Biological activity exceeds biogenic structure in influencing sediment nitrogen cycling in experimental oyster reefs

Oysters are estuarine ecosystem engineers, in that their physical structure and biological function affect ecosystem processes such as organic matter and nutrient cycling. Oysters deliver material to the sediments through biodeposition and sedimentation caused by modification of flow around the reef. We conducted an experiment to distinguish between biotic effects and physical structure of oyster reefs on sediment nitrogen cycling. Experimental reefs consisting of live oysters, oyster shells alone and mudflats (controls) were sampled for a period of 4 wk for sediment organic matter, C and N content and fluxes of nitrogen (NH4 +, NOX and N2) and oxygen (O2). We hypothesized that the biological activity of the oyster would deposit more, higher quality organic matter compared to deposition from flow modification alone, thus facilitating denitrification and having a larger impact on sediment nitrogen cycling. Compared to the controls, the live oyster experimental reefs increased sediment denitrification by 61% and the shell experimental reefs showed a 24% increase. The live oyster experimental reef also had the largest O2 demand and NH4 + production. Reef structure likely increased organic matter deposition, but the higher quality and larger quantity of organic matter associated with live oysters increased denitrification and microbial respiration. This experiment shows that the ecosystem service of nitrogen removal provided by oysters is primarily driven by the biological function of the oysters and secondarily from the physical structure of the reef. Our increased understanding of how oysters engineer ecosystems and modify nutrient cycling can help guide future oyster restoration effort

Mechanism of homodimeric cytokine receptor activation and dysregulation by oncogenic mutations

Homodimeric class I cytokine receptors are assumed to exist as preformed dimers that are activated by ligand-induced conformational changes. We quantified the dimerization of three prototypic class I cytokine receptors in the plasma membrane of living cells by single-molecule fluorescence microscopy. Spatial and spatiotemporal correlation of individual receptor subunits showed ligand-induced dimerization and revealed that the associated Janus kinase 2 (JAK2) dimerizes through its pseudokinase domain. Oncogenic receptor and hyperactive JAK2 mutants promoted ligand-independent dimerization, highlighting the formation of receptor dimers as the switch responsible for signal activation. Atomistic modeling and molecular dynamics simulations based on a detailed energetic analysis of the interactions involved in dimerization yielded a mechanistic blueprint for homodimeric class I cytokine receptor activation and its dysregulation by individual mutations.</p

Design and Function of a Dendrimer-Based Therapeutic Nanodevice Targeted to Tumor Cells Through the Folate Receptor

Purpose . We sought to develop nanoscale drug delivery materials that would allow targeted intracellular delivery while having an imaging capability for tracking uptake of the material. A complex nanodevice was designed and synthesized that targets tumor cells through the folate receptor.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41493/1/11095_2004_Article_378868.pd

IL-4 receptor-alpha-dependent control of Cryptococcus neoformans in the early phase of pulmonary infection

Cryptococcus neoformans is an opportunistic fungal pathogen that causes lung inflammation and meningoencephalitis in immunocompromised people. Previously we showed that mice succumb to intranasal infection by induction of pulmonary interleukin (IL)-4Rα-dependent type 2 immune responses, whereas IL-12-dependent type 1 responses confer resistance. In the experiments presented here, IL-4Rα −/− mice unexpectedly show decreased fungal control early upon infection with C. neoformans , whereas wild-type mice are able to control fungal growth accompanied by enhanced macrophage and dendritic cell recruitment to the site of infection. Lower pulmonary recruitment of macrophages and dendritic cells in IL-4Rα −/− mice is associated with reduced pulmonary expression of CCL2 and CCL20 chemokines. Moreover, IFN-γ and nitric oxide production are diminished in IL-4Rα −/− mice compared to wild-type mice. To directly study the potential mechanism(s) responsible for reduced production of IFN-γ, conventional dendritic cells were stimulated with C. neoformans in the presence of IL-4 which results in increased IL-12 production and reduced IL-10 production. Together, a beneficial role of early IL-4Rα signaling is demonstrated in pulmonary cryptococcosis, which contrasts with the well-known IL-4Rα-mediated detrimental effects in the late phase