In search of the aim of the free movement of persons provisions: has the Court of Justice missed the point?

The Court of Justice has, over the years, often been vilified for exceeding the limits of its jurisdiction by interpreting the provisions of Community legislation in a way not seem originally envisaged by its drafters. A recent example of this approach was a cluster of cases in the context of the free movement of workers and the freedom of establishment (Ritter-Coulais and its progeny), where the Court included within the scope of those provisions situations which, arguably, did not present a sufficient link with their (economic) aim. In particular, in that case law the Court accepted that the mere exercise of free movement for the purpose of taking up residence in the territory of another Member State whilst continuing to exercise an economic activity in the State of origin, suffices for bringing a Member State national within the scope of Articles 39 and 43 EC. It is argued that the most plausible explanation for this approach is that the Court now wishes to re-read the economic fundamental freedoms in such a way as to include within their scope all economically active Union citizens, irrespective of whether their situation presents a sufficient link with the exercise of an economic activity in a cross-border context. It is suggested that this approach is problematic for a number of reasons. It is, therefore, concluded that the Court should revert to its orthodox approach, according to which only situations that involve Union citizens who have moved between Member States for the purpose of taking up an economic activity should be included within the scope of the market freedoms.

Endothelin-converting enzyme-1 regulates trafficking and signalling of the neurokinin 1 receptor in endosomes of myenteric neurones

Neuropeptide signalling at the plasma membrane is terminated by neuropeptide degradation by cell-surface peptidases, and by beta-arrestin-dependent receptor desensitization and endocytosis. However, receptors continue to signal from endosomes by beta-arrestin-dependent processes, and endosomal sorting mediates recycling and resensitization of plasma membrane signalling. The mechanisms that control signalling and trafficking of receptors in endosomes are poorly defined. We report a major role for endothelin-converting enzyme-1 (ECE-1) in controlling substance P (SP) and the neurokinin 1 receptor (NK(1)R) in endosomes of myenteric neurones. ECE-1 mRNA and protein were expressed by myenteric neurones of rat and mouse intestine. SP (10 nM, 10 min) induced interaction of NK(1)R and beta-arrestin at the plasma membrane, and the SP-NK(1)R-beta-arrestin signalosome complex trafficked by a dynamin-mediated mechanism to ECE-1-containing early endosomes, where ECE-1 can degrade SP. After 120 min, NK(1)R recycled from endosomes to the plasma membrane. ECE-1 inhibitors (SM-19712, PD-069185) and the vacuolar H(+)ATPase inhibitor bafilomycin A(1), which prevent endosomal SP degradation, suppressed NK(1)R recycling by >50%. Preincubation of neurones with SP (10 nM, 5 min) desensitized Ca(2+) transients to a second SP challenge after 10 min, and SP signals resensitized after 60 min. SM-19712 inhibited NK(1)R resensitization by >90%. ECE-1 inhibitors also caused sustained SP-induced activation of extracellular signal-regulated kinases, consistent with stabilization of the SP-NK(1)R-beta-arrestin signalosome. By degrading SP and destabilizing endosomal signalosomes, ECE-1 has a dual role in controlling endocytic signalling and trafficking of the NK(1)R: promoting resensitization of G protein-mediated plasma membrane signalling, and terminating beta-arrestin-mediated endosomal signalling.

Trafficking and signaling of G protein-coupled receptors in the nervous system: implications for disease and therapy

G protein-coupled receptors (GPCRs) are expressed throughout the nervous system where they regulate multiple physiological processes, participate in neurological diseases, and are major targets for therapy. Given that many GPCRs respond to neurotransmitters and hormones that are present in the extracellular fluid and which do not readily cross the plasma membrane, receptor trafficking to and from the plasma membrane is a critically important determinant of cellular responsiveness. Moreover, trafficking of GPCRs throughout the endosomal system can initiate signaling events that are mechanistically and functionally distinct from those operating at the plasma membrane. This review discusses recent advances in the relationship between signaling and trafficking of GPCRs in the nervous system. It summarizes how receptor modifications influence trafficking, discusses mechanisms that regulate GPCR trafficking to and from the plasma membrane, reviews the relationship between trafficking and signaling, and considers the implications of GPCR trafficking to drug development.

