DUB-1, a deubiquitinating enzyme with growth-suppressing activity.

Cytokines regulate cell growth by inducing the expression of specific target genes. Using the differential display method, we have cloned a cytokine-inducible immediate early gene, DUB-1 (for deubiquitinating enzyme). DUB-1 is related to members of the UBP superfamily of deubiquitinating enzymes, which includes the oncoprotein Tre-2. A glutathione S-transferase-DUB-1 fusion protein cleaved ubiquitin from a ubiquitin-beta-galactosidase protein. When a conserved cysteine residue of DUB-1, required for ubiquitin-specific thiol protease activity, was mutated to serine (C60S), deubiquitinating activity was abolished. Continuous expression of DUB-1 from a steroid-inducible promoter induced growth arrest in the G1 phase of the cell cycle. Cells arrested by DUB-1 expression remained viable and resumed proliferation upon steroid withdrawal. Our results suggest that DUB-1 regulates cellular growth by modulating either the ubiquitin-dependent proteolysis or the ubiquitination state of an unknown growth regulatory factor(s).

A close relative of the adrenoleukodystrophy (ALD) gene codes for a peroxisomal protein with a specific expression pattern.

Adrenoleukodystrophy (ALD), a severe demyelinating disease, is caused by mutations in a gene coding for a peroxisomal membrane protein (ALDP), which belongs to the superfamily of ATP binding cassette (ABC) transporters and has the structure of a half transporter. ALDP showed 38% sequence identity with another peroxisomal membrane protein, PMP70, up to now its closest homologue. We describe here the cloning and characterization of a mouse ALD-related gene (ALDR), which codes for a protein with 66% identity with ALDP and shares the same half transporter structure. The ALDR protein was overexpressed in COS cells and was found to be associated with the peroxisomes. The ALD and ALDR genes show overlapping but clearly distinct expression patterns in mouse and may thus play similar but nonequivalent roles. The ALDR gene, which appears highly conserved in man, is a candidate for being a modifier gene that could account for some of the extreme phenotypic variability of ALD. The ALDR gene is also a candidate for being implicated in one of the complementation groups of Zellweger syndrome, a genetically heterogeneous disorder of peroxisome biogenesis, rare cases of which were found to be associated with mutations in the PMP70 (PXMP1) gene.

Activation of Tsk and Btk tyrosine kinases by G protein beta gamma subunits.

Tsk/Itk and Btk are members of the pleckstrin-homology (PH) domain-containing tyrosine kinase family. The PH domain has been demonstrated to be able to interact with beta gamma subunits of heterotrimeric guanine nucleotide-binding proteins (G proteins) (G beta gamma) and phospholipids. Using cotransfection assays, we show here that the kinase activities of Tsk and Btk are stimulated by certain G beta gamma subunits. Furthermore, using an in vitro reconstitution assay with purified bovine brain G beta gamma subunits and the immunoprecipitated Tsk, we find that Tsk kinase activity is increased by G beta gamma subunits and another membrane factor(s). These results indicate that this family of tyrosine kinases could be an effector of heterotrimeric G proteins.

Suppression of heat-induced hsp70 expression by the 70-kDa subunit of the human Ku autoantigen.

Expression of the 70-kDa polypeptide of human Ku autoantigen in rat cells is shown to suppress specifically the induction of hsp70 upon heat shock. Thermal induction of other heat shock proteins is not significantly affected, nor is the state of phosphorylation or the DNA-binding ability of the heat shock transcription factor HSF1. These findings support a model in which hsp70 gene expression is controlled by a second regulatory factor in addition to the positive activator HSF1. The Ku autoantigen, or a protein closely related to it, is likely to be involved in the regulation of hsp70 expression.

Regulation of CD45 engagement by the B-cell receptor CD22.

The B-cell receptor CD22 binds sialic acid linked alpha-2-6 to terminal galactose residues on N-linked oligosaccharides associated with several cell-surface glycoproteins. The first of these sialoglycoproteins to be identified was the receptor-linked phosphotyrosine phosphatase CD45, which is required for antigen/CD3-induced T-cell activation. In the present work, we examine the effect of interaction between the extracellular domain of CD45 and CD22 on T-cell activation. Using soluble CD22-immunoglobulin fusion proteins and T cells expressing wild-type and chimeric CD45 forms, we show that engagement of CD45 by soluble CD22 can modulate early T-cell signals in antigen receptor/CD3-mediated stimulation. We also show that addition of sialic acid by beta-galactoside alpha-2,6-sialyltransferase to the CD22 molecule abrogates interactions between CD22 and its ligands. Together, these observations provide direct evidence for a functional role of the interaction between the extracellular domain of CD45 and a natural ligand and suggest another regulatory mechanism for CD22-mediated ligand engagement.

