Two signaling mechanisms for activation of alphaM beta2 avidity in polymorphonuclear neutrophils

Circulating polymorphonuclear neutrophils (PMN) are quiescent, nonadherent cells that rapidly activate at sites of inflammation, where they develop the capacity to perform a repertoire of functions that are essential for host defense. Induction of integrin-mediated adhesion, which requires an increase in integrin avidity, is critical for the development of these effector functions. Although a variety of stimuli can activate integrins in PMN, the signaling cascades involved are unclear. Phosphatidylinositol (PI) 3-kinase has been implicated in integrin activation in a variety of cells, including PMN. In this work, we have examined activation of the PMN integrin alphaM beta2, assessing both adhesion and generation of the epitope recognized by the activation-specific antibody CBRM1/5. We have found that PI 3-kinase has a role in activation of alphaM beta2 by immune complexes, but we have found no role for it in alphaM beta2 activation by ligands for trimeric G protein-coupled receptors, including formylmethionylleucylphenylalanine (fMLP), interleukin-8, and C5a. Cytochalasin D inhibition suggests a role for the actin cytoskeleton in immune complex activation of alphaM beta2, but cytochalasin has no effect on fMLP-induced activation. Similarly, immune complex activation of the Rac/Cdc42-dependent serine/threonine kinase Pak1 is blocked by PI 3-kinase inhibitors, but fMLP-induced activation is not. These results demonstrate that two signaling pathways exist in PMN for activation of alphaM beta2. One, induced by FcgammaR ligation, is PI 3-kinase-dependent and requires the actin cytoskeleton. The second, initiated by G protein-linked receptors, is PI 3-kinase-independent and cytochalasin-insensitive. Pak1 may be in a final common pathway leading to activation of alphaM beta2.     

Report of the WHO working group on the assessment of health risks for human infants from exposure to PCDDs, PCDFs and PCBs

On Nov. 20-22, 1995, a World Health Organization working group consisting of 12 scientific representatives from 6 different countries met to reassess the health risks to infants associated with perinatal exposure to polyhalogenated aromatic hydrocarbons (PHAHs). Following a review of previous WHO/EURO consultations, as part of their comprehensive programme on PCDDs, PCDFs and PCBs, current exposure information and recent experimental and epidemiologic data were discussed. Exposure assessments within the past decade have revealed that in the case of breast milk samples concentrations of PCDDs/DFs and PCBs have shown a continual decline, in certain countries by up to 50%. New experimental data has revealed that a variety of structural, functional and behaviourial alterations can be induced in rodent species following exposure to PHAHs while a Dutch collaborative PCB/dioxin study has illustrated subtle clinical, endocrine and mental/psychomotor development effects can occur in breast fed infants. The provisional conclusions of the working group were: 1) current evidence does not warrant altering the previous WHO recommendation for promotion/support of breast feeding and 2) based on new clinical data which supports the biological plausibility of certain observed experimental observations, continued and enhanced effort should be directed towards identifying and controlling sources of environmental input for these contaminants.     

Patterns of scent-mounding in a population of beaver (Castor canadensis)

The frequency and pattern of distribution of scent-mound construction were studied in a population of beaver in southeast Ohio from 1975 through 1977. The study addressed the questions of whether or not the frequency of scent-mound construction varied with season, site, year, and degree of contact with other family groups, and whether the pattern of scent-mounding activity was parsimonious with the idea of territorial marking. The number of scent-mounds constructed was determined weekly for each site throughout the ice-free season. Scent-mounding activity was highest in spring and declined and remained low during summer and fall. Significant differences were found amoung sites and over years. Contact with other resident family groups altered both frequency and pattern of scent-mound construction. Scent-mounds did not conform to a scent-fence model. The most parsimonious interpretation of function of odor cues deposited on scent-mounds is the effect on the motivational state of residents and nonresidents, increasing the confidence and reducing anxiety in residents smelling their own scent-mound and decreasing the confidence and increasing the readiness to flee in trespassers encountering a strange scent-mound.     

