102 research outputs found

    Buongiorno, documenti : il pregiudizio come strumento di lavoro? Storie di migranti e Polizia Municipale

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    L'incontro tra l'esigenza della gestione del fenomeno migratorio e la precedente presenza, all'interno del sistema del diritto penale italiano, di misure decisamente originali atte alla lotta contro il nemico (Sbriccoli, 1998) hanno dato vita ad uno strano sistema di contrasto dell'immigrazione irregolare in Italia, giocato su ambo i piani del diritto, quello amministrativo e quello penale. L'utilizzo del piano amministrativo permette di intervenire sulla sfera della libert\ue0 personale del migrante aldil\ue0 delle garanzie poste dal diritto penale, mentre grazie all'utilizzo del diritto penale si realizza la sovrapposizione tra criminale e migrante irregolare, e tra questo e il nemico. Ma questo non \ue8 l\u2019unico fattore di complessit\ue0: il controllo dell'immigrazione irregolare in Italia \ue8 in massima parte affidato alle forze di polizia che a loro volta legate a doppio filo al diritto. La polizia, infatti, deve muoversi entro determinati confini tracciati dalle leggi, e allo stesso tempo utilizza quelle leggi come una risorsa utile a risolvere certi urgenti problemi pratici che eventualmente incontra durante l'attivit\ue0 di controllo del territorio. L\u2019ipotesi che verr\ue0 discussa \ue8 la seguente: all'interno del campo definito dalla stretta interdipendenza tra migranti e polizia, per effetto del continuo incontro e scontro tra i due agenti, prende forma il soggetto produttivo/migrante: lo straniero non-europeo irregolarmente presente in Italia ma inserito nel circuito del lavoro informale. Una ricerca da me svolta nel territorio del comune di Bologna, durante la quale migranti e operatori di polizia Municipale sono stati intervistati rispetto al momento del controllo dei documenti, ha messo in luce l'effettiva opera di chirurgia sociale effettuata dalle forze di polizia: attraverso le pratiche utilizzate durante l'attivit\ue0 di controllo e di gestione dell'immigrazione irregolare, gli operatori di polizia tracciano una linea di demarcazione tra il migrante irregolare disfunzionale, inserito nel circuito del lavoro illegale, e il migrante irregolare funzionale, inserito nel circuito dell'economia informale, e indicano a quest'ultimo precisi schemi di comportamento a cui attenersi per poter rimanere entro i confini territoriali, anche senza la \u201cnecessaria\u201d autorizzazione legale Dunque, sebbene in apparenza sembrino sfidare e minacciare il diritto, in realt\ue0 le pratiche di polizia finiscono per cooperare con esso nel produrre forza di lavoro migrante, fondamentale all\u2019interno della struttura economica italiana. Ci\uf2 che emerge \ue8 un meccanismo di disciplinamento \u201cin seconda battuta\u201d del migrante irregolare presente in Italia, parallelo e ulteriore rispetto alla dimensione di ricatto che il migrante regolare, stretto tra permesso di soggiorno e contratto di lavoro, subisce

    BORDERING SUBJECTS. THE UNSPOKEN INCORPORATION OF UNDOCUMENTED MIGRANTS IN ITALY.

