interaction of CD103 on the surface of TIL with a recombinant molecule E-cadherin is sufficient to induce the polarization of cytolytic granules by ERK and PLC-γ1 pathway thus this integrin has not only a function of adherence, but also a function of costimulatory signal TCR of TIL. We sought to better understand the signaling of integrin CD103, by identifying the cytoplasmic domains of the subunit αE involved in its activation. We have constructed a fusion protein CD103-GFP and several mutants of intracytoplasmic domain of the subunit αE which were then transfected into the Jurkat Tag cell line CD103-/ β7+. Our results showed that the intracytoplasmic domain of CD103 is not necessary for ligand recognition, E-cadherin. By cons, we have shown that this area is involved in the phenomenon of clustering of integrin and its polarization to the contact area with balls covered with E-cadherin-Fc. We have identified a range of 8 amino acids (ESIRKAQL) containing a potentially phosphorylatable serine in position 1163, which is essential for integrin signaling. In addition, our work has shown that this area ESIRKAQL is necessary for the phosphorylation of ERK1/2 and PLC-g1. Thus, a better understanding of the molecular mechanisms that regulate the functions of CD103 may contribute to the development and improvement of the antitumor response exerted by CTL
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Pilati, Filippo. "I "Fatti di Cesare" nel Veneto e le "Zesarie batalie romane" del ms. Canon. Ital. 136 di Oxford". Doctoral thesis, Università di Siena, 2020. http://hdl.handle.net/11365/1105152.
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Questa tesi si pone l’obiettivo di studiare la fortuna e la circolazione nel Veneto dei "Fatti di Cesare", con una proposta di edizione critica delle inedite "Zesarie batalie romane contenute nel ms. Oxford, Bodleian Library, Canonicianus Italicus 136. Nel fare questo si è anzitutto offerto, nella parte I di questo lavoro, una disamina attenta dei numerosi volgarizzamenti italiani dei "Faits des Romains", con l’ampia discussione della bibliografia esistente sulla questione e un riesame complessivo delle diverse testimonianze manoscritte, unito anche a un controllo sulla tradizione del testo francese. Ѐ stata quindi proposta, sulla base di nuovi dati ricavati dalle nostre indagini, una nuova classificazione di tutti i volgarizzamenti italiani dei "Faits des Romains" in otto diversi raggruppamenti. La parte II è invece focalizzata sulla tradizione manoscritta dei "Fatti di Cesare", uno dei più diffusi e fortunati volgarizzamenti dei "Faits des Romains", contraddistinto per essere una versione abbreviata del testo francese che godette, tra i secc. XIV e XV, di una consistente circolazione, attestata anche nell’Italia settentrionale e, in particolare, nel Veneto. A partire da una nuova ricognizione dell’intero testimoniale manoscritto dei Fatti di Cesare, che ha permesso inoltre di incrementare la tradizione con alcuni codici finora mai segnalati, è stata dapprima studiata da un punto di vista materiale la diffusione e la circolazione di questo testo in spazi e tempi diversi. Tutti i codici di questa tradizione sono stati visionati direttamente e descritti tramite l’esame codicologico di ogni singolo testimone, supportato inoltre da un controllo sui cataloghi delle principali biblioteche, sui database digitali disponibili e sulla più aggiornata bibliografia filologica. Si è quindi proceduto con una recensio codicum dell’intera tradizione manoscritta, che, condotta tramite la collazione di loci critici opportunamente selezionati, ha permesso una precisa classificazione dei numerosi codici dei Fatti di Cesare, operazione indispensabile, in attesa di un’edizione critica del testo, per poterne studiare, in una prospettiva ecdotica, la circolazione nel Veneto. Ѐ stato così possibile dimostrare da quale snodo della tradizione abbiano avuto origine le "Zesarie batalie romane" – adattamento quattrocentesco in dialetto veneziano dei Fatti di Cesare –, il cui studio è stato dedicato alla terza ed ultima