Profiling of the secreted proteins during 3T3-L1 adipocyte differentiation leads to the identification of novel adipokines

Adipose tissue is an endocrine organ capable of secreting a number of adipokines with a role in the regulation of adipose tissue and whole-body metabolism. We used two-dimensional gel electrophoresis combined with mass spectrometry to profile the secreted proteins from (pre)adipocytes. The culture medium of 3T3-L1 cells during adipocyte differentiation was screened, and 41 proteins that responded to blocking of secretion by 20°C treatment and/or brefeldin A treatment were identified. Prohibitin, stress-70 protein, and adhesion-regulating molecule 1 are reported for the first time as secreted proteins. In addition, procollagen C-proteinase enhancer protein, galectin-1, cyclophilin A and C, and SF20/IL-25 are newly identified as adipocyte secreted factors. Secretion profiles indicated a dynamic environment including an actively remodeling extracellular matrix and several factors involved in growth regulation.Received 15 June 2004; received after revision 26 July 2004; accepted 2 August 2004     

Widespread uplift and 'trapdoor' faulting on Galápagos volcanoes observed with radar interferometry

Volcanic uplift, caused by the accumulation of magma in subsurface reservoirs, is a common precursor to eruptions. But, for some volcanoes, uplift of metres or more has not yet led to an eruption. Here we present displacement maps of volcanoes in the Galápagos Islands, constructed using satellite radar interferometry, that might help explain this dichotomy. We show that all but one of the seven volcanoes on the islands of Isabela and Fernandina deformed during 1992-99. Cerro Azul and Fernandina erupted during the observation period and show evidence of inflation, co-eruptive deflation and shallow dyke intrusion. In contrast, the largest volcano, Sierra Negra, has not erupted, yet exhibits spatially and temporally variable deformation, with a maximum uplift of 2.7 m between 1992 and 1999, which can be modelled by a shallow inflating sill. Inflation during 1997-98, however, was accompanied by 'trapdoor' faulting on a steeply dipping fracture system within the caldera. Repeated trapdoor faulting over geological time has formed an arcuate intra-caldera ridge within Sierra Negra and may have acted to relax stresses above the magma chamber, inhibiting summit eruptions. Similar processes may help explain large uplift unaccompanied by eruptive activity at other volcanoes.     

TLR4 mutations are associated with endotoxin hyporesponsiveness in humans

There is much variability between individuals in the response to inhaled toxins, but it is not known why certain people develop disease when challenged with environmental agents and others remain healthy. To address this, we investigated whether TLR4 (encoding the toll-like receptor-4), which has been shown to affect lipopolysaccharide (LPS) responsiveness in mice, underlies the variability in airway responsiveness to inhaled LPS in humans. Here we show that common, co-segregating missense mutations (Asp299Gly and Thr399Ile) affecting the extracellular domain of the TLR4 receptor are associated with a blunted response to inhaled LPS in humans. Transfection of THP-1 cells demonstrates that the Asp299Gly mutation (but not the Thr399Ile mutation) interrupts TLR4-mediated LPS signalling. Moreover, the wild-type allele of TLR4 rescues the LPS hyporesponsive phenotype in either primary airway epithelial cells or alveolar macrophages obtained from individuals with the TLR4 mutations. Our findings provide the first genetic evidence that common mutations in TLR4 are associated with differences in LPS responsiveness in humans, and demonstrate that gene-sequence changes can alter the ability of the host to respond to environmental stress.     

The accumulation pattern of ingested gossypol in selected organs of the rat.

Bound gossypol levels in the spleen and kidney of rats ingesting dietary gossypol (0.98%) varied directly with the feeding intervals of 6, 14, 28 and 35 days. Free gossypol level in the kidney, spleen and lungs increased for 14 days and then tended to decrease as the feeding period was extended.