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    Socio-legal and criminological research make sense of the mechanisms of border control by taking for granted that the main aim of logic of control is one to exclude, therefore they generally focus on removal procedures. My research takes a different approach: my focus is on the far more frequent conditions under which undocumented migrants are informally allowed to remain despite official permission. Therefore, in looking at the immigration control regimes, my focus will be on undocumented migrants living inside national territories rather than removal procedures. Undocumented migrants are generally seen as resulting from immigration law failing to enforce removal. On the contrary, I argue that undocumented migrants living inside national territories may be seen as the very product of law instead of its failure. In a sense, immigration control regimes are mechanisms that exclude through removal and at the same time processes of production of a new subject, that is, the undocumented migrant living inside national territories despite official permission. This thesis aims to enrich the literature on control by looking at the differential inclusion of those many undocumented migrants living in the territory. Differential inclusion is a concept elaborated by Sandro Mezzadra and Brett Neilson (2013); it is an invitation to look at the mechanisms of inclusion that can involve various degrees of subordination, rule, discrimination, racism, disenfranchisement, exploitation and segmentation. In this line, the foucauldian concept of discipline goes exactly in the direction of acknowledging punishment, specifically imprisonment, as a tool to normalize individuals, in order to make them to conform to the norm and include them in disciplined societies (Foucault, 1977). Hence, inclusion and exclusion are assembled logics. As well as it seems a logic of inclusion the one behind imprisonment, at least at the origin of capitalism and the modern state: prison is aimed at disciplining the individual to labour, at producing the disciplined worker useful for the development of capitalistic economy (Melossi and Pavarini, 1981). My theoretical perspective will move from here. One main concern of the present work is that, even if internal border control relies on similar discourses, power relations, and laws at the global level, I argue that it produce dissimilar outcomes depending on the local context. Therefore, by accepting Saskia Sassen\u2019s invitation to see \u201cthe global inside the national\u201d (Sassen, 2010), my aim is to show that the global logics meet other logics, conditions, and history at the local level, which affects the expected outcomes. On the one hand, the outcomes of global borders control depend on the local level; on the other hand, the local dimension is the only dimension where it is possible to study, recognize and understand even global dynamics. Using a case study of internal border control in Bologna, Italy, I will examine the logics underpinning global border control at the local level, as this may question the logics of global border control often taken for granted. The core of investigation will be the interaction between police and undocumented migrants at the internal borders, that is, once migrants have crossed external borders and live inside the territory. My case study looks at undocumented migrants in Bologna (Italy) continually undergoing police checks, being charged, and even detained. Few are actually removed; the great majority remains and finds their place in the Italian shadow economy. I argue that what we see in Bologna is a logic of subordinated inclusion rather than exclusion, whose main result is the production of a subject who may not completely belong, yet is not completely excluded either. Police are at the core of present investigation, as the Italian immigration law entrusts the control over undocumented immigration to general police (a specific immigration police have never been issued in Italy indeed). Even so, police practices are not taken into consideration alone: what really stands at the core of present research is the interaction between migrants and police. I consider that migrants are not passive subjects in the immigration control regime, but by enacting strategies of resistance, they oppose the police, force them towards negotiation, and contribute to the final results of interaction. The present analysis acknowledges that migrants oppose strategies of subjectivation to the strategies of subjection enacted by the police, which originates that migrants are active agents in the mechanisms of control that produce them as subjects. The conclusions discuss the importance to broaden our consideration of the elements taking part in the immigration control regime. They proposes that immigration penalty is much wider than just removal procedures. They summarize the process of creation of the peculiar subject of the present case study, underling global and local dynamics of power, and it will shed light on the connection between penalty, border, and economy. The process of bordering subjects in the specific case study of this investigation opens up for two additional considerations. 1 the analysis of border control should also take economy into account. 2) the bodies of undocumented migrants are the concrete manifestation of the link between economy and penalty. I argue that the complex processes through which undocumented migrants are produced as subject may be analysed as one segment of \u201cthe discursive interactions of all the actors\u201c (Melossi 2008: 7) which link penalty and economy. The research is aimed at answering the crucial question of how such mechanisms come to be. In fact, rather than as a well-organized and preconceived apparatus, the mechanisms of control is intended as the result of not planned actions of individual actors, who time after time look for the \u201cbest\u201d way to manage the complex situation of undocumented immigration

    Design, synthesis and preliminary biological evaluation of 3-cyclopropyl-4-phenoxy-1H-pyrazole derivatives as small molecular ligands of RAGE

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    Receptor for advanced glycation end products (RAGE) is a multiligand receptor belonging to the immunoglobulin superfamily and plays a crucial role in the development of many human diseases such as neurodegenerative diseases, diabetes, cardiovascular diseases and cancer.1 RAGE is involved in a number of cell processes such as neuroinflammation, apoptosis, proliferation and autophagy, and therefore it is of considerable interest as a promising drug target for innovative therapeutic approaches. It consists of an extracellular region, a short hydrophobic transmembrane spanning region, and a highly charged amino acid cytoplasmatic tail. The extracellular region contains a signal peptide, followed by one N-terminal V-type immunoglobulin domain and two C-type (C1 and C2) immunoglobulin domains.2 RAGE is able to interact with a large number of pro-inflammatory and regulatory molecules, such as advanced glycation end-products (AGEs), quinolinic acid, beta amyloid (A\u3b2), high mobility group box 1 (HMGB1), S100/calgranulin family proteins.3,4 However, due to the structural heterogeneity of these endogenous ligands, little is known about the key pharmacophore elements for ligand-RAGE interaction and the specific mode of binding. On these grounds, we aimed at designing new small molecules able to bind the VC1 extracellular domains of RAGE, in order to clarify the structural features that account for RAGE affinity and activation, and to identify new drug-like compounds. Following a process of structural simplification of known pyrazole-5-carboxamide RAGE ligands,1 we planned a set of novel derivatives characterized by a variously functionalized 3-cyclopropyl-4-phenoxy-1H-pyrazole scaffold (Figure 1). The design and synthesis of the new putative RAGE ligands will be presented and discussed, together with the results of their in vitro screening by means of a surface plasmon resonance (SPR)-based assay to estimate their binding ability to the RAGE extracellular domain. References 1. Bongarzone S., Savickas V., Luzi F., Gee A. D. J. Med. Chem. 2017, 60, 7213-7232. 2. Hudson B. I., Carter A. M., Harja E., Kalea A. Z., Arriero M., Yang H., Grant P. J., Schmidt A. M. FASEB J. 2008, 22, 1572-1580. 3. Xue J., Rai V., Singer D., Chabierski S., Xie J., Reverdatto S., Burz D. S., Schmidt A. M., Hoffmann R., Shekhtman A. Structure 2011, 19, 722\u2013732. 4. Koch M., Chitayat S., Dattilo B. M., Schiefner A., Diez J., Chazin W. J., Fritz, G. Structure 2010, 18, 1342-1352

