The Symbolic Legitimation of the European Union : Patterns and Problems

Despite the European Union\u2019s economic and institutional importance, its citizens lack a widespread feeling of belonging that binds them together and provides the EU with integrative force. This problem is at the core of Foret\u2019s book, Religion and Politics in the European Union [2015, New York: Cambridge University Press], which conceptualizes European secularism as capable of covering the EU\u2019s polity system with a \u201csecular canopy\u201d that makes it worthy of respect. This paper examines the possibilities and limits of a founding narrative for the European Union in light of symbols and rituals representing the EU and its integration process

Optical coherence tomography angiography in Tuberous sclerosis complicated with macular choroidal neovascularization

This study describe the optical coherence tomography angiography (OCTA) features of a young patient with Tuberous sclerosis complicated with CNV unilateral macular choroidal neovascularization during the ranibizumab therapy. OCTA scans of macular region of right eye, revealed a dense microvascular network confirming the diagnosis of CNV. After four monthly intravitreal injections, OCTA revealed a decrease of size and activity of CNV. OCTA is a valid, non-invasive, dyeless, and reliable method that could improve the diagnosis and management of CNV in child with Tuberous sclerosis

Management of patients with Graves' disease and orbital involvement: role of spectral domain optical coherence tomography

PURPOSE: To investigate the role of choroidal thickness evaluation with spectral domain optical coherence tomography (SDOCT) and enhanced depth imaging (EDI) technique in the management of patients with Graves' disease and orbitopathy (GO). METHODS: Thirty-six eyes of 18 patients with GO and 36 eyes of 18 age-matched control subjects were included in this retrospective observational study. All the subjects underwent a complete ophthalmological evaluation, including clinical activity score (CAS) and exophthalmometry. The SDOCT images of the choroid were obtained by EDI modality. RESULTS: Choroidal thickness was significantly increased in GO than in control eyes (p < 0.01). A significant correlation was found between choroidal thickness and CAS, proptosis, and the duration of disease (p < 0.05). CONCLUSION: This study shows that choroidal thickness, evaluated with EDI-OCT, is significantly increased in patients with GO and correlates with the activity of the disease, proptosis, and duration of the disease. The choroidal thickening may reflect the ocular hemodynamic changes, and enhanced depth imaging optical coherence tomography may be a useful tool for the evaluation of orbital congestion and management of patients with Graves' disease and orbital involvement

Experimental characterization of the interaction between the n-terminal sh3 domain of crkl and c3g

Crkl is a protein involved in the onset of several cancer pathologies that exerts its function only through its protein–protein interaction domains, a SH2 domain and two SH3 domains. SH3 domains are small protein interaction modules that mediate the binding and recognition of proline-rich sequences. One of the main physiological interactors of Crkl is C3G (also known as RAPGEF1), an interaction with key implications in regulating cellular growth and differentiation, cell morphogenesis and adhesion processes. Thus, understanding the interaction between Crkl and C3G is fundamental to gaining information about the molecular determinants of the several cancer pathologies in which these proteins are involved. In this paper, through a combination of fast kinetics at different experimental conditions and site-directed mutagenesis, we characterize the binding reaction between the N-SH3 domain of Crkl and a peptide mimicking a specific portion of C3G. Our results show a clear effect of pH on the stability of the complex, due to the protonation of negatively charged residues in the binding pocket of N-SH3. Our results are discussed under the light of previous work on SH3 domains

Variability in Floral Scent in Rewarding and Deceptive Orchids: The Signature of Pollinator-imposed Selection?

