Prevention and treatment of respiratory syncytial virus bronchiolitis and postbronchiolitic wheezing

Growth factors mediate tissue interactions and regulate a variety of cellular functions that are critical for normal lung development and homeostasis. Besides their involvement in lung pattern formation, growth and cell differentiation during organogenesis, these factors have been also implicated in modulating injury-repair responses of the adult lung. Altered expression of growth factors, such as transforming growth factor β1, vascular endothelial growth factor and epidermal growth factor, and/or their receptors, has been found in a number of pathological lung conditions. In this paper, we discuss the dual role of these molecules in mediating beneficial feedback responses or responses that can further damage lung integrity; we shall also discuss the basis for their prospective use as therapeutic agents.     

Mammalian progesterone receptor shows differential sensitivity to sulfhydryl group modifying agents when bound to agonist and antagonist ligands

Modulation of calf uterine progesterone receptor (PR), in relation to its binding to synthetic steroids with known agonist (R5020) and antagonist (RU486) properties, was studied in the presence of iodoacetamide (IA), N-ethylmaleimide (NEM), beta-mercaptoethanol (MER), and dithiothreitol (DTT). Pretreatment of uterine cytosol at 4 degrees C with NEM (4-10 mM) reduced the binding of [3H]RU486 to PR by 40%, but [3H] R5020 binding was completely abolished. Whereas IA (2-10 mM) treatment did not affect [3H]RU486 binding, [3H]R5020 binding was totally eliminated. DTT or MER increased the binding of both steroids slightly (15%). [3H]R5020- or [3H]RU486-receptor complexes (Rc) migrated in the 8 S region and were eliminated upon pretreatment with NEM. At 23 degrees C, DTT increased the amount of 4 S [3H]R5020-Rc, but had no effect on the [3H]RU486-Rc. In the control, [3H]RU486 binding to the 8 S PR could be competed with radioinert R5020 or RU486, but R5020 failed to compete in the presence of IA. The heat-treated [3H]R5020- and [3H]RU486-Rc showed reduced binding to DNA-cellulose in the presence of NEM and IA. The results of our study suggest that SH group modifications differentially influence the properties of mammalian PR complexed with either R5020 or RU486. In the presence of IA, the [3H]RU486-Rc remained in the 8 S form when incubated at 23 degrees C, indicating that RU486 binding causes conformational changes in PR which are distinct from those that result upon R5020 binding.     

Uncoupling of protein kinase D from suppression of EGF-dependent c-Jun phosphorylation in cancer cells

Protein kinase D (PKD) has been established as a negative modulator of the c-Jun N-terminal kinase (JNK) signaling pathway. We previously demonstrated that induced expression of constitutively active PKD (PKD-S744/748E) that mimics phosphorylation by PKC is sufficient to attenuate epidermal growth factor (EGF) stimulated c-Jun Ser 63 phosphorylation, a natural substrate of JNK, in HEK 293 cells. Because the JNK pathway has been implicated in sustaining both lung and pancreatic cancerous phenotypes, we have utilized stable inducible expression of PKD-S744/748E in clones of A549 non-small cell lung cancer (NSCLC) and Panc1, pancreatic cancer cells to determine its effects on JNK signaling in the context of the cancerous phenotype. In contrast to HEK 293 cells, induced expression of PKD-S744/748E in either A549 NSCLC or Panc1 cells failed to attenuate EGF dependent phosphorylation of c-Jun, indicating that EGF stimulated JNK phosphorylation of c-Jun is uncoupled from PKD suppression in these cancer cells.     

Disturbance,coral reef communities,and changing ecological paradigms

We examine changing ecological theory regarding the role of disturbance in natural communities and relate past and emerging paradigms to coral reefs. We explore the elements of this theory, including patterns (diversity, distribution, and abundance) and processes (competition, succession, and disturbance), using currently evolving notions concerning matters of scale (temporal and spatial), local versus regional species richness, and the equilibrium versus nonequilibrium controversy. We conclude that any attempt to categorize coral reef communities with respect to disturbance regimes will depend on the question being asked and the desired level of resolution: local assemblage versus regional species pool, successional versus geological time, and on the taxonomic and tropic affinities of species included in the study. As with many communities in nature, coral reefs will prove to be mosaics of species assemblages with equilibrial and nonequilibrial dynamics.     

Boundary-layers around bladed aquatic macrophytes

This paper describes a model of the diffusive boundary-layer around anaquatic macrophyte blade. Nutrient uptake at the base of the modelledboundary-layer was examined using previously published laboratory data. Theanalysis showed that, over the outer velocity range 0.01–0.16ms^–1, nutrient uptake varied between that predicted byflat-plate boundary-layer theory and that expected with no mean advection. Aratio of theoretical and actual nutrient uptake rates was defined as a meansof categorising the transition between the two transport models. Themodelling was extended to show how fluctuating boundary conditions mayenhance nutrient uptake by the macrophyte; the scenario examined heresuggested that at otherwise low outer velocities, periodic stripping of theboundary-layer by passing waves increased nutrient uptake by a factor of 10.