The asymmetric spatial distribution of bacterial signal transduction proteins coordinates cell cycle events

The polar localization of signaling proteins that are essential for Caulobacter cell cycle control is temporally regulated. Here we provide evidence that phosphorylation of the essential response regulator, DivK, is required for both its function and its cell cycle-regulated localization. The asymmetric location of the DivJ and PleC histidine kinases and their antagonistic activities on the cellular concentration of phosphorylated DivK provide positional and temporal information for the ordered sequence of DivK localization during the cell cycle. DivJ activity on DivK affects its correct localization, which, in turn, is required for PleC function. Since DivJ and PleC regulate different cell cycle events, the interconnected function of these two histidine kinases through localization of a common response regulator provides a mechanism for coordinating cell cycle progression. Study of a DivK homolog in the morphologically symmetric bacterium Sinorhizobium meliloti suggests that this type of cell cycle mechanism is widespread in prokaryotes.     

On the sensitivity of wall stresses in diseased arteries to variable material properties

Accurate estimates of stress in an atherosclerotic lesion require knowledge of the material properties of its components (e.g., normal wall, fibrous plaque, calcified regions, lipid pools) that can only be approximated. This leads to considerable uncertainty in these computational predictions. A study was conducted to test the sensitivity of predicted levels of stress and strain to the parameter values of plaque used in finite element analysis. Results show that the stresses within the arterial wall, fibrous plaque, calcified plaque, and lipid pool have low sensitivities for variation in the elastic modulus. Even a +/- 50% variation in elastic modulus leads to less than a 10% change in stress at the site of rupture. Sensitivity to variations in elastic modulus is comparable between isotropic nonlinear, isotropic nonlinear with residual strains, and transversely isotropic linear models. Therefore, stress analysis may be used with confidence that uncertainty in the material properties generates relatively small errors in the prediction of wall stresses. Either isotropic nonlinear or anisotropic linear models provide useful estimates, however the predictions in regions of stress concentration (e.g., the site of rupture) are somewhat more sensitive to the specific model used, increasing by up to 30% from the isotropic nonlinear to orthotropic model in the present example. Changes resulting from the introduction of residual stresses are much smaller.     

A mathematical model of phytoremediation for petroleum contaminated soil: sensitivity analysis

Phytoremediation is an attractive treatment technology for many contaminated sites due to its cost effectiveness and public acceptance. We present a sensitivity analysis of important parameters from a screening level model for phytoremediation by grass species of weathered petroleum-contaminated sites. The conceptual framework is that root movement through contaminated soil will enhance contaminant biodegradation by providing a local environment more favorable for petroleum degrading microorganisms—the so-called rhizosphere effect. Common questions in phytoremediation are, “What species should be planted?” and “What management practices should be followed?” These choices may affect degradation kinetics, root biomass (and therefore rhizosphere volume), and the root turnover. Important model parameters are the rate constants, rhizosphere volume, and the rate of root turnover. We present a sensitivity analysis with the aim of identifying the most important factors for improving phytoremediation effectiveness. For simulations of the phytoremediation of weathered diesel range organics, our results indicate that annual species, with higher root turnover, are preferred over perennial species with the caveat of equal degradation rate constants, that is, no species-dependent effects. In addition, the results suggest that the management of nonrhizosphere soil could play an important role in the overall effectiveness of phytoremediation. Finally, the effect of increasing root biomass or increasing the rhizosphere thickness is approximately equivalent with respect to the ultimate removal of the contaminants.     

Expression of the baculovirus p35 protein in tobacco affects cell death progression and compromises N gene-mediated disease resistance response to Tobacco mosaic virus

The p35 protein from baculovirus is a broad-range caspase inhibitor and suppresses programmed cell death in animals. We report here the effects of transgenic expression in tobacco of the p35 protein during the hypersensitive response (HR). Expression of p35 causes partial inhibition of nonhost HR triggered by bacteria and gene-for-gene HR triggered by virus. Infection of p35-expressing tobacco plants with Tobacco mosaic virus (TMV) disrupts N-mediated disease resistance, causing systemic spreading of the virus within a resistant background. Mutant variants altered in aspartate residues within the loop region of p35 are inefficient substrates for caspases in vitro, and they do not suppress caspase proteolytic activity in animal systems. Tobacco plants expressing these mutant variants of the p35 protein do not show inhibition of HR cell death or enhanced virus systemic movement. Thus, HR inhibition and TMV systemic spreading phenotype in p35-expressing plants correlate with the ability of the p35 protein to suppress caspase activity in animal systems. In addition, a C-terminal truncated variant of p35 is unable to suppress cell death in animals as well as HR cell death in transgenic tobacco. Our results provide evidence for the participation of caspase-like proteases during the HR. In addition, they suggest that timely activation of cell death is necessary for effective TMV containment within the primary infection site.     

Synthesis of a novel family of diterpenes and their evaluation as anti-inflammatory agents

The synthesis and biological evaluation of a new family of diterpenes, represented by structures 2 and 3, is presented. These compounds constitute isomeric analogues of acanthoic acid (1) and were examined as potent anti-inflammatory agents. Among them, methyl ester 12 exhibited a low non-specific cytotoxicity, inhibited TNF-alpha synthesis and displayed good specificity in suppressing cytokine expression.     

B-cell maturation protein, which binds the tumor necrosis factor family members BAFF and APRIL, is dispensable for humoral immune responses

B-cell maturation protein (BCMA) is a member of the tumor necrosis factor (TNF) receptor family and is expressed in B lymphocytes. BCMA binds two TNF family members, BAFF and APRIL, that stimulate cellular proliferation. BAFF in particular has been shown to influence B-cell survival and activation, and transgenic mice overexpressing BAFF have a lupus-like autoimmune disorder. We have inactivated BCMA in the mouse germ line. BCMA(-/-) mice have normal B-cell development, and the life span of mutant B lymphocytes is comparable to that of wild-type B cells. The humoral immune responses of BCMA(-/-) mice to T-cell-independent antigens as well as high and low doses of T-cell-dependent antigens are also intact. In addition, mutant mice have normal splenic architecture, and germinal centers are formed during an ongoing immune response. These data suggest a functional redundancy of BCMA in B-cell physiology that is probably due to the presence of TACI, another TNF receptor family member that is expressed on B cells and that can also bind BAFF and APRIL.     

Nuclear targeting signal recognition: a key control point in nuclear transport?

Recent progress indicates that there are multiple pathways of nucleocytoplasmic transport which involve specific targeting sequences, such as nuclear localization sequences (NLSs), and cytosolic receptor molecules of the importin/karyopherin superfamily which recognise and dock the NLS-containing proteins at the nuclear pore. This first step of nuclear import/export is of central importance, with the affinity of the importin-targeting sequence interaction a critical parameter in determining transport efficiency. Different importins possess distinct NLS-binding specificities, which allows the system to be modulated through differential expression of the importins themselves, as well as through competition between different importins for the same protein, and between different proteins for the same importin. The targeting sequence-importin interaction can also be influenced directly by phosphorylation increasing the affinity of the interaction with importins or by targeting sequence masking through phosphorylation or specific protein binding. Targeting sequence recognition thus appears to represent a key control point in the regulation of nuclear transport. BioEssays 22:532-544, 2000.