107 research outputs found

    Writing under the influence: The fiction of the artist under contract in novels of organized crime from Italy and Mexico

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    Fiction writers have sought to provide original descriptions of the mafia's obscure and changing worlds and reflect on their own representational strategies by using metaliterary devices. In Yuri Herrera’s Trabajos del reino (2004), Walter Siti’s Resistere non serve a niente (2012) and Víctor Hugo Rascón Banda’s Contrabando (2008), the representation of the artist under contract with organized crime provides a narrative content and a metaliterary figure which can help us make sense of the complex relationship between literary fiction and organized crime. The artist under contract is shown to put their own credibility at risk and reflect from a position of fragility and dependence. From the intra-diegetic representation of an author under contract with organized crime—a key aspect of Herrera’s Trabajos del reino—, to the blurring of the autobiographical pact with the reader in Resistere non serve a niente and Contrabando, this article asks how authors creatively question the credibility and the authority of their own literary discourse on organized crime? Through the study of the contractual aspects of the literary text (as an intra-diegetic component and a constitutive element of the autofiction genre), the article discusses the hermeneutic value of fiction: is there a productive use of ambiguity that can facilitate the interpretation of the secretive and ambiguous worlds of organized crime

    PIP30/FAM192A is a novel regulator of the nuclear proteasome activator PA28Îł

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    PA28Îł is a nuclear activator of the 20S proteasome involved in the regulation of several essential cellular processes, such as cell proliferation, apoptosis, nuclear dynamics, and cellular stress response. Unlike the 19S regulator of the proteasome, which specifically recognizes ubiquitylated proteins, PA28Îł promotes the degradation of several substrates by the proteasome in an ATP- and ubiquitin-independent manner. However, its exact mechanisms of action are unclear and likely involve additional partners that remain to be identified. Here we report the identification of a cofactor of PA28Îł, PIP30/FAM192A. PIP30 binds directly and specifically via its C-terminal end and in an interaction stabilized by casein kinase 2 phosphorylation to both free and 20S proteasome-associated PA28Îł. Its recruitment to proteasome-containing complexes depends on PA28Îł and its expression increases the association of PA28Îł with the 20S proteasome in cells. Further dissection of its possible roles shows that PIP30 alters PA28Îł-dependent activation of peptide degradation by the 20S proteasome in vitro and negatively controls in cells the presence of PA28Îł in Cajal bodies by inhibition of its association with the key Cajal body component coilin. Taken together, our data show that PIP30 deeply affects PA28Îł interactions with cellular proteins, including the 20S proteasome, demonstrating that it is an important regulator of PA28Îł in cells and thus a new player in the control of the multiple functions of the proteasome within the nucleus

    Identification of the Sex Pheromone of a Protected Species, the Spanish Moon Moth Graellsia isabellae

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    Sex attractant pheromones are highly sensitive and selective tools for detecting and monitoring populations of insects, yet there has been only one reported case of pheromones being used to monitor protected species. Here, we report the identification and synthesis of the sex pheromone of a protected European moth species, Graellsia isabellae (Lepidoptera: Saturniidae), as the single component, (4E,6E,11Z)-hexadecatrienal. In preliminary field trials, lures loaded with this compound attracted male moths from populations of this species at a number of widely separated field sites in France, Switzerland, and Spain, clearly demonstrating the utility of pheromones in sampling potentially endangered insect species

    Dynamics of human replication factors in the elongation phase of DNA replication

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    In eukaryotic cells, DNA replication is carried out by coordinated actions of many proteins, including DNA polymerase ÎŽ (pol ÎŽ), replication factor C (RFC), proliferating cell nuclear antigen (PCNA) and replication protein A. Here we describe dynamic properties of these proteins in the elongation step on a single-stranded M13 template, providing evidence that pol ÎŽ has a distributive nature over the 7 kb of the M13 template, repeating a frequent dissociation–association cycle at growing 3â€Č-hydroxyl ends. Some PCNA could remain at the primer terminus during this cycle, while the remainder slides out of the primer terminus or is unloaded once pol ÎŽ has dissociated. RFC remains around the primer terminus through the elongation phase, and could probably hold PCNA from which pol ÎŽ has detached, or reload PCNA from solution to restart DNA synthesis. Furthermore, we suggest that a subunit of pol ÎŽ, POLD3, plays a crucial role in the efficient recycling of PCNA during dissociation–association cycles of pol ÎŽ. Based on these observations, we propose a model for dynamic processes in elongation complexes

