Addressing Health Disparities Through Voter Engagement.

Although the public's essential capacity for self-rule in the United States lies in the power of the ballot, there exist many barriers to voting, particularly for marginalized communities. These barriers cultivate less representative government and less inclusive public policy. Nonprofit and private health organizations, and in particular community health centers and safety-net hospitals, can help marginalized voting-eligible individuals overcome barriers to the ballot. With augmented, unbiased voter participation, elections would yield government that is more representative and public policy that is more equitable, while reducing costly and preventable health disparities. Health organizations can promote comprehensive, nonpartisan voter engagement through registration, mobilization, education, and protection of all voters.

HIV prevention: A 3-pronged approach.

HIV infection may not command the headlines it once did, but the public health threat it poses is still formidable. These steps can help us get ahead of it.

RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels.

Therapeutics that discriminate between the genetic makeup of normal cells and tumour cells are valuable for treating and understanding cancer. Small molecules with oncogene-selective lethality may reveal novel functions of oncoproteins and enable the creation of more selective drugs. Here we describe the mechanism of action of the selective anti-tumour agent erastin, involving the RAS-RAF-MEK signalling pathway functioning in cell proliferation, differentiation and survival. Erastin exhibits greater lethality in human tumour cells harbouring mutations in the oncogenes HRAS, KRAS or BRAF. Using affinity purification and mass spectrometry, we discovered that erastin acts through mitochondrial voltage-dependent anion channels (VDACs)--a novel target for anti-cancer drugs. We show that erastin treatment of cells harbouring oncogenic RAS causes the appearance of oxidative species and subsequent death through an oxidative, non-apoptotic mechanism. RNA-interference-mediated knockdown of VDAC2 or VDAC3 caused resistance to erastin, implicating these two VDAC isoforms in the mechanism of action of erastin. Moreover, using purified mitochondria expressing a single VDAC isoform, we found that erastin alters the permeability of the outer mitochondrial membrane. Finally, using a radiolabelled analogue and a filter-binding assay, we show that erastin binds directly to VDAC2. These results demonstrate that ligands to VDAC proteins can induce non-apoptotic cell death selectively in some tumour cells harbouring activating mutations in the RAS-RAF-MEK pathway.