O princípio da ofensividade como complemento necessário à regra da legalidade penal no Estado Democrático de Direito

As ideias políticas e filosóficas que influenciaram a criação da regra da legalidade penal e do princípio da ofensividade têm origem no Iluminismo. Principalmente durante a Idade Média e o Antigo Regime, confundia-se crime com pecado e as pessoas podiam ser punidas por mero capricho do soberano, sem que existisse lei. As arbitrariedades eram gritantes. A finalidade de ambas as teorias surgidas no período da Ilustração, portanto ao pregarem que era necessária a existência de lei prévia para que alguém fosse punido (regra da legalidade) e que o crime pressupunha uma lesão a direito ou bem jurídico de terceiro (princípio da ofensividade) , era a mesma: limitar o poder punitivo. No entanto, a regra da legalidade penal foi muito mais absorvida pelo discurso dogmático-jurídico do que o princípio da ofensividade, sendo oportuno, pois, analisar as razões pelas quais isso ocorreu. Algumas delas serão analisadas neste estudo como, por exemplo, a ausência de previsão explícita desse princípio nas Constituições, a suposta incompatibilidade desse princípio com a separação de poderes e com a própria regra da legalidade penal e a insegurança jurídica que a aplicação de princípios poderia gerar. Além disso, há um fator político de destaque: a consolidação da burguesia exigia a imposição de limites formais ao poder estatal, mas não limites materiais. Outro fator importante foi o advento do positivismo criminológico, no final do século XIX, que, ao confundir crime com doença, retornou ao paradigma do direito penal do autor que havia vigorado na Idade Média. Finalmente, para demonstrar o que impediu a consolidação do princípio da ofensividade especificamente no Brasil, será analisada a influência da doutrina europeia na dogmática nacional.

Componentes genéticos que afetam a via de direcionamento de proteínas organelares em Arabidopsis thaliana

Nos eucariotos, a evolução dos sistemas de transporte molecular foi essencial pois seu alto grau de compartimentalização requer mecanismos com maior especificidade para a localização de proteínas. Com o estabelecimento das mitocôndrias e plastídeos como organelas da célula eucariota, grande parte dos genes específicos para sua atividade e manutenção foram transferidos ao núcleo. Após a transferência gênica, a maioria das proteínas passaram a ser codificadas pelo núcleo, sintetizadas no citosol e direcionadas às organelas por uma maquinaria complexa que envolve receptores nas membranas das organelas, sequências de direcionamento nas proteínas e proteínas citossólicas que auxiliam o transporte. A importação depende em grande parte de uma sequência na região N-terminal das proteínas que contém sinais reconhecidos pelas membranas organelares. No entanto, muito ainda não é compreendido sobre o transporte de proteínas organelares e fatores ainda desconhecidos podem influenciar o direcionamento sub-celular. O objetivo deste trabalho foi a caracterização da General Regulatory Factor 9 (GRF9), uma proteína da família 14-3-3 de Arabidopsis thaliana potencialmente envolvida no direcionamento de proteínas organelares, e a geração de um genótipo para ser utilizado na obtenção de uma população mutante para genes que afetam o direcionamento da proteína Tiamina Monofosfato Sintetase (TH-1). Após experimentos in vivo e in planta, foi observado que GRF9 interage com as proteínas duplo-direcionadas Mercaptopyruvate Sulfurtransferase1 (MST1) e a Thiazole Biosynthetic Enzyme (THI1), e com a proteína direcionada aos cloroplastos TH-1. Experimentos de deleção e interação in vivo mostraram que a região Box1 de GRF9 é essencial para a interação com THI1 e MST1. Com a finalidade de dar continuidade a caracterização da GRF9 e para realização de testes com relação a sua função no direcionamento de proteínas organelares foi gerada uma linhagem homozigota que superexpressa GRF9. Plantas expressando o transgene TH-1 fusionado a Green Fluorescent Protein (GFP) em genótipo deficiente na TH-1 (CS3469/TH-1-GFP) foram obtidas para a geração de população mutante que possibilitará a descoberta de componentes genéticos ainda desconhecidos e responsáveis pelo direcionamento de proteínas aos cloroplastos.

