976 resultados para cyclic K48-linked di-ubiquitin


Relevância:

20.00% 20.00%

Publicador:

Resumo:

The work examines the change involving the Church in Tunisia from the period of the Protectorate to the present through the fundamental moments of independence (1956) and the signing of the ‘Modus vivendi’ (1964). In the first structure of the “modern” Church, a fundamental role was played by the complex figure of the French Cardinal Charles-Allemand Lavigerie who, while giving strong impulse to setting up disinterested charitable social initiatives by the congregations (Pères Blancs, Soeurs Blanches and others), also represented the ideal of the ‘evangelizing’ (as well as colonial) Church which, despite its declared will to avoid proselytism, almost inevitably tended to slip into it. During the French Protectorate (1881-1956) the ecclesiastic institution concentrated strongly on itself, with little heed for the sensitivity of its host population, and developed its activities as if it were in a European country. From the social standpoint, the Church was mostly involved in teaching, which followed the French model, and health facilities. In the Church only the Pères Blancs missionaries were sincerely committed to promoting awareness of the local context and dialogue with the Muslims. The Catholic clergy in the country linked its religious activity close to the policy of the Protectorate, in the hope of succeeding in returning to the ancient “greatness of the African Church”, as the Eucharistic Congress in Carthage in 1930 made quite clear. The Congress itself planted the first seed in the twentyfive- year struggle that led the Tunisian population to independence in 1956 and the founding of the Republic in 1957. The conquest of independence and the ‘Modus vivendi’ marked a profound change in the situation and led to an inversion of roles: the Catholic community was given the right to exist only on the condition that it should not interfere in Tunisian society. The political project of Bourguiba, who led the Republic from 1957 to 1987, aimed to create a strongly egalitarian society, with a separation between political and religious powers. In particular, in referring to the Church, he appeared as a secularist with no hostility towards the Catholics who were, however, considered as “cooperators”, welcome so long as they were willing to place their skills at the service of the construction of the state. So, in the catholic Community was a tension between the will of being on the side of the country and that of conserving a certain distance from it and not being an integral part of it. In this process of reflection, the role of the Second Vatican Council was fundamental: it spread the idea of a Church open to the world and the other religions, in particular to Islam: the teaching of the Council led the congregations present in the country to accept the new condition. This new Church that emerged from the Council saw some important events in the process of “living together”, of “cultural mixing” and the search for a common ground between different realities. The almost contemporary arrival of Arab bishops raised awareness among the Tunisians of the existence of Christian Arabs and, at the same time, the Catholic community began considering their faith in a different way. In the last twenty years the situation has continued to change. Side by side with the priests present for decades or even those born there, some new congregations have begun to operate, albeit in small numbers: they have certainly revitalized the community of the faithful, but they sometimes appear more devoted to service “within” the Church, than to services for the population, and are thus characterized by exterior manifestations of their religion. This sort of presence has made it possible for Bourguiba's successor, Ben Ali (president from 1987 to 2011), to practice forms of tolerance even more clearly, but always limited to formal relations; the Tunisians are still far from having a real understanding of the Catholic reality, with certain exceptions connected to relations on a personal and not structured plane, as was the case in the previous period. The arrival of a good number of young people from sub-Saharan Africa, most of all students, belonging to the JCAT, and personnel of the BAD has “Africanized” the Church in Tunisia and has brought about an increase in Christians' exterior manifestations; but this is a visibility that is not blatant but discreet, with the implicit risk of the Church continuing to be perceived as a sort of exterior body, alien to the country; nor can we say, lacking proper documentation, how it will be possible to build a bridge between different cultures