Trafficking of storage proteins in developing grain of wheat

The processing properties of the wheat flour are largely determined by the structures and interactions of the grain storage proteins (also called gluten proteins) which form a continuous visco-elastic network in dough. Wheat gluten proteins are classically divided into two groups, the monomeric gliadins and the polymeric glutenins, with the latter being further classified into low molecular weight (LMW) and high molecular weight (HMW) subunits. The synthesis, folding and deposition of the gluten proteins take place within the endomembrane system of the plant cell. However, determination of the precise routes of trafficking and deposition of individual gluten proteins in developing wheat grain has been limited in the past by the difficulty of developing monospecific antibodies. To overcome this limitation, a single gluten protein (a LMW subunit) was expressed in transgenic wheat with a C-terminal epitope tag, allowing the protein to be located in the cells of the developing grain using highly specific antibodies. This approach was also combined with the use of wider specificity antibodies to compare the trafficking and deposition of different gluten protein groups within the same endosperm cells. These studies are in agreement with previous suggestions that two trafficking pathways occur in wheat, with the proteins either being transported via the Golgi apparatus into the vacuole or accumulating directly within the lumen of the ER. They also suggest that the same individual protein could be trafficked by either pathway, possibly depending on the stage of development, and that segregation of gluten proteins both between and within protein bodies may occur.

The trafficking pathway of a wheat storage protein in transgenic rice endosperm

Background and Aims The trafficking of proteins in the endoplasmic reticulum (ER) of plant cells is a topic of considerable interest since this organelle serves as an entry point for proteins destined for other organelles, as well as for the ER itself. In the current work, transgenic rice was used to study the pattern and pathway of deposition of the wheat high molecular weight (HMW) glutenin sub-unit (GS) 1Dx5 within the rice endosperm using specific antibodies to determine whether it is deposited in the same or different protein bodies from the rice storage proteins, and whether it is located in the same or separate phases within these. Methods The protein distribution and the expression pattern of HMW sub-unit 1Dx5 in transgenic rice endosperm at different stages of development were determined using light and electron microscopy after labelling with antibodies. Key results The use of HMW-GS-specific antibodies showed that sub-unit 1Dx5 was expressed mainly in the sub-aleurone cells of the endosperm and that it was deposited in both types of protein body present in the rice endosperm: derived from the ER and containing prolamins, and derived from the vacuole and containing glutelins. In addition, new types of protein bodies were also formed within the endosperm cells. Conclusions The results suggest that the HMW 1Dx5 protein could be trafficked by either the ER or vacuolar pathway, possibly depending on the stage of development, and that its accumulation in the rice endosperm could compromise the structural integrity of protein bodies and their segregation into two distinct populations in the mature endosperm.

Transitional justice in Nepal: the Commission on Investigation of Disappeared Persons, Truth and Reconciliation Act 2014

The Commission on Investigation of Disappeared Persons, Truth and Reconciliation Act 2014 is Nepal’s latest attempt to establish a transitional programme to respond to conflict era abuses. In part, the Act remedies the inadequacies of the 2013 Ordinance. It creates two commissions, on truth and reconciliation and enforced disappearances, makes provision for the establishment of a Special Court to try past abuses and incorporates systems to enable vulnerable witnesses to participate in truth seeking. Yet in a number of respects it continues to fall short of international legal standards, not least in the possibility of amnesty for international crimes and gross violations of human rights. In addition, the relationship between the three mechanisms – truth seeking, amnesty and prosecution – remains unclear and safeguards for individual rights are lacking. This paper explores these recent developments, highlighting issues that must be remedied if transitional justice objectives are to be achieved in Nepal.

The notions of 'restriction' and 'discrimination' in the context of the free movement of persons provisions: from a relationship of interdependence to one of (almost complete) independence

This article aims to analyse how the meaning of the notions of ‘restrictions’ and ‘discrimination’ in EU free movement law has developed through the years, and to explore how the relationship between them has evolved. It is explained that the two concepts under examination had originally been closely intertwined, in the sense that one defined the other, the element holding them together being the aim of the relevant provisions to liberalise the inter-State movement of persons in the EU, as part of the process of establishing an internal market. Yet, more recently, the way that the Court has chosen to delimit their scope, illustrates that each of these notions can now have a life of its own, meaning that ‘discrimination’ can include discriminatory measures which do not lead to restrictions that are contrary to the free movement provisions, and ‘restriction’ can cover national measures that are not discriminatory.

