Illicit Cycle of Narcotics from a Human Rights Perspective

The purpose of this article is to analyse the illicit cycle of narcotics within a human rights framework. It begins by illustrating the benefits of adopting a human rights framework, such as its ability to promote victim-centred and holistic approaches. The article then identifies key human rights issues such as poverty, forced labour, law enforcement practices and addiction to narcotics. It continues with an analysis of the nature and the extent of obligations imposed upon States. This article focuses on three categories of human rights obligations to address: 1) the supply of narcotics; 2) narcotics trafficking; and 3) the demand for narcotics. The main conclusion reached is that a human rights framework can strengthen the global action against the illicit cycle of narcotics.

ARTICLE: On the Curious Disappearance of Human Servitude from General International Law

The following study considers the fragmentation of law which occurred in 1956 with regard to the law on servitude. As States were unwilling to go as far as the Universal Declaration on Human in establishing that "no one shall be held in [...] servitude", the negotiators of the 1956 Supplementary Conventions moved to expunge the very term 'servitude' from the text and to replace it with the phrase 'institutions and practices similar to slavery' which could then be abolished 'progressively and as soon as possible'. The negotiation history of the 1956 Convention clear demonstrate that the Universal Declaration on Human was the elephant in the room and that it ultimately lead to a fragmentation of the law as between general international law manifest in the 1956 Supplementary Convention on the one hand and international human rights law on the other. It is for this reason that, for instance the 2001 UN and 2005 Council of Europe trafficking conventions mention both 'practices similar to slavery' and 'servitude' as types of human exploitation to be suppressed in their definition of 'trafficking in persons'.

A novel reciprocal and biphasic relationship between membrane cholesterol and beta-secretase activity in SH-SY5Y cells and in human platelets.

Research into the cause of Alzheimer's disease (AD) has identified strong connections to cholesterol. Cholesterol and cholesterol esters can modulate amyloid precursor protein (APP) processing, thus altering production of the A beta peptides that deposit in cortical amyloid plaques. Processing depends on the encounter between APP and cellular secretases, and is thus subject to the influence of cholesterol-dependent factors including protein trafficking, and distribution between membrane subdomains. We have directly investigated endogenous membrane beta-secretase activity in the presence of a range of membrane cholesterol levels in SH-SY5Y human neuroblastoma cells and human platelets. Membrane cholesterol significantly influenced membrane beta-secretase activity in a biphasic manner, with positive correlations at higher membrane cholesterol levels, and negative correlations at lower membrane cholesterol levels. Platelets from individuals with AD or mild cognitive impairment (n = 172) were significantly more likely to lie within the negative correlation zone than control platelets (n = 171). Pharmacological inhibition of SH-SY5Y beta-secretase activity resulted in increased membrane cholesterol levels. Our findings are consistent with the existence of a homeostatic feedback loop between membrane cholesterol level and membrane beta-secretase activity, and suggest that this regulatory mechanism is disrupted in platelets from individuals with cognitive impairment.

Burkholderia multivorans survival and trafficking within macrophages

Cystic fibrosis (CF) patients are at great risk of opportunistic lung infection, particularly by members of the Burkholderia cepacia complex (Bcc). This group of bacteria can cause damage to the lung tissue of infected patients and are very difficult to eradicate due to their high levels of antibiotic resistance. Though the highly virulent B. cenocepacia has been the focus of virulence research for the past decade, B. multivorans is emerging as the most prevalent Bcc species infecting CF patients in North America. Despite several studies detailing the intramacrophage trafficking and survival of B. cenocepacia, no such data exists for B. multivorans. Our results demonstrated that clinical CF isolates, C5568 and C0514, and an environmental B. multivorans isolate, ATCC17616, were able to replicate and survive within murine macrophages in a manner similar to B. cenocepacia K56-2. These strains were also able to survive but were unable to replicate within human THP-1 macrophages. Differences in macrophage uptake were observed among all three B. multivorans strains; these variances were attributed to major differences in O-antigen production. Unlike B. cenocepacia-containing vacuoles, which delay phagosomal maturation in murine macrophages by 6 h, all B. multivorans containing vacuoles co-localized with late endosome/lysosomal marker LAMP-1 and the lysosomal marker dextran within 2 h of uptake. Together, these results indicate that while both Bcc species are able to survive and replicate within macrophages, they utilize different intramacrophage survival strategies. To observe differences in virulence the strains were compared using the Galleria mellonella model. When compared to the B. multivorans strains tested, B. cenocepacia K56-2 is highly virulent in this model and killed all worms within 24 h when injected at 107 CFU. B. multivorans clinical isolates C5568 and C0514 were significantly more virulent than the soil isolate ATCC17616, which was avirulent, even when worms were injected with 107 CFU. These results suggest strain differences in the virulence of B. multivorans isolates.