    Targeting SMYD3 to sensitize homologous recombination-proficient tumors to PARP-mediated synthetic lethality

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    SMYD3 is frequently overexpressed in a wide variety of cancers. Indeed, its inactivation reduces tumor growth in preclinical in vivo animal models. However, extensive characterization in vitro failed to clarify SMYD3 function in cancer cells, although confirming its importance in carcinogenesis. Taking advantage of a SMYD3 mutant variant identified in a high-risk breast cancer family, here we show that SMYD3 phosphorylation by ATM enables the formation of a multiprotein complex including ATM, SMYD3, CHK2, and BRCA2, which is required for the final loading of RAD51 at DNA double-strand break sites and completion of homologous recombination (HR). Remarkably, SMYD3 pharmacological inhibition sensitizes HR-proficient cancer cells to PARP inhibitors, thereby extending the potential of the synthetic lethality approach in human tumors

    Ribonucleoprotein Particles Containing Non-Coding Y RNAs, Ro60, La and Nucleolin Are Not Required for Y RNA Function in DNA Replication

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    BACKGROUND: Ro ribonucleoprotein particles (Ro RNPs) consist of a non-coding Y RNA bound by Ro60, La and possibly other proteins. The physiological function of Ro RNPs is controversial as divergent functions have been reported for its different constituents. We have recently shown that Y RNAs are essential for the initiation of mammalian chromosomal DNA replication, whereas Ro RNPs are implicated in RNA stability and RNA quality control. Therefore, we investigate here the functional consequences of RNP formation between Ro60, La and nucleolin proteins with hY RNAs for human chromosomal DNA replication. METHODOLOGY/PRINCIPAL FINDINGS: We first immunoprecipitated Ro60, La and nucleolin together with associated hY RNAs from HeLa cytosolic cell extract, and analysed the protein and RNA compositions of these precipitated RNPs by Western blotting and quantitative RT-PCR. We found that Y RNAs exist in several RNP complexes. One RNP comprises Ro60, La and hY RNA, and a different RNP comprises nucleolin and hY RNA. In addition about 50% of the Y RNAs in the extract are present outside of these two RNPs. Next, we immunodepleted these RNP complexes from the cytosolic extract and tested the ability of the depleted extracts to reconstitute DNA replication in a human cell-free system. We found that depletion of these RNP complexes from the cytosolic extract does not inhibit DNA replication in vitro. Finally, we tested if an excess of recombinant pure Ro or La protein inhibits Y RNA-dependent DNA replication in this cell-free system. We found that Ro60 and La proteins do not inhibit DNA replication in vitro. CONCLUSIONS/SIGNIFICANCE: We conclude that RNPs containing hY RNAs and Ro60, La or nucleolin are not required for the function of hY RNAs in chromosomal DNA replication in a human cell-free system, which can be mediated by Y RNAs outside of these RNPs. These data suggest that Y RNAs can support different cellular functions depending on associated proteins

    A genomic island in Vibrio cholerae with VPI-1 site-specific recombination characteristics contains CRISPR-Cas and type VI secretion modules.