parte di questo lavoro. L’edizione del testo è stata preceduta da alcune annotazioni sulla lingua delle "Zesarie batalie romane, con uno studio della grafia, della fonetica e della morfologia, che permetta di apprezzarne la particolare stratigrafia linguistica, caratterizzata da un diasistema in cui, alla lingua primaria del modello toscano, si sovrappone la patina linguistica del veneziano. Il testo critico è stato infine presentato, come è norma comune nell’edizione di testi veneti antichi, secondo criteri prudentemente interpretativi, che, pur tenendo conto delle peculiarità del manoscritto, testimone, nella sua specificità, di una precisa modalità di riuso dei "Fatti di Cesare" nel Veneto, non rinuncia a intervenire laddove necessario ai fini di una migliore fruibilità e leggibilità del testo. Naturalmente, si è sempre dato conto di ogni singolo intervento, segnalando in un apposito apparato la lezione del manoscritto, in modo da consentire, a chi lo desideri, la costante ricostruzione della facies originaria. L’edizione critica delle "Zesarie batalie romane", che qui si pubblica per la prima volta, costituisce dunque un’importante acquisizione per lo studio dei volgarizzamenti italiani dei "Faits des Romains", permettendoci di apprezzare le complesse modalità di ricezione, circolazione e riuso nei secoli di un testo che ebbe una tale fortuna nel corso di tutto il Medioevo e che significò molto per la storia dei volgarizzamenti in Italia.This work aims to study the fortune and circulation in the Veneto region of the "Fatti di Cesare" with a critical edition of the unpublished "Zesarie batalie romane" of the ms. Oxford, Bodleian Library, Canonicianus Italicus 136. The first part of this work offers a careful examination of the numerous Italian vernaculars of the Faits des Romains, with an extensive discussion of all the bibliography on the issue and a comprehensive review of the various manuscripts, together with a check on the tradition of the French text. The second part focuses on the manuscript tradition of the "Fatti di Cesare", one of the most widespread and successful vernaculars of the "Faits des Romains", distinguished by being an abbreviated version of the French text that enjoyed, between the 14th and 15th centuries, a consistent circulation, also attested in northern Italy and, in particular, in the Veneto region. A recensio of the entire manuscript tradition was then carried out through the collation of suitably selected loci criciti, allowing a precise classification of the numerous codices of the "Fatti di Cesare", an indispensable operation, pending a critical edition of the text, in order to study, from a textual perspective, its circulation in the Veneto region. It has thus been possible to identify the origin of the" Zesarie batalie romane" – fifteenth-century adaptation in Venetian dialect of the "Fatti di Cesare" –, whose study has been dedicated to the third and last part of this work. The edition of the text was preceded by some notes on the language of the "Zesarie batalie romane", with a study of handwriting, phonetics and morphology, As is the common norm in the edition of ancient Venetian texts, the critical text was presented according to prudently interpretative criteria, considering the peculiarities of the manuscript, which testifies, in its specificity, to a precise willingness to reuse the material of the "Fatti di Cesare" in Veneto region. By the way, in order to the readability of the text, we do not renounce to correct it where necessary. Every single intervention on the text has always been considered, pointing out the lesson of the manuscript in a special apparatus, so as to allow the constant reconstruction of the original facies. The critical edition of the Zesarie batalie romane, which is published here for the first time, is therefore an important acquisition for the study of the Italian vernaculars of the Faits des Romains, allowing us to appreciate the complex ways of receiving, circulating and reusing over the centuries of such a significant text in the history of vernaculars in Italy.
