Schwannoma-Derived Growth Factor Interacts with the Epidermal Growth Factor Receptor

Abstract: Schwannoma-derived growth factor (SDGF) is a potent mitogen and neuronal differentiation factor. Because of its relationship to epidermal growth factor (EGF) and the heregulins, it was asked if SDGF interacts with the EGF receptor or HER2/neu. SDGF binds to and causes the phosphorylation on tyrosine of the EGF receptor but not HER2/neu.     

Modelling HIV immune response and validation with clinical data

A system of ordinary differential equations is formulated to describe the pathogenesis of HIV infection, wherein certain features that have been shown to be important by recent experimental research are incorporated in the model. These include the role of CD4+memory cells that serve as a major reservoir of latently infected cells, a critical role for T-helper cells in the generation of CD8 memory cells capable of efficient recall response, and stimulation by antigens other than HIV. A stability analysis illustrates the capability of this model in admitting multiple locally asymptotically stable (locally a.s.) off-treatment equilibria. We show that this more biologically detailed model can exhibit the phenomenon of transient viremia experienced by some patients on therapy with viral load levels suppressed below the detection limit. We also show that the loss of CD4+T-cell help in the generation of CD8+memory cells leads to larger peak values for the viral load during transient viremia. Censored clinical data is used to obtain parameter estimates. We demonstrate that using a reduced set of 16 free parameters, obtained by fixing some parameters at their population averages, the model provides reasonable fits to the patient data and, moreover, that it exhibits good predictive capability. We further show that parameter values obtained for most clinical patients do not admit multiple locally a.s off-treatment equilibria. This suggests that treatment to move from a high viral load equilibrium state to an equilibrium state with a lower (or zero) viral load is not possible for these patients.     

Recruitment of Nox4 to a Plasma Membrane Scaffold Is Required for Localized Reactive Oxygen Species Generation and Sustained Src Activation in Response to Insulin-like Growth Factor-I

Nox4-derived ROS is increased in response to hyperglycemia and is required for IGF-I-stimulated Src activation. This study was undertaken to determine the mechanism by which Nox4 mediates sustained Src activation. IGF-I stimulated sustained Src activation, which occurred primarily on the SHPS-1 scaffold protein. In vitro oxidation experiments indicated that Nox4-derived ROS was able to oxidize Src when they are in close proximity, and Src oxidation leads to its activation. Therefore we hypothesized that Nox4 recruitment to the plasma membrane scaffold SHPS-1 allowed localized ROS generation to mediate sustained Src oxidation and activation. To determine the mechanism of Nox4 recruitment, we analyzed the role of Grb2, a component of the SHPS-1 signaling complex. We determined that Nox4 Tyr-491 was phosphorylated after IGF-I stimulation and was responsible for Nox4 binding to the SH2 domain of Grb2. Overexpression of a Nox4 mutant, Y491F, prevented Nox4/Grb2 association. Importantly, it also prevented Nox4 recruitment to SHPS-1. The role of Grb2 was confirmed using a Pyk2 Y881F mutant, which blocked Grb2 recruitment to SHPS-1. Cells expressing this mutant had impaired Nox4 recruitment to SHPS-1. IGF-I-stimulated downstream signaling and biological actions were also significantly impaired in Nox4 Y491F-overexpressing cells. Disruption of Nox4 recruitment to SHPS-1 in aorta from diabetic mice inhibited IGF-I-stimulated Src oxidation and activation as well as cell proliferation. These findings provide insight into the mechanism by which localized Nox4-derived ROS regulates the sustained activity of a tyrosine kinase that is critical for mediating signal transduction and biological actions.     

Gas exchange and resource-use patterns along a Mediterranean successional gradient

Abstract. Gas exchange, leaf-nitrogen concentration and water potential were measured in early and late spring in early successional herbaceous plants occurring after cutting and after fire, and in mature woody species from the Mediterranean climax community Quercetum ilicis in central Italy. Net photosynthesis peaked in early spring in all species studied when values for temperature and light were lower but leaf-nitrogen content was higher as compared to late spring, suggesting that nitrogen more than energy input controlled photosynt-hetic rates. Herbaceous pioneer species occurring after cutting showed higher field photo synthetic capacity than evergreen climax trees and shrubs. By contrast, net photosynthesis of herbaceous species occurring in a persistent stage after fire, was in the same range as that of climax trees. This evidence suggests that carbon-gaining appears to be partly related to the dynamic stage of succession and not solely to the growth form.     

Reduced sexual dimorphism in upper arm muscle circumference associated with protein-deficient diet in a South American population

Animal experiments have demonstrated that individuals exhibit differing tendencies to arrest growth and resorb muscle tissue under nutritional stress. Since placental and adrenocortical hormones are active in promoting muscle tissue resorption, sex differences may exist. In order to identify such sex differences, the upper arm circumferences of 362 individuals, aged one to 60 years, living in an area of chronic protein-calorie malnutrition were compared by age and sex with published data collected from U.S. and highland Peruvian populations. Sexual dimorphism for arm muscle circumference in the malnourished population is less than in U.S. samples of comparable age-categories. The highland population is closer to U.S. samples in the degree of dimorphism. The reduction in muscle circumference of males in the malnourished population appears to be the cause of the comparatively greater similarity of the sexes where protein-calorie malnutrition is experienced from infancy through adolescence. High muscle relief and excellent tonus in these same males indicate that reduced muscle circumference is not the result of flaccidity or higher ratios of compressible fat to muscle tissue. Reduction of muscle tissue in undernourished males is a reduction in total metabolic demand. Such reductions are adaptive in areas of chronic nutritional stress.     

