The role of TGF-alpha in resistance to mesothelioma chemotherapy

Diverse speeche and writing (2012)

Role of TGF-beta1-independent changes in protein neosynthesis, p38alphaMAPK, and cdc42 in hydrogen peroxide-induced senescence-like morphogenesis.

in Free Radical Biology & Medicine (2008), 44(9), 1732-51

The role of TGF-beta1 in hydrogen peroxide-induced senescence-like morphogenesis has been described. The aim of this work was to investigate whether TGF-beta1-independent changes in protein synthesis are ... [more ▼]

The role of TGF-beta1 in hydrogen peroxide-induced senescence-like morphogenesis has been described. The aim of this work was to investigate whether TGF-beta1-independent changes in protein synthesis are involved in this morphogenesis and to study possible mechanisms occurring earlier than TGF-beta1 overexpression. Among the multiple TGF-beta1-independent changes in protein neosynthesis, followed or not by posttranslational modifications, identified by proteomic analysis herein, those of ezrin, L-caldesmon, and HSP27 were particularly studied. Rho-GTPase cdc42 was shown to be responsible for p38(MAPK) activation, in turn triggering phosphorylation of L-caldesmon and HSP27. Cdc42 was also shown to be mainly responsible for the increase in TGF-beta1 mRNA level observed at 24 h after treatment with H(2)O(2) and onward. This study further clarified the mechanisms of senescence-like morphogenesis in addition to the previously demonstrated role of TGF-beta1 signaling pathways. [less ▲]

The role of the bovine growth hormone receptor and prolactin receptor genes in milk, fat and protein production in Finnish Ayrshire dairy cattle

in Genetics (2006), 173(4), 2151-2164

We herein report new evidence that the QTL effect on chromosome 20 in Finnish Ayrshire can be explained by variation in two distinct genes, growth hormone receptor (GHR) and prolactin receptor (PRLR). In ... [more ▼]

We herein report new evidence that the QTL effect on chromosome 20 in Finnish Ayrshire can be explained by variation in two distinct genes, growth hormone receptor (GHR) and prolactin receptor (PRLR). In a previous study in Holstein-Friesian dairy cattle an F279Y polymorphism in the transmembrane domain of GHR was found to be associated with an effect on milk yield and composition. The result of our multimarker regression analysis suggests that in Finnish Ayrshire two QTL segregate on the chromosomal region including GHR and PRLR. By sequencing the coding sequences of GHR and PRLR and the sequence of three GHR promoters from the pooled samples of individuals of known QTL genotype, we identified two substitutions that were associated with milk production traits: the previously reported F-to-Y substitution in the transmembrane domain of GHR and an S-to-N substitution in the signal peptide of PRLR. The results provide strong evidence that the effect of PRLR S18N polymorphism is distinct from the GHR F279Y effect. In particular, the GHR F279Y has the highest influence on protein percentage and fat percentage while PRLR S18N markedly influences protein and fat yield. Furthermore, an interaction between the two loci is suggested. [less ▲]

The role of the cell coat in palatal shelves adhesion

in Lectins Biology, Biochemistry, Clinical Biochemistry (1982)

Role of the Conserved Amino Acids of the 'Sdn' Loop (Ser130, Asp131 and Asn132) in a Class a Beta-Lactamase Studied by Site-Directed Mutagenesis

in Biochemical Journal (1990), 271(2), 399-406

Ser130, Asp131 and Asn132 ('SDN') are highly conserved residues in class A beta-lactamases forming one wall of the active-site cavity. All three residues of the SDN loop in Streptomyces albus G beta ... [more ▼]

Ser130, Asp131 and Asn132 ('SDN') are highly conserved residues in class A beta-lactamases forming one wall of the active-site cavity. All three residues of the SDN loop in Streptomyces albus G beta-lactamase were modified by site-directed mutagenesis. The mutant proteins were expressed in Streptomyces lividans, purified from culture supernatants and their kinetic parameters were determined for several substrates. Ser130 was substituted by Asn, Ala and Gly. The first modification yielded an almost totally inactive protein, whereas the smaller-side-chain mutants (A and G) retained some activity, but were less stable than the wild-type enzyme. Ser130 might thus be involved in maintaining the structure of the active-site cavity. Mutations of Asp131 into Glu and Gly proved to be highly detrimental to enzyme stability, reflecting significant structural perturbations. Mutation of Asn132 into Ala resulted in a dramatically decreased enzymic activity (more than 100-fold) especially toward cephalosporin substrates, kcat. being the most affected parameter, which would indicate a role of Asn132 in transition-state stabilization rather than in ground-state binding. Comparison of the N132A and the previously described N132S mutant enzymes underline the importance of an H-bond-forming residue at position 132 for the catalytic process. [less ▲]

The Role of the European Court of Justice

in Zwaan, Karin (Ed.) The Qualification Directive: Central Themes, Problems Issues and Implementation in Selected Member States (2007)

Role of the Focal Adhesion Protein Kindlin-1 in Breast Cancer Growth and Lung Metastasis.