    PCNA dependent cellular activities tolerate dramatic perturbations in PCNA client interactions

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    Proliferating cell nuclear antigen (PCNA) is an essential cofactor for DNA replication and repair, recruiting multiple proteins to their sites of action. We examined the effects of the PCNA(S228I) mutation that causes PCNA-associated DNA repair disorder (PARD). Cells from individuals affected by PARD are sensitive to the PCNA inhibitors T3 and T2AA, showing that the S228I mutation has consequences for undamaged cells. Analysis of the binding between PCNA and PCNA-interacting proteins (PIPs) shows that the S228I change dramatically impairs the majority of these interactions, including that of Cdt1, DNMT1, PolD3(p66) and PolD4(p12). In contrast p21 largely retains the ability to bind PCNA(S228I). This property is conferred by the p21 PIP box sequence itself, which is both necessary and sufficient for PCNA(S228I) binding. Ubiquitination of PCNA is unaffected by the S228I change, which indirectly alters the structure of the inter-domain connecting loop. Despite the dramatic in vitro effects of the PARD mutation on PIP-degron binding, there are only minor alterations to the stability of p21 and Cdt1 in cells from affected individuals. Overall our data suggests that reduced affinity of PCNA(S228I) for specific clients causes subtle cellular defects in undamaged cells which likely contribute to the etiology of PARD

    Characterization of Human DNA Polymerase Delta and Its Subassemblies Reconstituted by Expression in the Multibac System

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    Mammalian DNA polymerase ÎŽ (Pol ÎŽ), a four-subunit enzyme, plays a crucial and versatile role in DNA replication and DNA repair processes. We have reconstituted human Pol ÎŽ complexes in insect cells infected with a single baculovirus into which one or more subunits were assembled. This system allowed for the efficient expression of the tetrameric Pol ÎŽ holoenzyme, the p125/p50 core dimer, the core+p68 trimer and the core+p12 trimer, as well as the p125 catalytic subunit. These were isolated in milligram amounts with reproducible purity and specific activities by a highly standardized protocol. We have systematically compared their activities in order to gain insights into the roles of the p12 and p68 subunits, as well as their responses to PCNA. The relative specific activities (apparent kcat) of the Pol ÎŽ holoenzyme, core+p68, core+p12 and p125/p50 core were 100, 109, 40, and 29. The corresponding apparent Kd's for PCNA were 7.1, 8.7, 9.3 and 73 nM. Our results support the hypothesis that Pol ÎŽ interacts with PCNA through multiple interactions, and that there may be a redundancy in binding interactions that may permit Pol ÎŽ to adopt flexible configurations with PCNA. The abilities of the Pol ÎŽ complexes to fully extend singly primed M13 DNA were examined. All the subassemblies except the core+p68 were defective in their abilities to completely extend the primer, showing that the p68 subunit has an important function in synthesis of long stretches of DNA in this assay. The core+p68 trimer could be reconstituted by addition of p12

    Autoantibodies against type I IFNs in humans with alternative NF-ÎșB pathway deficiency

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    Structure, thermicité et évolution géodynamique de la Zone Interne Métamorphique des Pyrénées

