Increased migration of olfactory ensheathing cells secreting the Nogo receptor ectodomain over inhibitory substrates and lesioned spinal cord

Olfactory ensheathing cell (OEC) transplantation emerged some years ago as a promising therapeutic strategy to repair injured spinal cord. However, inhibitory molecules are present for long periods of time in lesioned spinal cord, inhibiting both OEC migration and axonal regrowth. Two families of these molecules, chondroitin sulphate proteoglycans (CSPG) and myelin-derived inhibitors (MAIs), are able to trigger inhibitory responses in lesioned axons. Mounting evidence suggests that OEC migration is inhibited by myelin. Here we demonstrate that OEC migration is largely inhibited by CSPGs and that inhibition can be overcome by the bacterial enzyme Chondroitinase ABC. In parallel, we have generated a stable OEC cell line overexpressing the Nogo receptor (NgR) ectodomain to reduce MAI-associated inhibition in vitro and in vivo. Results indicate that engineered cells migrate longer distances than unmodified OECs over myelin or oligodendrocyte-myelin glycoprotein (OMgp)-coated substrates. In addition, they also show improved migration in lesioned spinal cord. Our results provide new insights toward the improvement of the mechanisms of action and optimization of OEC-based cell therapy for spinal cord lesion.     

Alpha 1-adrenoceptor subtypes linked to different mechanisms for increasing intracellular Ca2+ in smooth muscle

Receptor-mediated increases in intracellular Ca2+ levels can be caused by release from intracellular organelles and/or influx from the extracellular fluid. Noradrenaline (NA) released from sympathetic nerves acts on alpha 1-adrenoceptors to increase cytosolic Ca2+ and promote smooth muscle contraction. In many cells activation of alpha 1-adrenoceptors causes formation of inositol 1,4,5-trisphosphate which promotes Ca2+ release from intracellular stores. The mechanism by which receptor activation opens cell surface Ca2+ channels is not known, although in some cases it may be secondary to formation of inositol phosphates or release of stored intracellular Ca2+ (ref. 3). However, alpha 1-adrenoceptors have recently been shown to have different pharmacological properties in different tissues, and it has been proposed that different alpha 1-adrenoceptor subtypes may control mobilization of intracellular Ca2+ and gating of extracellular Ca2+ influx. We here report evidence for two subtypes of alpha 1-adrenoceptors which cause contractile responses through different molecular mechanisms. One subtype stimulates inositol phosphate (InsP) formation and causes contractions which are independent of extracellular Ca2+, and the other does not stimulate inositol phosphate formation and causes contractions which require the influx of extracellular Ca2+ through dihydropyridine-sensitive channels. These results suggest that neurotransmitters and hormones may control Ca2+ release from intracellular stores and influx through voltage-gated membrane channels through distinct receptor subtypes.     

Increasing dominance of large lianas in Amazonian forests

Ecological orthodoxy suggests that old-growth forests should be close to dynamic equilibrium, but this view has been challenged by recent findings that neotropical forests are accumulating carbon and biomass, possibly in response to the increasing atmospheric concentrations of carbon dioxide. However, it is unclear whether the recent increase in tree biomass has been accompanied by a shift in community composition. Such changes could reduce or enhance the carbon storage potential of old-growth forests in the long term. Here we show that non-fragmented Amazon forests are experiencing a concerted increase in the density, basal area and mean size of woody climbing plants (lianas). Over the last two decades of the twentieth century the dominance of large lianas relative to trees has increased by 1.7-4.6% a year. Lianas enhance tree mortality and suppress tree growth, so their rapid increase implies that the tropical terrestrial carbon sink may shut down sooner than current models suggest. Predictions of future tropical carbon fluxes will need to account for the changing composition and dynamics of supposedly undisturbed forests.     

Lipoprotein lipase activator deficiency in very low density lipoproteins in rat nephrotic syndrome.

Marked urinary loss of lipoprotein lipase activator in experimental rat nephrotic syndrome may be partly responsible for its deficiency in plasma very low density lipoproteins.     

Plasma steroid and protein hormone concentrations in patients with benign prostatic hypertrophy and in normal men.

Serum levels of testosterone, FSH, LH and prolactin were measured by RIA in patients with BPH (benign prostatic hypertrophy) and in control men. The testosterone concentrations in the BPH group were significantly lower than that of the control group. Serum concentrations of FSH, LH, prolactin and estradiol, did not differ significantly in the 2 groups.     

Plasma steroid and protein hormone concentrations in patients with benign prostatic hypertrophy and in normal men

Summary Serum levels of testosterone, FSH, LH and prolactin were measured by RIA in patients with BPH (benign prostatic hypertrophy) and in control men. The testosterone concentrations in the BPH group were significantly lower than that of the control group. Serum concentrations of FSH, LH, prolactin and estradiol, did not differ significantly in the 2 groups.     

A comparison of official population projections with Bayesian time series forecasts for England and Wales

We compare official population projections with Bayesian time series forecasts for England and Wales. The Bayesian approach allows the integration of uncertainty in the data, models and model parameters in a coherent and consistent manner. Bayesian methodology for time-series forecasting is introduced, including autoregressive (AR) and stochastic volatility (SV) models. These models are then fitted to a historical time series of data from 1841 to 2007 and used to predict future population totals to 2033. These results are compared to the most recent projections produced by the Office for National Statistics. Sensitivity analyses are then performed to test the effect of changes in the prior uncertainty for a single parameter. Finally, in-sample forecasts are compared with actual population and previous official projections. The article ends with some conclusions and recommendations for future work.