L’objectif principal de ce travail a été d’étudier la fortune italienne des "Faits des Romains" et, notamment, leur réception en Vénétie; mon étude est complétée par l’édition critique des "Zesarie batalie romane" du ms. Oxford, Bodleian Library, Canonicianus Italicus 136, jusqu’alors inédites. Celles-ci constituent une transposition en vernaculaire vénitien librement adaptée d’une version toscane des "Faits des Romains" connue sous le nom de "Fatti di Cesare" et dotée d’une grande fortune même hors de Toscane, devenant la source de beaucoup d’autres textes. Dans la première partie de ce travail, je présente un examen attentif des nombreuses traductions italiennes des "Faits des Romains". Sur la base de mes enquêtes, conduites à partir d’une discussion approfondie de toute la bibliographie existante sur la question et d’une analyse des différents témoignages manuscrits, aussi bien français qu’italiens, je propose une nouvelle classification de toutes les versions italiennes des "Faits des Romains". La deuxième partie est centrée sur la tradition manuscrite des "Fatti di Cesare". À partir d’une nouvelle recognitio codicum des "Fatti di Cesare", qui m’a permis de dénombrer 49 manuscrits survivants de cette tradition, parmi lesquels deux manuscrits jamais mentionnés auparavant, j’ai d’abord étudié d’un point de vue matériel la diffusion et la circulation de ce texte dans différents espaces et époques. J’ai ensuite procédé à une recensio codicum de toute la tradition manuscrite, qui, grâce à une collation pour loci critici choisis, m’a permis de classer avec précision les nombreux manuscrits des "Fatti di Cesare", opération indispensable, en attendant l’édition critique du texte, pour en étudier même dans une perspective textuelle sa circulation en Vénétie. La troisième partie de ce travail a été finalement dédiée à l’étude des "Zesarie batalie romane". L’édition du texte a été précédée de quelques annotations sur la langue du texte avec une étude de la graphie, de la phonétique et de la morphologie. A cause de la stratigraphie linguistique de ce texte, caractérisée par un diastème dans lequel la patine linguistique du vénitien se superpose à la langue primaire du modèle toscan, il n’a pas toujours été possible d’isoler avec certitude les éléments attribuables au système primaire ou secondaire. De plus, en raison de la datation du ms. Canonicianus Italicus 136, à savoir l’année 1454, il était légitime d’y attendre, également au niveau du système linguistique vénitien-padan, un degré plus ou moins élevé de phénomènes typiquement toscans, et pour cette raison superposable au système linguistique de l’antigraphe toscan. Pour tout cela, j’ai décidé de proposer une analyse linguistique de nature purement descriptive, qui sans viser une analyse linguistique complète, peut présenter un examen attentif des phénomènes les plus importants retraçables dans le texte. Le texte critique a été présenté, comme d’ordinaire pour l’édition des anciens textes vénitiens, selon des critères prudemment interprétatifs, qui, tout en tenant compte des particularités du manuscrit Canonicianus, ne renonce pas à intervenir là où cela est nécessaire pour une meilleure lisibilité du texte. Naturellement, j’ai rendu compte de chaque intervention dans un apparat, où j’ai toujours indiqué la leçon du manuscrit, afin de permettre aux lecteurs la reconstruction constante de la facies original. L’édition critique des "Zesarie batalie romane", qui est publiée ici pour la première fois, est donc une acquisition importante pour l’étude des versions italiennes des "Faits des Romains", nous permettant d’apprécier les méthodes complexes de réception, de circulation et de réutilisation au cours des siècles d’un texte qui a connu un tel succès tout au long du Moyen Âge.
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Holtkötter, Olaf. "Inaktivierung des ITGA2-Gens in der Maus neue Erkenntnisse über die Funktion des [alpha]2[beta]1-Integrinrezeptors [alpha2beta1-Integrinrezeptors] in vivo /". [S.l. : s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=966631803.
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Maestrello, Chadia Chahud. "Produção de celulases e xilanases pelo fungo Aspergillus labruscus ITAL 22.223 cultivado em fermentação em estado sólido utilizando resíduos agroindustriais /". Araraquara, 2018. http://hdl.handle.net/11449/153200.