Background and Aims A comparative investigation was made of floral scent variation in the closely related, food-rewarding Anacamptis coriophora and the food-deceptive Anacamptis morio in order to identify patterns of variability of odour compounds in the two species and their role in pollinator attraction/avoidance learning. Methods Scent was collected from plants in natural populations and samples were analysed via quantitative gas chromatography and mass spectrometry. Combined gas chromatography and electroantennographic detection was used to identify compounds that are detected by the pollinators. Experimental reduction of scent variability was performed in the field with plots of A. morio plants supplemented with a uniform amount of anisaldehyde. Key Results Both orchid species emitted complex odour bouquets. In A. coriophora the two main benzenoid compounds, hydroquinone dimethyl ether (1,4-dimethoxybenzene) and anisaldehyde (methoxybenzaldehyde), triggered electrophysiological responses in olfactory neurons of honey-bee and bumble-bee workers. The scent of A. morio, however, was too weak to elicit any electrophysiological responses. The overall variation in scent was significantly lower in the rewarding A. coriophora than in the deceptive A. morio, suggesting pollinator avoidance-learning selecting for high variation in the deceptive species. A. morio flowers supplemented with non-variable scent in plot experiments, however, did not show significantly reduced pollination success. Conclusions Whereas in the rewarding A. coriophora stabilizing selection imposed by floral constancy of the pollinators may reduce scent variability, in the deceptive A. morio the emitted scent seems to be too weak to be detected by pollinators and thus its high variability may result from relaxed selection on this floral trai

Unveiling induced folding of intrinsically disordered proteins – Protein engineering, frustration and emerging themes

Intrinsically disordered proteins (IDPs) can be generally described as a class of proteins that lack a well-defined ordered structure in isolation at physiological conditions. Upon binding to their physiological ligands, IDPs typically undergo a disorder-to-order transition, which may or may not lead to the complete folding of the IDP. In this short review, we focus on some of the key findings pertaining to the mechanisms of such induced folding. In particular, first we describe the general features of the reaction; then, we discuss some of the most remarkable findings obtained from applying protein engineering in synergy with kinetic studies to induced folding; and finally, we offer a critical view on some of the emerging themes when considering the structural heterogeneity of IDPs vis-à-vis to their inherent frustration

Determining folding and binding properties of the C-terminal SH2 domain of SHP2

SH2 domains are a class of protein–protein interaction modules with the function to recognize and bind sequences characterized by the presence of a phosphorylated tyrosine. SHP2 is a protein phosphatase involved in the Ras-ERK1/2 signaling pathway that possess two SH2 domains, namely, N-SH2 and C-SH2, that mediate the interaction of SHP2 with various partners and determine the regulation of its catalytic activity. One of the main interactors of the SH2 domains of SHP2 is Gab2, a scaffolding protein with critical role in determining cell differentiation. Despite their key biological role and the importance of a correct native fold to ensure it, the mechanism of binding of SH2 domains with their ligands and the determinants of their stability have been poorly characterized. In this article, we present a comprehensive kinetic study of the folding of the C-SH2 domain and the binding mechanism with a peptide mimicking a region of Gab2. Our data, obtained at different pH and ionic strength conditions and supported by site-directed mutagenesis, highlight the role of electrostatic interactions in the early events of recognition. Interestingly, our results suggest a key role of a highly conserved histidine residue among SH2 family in the interaction with negative charges carried by the phosphotyrosine of Gab2. Moreover, the analysis of the equilibrium and kinetic folding data of C-SH2 describes a complex mechanism implying a change in rate-limiting step at high denaturant concentrations. Our data are discussed under the light of previous works on N-SH2 domain of SHP2 and other SH2 domains

On the Effects of Disordered Tails, Supertertiary Structure and Quinary Interactions on the Folding and Function of Protein Domains

The vast majority of our current knowledge about the biochemical and biophysical properties of proteins derives from in vitro studies conducted on isolated globular domains. However, a very large fraction of the proteins expressed in the eukaryotic cell are structurally more complex. In particular, the discovery that up to 40% of the eukaryotic proteins are intrinsically disordered, or possess intrinsically disordered regions, and are highly dynamic entities lacking a well-defined three-dimensional structure, revolutionized the structure–function paradigm and our understanding of proteins. Moreover, proteins are mostly characterized by the presence of multiple domains, in-fluencing each other by intramolecular interactions. Furthermore, proteins exert their function in a crowded intracellular milieu, transiently interacting with a myriad of other macromolecules. In this review we summarize the literature tackling these themes from both the theoretical and experimental perspectives, highlighting the effects on protein folding and function that are played by (i) flanking disordered tails; (ii) contiguous protein domains; (iii) interactions with the cellular environment, defined as quinary structures. We show that, in many cases, both the folding and function of protein domains is remarkably perturbed by the presence of these interactions, pinpointing the importance to increase the level of complexity of the experimental work and to extend the efforts to characterize protein domains in more complex contexts