Person:

Zhou, Yan

Escherichia coli-induced meningitis remains a life-threatening disease despite recent advances in the field of antibiotics-based therapeutics, necessitating continued research on its pathogenesis. The current study aims to elucidate the mechanism through which hemolysin-coregulated protein 1 (Hcp1) induces the apoptosis of human brain microvascular endothelial cells (HBMEC). Co-immunoprecipitation coupled with mass spectrometric (MS) characterization led to the identification of IQ motif containing GTPase activating protein 1 (IQGAP1) as a downstream target of Hcp1. IQGAP1 was found to be up-regulated by Hcp1 treatment and mediate the stimulation of HBMEC apoptosis. It was shown that Hcp1 could compete against Smurf1 for binding to IQGAP1, thereby rescuing the latter from ubiquitin-dependent degradation. Subsequent study suggested that IQGAP1 could stimulate the MAPK signaling pathway by promoting the phosphorylation of ERK1/2, an effect that was blocked by U0126, an MAPK inhibitor. Furthermore, U0126 also demonstrated therapeutic potential against E. coli meningitis in a mouse model. Taken together, our results suggested the feasibility of targeting the MAPK pathway as a putative therapeutic strategy against bacterial meningitis.

What does it mean in practice for a company to respect human rights? The paper examines the operational implications of a "corporate responsibility to respect human rights", a pillar of the recent framework put forward by UN SRSG John Ruggie under the title "Protect, Respect and Remedy." The authors define an approach to due diligence based on assessing the risk of company involvement in human rights violations. The authors draw on the work of Statoil Hydro in developing a human rights risk assessment method for its global operations and argue that due diligence and risk are proven approaches to guarding against social harm by companies. The paper outlines a practical approach to human rights due diligence based on the assumption that the nature of a company's business activities and relationships decides the environment of human rights risk in which the company must operate. The authors argue that companies are able to exercise greater control over their exposure to human right related risk than generally assumed possible and that an empirically-grounded, risk-based approach to due diligence permits companies to more effectively manage their responsibility to respect human rights and their responsibility to turn a profit.