Influence of galacto-oligosaccharide mixture (B-GOS) on gut microbiota, immune parameters and metabonomics in elderly persons

It is recognised that ageing induces various changes to the human colonic microbiota. Most relevant is a reduction in bifidobacteria, which is a health-positive genus. Prebiotics, such as galacto-oligosaccharides (GOS), are dietary ingredients that selectively fortify beneficial gut microbial groups. Therefore, they have the potential to reverse the age-related decline in bifidobacteria and modulate associated health parameters. We assessed the effect of GOS mixture (Bimuno (B-GOS)) on gut microbiota, markers of immune function and metabolites in forty elderly (age 65-80 years) volunteers in a randomised, double-blind, placebo (maltodextrin)-controlled, cross-over study. The intervention periods consisted of 10 weeks with daily doses of 5·5 g/d with a 4-week washout period in between. Blood and faecal samples were collected for the analyses of faecal bacterial populations and immune and metabolic biomarkers. B-GOS consumption led to significant increases in bacteroides and bifidobacteria, the latter correlating with increased lactic acid in faecal waters. Higher IL-10, IL-8, natural killer cell activity and C-reactive protein and lower IL-1β were also observed. Administration of B-GOS to elderly volunteers may be useful in positively affecting the microbiota and some markers of immune function associated with ageing.

Protections for persons deprived of their liberty in international armed conflict

This contribution is about the protection of detained persons in international armed conflict. In particular, it compares how the relationship between IHL and IHRL is understood depending on whether one is speaking of the substantive or the procedural rules of protection for detainees. It will be suggested that, whereas the relationship between IHL and IHRL raises fewer problems when speaking of substantive rules, the situation is very different when speaking of procedural rules.

Problems with accessibility to health services by persons with disabilities in Sao Paulo, Brazil

Purpose. To describe the occurrence of self-reported problems of accessibility to health services used by persons with disabilities in terms of social and health services variables. Methods. We performed a cross-sectional household survey designed to assess problems with accessibility to health services faced by persons with disabilities. We interviewed 333 persons in Sao Paulo city, in 2007. Variables related to the presence of accessibility problems, disabilities, gender, age, family head income, ethnicity, use of health services and others were analysed using frequencies, percentages, chi(2)-test, ANOVA and Poisson regression models. Results. 15.92% of the interviewed persons reported problems with accessibility to health services. Persons having multiple (prevalence ratios; PR = 2.91) or mobility disability (PR = 6.46) had more problems with accessibility than persons with hearing disability. Persons younger than 78 years old had more problems with accessibility; those who needed help to go to the health service (PR = 3.01) also. Conclusions. Persons with multiple or mobility disability, younger than 78 years, and those who needed help of others to go to the health service were more likely to have problems with accessibility to health services. This information could be one of the first steps to the management and/or planning of appropriate health services for persons with disabilities.

Internally Displaced Persons Rights in Human Rights Perspective(Specifically Focused on Pakistani IDPs Example) : “Basic Human Rights of IDPs to Attain Equality in Dignity and Rights”

After the WWII, there was much concern to protect human rights situation all over the world. During the cold wars, huge displacement took place within different countries due to internal arms/ethnic conflicts. Millions of IDPs, who were uprooted by armed conflict or ethnic strife faced human rights violence. In 2002, there were estimated between 20-25 millions IDPs in the world (Phuong, p.1). Internally displacement is a worldwide problem and millions of the people displaced in Africa and Asia. These all Internal displacements of the people are only the result of the conflicts or the violations of the Human Rights but also sometimes it happened because of the natural disasters. “All human beings are born free and equal in dignity and rights..."(Streich, Article 1) This article works as the foundation of human rights which gives every human being an equal rights and opportunity to maintain his/her dignity. Human Rights issues related to human dignity must be taken very seriously and should not be ignored at any level; Many human rights issues are not always visible, issues such as: privacy, security, equality, protection of social and cultural values etc. In this paper I am going to apply theoretical approach of “all human being are equal in dignity and rights” to defend IDPs rights.