The growing body of ‘right to die’ case law illustrates the issue’s growing prominence

The legal position of those who wish to end their own lives with assistance from another person has been consistently ambiguous, with politicians unable to come to a unified position, and the courts reluctant to take the initiative. Claire Overman takes a look back over the legal system’s attempts to deal with the issue, observing that the amount of accumulated law now on the statute book reflects a growing public awareness of the issues at stake

“An opportunist piece of electioneering”: experts criticise the Conservatives’ Human Rights Act repeal pledge

David Cameron recently announced his intention to repeal the Human Rights Act were his Conservative Party to be returned to Government following the General Election scheduled for May 2015. Democratic Audit asked human rights experts to contribute their assesment of the idea, particularly in light of further details of the proposal outlined by the Justice Secretary Chris Grayling. Part one can be found here

Structural basis of Lewis(b) antigen binding by the Helicobacter pylori adhesin BabA

Helicobacter pylori is a leading cause of peptic ulceration and gastric cancer worldwide. To achieve colonization of the stomach, this Gram-negative bacterium adheres to Lewis(b) (Le(b)) antigens in the gastric mucosa using its outer membrane protein BabA. Structural information for BabA has been elusive, and thus, its molecular mechanism for recognizing Le(b) antigens remains unknown. We present the crystal structure of the extracellular domain of BabA, from H. pylori strain J99, in the absence and presence of Le(b) at 2.0- and 2.1-Å resolutions, respectively. BabA is a predominantly α-helical molecule with a markedly kinked tertiary structure containing a single, shallow Le(b) binding site at its tip within a β-strand motif. No conformational change occurs in BabA upon binding of Le(b), which is characterized by low affinity under acidic [K D (dissociation constant) of ~227 μM] and neutral (K D of ~252 μM) conditions. Binding is mediated by a network of hydrogen bonds between Le(b) Fuc1, GlcNAc3, Fuc4, and Gal5 residues and a total of eight BabA amino acids (C189, G191, N194, N206, D233, S234, S244, and T246) through both carbonyl backbone and side-chain interactions. The structural model was validated through the generation of two BabA variants containing N206A and combined D233A/S244A substitutions, which result in a reduction and complete loss of binding affinity to Le(b), respectively. Knowledge of the molecular basis of Le(b) recognition by BabA provides a platform for the development of therapeutics targeted at inhibiting H. pylori adherence to the gastric mucosa

Analogues of Marine Guanidine Alkaloids Are in Vitro Effective against Trypanosoma cruzi and Selectively Eliminate Leishmania (L.) infantum Intracellular Amastigotes

Synthetic analogues of marine sponge guanidine alkaloids showed in vitro antiparasitic activity against Leishmania (L.) infantum and Trypanosoma cruzi. Guanidines 10 and 11 presented the highest selectivity index when tested against Leishmania. The antiparasitic activity of 10 and 11 was investigated in host cells and in parasites. Both compounds induced depolarization of mitochondrial membrane potential, upregulation of reactive oxygen species levels, and increased plasma membrane permeability in Leishmania parasites. Immunomodulatory assays suggested an NO-independent effect of guanidines 10 and 11 on macrophages. The same compounds also promoted anti-inflammatory activity in L. (L.) infantum-infected macrophages cocultived with splenocytes, reducing the production of cytokines MCP-1 and IFN-γ. Guanidines 10 and 11 affect the bioenergetic metabolism of Leishmania, with selective elimination of parasites via a host-independent mechanism

Small molecule binding sites on the Ras:SOS complex can be exploited for inhibition of Ras activation.

Constitutively active mutant KRas displays a reduced rate of GTP hydrolysis via both intrinsic and GTPase-activating protein-catalyzed mechanisms, resulting in the perpetual activation of Ras pathways. We describe a fragment screening campaign using X-ray crystallography that led to the discovery of three fragment binding sites on the Ras:SOS complex. The identification of tool compounds binding at each of these sites allowed exploration of two new approaches to Ras pathway inhibition by stabilizing or covalently modifying the Ras:SOS complex to prevent the reloading of Ras with GTP. Initially, we identified ligands that bound reversibly to the Ras:SOS complex in two distinct sites, but these compounds were not sufficiently potent inhibitors to validate our stabilization hypothesis. We conclude by demonstrating that covalent modification of Cys118 on Ras leads to a novel mechanism of inhibition of the SOS-mediated interaction between Ras and Raf and is effective at inhibiting the exchange of labeled GDP in both mutant (G12C and G12V) and wild type Ras

The legal regulation of Muslim dress is controversial in theUK, but education could help eradicate prejudice

Segments of British society continue to feel uneasy about the idea of Muslim religious dress, particularly when it concerns the covering of women’s faces. The recent debate triggered by a Birmingham court’s introduction and then reversion of a ban on defendants wearing the veil presents a meaningful opportunity for non-Muslims to learn about the significance of religious dress to Islam, argues Claire Overman

The “right to be forgotten” demonstrates the need for legislative coverage of internet data protection

The rise of social media, and the data gathering potential that it holds, have made the issue of online privacy increasingly prevalent, with citizens often unaware of what is being done with information they had previously assumed would be used responsibly. Commenting on a recent Court of Justice of the European Union case, Claire Overman argues that the need for legislative coverage of internet data protection has never been more sorely needed

The European Court of Human Rights’ decision in MH v UKhighlights the shortcomings in Britain’s mental health law

The European Court of Human Rights has ruled in MH v UK that the inability of a woman with Down’s Syndrome to challenge her detention in a hospital under the Mental Health Act 1983 violated her human rights. Claire Overman argues that this judgment throws a spotlight on the issue of the protection available to those with mental illnesses, and demonstrates that there are shortcomings in the existing regime of admission to hospital under the Act

Book review: human rights and democracy: the precarious triumph of ideals

Human Rights and Democracy: the Precarious Triumph of Ideals assesses the progress of human rights in and since the 20th Century, against a backdrop of repressive regimes and mass slaughter in a rigorous yet accessible way, writes Claire Overman. Despite some confusing structuring, Todd Landman illustrates the complexities of the human rights agenda in a way that non-experts and experts alike will find both convincing and readable

The Home Office’s exclusion of Dieudonné raises important issues regarding the protection of freedom of expression

The recent exclusion from the UK of French comedian Dieudonné M’Bala M’Bala raises important questions concerning the limits of freedom of expression. Whilst restrictions are certainly permissible under UK and European law, their justification must be clearly laid out, if freedom of expression is not to be unduly limited, says Claire Overman