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    The understanding of the processes and scenarios of the inversion of extensional systems, and more specifically of hyper-extended margins, in collision thrust belts is a major issue. The intracontinental belt of the Pyrenees is an example of inversion of hyper-extended margins, associated with a HT-LP metamorphism and then integrated within the orogenic wedge. The first part of this study is focused on the distribution of the HT-LP metamorphism associated with rifting and the exhumation of lithospheric mantle. A new set of TRSCM data allows the recognition of the geometry of the IMZ, characterized with temperature ranging from 400 to 630°C and shows the absence of a regional gradient at this scale. This study then shows significant temperature gaps across major faults and distinguishes lateral temperature gradients at the scale of the different basins constituting the IMZ, especially in the westernmost part of the belt, in the Nappe des Marbres Basin. This part of the study moreover shows the importance of a salt tectonics prior to the HT-LP metamorphism. The second part shows the existence of three main tectonics phases during the Pyrenean orogeny and the role played by the Late Triassic evaporites as a decollement level in the generalized allochthony of the IMZ. A left-lateral component along the main faults within and along the boundaries of the North Pyrenean Zone (ZNP) is also shown. The interpretation of these observations is that the IMZ and ZNP form a single tectonic unit, decoupled from the Variscan basement by the decollement in the Late Triassic deposits and displaced above shallow-dipping thrust faults inherited from the rifting episode, during the first stages of the convergence. Deformation mode is then thin-skinned and becomes thick-skinned when the two paleomargins collide, with the development of major steeper faults linked with the exhumation of basement blocks (North Pyrenean Massifs) that dissected the IMZ.La comprĂ©hension des processus et des modalitĂ©s de l’inversion des systĂšmes extensifs et plus particuliĂšrement les domaines de marges amincies, dans les chaines de collision est un enjeu majeur. La chaĂźne intracontinentale des PyrĂ©nĂ©es constitue un exemple d’inversion de marges passives hyper-amincies, associĂ©es Ă  un mĂ©tamorphisme HT-BP et intĂ©grĂ©es dans le prisme orogĂ©nique. La premiĂšre partie de cette Ă©tude est centrĂ©e sur l’étude de la rĂ©partition du mĂ©tamorphisme HT-BP associĂ© Ă  la phase de rifting et de l’exhumation du manteau lithosphĂ©rique. L’apport des donnĂ©es de TRSCM a permis, dans un premier temps, de dĂ©finir l’enveloppe de la ZIM caractĂ©risĂ©e par des tempĂ©ratures comprises entre 400 et 630°C Ă  l’échelle de l’ensemble de la chaĂźne et de montrer qu’il n’existe pas de gradient significatif des tempĂ©ratures maximales Ă  cette Ă©chelle. Dans un second temps, cette Ă©tude a permis de mettre en Ă©vidence des sauts de tempĂ©rature importants au travers de failles majeures et de distinguer des gradients de tempĂ©ratures latĂ©raux Ă  l’échelle des diffĂ©rents bassins constituant la ZIM, en particulier dans l’ouest de la chaĂźne sur l’exemple de la Nappe de Marbres. Cette partie de l’étude montre Ă©galement l’importance d’une tectonique salifĂšre antĂ©rieure au mĂ©tamorphisme de HT-BP. La seconde partie de cette Ă©tude, concernant la structure de la ZIM met en Ă©vidence trois phases de dĂ©formation, associĂ©es Ă  l’orogenĂšse pyrĂ©nĂ©enne ainsi que le rĂŽle du niveau de dĂ©collement des Ă©vaporites du Trias supĂ©rieur dans l’allochtonie gĂ©nĂ©ralisĂ©e de la ZIM. De plus, les failles majeures observĂ©es dans la ZNP, montrent un mouvement inverse avec une composante dĂ©crochante sĂ©nestre. L’interprĂ©tation de l’ensemble de ces rĂ©sultats suggĂšre que la ZIM et la ZNP ne forme qu’une seule unitĂ© dĂ©couplĂ©e du socle varisque au niveau du Trias supĂ©rieur et dĂ©placĂ©e par des chevauchements plats issus de l’hĂ©ritage extensif, lors du dĂ©but de la convergence. Le mode de dĂ©formation est alors de type thin-skinned, puis devient, lors de la collision des deux palĂ©omarges, de type thick-skinned, avec le dĂ©veloppement de faille majeures associĂ©es Ă  l’exhumation des blocs de socle (Massifs Nord-PyrĂ©nĂ©ens) qui ont dĂ©coupĂ© l’ensemble de la ZIM

    Structure, thermicity and geodynamic evolution of the Internal Metamorphic Zone in the Pyrenees

