Inactivation of TNF signaling by rationally designed dominant-negative TNF variants

Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands.     

Island biology and ecosystem functioning in epiphytic soil communities

Although island attributes such as size and accessibility to colonizing organisms can influence community structure, the consequences of these for ecosystem functioning are little understood. A study of the suspended soils of spatially discrete epiphytes or treetop "islands" in the canopies of New Zealand rainforest trees revealed that different components of the decomposer community responded either positively or negatively to island size, as well as to the tree species that the islands occurred in. This in turn led to important differences between islands in the rates of ecosystem processes driven by the decomposer biota. This system serves as a model for better understanding how attributes of both real and habitat islands may affect key ecosystem functions through determining the community structure of organisms that drive these functions.     

Plant mycoplasmas: a cultivable spiroplasma causes corn stunt disease

A spiroplasma can be isolated and grown continuously in cell-free medium from stunted corn or from Drosophila injected with sap expressed from diseased corn. The organism is serologically related to, but not identical with, Spiroplasma citri, the causative agent of citrus stubborn disease. Leafhopers injected with cultured organisms induced typical symptoms of the corn stunt disease when placed on previously healthy corn plants.     

Temporal variability of the Atlantic meridional overturning circulation at 26.5 degrees N

The vigor of Atlantic meridional overturning circulation (MOC) is thought to be vulnerable to global warming, but its short-term temporal variability is unknown so changes inferred from sparse observations on the decadal time scale of recent climate change are uncertain. We combine continuous measurements of the MOC (beginning in 2004) using the purposefully designed transatlantic Rapid Climate Change array of moored instruments deployed along 26.5 degrees N, with time series of Gulf Stream transport and surface-layer Ekman transport to quantify its intra-annual variability. The year-long average overturning is 18.7 +/- 5.6 sverdrups (Sv) (range: 4.0 to 34.9 Sv, where 1 Sv = a flow of ocean water of 10(6) cubic meters per second). Interannual changes in the overturning can be monitored with a resolution of 1.5 Sv.     

Genome streamlining in a cosmopolitan oceanic bacterium

The SAR11 clade consists of very small, heterotrophic marine alpha-proteobacteria that are found throughout the oceans, where they account for about 25% of all microbial cells. Pelagibacter ubique, the first cultured member of this clade, has the smallest genome and encodes the smallest number of predicted open reading frames known for a free-living microorganism. In contrast to parasitic bacteria and archaea with small genomes, P. ubique has complete biosynthetic pathways for all 20 amino acids and all but a few cofactors. P. ubique has no pseudogenes, introns, transposons, extrachromosomal elements, or inteins; few paralogs; and the shortest intergenic spacers yet observed for any cell.     

Climatic control of riverine and seawater uranium-isotope ratios

The large variation in the ratio of uranium-234 to uranium-238 (234U/238U) in rivers is not well understood, but may provide information about past weathering and rainfall and is important because it controls seawater (234U/238U). Here, we demonstrate the importance of physical weathering and rainfall for (234U/238U), using rivers from South Island, New Zealand. These data allow interpretation of an existing speleothem (234U/238U) record and suggest that New Zealand glacier advance 13,000 years ago was influenced by increased rainfall rather than by Younger Dryas-like cooling. A model of seawater (234U/238U) during glacial cycles indicates that rejection of corals based on modern (234U/238U) +/- <0.01 is not merited and may reject the highest quality ages.