through the “accompaniment” of Christian wives of Tunisians. Today, the Church is living in a country that has less and less need of it; its presence, in the schools and in health facilities, is extremely reduced. And also in other sectors of social commitment, such as care for the disabled, the number of clergymen involved is quite small. The ‘revolution’ in 2011 and the later developments up to the present have brought about another socio-political change, characterized by a climate of greater freedom, but with as yet undefinable contours. This change in the political climate will inevitable have consequences in Tunisia’s approach to religious and cultural minorities, but it is far too soon to discuss this on the historical and scientific planes.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The High Grade Metamorphic Complex (HGMC) of Variscan basement of north Sardinia is characterized by the widespread of migmatites. This study is focused on two localities of NE Sardinia (Porto Ottiolu and Punta Sirenella) where ortho- and para-derivates migmatites outcrop. A geological and structural survey was carried out, leading to the realization of a geological schematic map of Punta Sirenella area. Several samples of different rocks were collected for petrographic, micro-structural minero-chemical and geochemical analyses. In the Porto Ottiolu area three main deformation phases have been identified; D1, characterized by tight folds with sub-horizontal axes, rarely preserved in paragneisses; D2, that produce a pervasive foliation oriented N100° 45°SW marked by biotite and sillimanite blastesis and locally transposed by shear zone oriented N170°; D3, late deformation phase caused symmetric folds with sub-horizontal axes with no axial plane schistosity. Leucosomes form pods and layers along S2 schistosity but also leucosomes along shear zones have been observed. In the Punta Sirenella area, three main deformation phases have been identified; D1, is manifested by the transposition of centimeter-sized leucosomes and is rarely observed in paragneisses were produce open folds with sub-vertical axes; D2, NW-SE oriented on whose XY plane three mineralogical lineation (quartz+plagioclase, fibrolite+quarz and muscovite) lie; D3, a ductile-brittle deformation phase that produce a mylonitc S3 foliation that locally become the most evident schistosity in the field oriented N140° steeply dipping toward NE. In both areas, leucosomes of sedimentary-derived migmatites are generally trondhjemitic pointing out for a H2O fluxed melting reaction, but also granitic leucosomes have been found, produced by muscovite dehydration melting. Leucosomes of migmatitic orthogneiss instead, have granitic compositions. Migmatization started early, during the compressional and crustal thickening (sin-D1, pre-D2) and was still active during exhumation stage. For each studied outcrop of migmatite pseudosections for the average mesosome composition have been calculated; these pseudosections have been used to model the P-T conditions of anatexis on the basis of the melt volume (%) of melt, Si/Al and Na/K molar ratios, modal content of garnet and Si content in metamorphic white mica. Further pseudosections have been calculated for the average composition of leucosomes in order to define the P-T conditions of the end of the crystallization through intersection of solidus curve and isopleths of Si content in white mica and/or XMg ratio in biotite. Thermodynamic modeling on ortho- and sedimentary-derived migmatites of Punta Sirenella yield P-T conditions of 1.1-1.3 GPa - 670-740°C for migmatitic event and 0.75-0.90 GPa - 660-730°C for the end of crystallization. These conditions are fit well with previous studies on adjacent rocks. Modeling of Porto Ottiolu ortho- and sedimentary-derived migmatites yield P-T conditions of 0.85-1.05 GPa - 690-730°C for migmatitic event and 0.35-0.55 GPa - 630-690°C strongly affected by re-equilibration during exhumation, expecially for crystallization conditions. Geochemical analyses of samples belonging to Porto Ottiolu and Punta Sirenella orthogneisses show a strong link with those of other orthogneisses outcropping in NE Sardinia (for instance, Lode-Mamone and Golfo Aranci) that are considered the intrusive counterparts of middle-Ordovician metavolcanics rocks outcropping in the Nappe Zone. Thus, the studied ortogneiss bodies, even lacking radiometric data, can be considered as belonging to the same magmatic cycle.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Trotter, David, 'Les manuscrits latins de la Chirurgia d'Albucasis et la lexicographie du latin m?di?val', Archivum Latinitatis Medii Aevi (Bulletin Du Cange) (2001) 59(1) pp.181-202 RAE2008