in Journal of the National Cancer Institute (2011), 103

Background Fermitin family member 1 (FERMT1, Kindlin-1) is an epithelial-specific regulator of integrin functions and is associated with Kindler syndrome, a genetic disorder characterized by skin ... [more ▼]

Background Fermitin family member 1 (FERMT1, Kindlin-1) is an epithelial-specific regulator of integrin functions and is associated with Kindler syndrome, a genetic disorder characterized by skin blistering, atrophy, and photosensitivity. However, the possible role of kindlin-1 in cancer remains unknown. Methods Kindlin-1 expression was quantified in several human cancers using quantitative real-time polymerase chain reaction and published microarray datasets. The association between kindlin-1 expression and patient metastasis-free survival (N = 516) was assessed with Kaplan-Meier analyses. Effects of ectopic expression or silencing of kindlin-1 on cell signaling, migration, and invasion were assessed in human breast cancer cell lines using western blotting, immunofluorescence, wound healing assays, and invasion on Matrigel or type I collagen substrates. Breast tumor growth and lung metastasis were evaluated in 12-week-old female BALB/c mice (10 controls and six Kindlin-1-knockdown mice). All statistical tests were two-sided. Results Kindlin-1 expression was consistently higher in tumors than in normal tissues in various cancer types metastasizing to the lungs, including colon and bladder cancer. Kindlin-1 expression was associated with metastasis-free survival in both breast and lung adenocarcinoma (breast cancer: hazard ratio of lung metastasis = 2.55, 95% confidence intervals [CI] = 1.39 to 4.69, P = .001; lung cancer: hazard ratio of metastasis = 1.96, 95% CI = 1.25 to 3.07, P = .001). Overexpression of kindlin-1 induced changes indicating epithelial-mesenchymal transition and transforming growth factor beta (TGFbeta) signaling, constitutive activation of cell motility, and invasion (number of migrating cells, Kindlin-1 cells vs control, mean = 164.66 vs 19.00, difference = 145.6, 95% CI = 79.1 to 212.2, P = .004; invasion rate, Kindlin-1-cells vs control = 9.65% vs 1.92%, difference = 7.73%, 95% CI = 4.75 to 10.70, P < .001). Finally, Kindlin-1 depletion in an orthotopic mouse model statistically significantly inhibited breast tumor growth (P < .001) and lung metastasis (P = .003). Conclusion These results suggest a role for kindlin-1 in breast cancer lung metastasis and lung tumorigenesis and advance our understanding of kindlin-1 as a regulator of TGFbeta signaling, offering new avenues for therapeutic intervention against cancer progression. [less ▲]

The Role of the Iberian States on the EU-LA Interregionalism

in Söderbaum, Fredrik; Baert, Francis; Scaramagli, Tiziana (Eds.) Intersecting Inter-Regionalism, New Regionalism, Multilateralism and the EU (in press)

La présente contribution se penche sur le rôle des Etats européens dans la construction de la stratégie de l'UE à l'égard de l'Amérique latine. Les pays ibériques et plus particulièrement l'Espagne ... [more ▼]

La présente contribution se penche sur le rôle des Etats européens dans la construction de la stratégie de l'UE à l'égard de l'Amérique latine. Les pays ibériques et plus particulièrement l'Espagne constituent les interfaces entre l'Europe communautaire et l'Amérique latine. [less ▲]

The role of the insurance industry in piloting private sector security and prevention policy

in European Journal on Criminal Policy and Research (1995), 3.1

Role Of The Lid Hydrophobicity Pattern In Pancreatic Lipase Activity

in Journal of Biological Chemistry (2005), 280(48), 40074-83

Pancreatic lipase is a soluble globular protein that must undergo structural modifications before it can hydrolyze oil droplets coated with bile salts. The binding of colipase and movement of the lipase ... [more ▼]

Pancreatic lipase is a soluble globular protein that must undergo structural modifications before it can hydrolyze oil droplets coated with bile salts. The binding of colipase and movement of the lipase lid open access to the active site. Mechanisms triggering lid mobility are unclear. The *KNILSQIVDIDGI* fragment of the lid of the human pancreatic lipase is predicted by molecular modeling to be a tilted peptide. Tilted peptides are hydrophobicity motifs involved in membrane fusion and more globally in perturbations of hydrophobic/hydrophilic interfaces. Analysis of this lid fragment predicts no clear consensus of secondary structure that suggests that its structure is not strongly sequence determined and could vary with environment. Point mutations were designed to modify the hydrophobicity profile of the [240-252] fragment and their consequences on the lipase-mediated catalysis were tested. Two mutants, in which the tilted peptide motif was lost, also have poor activity on bile salt-coated oil droplets and cannot be reactivated by colipase. Conversely, one mutant in which a different tilted peptide is created retains colipase dependence. These results suggest that the tilted hydrophobicity pattern of the [240-252] fragment is neither important for colipase binding to lipase, nor for interfacial binding but is important to trigger the maximal catalytic efficiency of lipase in the presence of bile salt. [less ▲]