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Orientador: Luis Henrique Souza GuimarãesBanca: Daniela Alonso Bocchini
Banca: Valéria de Carvalho Santos Ebinuma
Resumo: A prospecção de enzimas fúngicas tem sido amplamente estudada nos ultimos anos, principalmente utilizando a Fermentação em Estado Sólido (FES). A procura por enzimas microbianas, principalmente de fungos filamentosos, capazes de degradar material lignocelulósico, tem despertado grande interesse para processos biotecnológicos como, por exemplo, na produção de bioetanol, a partir do bagaço de cana-de-açúcar. Fungos do gênero Aspergillus são reconhecidos como ótimos produtores de enzimas do complexo celulolítico e hemicelulolítico, e a busca por novas linhagens com potencial de produção destas torna-se um grande desafio. Aspergillus labruscus ITAL 22.223 é um fungo filamentoso recentemente isolado no sul do Brasil e, por este motivo, não há estudos na literatura sobre seu potencial de produzir enzimas celulolíticas e hemicelulolíticas. Diante do exposto, este estudo visou a produção e quantificação de enzimas do complexo celulolítico (celulase total, endoglucanase e β-glicosidase) e hemicelulolítico (xilanase), a partir de fermentação em estado sólido utilizando resíduos/produtos agroindustriais como substratos. Neste contexto, a maior atividade enzimática de xilanase foi obtida na presença de farelo de trigo (74,83 U/g de substrato) e de β-glicosidase em farelo de aveia (6,35 U/g de substrato) como substratos/fontes de carbono. Sendo a produção de xilanase em FES a que mais se destacou, algumas características da enzima contida no extrato bruto foram determinadas. Apresentou te... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Prospecting of fungal enzymes has been largely studied in recent years, especially by means of Solid-State Fermentation (SSF). The search for microorganisms' enzymes able to degrade lignocellulosic material, mainly those of filamentous fungi, has attracted interest for application in biotechnological processes, such as in production of cellulosic ethanol from sugarcane bagasse. Aspergillus species are well known for their capability to produce cellulosic and hemicellulosic enzymes complex and the search for strains with this potential is an important challenge. Aspergillus labruscus ITAL 22.223 is a filamentous fungus recently isolated in south of Brazil with unknown potential to produce cellulolytic or hemicellulolytic enzymes. This study aimed the production and quantitation of enzymes of the complex cellulolytic (total cellulose, endoglucanase and and β-glucosidase) and hemicellulolytic (xylanse) obtained under solid-state fermentation using agroindustrial waste and product as substrates. According to this, the greatest enzymatic productions of xylanase (74.83 U/g of substrate) and β-glucosidase (6.35 U/g of substrate) were obtained using wheat bran and oat bran as substrates during SSF fermentation, respectively. Taking in account the best production of xylanase in SSF, some biochemical characteristics were determined for the enzyme contained in the crude extract. Optimal of temperature for enzyme activity was 55ºC and optimal pH was 5.5. Regarding its thermal stability, ... (Complete abstract click electronic access below)
Mestre
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Cuneo, Passalacqua Gian Piero, i Miranda Juan José Ricaldi. "Incremento de la productividad de tabiques de albañilería confinada utilizando el sistema constructivo de bloques apilables en seco y autoencajables Ital Block". Bachelor's thesis, Universidad Peruana de Ciencias Aplicadas (UPC), 2019. http://hdl.handle.net/10757/629501.
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El objetivo principal de la presente investigación es idear un sistema que logre disminuir el costo y el tiempo de elaboración de muros no portantes de albañilería confinada. Para lograrlo se ha diseñado un sistema de bloques de arcilla apilables en seco y autoencajables que cumple con todas las normas imputables.
Para determinar el rendimiento del sistema diseñado se fabricaron las piezas y se construyó un muro con medidas típicas. Los resultados para dicho caso de estudio se resumen en un ahorro de 17% en el costo directo (considerando todo el muro en su conjunto) y 76% en el tiempo empleado (solo en el asentado de bloques).The principal objective of this research is to design a system that manage to reduce the cost and time in the construction of non-structural masonry walls. To achieve this, it has been designed a Mortarless Dry-Stacked Interlocking Masonry Clay Bricks which verifies all the imputable codes. To determine the performance of the system, the bricks were made and a wall with typical measurements was built. The results for this study are 17% of reduction in the direct cost (considering the whole wall) and 76 % less time used (alone in the brick seating).
Tesis
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Leibnitz, Alexander [Verfasser], Oliver [Akademischer Betreuer] Gross i Wolfgang [Akademischer Betreuer] Krick. "Einfluss der Kollagenrezeptoren ITGA2 und DDR1 in der Pathogenese von glomerulären Nierenerkrankungen am Doppelknockout-Tiermodell / Alexander Leibnitz. Gutachter: Oliver Gross ; Wolfgang Krick. Betreuer: Oliver Gross". Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2014. http://d-nb.info/1051977223/34.