Relevância:

20.00% 20.00%

Publicador:

Resumo:

UPNa. Instituto de Agrobiotecnología. Laboratorio de Biofilms Microbianos

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Neural models have proposed how short-term memory (STM) storage in working memory and long-term memory (LTM) storage and recall are linked and interact, but are realized by different mechanisms that obey different laws. The authors' data can be understood in the light of these models, which suggest that the authors may have gone too far in obscuring the differences between these processes.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The last 30 years have seen Fuzzy Logic (FL) emerging as a method either complementing or challenging stochastic methods as the traditional method of modelling uncertainty. But the circumstances under which FL or stochastic methods should be used are shrouded in disagreement, because the areas of application of statistical and FL methods are overlapping with differences in opinion as to when which method should be used. Lacking are practically relevant case studies comparing these two methods. This work compares stochastic and FL methods for the assessment of spare capacity on the example of pharmaceutical high purity water (HPW) utility systems. The goal of this study was to find the most appropriate method modelling uncertainty in industrial scale HPW systems. The results provide evidence which suggests that stochastic methods are superior to the methods of FL in simulating uncertainty in chemical plant utilities including HPW systems in typical cases whereby extreme events, for example peaks in demand, or day-to-day variation rather than average values are of interest. The average production output or other statistical measures may, for instance, be of interest in the assessment of workshops. Furthermore the results indicate that the stochastic model should be used only if found necessary by a deterministic simulation. Consequently, this thesis concludes that either deterministic or stochastic methods should be used to simulate uncertainty in chemical plant utility systems and by extension some process system because extreme events or the modelling of day-to-day variation are important in capacity extension projects. Other reasons supporting the suggestion that stochastic HPW models are preferred to FL HPW models include: 1. The computer code for stochastic models is typically less complex than a FL models, thus reducing code maintenance and validation issues. 2. In many respects FL models are similar to deterministic models. Thus the need for a FL model over a deterministic model is questionable in the case of industrial scale HPW systems as presented here (as well as other similar systems) since the latter requires simpler models. 3. A FL model may be difficult to "sell" to an end-user as its results represent "approximate reasoning" a definition of which is, however, lacking. 4. Stochastic models may be applied with some relatively minor modifications on other systems, whereas FL models may not. For instance, the stochastic HPW system could be used to model municipal drinking water systems, whereas the FL HPW model should or could not be used on such systems. This is because the FL and stochastic model philosophies of a HPW system are fundamentally different. The stochastic model sees schedule and volume uncertainties as random phenomena described by statistical distributions based on either estimated or historical data. The FL model, on the other hand, simulates schedule uncertainties based on estimated operator behaviour e.g. tiredness of the operators and their working schedule. But in a municipal drinking water distribution system the notion of "operator" breaks down. 5. Stochastic methods can account for uncertainties that are difficult to model with FL. The FL HPW system model does not account for dispensed volume uncertainty, as there appears to be no reasonable method to account for it with FL whereas the stochastic model includes volume uncertainty.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The watershed constituted by the historical novels of Leonardo Sciascia (1921- 1989), Vincenzo Consolo (1933-2012) and Andrea Camilleri (born 1925), are starting points for analysing subsequent writings of history in Sicily, particularly those that deal with the hermeneutical function of literature as a means of critically reading official historiography. Nevertheless, whereas ample critical attention has been paid to male writers, whose work is deemed ‘mainstream’, there has been insufficient analysis of the role of female authors in relation to literary representations of Sicilian history. By considering the distinctiveness of the Sicilian literary tradition, the thesis identifies a series of transformations of the genre which have occurred in recent years within the context of feminine writing, and examines the historical narratives of contemporary Sicilian writers Maria Attanasio, Silvana La Spina and Maria Rosa Cutrufelli produced between 1990 and 2007. The study problematizes the lack of critical debate about feminine narratives in Sicily, and places these works in relation to developments in gender and genre theory, focusing particularly on Margherita Ganeri’s studies on the historical genre and the canon. After an introductory chapter which argues the case for examining Sicilian female historical fiction as a distinct literary practice, the subsequent chapters feature textual analyses of each author’s main historical fiction works, supporting the reading of the texts with theoretical readings, including the micro-history of Carlo Ginzburg, the écriture féminine of Hélène Cixous, the abjection theory of Julia Kristeva, the theoretical propositions on “experience” by Joan Wallach Scott and Teresa De Lauretis, and the theory of gender as performance proposed by Judith Butler. The analyses underline the importance of the authors’ distinct feminine perspective over Sicilian history and ultimately suggest that the three writers represent significant examples of a “nomadic writing” to be placed outside the Sicilian male literary tradition.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The Lnx1 (Ligand of Numb protein X 1) and Lnx2 genes belong to a family of PDZ domain-containing RING finger domain E3 ubiquitin ligases. mRNA expression for both genes have been reported in early murine central nervous system. However, there have been limited reports with regards to the expression patterns for both the proteins in vivo. Hence, we have attempted to characterize the significance of these proteins in the context of morphology and physiology of the central nervous system. Through our studies, we have attempted to examine closely the expression of these two genes in the murine central nervous system. We have also looked at novel interacting ligands for both proteins. Interacting partners have been examined with particular relevance to possible roles of their interactions with LNX1 and LNX2 in the functioning of the nervous system. Moreover, we have performed loss-of-function studies by way of creation and characterization of knockout mice.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

