Stress control of deep rift intrusion at Mauna Loa volcano, Hawaii

Mauna Loa volcano, Hawaii, deforms by a combination of shallow dike intrusions in the rift zones and earthquakes along the base of the volcano, but it is not known how the spreading is accommodated in the lower part of the volcanic edifice. We present evidence from interferometric synthetic aperture radar data for secular inflation of a dike-like magma body at intermediate depth in the southwest rift zone during 2002 to 2005. Magma accumulation occurred in a section of the rift zone that was unclamped by previous dikes and earthquakes, suggesting that stress transfer plays an important role in controlling subsurface magma accumulation.     

The vaccine adjuvant monophosphoryl lipid A as a TRIF-biased agonist of TLR4

The inflammatory toxicity of lipopolysaccharide (LPS), a component of bacterial cell walls, is driven by the adaptor proteins myeloid differentiation factor 88 (MyD88) and Toll-interleukin 1 receptor domain-containing adapter inducing interferon-beta (TRIF), which together mediate signaling by the endotoxin receptor Toll-like receptor 4 (TLR4). Monophosphoryl lipid A (MPLA) is a low-toxicity derivative of LPS with useful immunostimulatory properties, which is nearing regulatory approval for use as a human vaccine adjuvant. We report here that, in mice, the low toxicity of MPLA's adjuvant function is associated with a bias toward TRIF signaling, which we suggest is likely caused by the active suppression, rather than passive loss, of proinflammatory activity of this LPS derivative. This finding may have important implications for the development of future vaccine adjuvants.     

Preparation of native chromatin and damage caused by shearing

Chromatin prepared by a method involving limited nuclease digestion contains the same repeating structure as chromatin in the nucleus, whereas chromatin prepared by conventional methods involving shear does not.     

A small molecule Smac mimic potentiates TRAIL- and TNFalpha-mediated cell death

We describe the synthesis and properties of a small molecule mimic of Smac, a pro-apoptotic protein that functions by relieving inhibitor-of-apoptosis protein (IAP)-mediated suppression of caspase activity. The compound binds to X chromosome- encoded IAP (XIAP), cellular IAP 1 (cIAP-1), and cellular IAP 2 (cIAP-2) and synergizes with both tumor necrosis factor alpha (TNFalpha) and TNF-related apoptosis-inducing ligand (TRAIL) to potently induce caspase activation and apoptosis in human cancer cells. The molecule has allowed a temporal, unbiased evaluation of the roles that IAP proteins play during signaling from TRAIL and TNF receptors. The compound is also a lead structure for the development of IAP antagonists potentially useful as therapy for cancer and inflammatory diseases.