Pełny tekst źródłaKsiążki na temat "ITGAL"
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Tiller, Robert. Marina/Ital. Maidenhead: Autodata, 1985.
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Kurisŭdo Taehakkyo (Korea). Nambuk T'onghap Chiwŏn Sent'ŏ, red. Pukhan it'al chumin ŭi ihae. Sŏul-si: Nanum ŭi Chip, 2009.
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(Korea), Sejong Yŏnʾguso, red. Pukhan itʻal chumin taechʻaek yŏnʾgu. Kyŏnggi-do Sŏngnam-si: Sejong Yŏnʾguso, 1998.
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Doğanay, Ezeli. Paket evlilikler: Ithal gelinlerin yakarışları. Cağaloğlu, İstanbul: Profil, 2007.
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1958-, Pak Yŏng-hŭi, red. Pukhan itʻal chumin kajok pokchiron. Sŏul-si: Nanum ŭi Chip, 2008.
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Minsal, Jesús B. Itgul: El guardián de la jungla. Ciudad de La Habana, Cuba: Editorial Gente Nueva, 2014.
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Yŏn'guwŏn, Han'gukhak Chungang, red. 21-segi tiasŭp'ora Pukhan it'al chumin. Kyŏnggi-do Sŏngnam-si: Han'gukhak Chungang Yŏn'guwŏn, 2014.
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1958-, Pak Yŏng-hŭi, red. Pukhan itʻal chumin sahoe pokchi silchʻŏnnon. Sŏul-si: Nanum ŭi Chip, 2008.
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Korea (South). Pŏmmubu. Pŏmmusil. T'ongil Pŏmmukwa. Pukhan it'al chumin kwa pŏmnyul saenghwal. Kwach'on-si: Pŏmmubu Pŏmusil T'ongil Pŏmmukwa, 2009.
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Sŏn-hwa, Kim, Pak Yŏng-hŭi 1958- i Kurisŭdo Taehakkyo (Korea). Nambuk T'onghap Chiwŏn Sent'ŏ, red. Pukhan it'al chumin sahoe pokchi silsŭp. Sŏul-si: Nanum ŭi Chip, 2008.
Znajdź pełny tekst źródłaCzęści książek na temat "ITGAL"
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Appleton, Kathryn M., Ian Cushman, Yuri K. Peterson, Balachandran Manavalan, Shaherin Basith, Sangdun Choi, Akihiro Kimura i in. "Itga4". W Encyclopedia of Signaling Molecules, 984. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4419-0461-4_100673.
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Heino, Jyrki. "Integrin α2 (ITGA2)". W Encyclopedia of Signaling Molecules, 2656–60. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-67199-4_238.
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Heino, Jyrki. "Integrin α1 (ITGA1)". W Encyclopedia of Signaling Molecules, 2653–56. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-67199-4_556.
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Heino, Jyrki. "Integrin α2 (ITGA2)". W Encyclopedia of Signaling Molecules, 1–5. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4614-6438-9_238-1.
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Heino, Jyrki. "Integrin α1 (ITGA1)". W Encyclopedia of Signaling Molecules, 1–4. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4614-6438-9_556-1.
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Appleton, Kathryn M., Ian Cushman, Yuri K. Peterson, Balachandran Manavalan, Shaherin Basith, Sangdun Choi, Akihiro Kimura i in. "Integrin α2 (ITGA2)". W Encyclopedia of Signaling Molecules, 962–66. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4419-0461-4_238.
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Appleton, Kathryn M., Ian Cushman, Yuri K. Peterson, Balachandran Manavalan, Shaherin Basith, Sangdun Choi, Akihiro Kimura i in. "Integrin α1 (ITGA1)". W Encyclopedia of Signaling Molecules, 959–62. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4419-0461-4_556.
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Kerr, Bethany A., i Tatiana V. Byzova. "Integrin Alpha V (ITGAV)". W Encyclopedia of Signaling Molecules, 2634–45. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-67199-4_619.
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Appleton, Kathryn M., Ian Cushman, Yuri K. Peterson, Balachandran Manavalan, Shaherin Basith, Sangdun Choi, Akihiro Kimura i in. "Integrin Alpha V (ITGAV)". W Encyclopedia of Signaling Molecules, 949–59. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4419-0461-4_619.