My research investigates a recent tendency in Italian literature, characterized by elements of renewal within the novel-writing tradition and of discontinuity with postmodern culture. It proposes an interpretation of the genres of the historical novel and crime fiction in the last fifteen years, in order to underline the important role played by these types of narrative in revitalizing contemporary Italian literature. These modalities of writing are considered both individually and in their connections beyond a traditional notion of genre, emphasizing those characteristics which may be assumed as irreconcilable with a postmodern approach to fiction and those which, furthermore, seem to indicate attempts to take a new course. In particular, my study analyses the recent literary tendency to combine the elements of ‘crime’ and ‘history’ in order to represent political and social reality, and how the works examined relate to postmodern narrative. For this reason, I pay particular attention to the relationship between literature and the past and to the socio-political aspects connected with the praxis of narrating, offering an original interpretation of the way in which the authors studied engage with these characteristics.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The p75 neurotrophin receptor (p75NTR) is a member of the tumour necrosis factor superfamily, which relies on the recruitment of cytosolic protein partners - including the TNF receptor associated factor 6 (TRAF6) E3 ubiquitin ligase - to produce cellular responses such as apoptosis, survival, and inhibition of neurite outgrowth. Recently,p75NTR was also shown to undergo γ-secretase-mediated regulated intramembrane proteolysis, and the receptor ICD was found to migrate to the nucleus where it regulates gene transcription. Moreover, γ-secretase-mediated proteolysis was shown to be involved in glioblastoma cell migration and invasion. In this study we report that TRAF6-mediated K63-linked polyubiquitination at multiple or alternative lysine residues influences p75NTR-ICD stability in vitro. In addition, we found that TRAF6-mediated ubiquitination of p75NTR is not influenced by inhibition of dynamin. Moreover, we report beta-transducin repeats-containing protein (β-TrCP) as a novel E3- ligase that ubiquitinates p75NTR, which is independent of serine phosphorylation of the p75NTR destruction motif. In contrast to its influence on other substrates, co-expression of β-TrCP did not reduce p75NTR stability. We created U87-MG glioblastoma cell lines stably expressing wild type, γ-secretaseresistant and constitutively cleaved receptor, as well as the ICD-stabilized mutant K301R. Interestingly, only wild-type p75NTR induces increased glioblastoma cell migration, which could be reversed by application of γ-secretase inhibitor. Microarray and qRT-PCR analysis of mRNA transcripts in these cell lines yielded several promising genes that might be involved in glioblastoma cell migration and invasion, such as cadherin 11 and matrix metalloproteinase 12. Analysis of potential transcription factor binding sites revealed that transcription of these genes might be regulated by well known p75NTR signalling cascades such as NF-κB or JNK signalling, which are independent of γ-secretase-mediated cleavage of the receptor. In contrast, while p75NTR overexpression was confirmed in melanoma cell lines and a patient sample of melanoma metastasis to the brain, inhibition of γ-secretase did not influence melanoma cell migration. Collectively, this study provides several avenues to better understand the physiological importance of posttranslational modifications of p75NTR and the significance of the receptor in glioblastoma cell migration and invasion.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The present research examines the issue of universal interventions designed to enhance wellbeing among a community-based adolescent population. The first phase saw a cross-sectional survey conducted among Transition Year students in 13 secondary schools in Cork city and county, Republic of Ireland, with a view towards identifying dimensions linked with wellbeing (operationalised as subjective happiness, life satisfaction, and depressive symptoms) and which might prove effective in informing intervention approaches. Arising from this, mindfulness, gratitude, and cognitive-behavioural dimensions emerged as predictors of wellbeing, and short interventions (four sessions/four weeks) informed by each were conducted with participant groups in three secondary schools, one intervention in each school. Results from statistical analysis showed that the mindfulness and cognitive-behavioural interventions facilitated significant reductions in depressive symptoms among active condition participants at post-test, but that these benefits were not sustained over time, while no statistically significant changes were detected on subjective happiness and life satisfaction. The gratitude intervention was found to have had no effect on the three outcome variables. The findings are discussed in the context of theory and past research, while limitations, implications, and possible future directions are also addressed.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The 78-kDa glucose-regulated protein (GRP78) is ubiquitously expressed in many cell types. Its promoter contains multiple protein-binding sites and functional elements. In this study we examined a high affinity protein-binding site spanning bp -198 to -180 of the rat grp78 promoter, using nuclear extracts from both B-lymphoid and HeLa cells. This region contains a sequence TGACGTGA which, with the exception of one base, is identical to the cAMP-response element (CRE). Site-directed mutagenesis reveals that this sequence functions as a major basal level regulatory element in hamster fibroblast cells and is also necessary to maintain high promoter activity under stress-induced conditions. By gel mobility shift analysis, we detect two specific protein complexes. The major specific complex I, while immunologically distinct from the 42-kDa CRE-binding protein (CREB), binds most strongly to the grp site, but also exhibits affinity for the CRE consensus sequence. As such, complex I may consist of other members of the CREB/activating transcription factor protein family. The minor specific complex II consists of CREB or a protein antigenically related to it. A nonspecific complex III consists of the Ku autoantigen, an abundant 70- to 80-kDa protein complex in HeLa nuclear extracts. By cotransfection experiments, we demonstrate that in F9 teratocarcinoma cells, the grp78 promoter can be transactivated by the phosphorylated CREB or when the CREB-transfected cells are treated with the calcium ionophore A23187. The differential regulation of the grp78 gene by cAMP in specific cell types and tissues is discussed.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Vertebrate eggs are arrested at Metaphase II by Emi2, the meiotic anaphase-promoting complex/cyclosome (APC/C) inhibitor. Although the importance of Emi2 during oocyte maturation has been widely recognized and its regulation extensively studied, its mechanism of action remained elusive. Many APC/C inhibitors have been reported to act as pseudosubstrates, inhibiting the APC/C by preventing substrate binding. Here we show that a previously identified zinc-binding region is critical for the function of Emi2, whereas the D-box is largely dispensable. We further demonstrate that instead of acting through a "pseudosubstrate" mechanism as previously hypothesized, Emi2 can inhibit Cdc20-dependent activation of the APC/C substoichiometrically, blocking ubiquitin transfer from the ubiquitin-charged E2 to the substrate. These findings provide a novel mechanism of APC/C inhibition wherein the final step of ubiquitin transfer is targeted and raise the interesting possibility that APC/C is inhibited by Emi2 in a catalytic manner.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Autophagy has been predominantly studied as a nonselective self-digestion process that recycles macromolecules and produces energy in response to starvation. However, autophagy independent of nutrient status has long been known to exist. Recent evidence suggests that this form of autophagy enforces intracellular quality control by selectively disposing of aberrant protein aggregates and damaged organelles--common denominators in various forms of neurodegenerative diseases. By definition, this form of autophagy, termed quality-control (QC) autophagy, must be different from nutrient-regulated autophagy in substrate selectivity, regulation and function. We have recently identified the ubiquitin-binding deacetylase, HDAC6, as a key component that establishes QC. HDAC6 is not required for autophagy activation per se; rather, it is recruited to ubiquitinated autophagic substrates where it stimulates autophagosome-lysosome fusion by promoting F-actin remodeling in a cortactin-dependent manner. Remarkably, HDAC6 and cortactin are dispensable for starvation-induced autophagy. These findings reveal that autophagosomes associated with QC are molecularly and biochemically distinct from those associated with starvation autophagy, thereby providing a new molecular framework to understand the emerging complexity of autophagy and therapeutic potential of this unique machinery.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