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    Cholera is a devastating diarrhoeal disease caused by certain strains of serogroup O1/O139 Vibrio cholerae. Mobile genetic elements such as genomic islands (GIs) have been pivotal in the evolution of O1/O139 V. cholerae. Perhaps the most important GI involved in cholera disease is the V. cholerae pathogenicity island 1 (VPI-1). This GI contains the toxin-coregulated pilus (TCP) gene cluster that is necessary for colonization of the human intestine as well as being the receptor for infection by the cholera-toxin bearing CTX phage. In this study, we report a GI (designated GIVchS12) from a non-O1/O139 strain of V. cholerae that is present in the same chromosomal location as VPI-1, contains an integrase gene with 94% nucleotide and 100% protein identity to the VPI-1 integrase, and attachment (att) sites 100% identical to those found in VPI-1. However, instead of TCP and the other accessory genes present in VPI-1, GIVchS12 contains a CRISPR-Cas element and a type VI secretion system (T6SS). GIs similar to GIVchS12 were identified in other V. cholerae genomes, also containing CRISPR-Cas elements and/or T6SS's. This study highlights the diversity of GIs circulating in natural V. cholerae populations and identifies GIs with VPI-1 recombination characteristics as a propagator of CRISPR-Cas and T6SS modules

    Insight into the Regulation of Glycan Synthesis in Drosophila Chaoptin Based on Mass Spectrometry

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    BACKGROUND: A variety of N-glycans attached to protein are known to involve in many important biological functions. Endoplasmic reticulum (ER) and Golgi localized enzymes are responsible to this template-independent glycan synthesis resulting glycoforms at each asparagine residues. The regulation mechanism such glycan synthesis remains largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: In order to investigate the relationship between glycan structure and protein conformation, we analyzed a glycoprotein of Drosophila melanogaster, chaoptin (Chp), which is localized in photoreceptor cells and is bound to the cell membrane via a glycosylphosphatidylinositol anchor. Detailed analysis based on mass spectrometry revealed the presence of 13 N-glycosylation sites and the composition of the glycoform at each site. The synthetic pathway of glycans was speculated from the observed glycan structures and the composition at each N-glycosylation site, where the presence of novel routes were suggested. The distribution of glycoforms on a Chp polypeptide suggested that various processing enzymes act on the exterior of Chp in the Golgi apparatus, although virtually no enzyme can gain access to the interior of the horseshoe-shaped scaffold, hence explaining the presence of longer glycans within the interior. Furthermore, analysis of Chp from a mutant (RNAi against dolichyl-phosphate alpha-d-mannosyltransferase), which affects N-glycan synthesis in the ER, revealed that truncated glycan structures were processed. As a result, the distribution of glycoforms was affected for the high-mannose-type glycans only, whereas other types of glycans remained similar to those observed in the control and wild-type. CONCLUSIONS/SIGNIFICANCE: These results indicate that glycan processing depends largely on the backbone structure of the parent polypeptide. The information we obtained can be applied to other members of the LRR family of proteins

    Identification of Genes Required for Neural-Specific Glycosylation Using Functional Genomics

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    Glycosylation plays crucial regulatory roles in various biological processes such as development, immunity, and neural functions. For example, Ξ±1,3-fucosylation, the addition of a fucose moiety abundant in Drosophila neural cells, is essential for neural development, function, and behavior. However, it remains largely unknown how neural-specific Ξ±1,3-fucosylation is regulated. In the present study, we searched for genes involved in the glycosylation of a neural-specific protein using a Drosophila RNAi library. We obtained 109 genes affecting glycosylation that clustered into nine functional groups. Among them, members of the RNA regulation group were enriched by a secondary screen that identified genes specifically regulating Ξ±1,3-fucosylation. Further analyses revealed that an RNA–binding protein, second mitotic wave missing (Swm), upregulates expression of the neural-specific glycosyltransferase FucTA and facilitates its mRNA export from the nucleus. This first large-scale genetic screen for glycosylation-related genes has revealed novel regulation of fucTA mRNA in neural cells

    Progress on lead-free metal halide perovskites for photovoltaic applications: a review

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    ABSTRACT: Metal halide perovskites have revolutionized the field of solution-processable photovoltaics. Within just a few years, the power conversion efficiencies of perovskite-based solar cells have been improved significantly to over 20%, which makes them now already comparably efficient to silicon-based photovoltaics. This breakthrough in solution-based photovoltaics, however, has the drawback that these high efficiencies can only be obtained with lead-based perovskites and this will arguably be a substantial hurdle for various applications of perovskite-based photovoltaics and their acceptance in society, even though the amounts of lead in the solar cells are low. This fact opened up a new research field on lead-free metal halide perovskites, which is currently remarkably vivid. We took this as incentive to review this emerging research field and discuss possible alternative elements to replace lead in metal halide perovskites and the properties of the corresponding perovskite materials based on recent theoretical and experimental studies. Up to now, tin-based perovskites turned out to be most promising in terms of power conversion efficiency; however, also the toxicity of these tin-based perovskites is argued. In the focus of the research community are other elements as well including germanium, copper, antimony, or bismuth, and the corresponding perovskite compounds are already showing promising properties. GRAPHICAL ABSTRACT: [Image: see text
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