Muffled price signals: Household water demand under increasing-block prices

In many areas of the world, including large parts of the United States, scarce water supplies are a serious resource and environmental concern. The possibility exists that water is being used at rates that exceed what would be dictated by efficiency criteria, particularly when externalities are taken into account. Because of this, much attention has been given by policy makers and others to the use of various techniques of demand management, including requirements for the adoption of specific technologies and restrictions on particular uses. A natural question for economists to ask is whether price would be a more effective instrument to facilitate efficient management of water resources. As a first step in such an investigation, this paper draws upon a newly available set of detailed data to estimate econometrically the demand function for household use of urban water supplies. Because of the diverse multiple-block pricing structures that abound, estimation of this relationship poses some challenging and interesting problems

Delta-9-tetrahydrocannabinol protects against MPP+ toxicity in SH-SY5Y cells by restoring proteins involved in mitochondrial biogenesis

This project was supported through a studentship awarded by the Plymouth University Peninsula Schools of Medicine and Dentistry.Proliferator-activated receptor γ (PPARγ) activation can result in transcription of proteins involved in oxidative stress defence and mitochondrial biogenesis which could rescue mitochondrial dysfunction in Parkinson's disease (PD).The PPARγ agonist pioglitazone is protective in models of PD; however side effects have limited its clinical use. The cannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) may have PPARγ dependent anti-oxidant properties. Here we investigate the effects of Δ9-THC and pioglitazone on mitochondrial biogenesis and oxidative stress. Differentiated SH-SY5Y neuroblastoma cells were exposed to the PD relevant mitochondrial complex 1 inhibitor 1-methyl- 4-phenylpyridinium iodide (MPP+). We found that only Δ9-THC was able to restore mitochondrial content in MPP+ treated SH-SY5Y cells in a PPARγ dependent manner by increasing expression of the PPARγ co-activator 1a (PGC-1a), the mitochondrial transcription factor (TFAM) as well as mitochondrial DNA content. Co-application of Δ9- THC with pioglitazone further increased the neuroprotection against MPP+ toxicity as compared to pioglitazone treatment alone. Furthermore, using lentiviral knock down of the PPARγ receptor we showed that, unlike pioglitazone, Δ9-THC resulted in a PPARγ dependent reduction of MPP+ induced oxidative stress. We therefore suggest that, in contrast to pioglitazone, Δ9-THC mediates neuroprotection via PPARγ-dependent restoration of mitochondrial content which may be beneficial for PD treatment.Publisher PDFPeer reviewe

Loss of SOX10 function contributes to the phenotype of human Merlin-null schwannoma cells.

Loss of the Merlin tumour suppressor causes abnormal de-differentiation and proliferation of Schwann cells and formation of schwannoma tumours in patients with neurofibromatosis type 2. Within the mature peripheral nerve the normal development, differentiation and maintenance of myelinating and non-myelinating Schwann cells is regulated by a network of transcription factors that include SOX10, OCT6 (now known as POU3F1), NFATC4 and KROX20 (also known as Egr2). We have examined for the first time how their regulation of Schwann cell development is disrupted in primary human schwannoma cells. We find that induction of both KROX20 and OCT6 is impaired, whereas enforced expression of KROX20 drives both myelin gene expression and cell cycle arrest in Merlin-null cells. Importantly, we show that human schwannoma cells have reduced expression of SOX10 protein and messenger RNA. Analysis of mouse SOX10-null Schwann cells shows they display many of the characteristics of human schwannoma cells, including increased expression of platelet derived growth factor receptor beta (PDGFRB) messenger RNA and protein, enhanced proliferation, increased focal adhesions and schwannoma-like morphology. Correspondingly, reintroduction of SOX10 into human Merlin-null cells restores the ability of these cells to induce KROX20 and myelin protein zero (MPZ), localizes NFATC4 to the nucleus, reduces cell proliferation and suppresses PDGFRB expression. Thus, we propose that loss of the SOX10 protein, which is vital for normal Schwann cell development, is also key to the pathology of Merlin-null schwannoma tumours

Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma

Profiling adult literacy facilitators in development contexts: An ethnographic study in Ethiopia

Teachers/facilitators in adult literacy learning programmes are recognised as being vital to successful learning outcomes. But little is known about them as a group. This small-scale research project comprising ethnographic-style case studies of five adult literacy facilitators (ALFs) in Ethiopia seeks to throw some light on these teachers, their backgrounds and what they bring to their teaching, with a view to improving the effectiveness of their work. The researchers found that all of the ALFs had high levels of commitment, but none of the ALFs received much in the way of training, and professional support for their role was in some cases missing. The degree (and their perception) of their own literacy practices varied greatly among them, even in their common use of mobile phones. It also emerged that while they had all fought very hard for their own education, one of the main reasons all of them stated for going into literacy teaching was not a general belief in the value of education but their priority need of a regular income. Another insight is that the female ALFs struggled more than their male counterparts in engaging learners; the women were criticised more excessively than the men. This research reveals something of the diversity of facilitators, and concludes that further such studies are needed in different contexts