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Mittelbrunn, Maria, i Francisco Sánchez-Madrid. "Integrin Alpha 4 (Itga 4)". W Encyclopedia of Signaling Molecules, 2630–34. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-67199-4_143.
Pełny tekst źródłaStreszczenia konferencji na temat "ITGAL"
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Khanal, Rajendra, Jovana Markovic, Ruomeng Li, Hildegard Büning, Asha Balakrishnan, Michael Ott i Amar Deep Sharma. "MicroRNA-ITGA6/ Has2 signaling regulates liver fibrosis". W 39. Jahrestagung der Deutschen Arbeitsgemeinschaft zum Studium der Leber. Georg Thieme Verlag, 2023. http://dx.doi.org/10.1055/s-0042-1759913.
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Vlasov, A. P., V. A. Trofimov, S. S. Al-Kubaysi, N. A. Myshkina, T. A. Muratova, L. N. Umnov i M. Yu Khachaturov. "Personalized approach in optimizing the treatment of acute pancreatitis". W VIII Vserossijskaja konferencija s mezhdunarodnym uchastiem «Mediko-fiziologicheskie problemy jekologii cheloveka». Publishing center of Ulyanovsk State University, 2021. http://dx.doi.org/10.34014/mpphe.2021-60-62.
Pełny tekst źródłaStreszczenie:
In order to determine the effectiveness of the use of remaxol based on a personalized approach in patients with acute pancreatitis, based on the establishment of gene polymorphism of integrin beta-3 (T1565C, ITGB3), integrin alpha-2 (C807T, ITGA2), fibrinogen (G(-455)A, FGB) and plasminogen activator inhibitor (5G(-675)4G, SERPINE1), a study of 84 patients with acute pancreatitis of varying severity was conducted. As a result of the study, it was proved that in order to increase the effectiveness of treatment of patients with severe acute pancreatitis upon admission, in addition to clinical, laboratory and instrumental studies, it is necessary to conduct genetic testing of the genotypes of the polymorphism of the GPIIa gene (T1565C), ITGA2 (C807T), FGB (G(-455)A) and SERPINE1 (5G(-675)4G) to develop a personalized approach in the treatment of this severe category of patients.
Key words: acute pancreatitis, genotype, DNA diagnostics, genetic testing of genotypes, personalized medicine.
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Mucha, László, Titanilla Oravecz i Gedeon Totth. "Pálinkafogyasztási szokások Magyarországon". W Társadalmi és gazdasági folyamatok elemzésének kérdései a XXI. században. Szeged: Szegedi Tudományegyetem Gazdaságtudományi Kar, 2020. http://dx.doi.org/10.14232/tgfek21sz.19.
Pełny tekst źródłaStreszczenie:
A pálinka megítélése az elmúlt két évtizedben pozitív irányban változott, a negatív sztereotípiák eltűnőben vannak, sikere töretlen, a fogyasztók számára a pálinka egyre inkább tradíciót, értéket képviselő igazi magyar ital. Jelen tanulmány célja a pálinkához kapcsolódó fogyasztói attitűd komponensek azonosítására irányuló empirikus kutatás szakirodalmi megalapozása. A többlépcsős kutatási folyamat első fázisa a hazai szakirodalom áttekintése, valamint egy 2018- as kvalitatív felmérés értékelése hagyományos tartalomelemzéssel. A pálinkával kapcsolatos attitűdökben az elmúlt 6-10 évben olyan változás történt, ami a pálinka-imázs javulásának lassulását jelentette. Mindenképpen érdemes továbbra is erősíteni a pálinka pozicionálását a minél szélesebb körű ismertség, és elismertség érdekében, hiszen a pálinka értékes alapanyagból előállított hazai szeszes ital, mely kategóriájában értékét tekintve felveszi a versenyt a világszerte elismert konkurens termékekkel.
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Peacock, Danielle L., Luciana P. Schwab i Tiffany N. Seagroves. "Abstract 3885: ITGA6 (CD49F) is directly regulated by hypoxia-inducible factors". W 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.am2014-3885.
