Dolly for dinner? Assessing commercial and regulatory trends in cloned livestock

As cloning technologies become more widely established, will products enter the food chain sooner than regulatory agencies and the public might be prepared for?     

Human atherosclerotic intima and blood of patients with established coronary artery disease contain high density lipoprotein damaged by reactive nitrogen species

High density lipoprotein (HDL) is the major carrier of lipid hydroperoxides in plasma, but it is not yet established whether HDL proteins are damaged by reactive nitrogen species in the circulation or artery wall. One pathway that generates such species involves myeloperoxidase (MPO), a major constituent of artery wall macrophages. Another pathway involves peroxynitrite, a potent oxidant generated in the reaction of nitric oxide with superoxide. Both MPO and peroxynitrite produce 3-nitrotyrosine in vitro. To investigate the involvement of reactive nitrogen species in atherogenesis, we quantified 3-nitrotyrosine levels in HDL in vivo. The mean level of 3-nitrotyrosine in HDL isolated from human aortic atherosclerotic intima was 6-fold higher (619 +/- 178 micromol/mol Tyr) than that in circulating HDL (104 +/- 11 micromol/mol Tyr; p < 0.01). Immunohistochemical studies demonstrated striking colocalization of MPO with epitopes reactive with an antibody to 3-nitrotyrosine. However, there was no significant correlation between the levels of 3-chlorotyrosine, a specific product of MPO, and those of 3-nitrotyrosine in lesion HDL. We also detected 3-nitrotyrosine in circulating HDL, and linear regression analysis demonstrated a strong correlation between the levels of 3-chlorotyrosine and levels of 3-nitrotyrosine. These observations suggest that MPO promotes the formation of 3-chlorotyrosine and 3-nitrotyrosine in circulating HDL but that other pathways also produce 3-nitrotyrosine in atherosclerotic tissue. Levels of HDL isolated from plasma of patients with established coronary artery disease contained twice as much 3-nitrotyrosine as HDL from plasma of healthy subjects, suggesting that nitrated HDL might be a marker for clinically significant vascular disease. The detection of 3-nitrotyrosine in HDL raises the possibility that reactive nitrogen species derived from nitric oxide might promote atherogenesis. Thus, nitrated HDL might represent a previously unsuspected link between nitrosative stress, atherosclerosis, and inflammation.     

Tactile Modulation of Whisking via the Brainstem Loop: Statechart Modeling and Experimental Validation

Rats repeatedly sweep their facial whiskers back and forth in order to explore their environment. Such explorative whisking appears to be driven by central pattern generators (CPGs) that operate independently of direct sensory feedback. Nevertheless, whisking can be modulated by sensory feedback, and it has been hypothesized that some of this modulation already occurs within the brainstem. However, the interaction between sensory feedback and CPG activity is poorly understood. Using the visual language of statecharts, a dynamic, bottom-up computerized model of the brainstem loop of the whisking system was built in order to investigate the interaction between sensory feedback and CPG activity during whisking behavior. As a benchmark, we used a previously quantified closed-loop phenomenon of the whisking system, touched-induced pump (TIP), which is thought to be mediated by the brainstem loop. First, we showed that TIPs depend on sensory feedback, by comparing TIP occurrence in intact rats with that in rats whose sensory nerve was experimentally cut. We then inspected several possible feedback mechanisms of TIPs using our model. The model ruled out all hypothesized mechanisms but one, which adequately simulated the corresponding motion observed in the rat. Results of the simulations suggest that TIPs are generated via sensory feedback that activates extrinsic retractor muscles in the mystacial pad. The model further predicted that in addition to the touching whisker, all whiskers found on the same side of the snout should exhibit a TIP. We present experimental results that confirm the predicted movements in behaving rats, establishing the validity of the hypothesized interaction between sensory feedback and CPG activity we suggest here for the generation of TIPs in the whisking system.     

The elastic properties of morsellised cortico-cancellous bone graft are dependent on its prior loading

Confined compression experiments were carried out on cortico-cancellous bone taken from bovine femoral condyles to assess the effect of prior loading on the elastic confined modulus, E(c) of morsellised cortico-cancellous bone (MCB). Measurements were taken to find the values of E(c) for MCB subjected to cyclic loading resulting in axial stresses in the range of 0.5-3.0 N mm(2). Two values of E(c) were considered: E(ic), the instantaneous modulus, and E(dc), the delayed modulus allowing for stress relaxation effects. It was found that the values of E(c) increased with increasing maximum axial stress. It was also found that for each stress level the values of E(c) increased as the number of load cycles increased. The dependence of E(c) on the maximum axial stress and the number of load cycles is seen to explain the wide range of values for the apparent modulus of MCB found in previous studies. Tests examining the stress relaxation behaviour of MCB are also discussed. The results indicate that a minimum of 10 compaction episodes are required for MCB to achieve around 90% of its predicted maximum stiffness for a given compaction force.     

Up-regulation of high density lipoprotein receptor activity by gamma-interferon associated with inhibition of cell proliferation

High density lipoprotein (HDL) binds to cell surface receptors and promotes selective removal of excess cholesterol from intracellular pools. The activity of this receptor is up-regulated when cells become loaded with cholesterol, but the relative degree of up-regulation depends on the growth state of the cells. The current study demonstrates that treatment of proliferating fibroblasts with gamma-interferon (IFN) increases the activity of the HDL receptor in association with a decrease in the rate of cell proliferation. Addition of IFN during the growth phase reduced the number of cells but had little effect on total cell protein, indicating that IFN inhibited cell proliferation but produced larger cells. IFN treatment increased the number of high affinity receptors for HDL on the surface of cholesterol-loaded fibroblasts, whether receptor binding was expressed per cell or per unit of cell surface area, cell protein, or cell cholesterol. IFN treatment also appeared to increase the amount of 110-kDa HDL binding protein in fibroblast membranes that has been postulated to represent the HDL receptor molecule. The IFN-induced increase in HDL receptor activity was associated with an enhanced ability of HDL3 to remove cholesterol from intracellular pools. These results are consistent with the hypothesis that inhibition of cell proliferation increases HDL receptor-mediated transport of excess cholesterol from cells, possibly to rid cells of cholesterol that accumulates in response to a reduced rate of membrane synthesis.     

The impact of local surface changes in Borneo on atmospheric composition at wider spatial scales: coastal processes, land-use change and air quality

We present results from the OP3 campaign in Sabah during 2008 that allow us to study the impact of local emission changes over Borneo on atmospheric composition at the regional and wider scale. OP3 constituent data provide an important constraint on model performance. Treatment of boundary layer processes is highlighted as an important area of model uncertainty. Model studies of land-use change confirm earlier work, indicating that further changes to intensive oil palm agriculture in South East Asia, and the tropics in general, could have important impacts on air quality, with the biggest factor being the concomitant changes in NO(x) emissions. With the model scenarios used here, local increases in ozone of around 50 per cent could occur. We also report measurements of short-lived brominated compounds around Sabah suggesting that oceanic (and, especially, coastal) emission sources dominate locally. The concentration of bromine in short-lived halocarbons measured at the surface during OP3 amounted to about 7 ppt, setting an upper limit on the amount of these species that can reach the lower stratosphere.