Everyday Indivisibility: How Exclusive Religious Practices Explain Variation in Subnational Violence Outcomes

This project explores the puzzle of religious violence variation. Religious actors initiate conflict at a higher rate than their secular counterparts, last longer, are more deadly, and are less prone to negotiated termination. Yet the legacy of religious peacemakers on the reduction of violence is undeniable. Under what conditions does religion contribute to escalated violence and under what conditions does it contribute to peace? I argue that more intense everyday practices of group members, or high levels of orthopraxy, create dispositional indivisibilities that make violence a natural alternative to bargaining. Subnational armed groups with members whose practices are exclusive and isolating bind together through ritual practice, limit the acceptable decisions of leaders, and have prolonged timeframes, all of which result in higher levels of intensity, intransigence and resolve during violent conflict. The theory challenges both instrumentalist and constructivist understandings of social identity and violence. To support this argument, I construct an original cross-national data-set that employs ethnographic data on micro-level religious practices for 724 subnational armed groups in both civil wars and terror campaigns. Using this data, I build an explanatory “religious practice index” for each observation and examine its relationship with conflict outcomes. Findings suggest that exclusive practice groups fight significantly longer with more intensity and negotiate less. I also apply the practice model to qualitative cases. Fieldwork in the West Bank and Sierra Leone reveals that groups with more exclusive religious practicing membership are principle contributors to violence, whereas those with inclusive practices can contribute to peace. The project concludes with a discussion about several avenues for future research and identifies the practical policy applications to better identify and combat religious extremism.

La futura vida cotidiana en España: la sociedad de consumo

Las dinámicas que durante décadas han dado forma a la sociedad de consumo en España han entrado en crisis. Las consecuencias sociales e ideológicas van mucho más allá de lo económico. El consumo como fuente de identidad social y de legitimación política de las desigualdades inicia una nueva etapa matizada por la irrupción de las nuevas tecnologías. El futuro muestra una clara discontinuidad respecto al pasado. Las clases medias deberán reinventarse mediante formas alternativas de consumo, empleando estrategias que protejan su imagen de “status”. Este cambio afecta directamente a la legitimación del sistema y anticipa un periodo de tensión social, ya plasmado en la Spanish Revolution.

La economía callejera en las ciudades contemporáneas. La redes efímeras de venta ambulante como modelo para la reconstrucción de lo urbano

Según Robert Neuwirth alrededor de 1.800 millones de personas trabajan en la economía informal, generando unos 10 billones de dólares anuales. Este autor afirma que si todas las personas vinculadas a dicho modelo económico se reunieran en un único país, éste sería la segunda potencia económica mundial. Junto a la importancia económica del modelo, su flexibilidad al contexto urbano es también destacable. La economía callejera, en particular, está vinculada a la construcción de redes urbanas complejas donde el individuo puede decidir y negociar. Este aspecto es lo que hace de este tipo de apropiación urbana una referencia fundamental para la innovación en la construcción de ciudad y, en especial, para el Urbanismo Táctico. En este artículo se analiza cómo las construcciones urbanas vinculadas a la economía callejera y a la venta ambulante se relacionan con los conceptos que diversos autores han empleado para definir las dinámicas contemporáneas. Primero se aborda la manera en que la venta ambulante teje, relaciona y transforma las redes urbanas existentes (sociales, productivas, económicas y de identidad) y busca su vínculo con los siguientes conceptos: ‘red’, ‘rizoma’, ‘radicante’, ‘punto de paso obligado’ y ‘hacker’. Seguidamente se reflexiona sobre la materialización de la economía informal en las ciudades actuales, relacionando este fenómeno con los siguientes conceptos: ‘el derecho a la ciudad’, ‘lo informal’, ‘TAZ’ y el urbanismo ‘emergente’, entre otros.

EU actorness and effectiveness under political pressure at the Copenhagen climate change negotiations

This paper analyses the extent of European Union (EU) actorness and effectiveness at the fifteenth United Nations Framework Convention on Climate Change (UNFCCC) Conference of the Parties (COP) meeting in Copenhagen in December 2009. For over a decade the European Union has been characterised as a leader in international climate policy-making and as an important actor in international climate change negotiations. The COP15 meeting in Copenhagen has overall brought about disappointing outcomes, especially from the perspective of the European Union. This casts doubts on EU leadership and begs the question of what has happened to EU actorness and effectiveness in this field. In terms of actorness we take Jupille and Caporaso (1998) as a point of departure and then specify a more parsimonious actorness framework that consists of cohesion and autonomy. Effectiveness (i.e. goal attainment) is seen as conceptually separate from actorness. Effectiveness is conceptualised as the result of actorness conditioned by the ‘opportunity structure’, i.e. the external context (of other actors, events and ideas) that enables or constrains EU actions. We hold that the EU’s actorness has been only moderate, especially given somewhat limited preference cohesion. In terms of the opportunity structure in Copenhagen we argue that the high degree of politicisation constrained the EU’s ability to negotiate and thus to attain its goals. Another external factor that had a substantial adverse impact on the EU’s effectiveness at the Copenhagen negotiations was the strong involvement of other actors with rather different positions, namely the United States (US) and the BASIC countries (Brazil, South Africa, India, and China).

