Critical role of the interleukin 2 (IL-2) receptor gamma-chain-associated Jak3 in the IL-2-induced c-fos and c-myc, but not bcl-2, gene induction.

The interleukin 2 receptor (IL-2R) consists of three subunits, the IL-2R alpha, IL-2R beta c, and IL-2R gamma c chains. Two Janus family protein tyrosine kinases (PTKs), Jak1 and Jak3, were shown to associate with IL-2R beta c and IL-2R gamma c, respectively, and their PTK activities are increased after IL-2 stimulation. A Jak3 mutant with truncation of the C-terminal PTK domain lacks its intrinsic kinase activity but can still associate with IL-2R gamma c. In a hematopoietic cell line, F7, that responds to either IL-2 or IL-3, overexpression of this Jak3 mutant results in selective inhibition of the IL-2-induced activation of Jak1/Jak3 PTKs and of cell proliferation. Of the three target nuclear protooncogenes of the IL-2 signaling, c-fos and c-myc genes, but not the bcl-2 gene, were found to be impaired. On the other hand, overexpression of the dominant negative form of the IL-2R gamma c chain, which lacks most of its cytoplasmic domain, in F7 cells resulted in the inhibition of all three protooncogenes. These results provide a further molecular basis for the critical role of Jak3 in IL-2 signaling and also suggest a Jak PTK-independent signaling pathway(s) for the bcl-2 gene induction by IL-2R.

Human Rights in the Democratic People's Republic of Korea and the Future of the Troubled State after Kim Jong-Il

Since 2008, international speculation about the viability of Kim Jong-Il's leadership in North Korea has been at the forefront of diplomatic discussions. North Korea is known to be a secretive state where human rights violations abound. This paper discusses the history of leadership and government in North Korea since World War II, the current human rights situation in the country, the role of China, and potential successors to Kim Jong-Il. The ramifications of impending regime change are discussed in terms of North Korea's human rights issues and economic problems. While current efforts at diplomacy have proved ineffective, the need for concerned nations, intergovernmental organizations, and non-governmental organizations to be prepared to engage North Korea after Kim Jong-Il is imperative.

La protezione delle minoranze in Italia e il mancato riconoscimento della minoranza rom: ragioni e conseguenze = "The protection of minorities in Italy and the non-recognition of the Roma minority: reasons and consequences." EDAP 03/2013

No abstract.

Narratives and counter-narratives on "marriage of convenience" : conjugality and (il)legality in portuguese migration policies and in couples’ experiences

Tese de doutoramento, Sociologia (Sociologia da Família, Juventude e das Relações do Género), Universidade de Lisboa, Instituto de Ciências Sociais, 2016

Dissecting the signaling mechanisms of IL-7-mediated autophagy regulation in T-cell acute lymphoblastic leukemia

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Il lavoro a termine nella giurisprudenza della Corte di giustizia [Jurisprudence in the Court of Justice]. WP C.S.D.L.E. "Massimo D'Antona" .INT - 93/2012

The paper analyzes the ECJ case law on fixed-term work, with specific regard to non-regression clause, measures to prevent abuses and the principle of non-discrimination. In particular, the Author points out that the principle of non-discrimination is to be regarded as being the core of the fixed-term work regulation; in this respect, especially in more recent judgments, the Court seems to maximize the scope of such principle.

L’Europa sociale e il diritto: il contributo del metodo comparato [Social Europe and the law: the contribution of the comparative method]. WP C.S.D.L.E. "Massimo D'Antona" .INT - 94/2012

The essay explores the evolution of comparative law and the contribution of its more recent methodological results on the process of European social integration through law. The analysis of the comparative method in general glides on a discipline, such a as labour law, traditionally linked to the "nomos" of the nation state and looks at the process of its own supranationalization through the lens which is the comparative method; a method used mainly by the juridical format (national and supranational courts). The analysis focuses on the fixed term contract and on the vexing question of collective social fundamental rights vis a vis fundamental economic freedoms in the EU where national constitutional traditions and supranational principals risk collision due also to the comparative method.

Que reste-t-il de la directive sur les services? = What remains of the Services Directive? Research Papers in Law, 5/2007

No abstract.

Compensatory T-Cell Regulation in Unaffected Relatives of SLE Patients, and Opposite IL-2/CD25-Mediated Effects Suggested by Coreferentiality Modeling

In human systemic lupus erythematosus (SLE), diverse autoantibodies accumulate over years before disease manifestation. Unaffected relatives of SLE patients frequently share a sustained production of autoantibodies with indiscriminable specificity, usually without ever acquiring the disease. We studied relations of IgG autoantibody profiles and peripheral blood activated regulatory T-cells (aTregs), represented by CD4(+)CD25(bright) T-cells that were regularly 70-90% Foxp3(+). We found consistent positive correlations of broad-range as well as specific SLE-associated IgG with aTreg frequencies within unaffected relatives, but not patients or unrelated controls. Our interpretation: unaffected relatives with shared genetic factors compensated pathogenic effects by aTregs engaged in parallel with the individual autoantibody production. To study this further, we applied a novel analytic approach named coreferentiality that tests the indirect relatedness of parameters in respect to multivariate phenotype data. Results show that independently of their direct correlation, aTreg frequencies and specific SLE-associated IgG were likely functionally related in unaffected relatives: they significantly parallelled each other in their relations to broad-range immunoblot autoantibody profiles. In unaffected relatives, we also found coreferential effects of genetic variation in the loci encoding IL-2 and CD25. A model of CD25 functional genetic effects constructed by coreferentiality maximization suggests that IL-2-CD25 interaction, likely stimulating aTregs in unaffected relatives, had an opposed effect in SLE patients, presumably triggering primarily T-effector cells in this group. Coreferentiality modeling as we do it here could also be useful in other contexts, particularly to explore combined functional genetic effects.