Abalone I: Analyzing Mark-Recapture-Recovery Data Incorporating Growth and Delayed Recovery

Abalone are semimobile marine gastropods that form the basis of Australia's second most valuable fishery. A site off the coast of Port Arthur, Tasmania, was visited on six occasions. On each occasion, any unmarked live abalone found were marked with a unique identification number and were recorded. Any previously marked abalone found had its identification number and whether or not it was still alive recorded. This results in integrated mark-recapture-recovery data, as in Catchpole et al. (1998, Biometrics 54, 33-46). During the study period, abalone grew in size, and we model the survival of individuals as a function of their size, estimated from a fitted growth curve. The shells of dead animals are long lasting, and we extend existing methodology to allow for the possibility that an animal found dead may have been dead but overlooked for several visits.     

Effects of clipping and soil compaction on growth,morphology and mycorrhizal colonization of Schizachyrium scoparium,a C4 bunchgrass

Summary A factorial design of clipping and compaction was used to study the responses of Schizachyrium scoparium and its mycorrhizal symbionts to these stresses. All treatment combinations significantly reduced the growth and biomass of plants relative to controls. Compaction significantly reduced tillering and crown expansion while clipping increased tillering early in the growing season and reduced it later. Mycorrhizal colonization of roots was highest in the clipped plots and lowest in compacted plots. Spore number was highest in compacted plots and lowest in clipped plots. It appears that spore number may be negatively correlated with root growth since any treatment that reduced plant growth yielded higher spore numbers. The combination of clipping and compaction reduced plant growth the most, but had intermediate effects on mycorrhizal colonization and spore number.     

Cooperation of epidermis and inner tissues in auxin-mediated growth of maize coleoptiles

The function of the epidermis in auxinmediated elongation growth of maize (Zea mays L.) coleoptile segments was investigated. The following results were obtained: i) In the intact organ, there is a strong tissue tension produced by the expanding force of the inner tissues which is balanced by the contracting force of the outer epidermal wall. The compression imposed by the stretched outer epidermal wall upon the inner tissues gives rise to a wall-pressure difference which can be transformed into a water-potential difference between inner tissues and external medium (water) by removal of the outer epidermal wall. ii) Peeled segments fail to respond to auxin with normal growth. The plastic extensibility of the inner-tissue cell walls (measured with a constant-load extensiometer using living segments) is not influenced by auxin (or abscisic acid) in peeled or nonpeeled segments. It is concluded that auxin induces (and abscisic acid inhibits) elongation of the intact segment by increasing (decreasing) the extensibility specifically in the outer epidermal wall. In addition, tissue tension (and therewith the pressure acting on the outer epidermal wall) is maintained at a constant level over several hours of auxin-mediated growth, indicating that the inner cells also contribute actively to organ elongation. However, this contribution does not involve an increase of cell-wall extensibility, but a continuous shifting of the potential extension threshold (i.e., the length to which the inner tissues would extend by water uptake after peeling) ahead of the actual segment length. Thus, steady growth involves the coordinated action of wall loosening in the epidermis and regeneration of tissue tension by the inner tissues. iii) Electron micrographs show the accumulation of striking osmiophilic material (particles of approx. 0.3 m diameter) specifically at the plasma membrane/cell-wall interface of the outer epidermal wall of auxin-treated segments. iv) Peeled segments fail to respond to auxin with proton excretion. This is in contrast to fusicoccin-induced proton excretion and growth which can also be readily demonstrated in the absence of the epidermis. However, peeled and nonpeeled segments show the same sensitivity to protons with regard to the induction of acid-mediated in-vivo elongation and cell-wall extensibility. The observed threshold at pH 4.5–5.0 is too low to be compatible with a second messenger function of protons also in the growth response of the inner tissues. Organ growth is described in terms of a physical model which takes into account tissue tension and extensibility of the outer epidermal wall as the decisive growth parameters. This model states that the wall pressure increment, produced by tissue tension in the outer epidermal wall, rather than the pressure acting on the inner-tissue walls, is the driving force of growth.Abbreviations and symbols E _el, E _pl elastic and plastic in-vitro cell-wall extensibility, respectively - E _tot E _el+E _pl - FC fusicoccin - IAA indole-3-acetic acid - IT inner tissue - ITW inner-tissue walls - OEW outer epidermal wall - osmotic pressure - P wall pressure - water potential     

Growth responses of tropical forage plant species to vesicular-arbuscular mycorrhizae

Summary Growth and mineral uptake of twenty-four tropical forage legumes and grasses were compared under glasshouse conditions in a sterile low P oxisol, one part inoculated and the other not inoculated with mycorrhizal fungi. Shoot and root dry weights and total uptake of P, N, K, Ca, and Mg of all the test plants were significantly increased by mycorrhizal inoculation. Mycorrhizal inoculation, with few exceptions, decreased the root/shoot ratio. Non-mycorrhizal plants contained always lower quantities of mineral elements than mycorrhizal plants. Plant species showed differences in percentage mycorrhizal root length and there was no correlation between percentage mycorrhizal infection and plant growth parameters. A great variation in dependence on mycorrhiza was observed among forage species. Total uptake of all elements by non-mycorrhizal legumes and uptake of P, N and K by non-mycorrhizal grasses correlated inversely with mycorrhizal dependency. Mycorrhizal plants of all species used significantly greater quantities of soil P than the nonmycorrhizal plants. Utilization of soil P by non-mycorrhizal plants was correlated inversely with mycorrhizal dependency.