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    La comprĂ©hension des processus et des modalitĂ©s de l’inversion des systĂšmes extensifs et plus particuliĂšrement les domaines de marges amincies, dans les chaines de collision est un enjeu majeur. La chaĂźne intracontinentale des PyrĂ©nĂ©es constitue un exemple d’inversion de marges passives hyper-amincies, associĂ©es Ă  un mĂ©tamorphisme HT-BP et intĂ©grĂ©es dans le prisme orogĂ©nique. La premiĂšre partie de cette Ă©tude est centrĂ©e sur l’étude de la rĂ©partition du mĂ©tamorphisme HT-BP associĂ© Ă  la phase de rifting et de l’exhumation du manteau lithosphĂ©rique. L’apport des donnĂ©es de TRSCM a permis, dans un premier temps, de dĂ©finir l’enveloppe de la ZIM caractĂ©risĂ©e par des tempĂ©ratures comprises entre 400 et 630°C Ă  l’échelle de l’ensemble de la chaĂźne et de montrer qu’il n’existe pas de gradient significatif des tempĂ©ratures maximales Ă  cette Ă©chelle. Dans un second temps, cette Ă©tude a permis de mettre en Ă©vidence des sauts de tempĂ©rature importants au travers de failles majeures et de distinguer des gradients de tempĂ©ratures latĂ©raux Ă  l’échelle des diffĂ©rents bassins constituant la ZIM, en particulier dans l’ouest de la chaĂźne sur l’exemple de la Nappe de Marbres. Cette partie de l’étude montre Ă©galement l’importance d’une tectonique salifĂšre antĂ©rieure au mĂ©tamorphisme de HT-BP. La seconde partie de cette Ă©tude, concernant la structure de la ZIM met en Ă©vidence trois phases de dĂ©formation, associĂ©es Ă  l’orogenĂšse pyrĂ©nĂ©enne ainsi que le rĂŽle du niveau de dĂ©collement des Ă©vaporites du Trias supĂ©rieur dans l’allochtonie gĂ©nĂ©ralisĂ©e de la ZIM. De plus, les failles majeures observĂ©es dans la ZNP, montrent un mouvement inverse avec une composante dĂ©crochante sĂ©nestre. L’interprĂ©tation de l’ensemble de ces rĂ©sultats suggĂšre que la ZIM et la ZNP ne forme qu’une seule unitĂ© dĂ©couplĂ©e du socle varisque au niveau du Trias supĂ©rieur et dĂ©placĂ©e par des chevauchements plats issus de l’hĂ©ritage extensif, lors du dĂ©but de la convergence. Le mode de dĂ©formation est alors de type thin-skinned, puis devient, lors de la collision des deux palĂ©omarges, de type thick-skinned, avec le dĂ©veloppement de faille majeures associĂ©es Ă  l’exhumation des blocs de socle (Massifs Nord-PyrĂ©nĂ©ens) qui ont dĂ©coupĂ© l’ensemble de la ZIM.The understanding of the processes and scenarios of the inversion of extensional systems, and more specifically of hyper-extended margins, in collision thrust belts is a major issue. The intracontinental belt of the Pyrenees is an example of inversion of hyper-extended margins, associated with a HT-LP metamorphism and then integrated within the orogenic wedge. The first part of this study is focused on the distribution of the HT-LP metamorphism associated with rifting and the exhumation of lithospheric mantle. A new set of TRSCM data allows the recognition of the geometry of the IMZ, characterized with temperature ranging from 400 to 630°C and shows the absence of a regional gradient at this scale. This study then shows significant temperature gaps across major faults and distinguishes lateral temperature gradients at the scale of the different basins constituting the IMZ, especially in the westernmost part of the belt, in the Nappe des Marbres Basin. This part of the study moreover shows the importance of a salt tectonics prior to the HT-LP metamorphism. The second part shows the existence of three main tectonics phases during the Pyrenean orogeny and the role played by the Late Triassic evaporites as a decollement level in the generalized allochthony of the IMZ. A left-lateral component along the main faults within and along the boundaries of the North Pyrenean Zone (ZNP) is also shown. The interpretation of these observations is that the IMZ and ZNP form a single tectonic unit, decoupled from the Variscan basement by the decollement in the Late Triassic deposits and displaced above shallow-dipping thrust faults inherited from the rifting episode, during the first stages of the convergence. Deformation mode is then thin-skinned and becomes thick-skinned when the two paleomargins collide, with the development of major steeper faults linked with the exhumation of basement blocks (North Pyrenean Massifs) that dissected the IMZ
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