Efficient Modelling and Simulation of Process Chains in Sheet Metal Forming and Processing

The ultimate aim of this work is the development of methods for the simulation of manufacturing process chains such as forming→cutting→heat treatment→joining, providving maximal efficiency without significant loss of accuracy. In the current work, we make the first step in this direction by considering the case of forming of the new high strength steel LH®800. The work begins with a characterization and metallographic investigation of this new steel. Following this, a combined hardening model appropriate for this steel is formulated and identified. The identified model is then validated with the help of the finite‐element simulation of draw‐bending. On this basis, the model was then used to simulate cup deep‐drawing. This process was also simulated with a so‐called one‐step solver which is much faster than the finite element simulation. The results of these two simulations are compared with the results of the deep‐drawing experiment.     

Experimental characterization of microstructure development during loading path changes in bcc sheet steels

Interstitial free sheet steels show transient work hardening behavior, i.e., the Bauschinger effect and cross hardening, after changes in the loading path. This behavior affects sheet forming processes and the properties of the final part. The transient work hardening behavior is attributed to changes in the dislocation structure. In this work, the morphology of the dislocation microstructure is investigated for uniaxial and plane strain tension, monotonic and forward to reverse shear, and plane strain tension to shear. Characteristic features such as the thickness of cell walls and the shape of cells are used to distinguish microstructural patterns corresponding to different loading paths. The influence of the crystallographic texture on the dislocation structure is analyzed. Digital image processing is used to create a “library” of schematic representations of the dislocation microstructure. The dislocation microstructures corresponding to uniaxial tension, plane strain tension, monotonic shear, forward to reverse shear, and plane strain tension to shear can be distinguished from each other based on the thickness of cell walls and the shape of cells. A statistical analysis of the wall thickness distribution shows that the wall thickness decreases with increasing deformation and that there are differences between simple shear and uniaxial tension. A change in loading path leads to changes in the dislocation structure. The knowledge of the specific features of the dislocation structure corresponding to a loading path may be used for two purposes: (i) the analysis of the homogeneity of deformation in a test sample and (ii) the analysis of a formed part.     

An assessment of the fate, behaviour and environmental risk associated with sunscreen TiO₂ nanoparticles in UK field scenarios

The fate of Ti was examined in an activated sludge plant serving over 200,000 people. These studies revealed a decrease of 30 to 3.2 μg/L of Ti < 0.45 μm from influent to effluent and a calculated Ti presence of 305 mg/kg DW in wasted sludge. Thus, using sludge as a fertiliser would result in a predicted deposition of up to 250 mg/m² of Ti to soil surfaces using a recommended maximal agricultural application rate. Given the major use of TiO₂ in many industrial and domestic applications where loss to the sewer is possible, this measured Ti was presumed to have been largely TiO₂, a proportion of which will be nanoparticle sized. To assess the behaviour of engineered nanoparticle (ENP) TiO₂ in sewage and toxicology studies, Optisol (Oxonica Materials Ltd) and P25 (Evonik Industries AG), which are representative of forms used in sunscreen and cosmetic products, were used. These revealed a close association of TiO₂ ENPs with activated sludge. Using commercial information on consumption, and removal rates for sewage treatment, predictions were made for river water concentrations for sunscreen TiO₂ ENPs for the Anglian and Thames regions in Southern England. The highest predicted value from these exercises was 8.8 μg/L for the Thames region in which it was assumed that one in four people used the recommended application of sunscreen during a low flow (Q95) period. Ecotoxicological studies using potentially vulnerable species indicated that 1000 μg/L TiO₂ ENP did not affect the viability of a mixed community of river bacteria in the presence of UV light. Direct exposure to TiO₂ ENPs did not impair the immuno-effectiveness of earthworm coelomocyte cells at concentrations greatly above those predicted for sewage sludge.