VCP (VCP/p97) is a ubiquitously expressed member of the AAA(+)-ATPase family of chaperone-like proteins that regulates numerous cellular processes including chromatin decondensation, homotypic membrane fusion and ubiquitin-dependent protein degradation by the proteasome. Mutations in VCP cause a multisystem degenerative disease consisting of inclusion body myopathy, Paget disease of bone, and frontotemporal dementia (IBMPFD). Here we show that VCP is essential for autophagosome maturation. We generated cells stably expressing dual-tagged LC3 (mCherry-EGFP-LC3) which permit monitoring of autophagosome maturation. We determined that VCP deficiency by RNAi-mediated knockdown or overexpression of dominant-negative VCP results in significant accumulation of immature autophagic vesicles, some of which are abnormally large, acidified and exhibit cathepsin B activity. Furthermore, expression of disease-associated VCP mutants (R155H and A232E) also causes this autophagy defect. VCP was found to be essential to autophagosome maturation under basal conditions and in cells challenged by proteasome inhibition, but not in cells challenged by starvation, suggesting that VCP might be selectively required for autophagic degradation of ubiquitinated substrates. Indeed, a high percentage of the accumulated autophagic vesicles contain ubiquitin-positive contents, a feature that is not observed in autophagic vesicles that accumulate following starvation or treatment with Bafilomycin A. Finally, we show accumulation of numerous, large LAMP-1 and LAMP-2-positive vacuoles and accumulation of LC3-II in myoblasts derived from patients with IBMPFD. We conclude that VCP is essential for maturation of ubiquitin-containing autophagosomes and that defect in this function may contribute to IBMPFD pathogenesis.