Pattern sensitivity to boundary and initial conditions in reaction-diffusion models

We consider Turing-type reaction-diffusion equations and study (via computer simulations) how the relationship between initial conditions and the asymptotic steady state solutions varies as a function of the boundary conditions. The results indicate that boundary conditions which are non-homogeneous with respect to the kinetic steady state give rise to spatial patterns which are much less sensitive to variations in the initial conditions than those obtained with homogeneous boundary conditions, such as zero flux conditions. We also compare linear pattern predictions with the numerical solutions of the full nonlinear problem.This work supported in part by U.S. Army Grant DAJA 37-81-C-0220 and the Science and Engineering Research Council of Great Britain Grant GR/c/63595     

Molecular characteristics of receptors for atrial natriuretic factor

Specific, high-affinity receptors for atrial natriuretic factor (ANF) have been identified on membranes from a variety of tissues and cultured cells. By affinity labeling procedures, radioactivity from 125I-labeled ANF was specifically incorporated into three different polypeptides of ca. 120,000, 70,000, and 60,000 daltons, which may represent the binding subunits of ANF receptors. These polypeptides were present in varying amounts in different target tissues. In rat adrenal membranes, the 120,000- and 70,000-dalton peptides were specifically labeled whereas in A10 rat smooth muscle cells, only the 60,000-dalton peptide was labeled. Membranes from rat kidney and rabbit aorta contain all three peptides. Gel filtration chromatography of solubilized receptors suggested that intact ANF receptors are large molecular complexes with apparent molecular masses in the range of 250,000-350,000 daltons. The differential labeling pattern observed with the various tissues suggested that there might be at least two different receptors composed of unique ANF-binding polypeptides.     

Experimental alteration of DNA methylation affects the phenotypic plasticity of ecologically relevant traits in <Emphasis Type="Italic">Arabidopsis thaliana</Emphasis>

Heritable phenotypic variation in plants can be caused not only by underlying genetic differences, but also by variation in epigenetic modifications such as DNA methylation. However, we still know very little about how relevant such epigenetic variation is to the ecology and evolution of natural populations. We conducted a greenhouse experiment in which we treated a set of natural genotypes of Arabidopsis thaliana with the demethylating agent 5-azacytidine and examined the consequences of this treatment for plant traits and their phenotypic plasticity. Experimental demethylation strongly reduced the growth and fitness of plants and delayed their flowering, but the degree of this response varied significantly among genotypes. Differences in genotypes’ responses to demethylation were only weakly related to their genetic relatedness, which is consistent with the idea that natural epigenetic variation is independent of genetic variation. Demethylation also altered patterns of phenotypic plasticity, as well as the amount of phenotypic variation observed among plant individuals and genotype means. We have demonstrated that epigenetic variation can have a dramatic impact on ecologically important plant traits and their variability, as well as on the fitness of plants and their ecological interactions. Epigenetic variation may thus be an overlooked factor in the evolutionary ecology of plant populations.     

A T-cell HCV vaccine eliciting effective immunity against heterologous virus challenge in chimpanzees

Three percent of the world's population is chronically infected with the hepatitis C virus (HCV) and at risk of developing liver cancer. Effective cellular immune responses are deemed essential for spontaneous resolution of acute hepatitis C and long-term protection. Here we describe a new T-cell HCV genetic vaccine capable of protecting chimpanzees from acute hepatitis induced by challenge with heterologous virus. Suppression of acute viremia in vaccinated chimpanzees occurred as a result of massive expansion of peripheral and intrahepatic HCV-specific CD8(+) T lymphocytes that cross-reacted with vaccine and virus epitopes. These findings show that it is possible to elicit effective immunity against heterologous HCV strains by stimulating only the cellular arm of the immune system, and suggest a path for new immunotherapy against highly variable human pathogens like HCV, HIV or malaria, which can evade humoral responses.     

Effect of NGF on the Subcellular Localization of Group IIA Secretory Phospholipase A2 (GIIA) in PC12 Cells: Role in Neuritogenesis

Phospholipases A(2) (PLA(2)s) are involved in neuritogenesis but the identity of the isoforms(s) contributing to this process is still not defined. Several reports have focused on secretory PLA(2)s (sPLA(2)) as the administration of exogenous sPLA(2)s to PC12 neuronal cells stimulates neurite outgrowth. The present study demonstrates that the endogenous group IIA sPLA(2) (GIIA), constitutively expressed in mammalian neural cells, changes its subcellular localization when PC12 cells are induced to differentiate by NGF treatment. Indeed, confocal analysis showed a time-dependent accumulation of GIIA in growth cones and neurite tips. Under identical conditions the subcellular distribution of another isoform (GV) was unaffected by NGF. Contrary to GX, another sPLA(2) isoform expressed by PC12 cells, the contribution of GIIA to neuritogenesis does not require its release in the extracellular medium.     

Molecular models of NS3 protease variants of the Hepatitis C virus

Background  

Hepatitis C virus (HCV) currently infects approximately three percent of the world population. In view of the lack of vaccines against HCV, there is an urgent need for an efficient treatment of the disease by an effective antiviral drug. Rational drug design has not been the primary way for discovering major therapeutics. Nevertheless, there are reports of success in the development of inhibitor using a structure-based approach. One of the possible targets for drug development against HCV is the NS3 protease variants. Based on the three-dimensional structure of these variants we expect to identify new NS3 protease inhibitors. In order to speed up the modeling process all NS3 protease variant models were generated in a Beowulf cluster. The potential of the structural bioinformatics for development of new antiviral drugs is discussed.     

History of yield improvements in the production of asperlicin byAspergillus alliaceus

Summary The natural product asperlicin is the first nonpeptide antagonist of cholecystokinin isolated from a microbial source. At discovery, production of asperlicin by the original soil isolate ofAspergillus alliaceus was between 15 and 30 mg/l. Selection of natural variants ofA. alliaceus, use of Plackett & Burman and Simplex experimental designs; formulation of synthetic media; amino acid supplementation of production media; analysis of complex nitrogen sources for their amino acid content; evaluation of promising media in fermentors; substitution of glycerol for glucose as a carbon source and rational mutant selection all contributed to titer increases to >900 mg/l.