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"Предикторная значимость полиморфизмов генов VEGFA, eNOS, IFNL3, IL-6, TP53, ITGA2". W Биоинформатика регуляции и структуры геномов / системная биология. ИЦиГ СО РАН, 2024. http://dx.doi.org/10.18699/bgrs2024-9.2-05.
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Haborets, Olha, i Artem Kushkovyi. "OSINT-Technologies: Applications and Challenges in the Dig-ital Age". W Socratic lectures 10. University of Lubljana Press, 2024. http://dx.doi.org/10.55295/psl.2024.i28.
Pełny tekst źródłaStreszczenie:
Abstract: The article examines the importance and application of open source intelligence tech-nologies (OSINT) in today's digital age. OSINT is defined as the systematic process of gathering and analysing information from open sources to draw informed conclusions and make effective decisions. The application of OSINT-technologies is becoming an integral part of the strategic analytical process in areas such as cyber security, intelli-gence, law enforcement, intelligence and public safety. The main focus of the study is a specific aspect of this broad spectrum – the OSINT Framework, which is a set of tools and resources for collecting and analysing infor-mation from open sources on the Internet. Using this framework allows us to study, monitor and analyse a variety of data to identify patterns, trends and potential threats. The article defines the purpose of scientific research and in-depth analysis of OSINT, in particular the OSINT Framework, with the aim of understanding its structure, func-tionality and effectiveness in solving tasks in the field of intelligence, cyber security and data analysis. The overall state of OSINT-technologies is defined by a wide variety of tools, including social networks, geospatial analysis, textual and visual information analysis, data mining platforms, and ethnographic analysis. The use of scientific methods and tech-nologies in this area allows you to optimize the processes of data collection and analy-sis, providing more insights for making informed decisions. Keywords: OSINT; OSINT Framework; Open source; Data collection and analysis
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Niemeyer, L., C. Thon, J. Bornschein, J. Weigt, P. Malfertheiner i A. Link. "Translationale Relevanz von ITGA5 Expression in präneoplastischen Magenveränderungen und H. pylori Infektion". W Viszeralmedizin 2019. Georg Thieme Verlag KG, 2019. http://dx.doi.org/10.1055/s-0039-1695421.
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Epstein Shochet, G., E. Brook, E. Edelstein, O. Wand, D. A. King i D. Shitrit. "Integrin A5 (ITGA5) Promotes Cellular Responses Facilitating Idiopathic Pulmonary Fibrosis (IPF) Progression". W American Thoracic Society 2019 International Conference, May 17-22, 2019 - Dallas, TX. American Thoracic Society, 2019. http://dx.doi.org/10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a5320.
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Yang, Heng-Yi, i Tian-Ni Mao. "ITGAX: A Potential Biomarker of Acute Myeloid Leukemia (AML) through Bioinformatic Analysis". W 2021 IEEE 9th International Conference on Bioinformatics and Computational Biology (ICBCB). IEEE, 2021. http://dx.doi.org/10.1109/icbcb52223.2021.9459204.
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Scholz, M., I. Wahler, H. Löser, W. Schröder, H. Fuchs, H. Schlösser, A. Quaas, C. Bruns i F. Gebauer. "Integrin alpha V (ITGAV) expression is associated with shortened overall-survival in esophageal adenocarcinoma". W Viszeralmedizin 2021 Gemeinsame Jahrestagung Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Sektion Endoskopie der DGVS, Deutsche Gesellschaft für Allgemein und Viszeralchirurgie (DGAV). Georg Thieme Verlag KG, 2021. http://dx.doi.org/10.1055/s-0041-1733480.
Pełny tekst źródłaRaporty organizacyjne na temat "ITGAL"
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Abbott, D., T. Amatuoni i C. Armstrong. Quasi-free ({ital e,e`p}) reactions: the first look from CEBAF. Office of Scientific and Technical Information (OSTI), listopad 1996. http://dx.doi.org/10.2172/396725.
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Krane, J., J. Barnly i D. Owen. The D-Zero luminosity monitor constant for {radical} {ital s} = 630 GeV. Office of Scientific and Technical Information (OSTI), czerwiec 1997. http://dx.doi.org/10.2172/647025.
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