Images of Europeans: In-Group Trust and Support for European Integration. Jean Monnet/Robert Schuman Paper Series Vol. 14 No. 3, March 2014

Prior research on citizen support for European integration does not consider how individuals’ evaluations of European nationalities are associated with support. This paper fills this gap by developing a political cohesion model based on social identity theory. I claim that the probability of supporting integration increases with greater levels of trust in fellow Europeans, which assumes to reflect their positive images. Also, trust in eastern European Union nationalities has the highest impact on the probability for support, followed by trust in the southern nationalities, and then northern nationalities due to the eastern and southern nationalities relatively lower economic development. Controlling for various factors, the ordered logistic regression analysis of the European Election Study (2004) data support these claims.

Evidence for a Myotomal Hox/Myf Cascade Governing Nonautonomous Control of Rib Specification within Global Vertebral Domains

Hox genes are essential for the patterning of the axial skeleton. Hox group 10 has been shown to specify the lumbar domain by setting a rib-inhibiting program in the presomitic mesoderm (PSM). We have now produced mice with ribs in every vertebra by ectopically expressing Hox group 6 in the PSM, indicating that Hox genes are also able to specify the thoracic domain. We show that the information provided by Hox genes to specify rib-containing and rib-less areas is first interpreted in the myotome through the regional-specific control of Myf5 and Myf6 expression. This information is then transmitted to the sclerotome by a system that includes FGF and PDGF signaling to produce vertebrae with or without ribs at different axial levels. Our findings offer a new perspective of how Hox genes produce global patterns in the axial skeleton and support a redundant nonmyogenic role of Myf5 and Myf6 in rib formation.

O jogo da distinção: C. A. Paulistano e Fluminense F. C.: um estudo das identidades clubísticas durante a fase amadora do futebol em São Paulo e no Rio de Janeiro (1902-1933)

Este trabalho investiga o processo de formação de identidades clubisticas durante a fase amadora do futebol brasileiro (1900 – 1933), tendo por foco os casos do C A Paulistano e do Fluminense F. C. Tal construção identitária costuma atribuir a estes clubes a marca da elitização calcada na distinção e no refinamento. Ao aprofundar e ao matizar essa versão consagrada pelo memorialismo esportivo, pretende-se analisar a história dessas duas agremiações, durante os anos iniciais do desenvolvimento do futebol na cidade do Rio de Janeiro e São Paulo, com destaque à relação do esporte com o desenvolvimento destas duas cidades. Para a demonstração de nosso argumento central, levantaremos os aspectos sociais, econômicos, políticos e culturais que podem ser considerados fundamentais na construção da imagem de distinção atribuída tanto ao Fluminense quanto ao Paulistano. Com o emprego do método comparativo, buscaremos apontar as semelhanças e diferenças na história desses clubes, tendo como pressupostos teóricos os trabalhos de Bourdieu sobre a distinção, de Hobsbawm e Ranger sobre a invenção das tradições e de Halbwachs sobre a memória coletiva. Junto aos acervos documentais das duas instituições examinadas, utilizaremos como fontes a documentação produzida pelos clubes no período e os periódicos da época. Procuraremos demonstrar, através dos relatos memoriais produzidos por escritores, dirigentes e ex-atletas, a perpetuação de uma série de valores simbólicos e de tradições que associaram o Paulistano e o Fluminense a um espaço de distinção e refinamento que se reproduziu ao longo das gerações e que permanece no imaginário esportivo até os dias atuais.

Attitude-behaviour consistency: the role of group norms, attitude accessibility, and mode of behavioural decision-making

The interplay between two perspectives that have recently been applied in the attitude area-the social identity approach to attitude-behaviour relations (Terry & Hogg, 1996) and the MODE model (Fazio, 1990a)-was examined in the present research. Two experimental studies were conducted to examine the role of group norms, group identification, attitude accessibility, and mode of behavioural decision-making in the attitude-behaviour relationship. In Study I (N = 211), the effects of norms and identification on attitude-behaviour consistency as a function of attitude accessibility and mood were investigated. Study 2 (N = 354) replicated and extended the first experiment by using time pressure to manipulate mode of behavioural decision-making. As expected, the effects of norm congruency varied as a function of identification and mode of behavioural decision-making. Under conditions assumed to promote deliberative processing (neutral mood/low time pressure), high identifiers behaved in a manner consistent with the norm. No effects emerged under positive mood and high time pressure conditions. In Study 2, there was evidence that exposure to an attitude-incongruent norm resulted in attitude change only under low accessibility conditions. The results of these studies highlight the powerful role of group norms in directing individual behaviour and suggest limited support for the MODE model in this context. Copyright (C) 2003 John Wiley Sons, Ltd.