Glucorticoid receptor in human cutaneous melanoma: immunohistochemical and immunofluorescence study

GR is a nuclear receptor which, when activated by its specific ligand, can act as a transcription factor that binds to glucocorticoid response elements (GRE) or negative GRE. It affects inflammatory responses, differentiation and cell proliferation. The ligand activated glucocorticoid receptor induces a G1 cell cycle arrest or apoptosis in immature thymocytes and impairs proliferation of fibroblasts of undifferentiated mammary epithelial cells. It impairs proliferation and differentiation of neural progenitor cells in vivo and in vitro. Glucocorticoids are widely used in cancer therapy and have cell type-specific pro- or antiapoptotic effects. In melanoma, however, the antitumor activity of glucocorticoids remains an open question. A recent report demonstrated that in mouse embryo tissue and in human undifferentiated cells, cytoplasmic accumulation of GR is determined by nestin in conjunction with vimentin, copolymerised into an intermediate filament system, and that this anchoring of GR to the nestin/vimentin etheromeric complex is related to the maintenance of a high proliferation rate. The aim of this study was to analyse the expression of subcellular GR in cutaneous melanoma by immunofluorescence, immunohistochemistry and laser scanning confocal microscopy and to evaluate any effect in melanoma progression. The results will be discussed

Melatonin MT1 receptors as a target for the psychopharmacology of bipolar disorder: a translational study

The treatment of bipolar disorder (BD) still remains a challenge. Melatonin (MLT), acting through its two receptors MT1 and MT2, plays a key role in regulating circadian rhythms which are dysfunctional in BD. Using a translational approach, we examined the implication and potential of MT1 receptors in the pathophysiology and psychopharmacology of BD. We employed a murine model of the manic phase of BD (Clock mutant (ClockΔ19) mice) to study the activation of MT1 receptors by UCM871, a selective partial agonist, in behavioral pharmacology tests and in-vivo electrophysiology. We then performed a high-resolution Nuclear Magnetic Resonance study on isolated membranes to characterize the molecular mechanism of interaction of UCM871. Finally, in a cohort of BD patients, we investigated the link between clinical measures of BD and genetic variants located in the MT1 receptor and CLOCK genes. We demonstrated that: 1) UCM871 can revert behavioral and electrophysiological abnormalities of ClockΔ19 mice; 2) UCM871 promotes the activation state of MT1 receptors; 3) there is a significant association between the number of severe manic episodes and MLT levels, depending on the genetic configuration of the MT1 rs2165666 variant. Overall, this work lends support to the potentiality of MT1 receptors as target for the treatment of BD

Environmental Law and Youth Protests: Future Generations Between Speech Acts and Political Representation

This article aims to provide a semiotic analysis of environmental law and youth protests. More precisely, drawing on speech act theory this article regards both as types of communication and teases out the inherent voice and message, specifically with regard to the interests of future generations. The argument unfolds in three steps. First, the article looks into speaker and speech of environmental law and argues that it speaks, as legislation does, in the first-person plural voice of a ‘we’. Second, the article examines a speech of Greta Thunberg through the lens of Stanley Cavell’s theory of passionate utterances. This interpretation will unlock the political stakes of Thunberg’s speech as she claims standing with those responsible for enacting environmental law. Finally, the consequences of this reading will be analysed by relating message and voice of environmental law. As youth protests question ordinary forms of political representation, new ways of safeguarding the interests of future generations are called upon

Law, time and inhumanity:Reflections on the imprescriptible

The crimes known as the core international crimes, such as crimes against humanity and genocide, are imprescriptible, i.e., no time bars apply for their prosecution. Ever since the atrocities of the Second World War, the notion of the imprescriptible has become synonymous with the law’s dealing with the most heinous criminal acts. Not only lawyers, also philosophers have reflected on the theme and related concepts such as forgiveness and revenge. In criminal law, imprescriptible crimes form an exception. Normally, alleged criminal behaviour is subject to a so-called statute of limitations. These are ‘statute(s) providing for a timeframe within which criminal proceedings must be instituted. Statutes of limitation provide for a non-exculpatory defense to a criminal defendant. Accordingly, even if the accused is allegedly culpable, a statute of limitations will bar prosecution if an action is not timely commenced. Statutes of limitation appear not only in criminal law, but in international, civil, administrative, or tax law as well.’ 2 These statutes tend to ‘limit two types of action: limitations to criminal actions and limitations to the enforcement of sentences.’ 3 In other words, the passage of time affects the question whether or not a crime can be prosecuted. Time thus co-determines whether something is a matter of law. As said, the absence of such a statute of limitations is in contradiction with the normal situation in criminal law, in which crimes are (basically) all subjected to a statute of limitations. The especially shocking nature of international crimes is usually regarded as the justification for this exception

Temporal boundaries of politics and law:Time out of joint [Introduction]

In the last decade, the changing role of time in society has once again taken centre stage in the academic debate. A prominent, but surely not the only, aspect of this debate hinges on the so-called acceleration of time and its societal consequences. Despite the fact that time is fundamental to the way in which law and politics function, the influenceof the contemporary experience of time on law and politics remains underdevelopped.Both law and politics employ time to order society but they are also limited by what can be effectuated by time. It is this very tension between temporal possibilities and limitations that the constributors to this collection - drawn from different fields of law, as well as from other disciplines - examine

Dehumanization by law

Luigi Corrias's contribution discusses dehumanization by legal means. While the law is neither a necessary nor a sufficient condition for dehumanization, Corrias's chapter shows that dehumanization by law can be an important step in a dehumanization process. The chapter introduces the concept of legal dehumanization and discusses the closely related anthropology of modern law. A legal act is dehumanizing if and only if it is an indefensible infringement of legal values, where this infringement constitutes a violation of an individual or a group of people in their status of a full juridical person, making it possible to treat the victim(s) as subhuman. It also studies a number of cases in which legal dehumanization occurred, more specifically the Nuremberg laws, the apartheid regime of South Africa, and the torture memos. Finally, Corrias will look into the question how legal dehumanization might be reversed

Law at the right time: A plea for slow law in hasty times

According to Willem Witteveen, ‘[s]low law is the true art of legislating’. 1 Law seems to be either too late or too soon, but never ‘in time’. It is often too late, because at the very moment that a statute is promulgated, after a lengthy legislative process, the social norms codified in the law may have changed. In adjudication, there is a growing pressure on judges to act quicker, so that more cases are decided in less time. 2 Increasingly, the legal forms that structure the process of law-making and law application are seen as a hindrance to what people seem to desire: justice on direct demand. As Ernst Jünger observes: ‘and even the fastest beat of legislation lags behind the march of life, which in each moment demands its right’. 3 At the same time, law sometimes appears to come too soon. People are not always ready for the norms that the law offers. Legislation with a high aspirational character, such as non-discrimination law or environmental law aiming at sustainable development, often meets with resistance in society. Moreover, the legislature is sometimes accused of issuing legislation too quickly, without having taken enough time for deliberation and reflection. As a result, the legislation may be of a bad quality, as for instance the phenomenon of ‘ad hoc legislation’ shows. 4