Urban water demand with fixed volumetric charging in a large municipality: the case of Brisbane, Australia

This paper uses suburb-level quarterly data to model residential water demand in Brisbane, Australia, from 1998 to 2003. In this system, residential consumption is charged using a fixed annual service fee with no water entitlement followed by a fixed volumetric charge per kilolitre. Water demand is specified as average quarterly household water consumption and the demand characteristics include the marginal price of water, household income and size, and the number of rainy and warm days. The findings not only confirm residential water as price and income inelastic, but also that the price and income elasticity of demand in owner-occupied households is higher than in rented households. The results also show that weather, particularly summer months and the number of rainy days, exerts a strong influence on residential water consumption.water management and policy, demand analysis, utility regulation and pricing, Resource /Energy Economics and Policy,

Methyl-CpG-binding (SmMBD2/3) and chromobox (SmCBX) proteins are required for neoblast proliferation and oviposition in the parasitic blood fluke Schistosoma mansoni

<div><p>While schistosomiasis remains a significant health problem in low to middle income countries, it also represents a recently recognised threat to more economically-developed regions. Until a vaccine is developed, this neglected infectious disease is primarily controlled by praziquantel, a drug with a currently unknown mechanism of action. By further elucidating how <i>Schistosoma</i> molecular components cooperate to regulate parasite developmental processes, next generation targets will be identified. Here, we continue our studies on schistosome epigenetic participants and characterise the function of a DNA methylation reader, the <i>Schistosoma mansoni</i> methyl-CpG-binding domain protein (SmMBD2/3). Firstly, we demonstrate that SmMBD2/3 contains amino acid features essential for 5-methyl cytosine (5mC) binding and illustrate that adult schistosome nuclear extracts (females > males) contain this activity. We subsequently show that SmMBD2/3 translocates into nuclear compartments of transfected murine NIH-3T3 fibroblasts and recombinant SmMBD2/3 exhibits 5mC binding activity. Secondly, using a yeast-two hybrid (Y2H) screen, we show that SmMBD2/3 interacts with the chromo shadow domain (CSD) of an epigenetic adaptor, <i>S</i>. <i>mansoni</i> chromobox protein (SmCBX). Moreover, fluorescent <i>in situ</i> hybridisation (FISH) mediated co-localisation of <i>Smmbd2/3</i> and <i>Smcbx</i> to mesenchymal cells as well as somatic- and reproductive- stem cells confirms the Y2H results and demonstrates that these interacting partners are ubiquitously expressed and found within both differentiated as well as proliferating cells. Finally, using RNA interference, we reveal that depletion of <i>Smmbd2/3</i> or <i>Smcbx</i> in adult females leads to significant reductions (46–58%) in the number of proliferating somatic stem cells (PSCs or neoblasts) as well as in the quantity of <i>in vitro</i> laid eggs. Collectively, these results further expand upon the schistosome components involved in epigenetic processes and suggest that pharmacological inhibition of SmMBD2/3 and/or SmCBX biology could prove useful in the development of future schistosomiasis control strategies.</p></div

Design, synthesis and anthelmintic activity of 7-keto-sempervirol analogues

The plant-derived, diterpenoid 7-keto-sempervirol was recently reported to display moderate activity against larval stages of Schistosoma mansoni (IC50 = 19.1 μM) and Fasciola hepatica (IC50 = 17.7 μM), two related parasitic blood and liver flukes responsible for the neglected tropical diseases schistosomiasis and fascioliasis, respectively. Here, we aimed to increase the potency of 7-keto-sempervirol by total synthesis of 30 structural analogues. Subsequent screening of these new diterpenoids against juvenile and adult lifecycle stages of both parasites as well as the human HepG2 liver cell line and the bovine MDBK kidney cell line revealed structure-activity relationship trends. The most active analogue, 7d, displayed improved dual anthelmintic activity over 7-keto-sempervirol (IC50 ≈ 6 μM for larval blood flukes; IC50 ≈ 3 μM for juvenile liver flukes) and moderate selectivity (SI ≈ 4–5 for blood flukes, 8–13 for liver flukes compared to HepG2 and MDBK cells, respectively). Phenotypic studies using scanning electron microscopy revealed substantial tegumental alterations in both helminth species, supporting the hypothesis that the parasite surface is one of the main targets of this family of molecules. Further modifications of 7d could lead to greater potency and selectivity metrics resulting in a new class of broad-spectrum anthelmintic

Open-label, proof-of-concept study of brexanolone in the treatment of severe postpartum depression

Preclinical evidence indicates that rapid changes in levels of allopregnanolone, the predominant metabolite of progesterone, confer dramatic behavioral changes and may trigger postpartum depression (PPD) in some women. Considering the pathophysiology of PPD (i.e., triggered by reproductive steroids), the need for fast‐acting, efficacious treatments and the negative consequences of untreated PPD, there is an increasing focus on developing PPD therapies. Brexanolone (USAN; formerly SAGE‐547 Injection), a proprietary injectable allopregnanolone formulation, was evaluated as a treatment for severe PPD in a proof‐of‐concept, open‐label study

Better reporting of interventions : template for intervention description and replication (TIDieR) checklist and guide

Peer reviewedPublisher PD

Identifying and validating the presence of Guanine-Quadruplexes (G4) within the blood fluke parasite Schistosoma mansoni

Schistosomiasis is a neglected tropical disease that currently affects over 250 million individuals worldwide. In the absence of an immunoprophylactic vaccine and the recognition that mono-chemotherapeutic control of schistosomiasis by praziquantel has limitations, new strategies for managing disease burden are urgently needed. A better understanding of schistosome biology could identify previously undocumented areas suitable for the development of novel interventions. Here, for the first time, we detail the presence of G-quadruplexes (G4) and putative quadruplex forming sequences (PQS) within the Schistosoma mansoni genome. We find that G4 are present in both intragenic and intergenic regions of the seven autosomes as well as the sex-defining allosome pair. Amongst intragenic regions, G4 are particularly enriched in 3´ UTR regions. Gene Ontology (GO) term analysis evidenced significant G4 enrichment in the wnt signalling pathway (p<0.05) and PQS oligonucleotides synthetically derived from wnt-related genes resolve into parallel and anti-parallel G4 motifs as elucidated by circular dichroism (CD) spectroscopy. Finally, utilising a single chain anti-G4 antibody called BG4, we confirm the in situ presence of G4 within both adult female and male worm nuclei. These results collectively suggest that G4-targeted compounds could be tested as novel anthelmintic agents and highlights the possibility that G4-stabilizing molecules could be progressed as candidates for the treatment of schistosomiasi

Analyzing Trends in Material Culture Evolution—a Case Study of Gravettian Points from Lower Austria and Moravia

Identifying, analyzing, and explaining trends in the development of material culture is one of the major concerns in prehistoric archaeology. The traditional recording of data in typologies, however, is not optimal for answering the question of diachronic change because typological data capture variability poorly and are often incompatible with multivariate statistics. To overcome these problems, we present PyREnArA (Python-R-Environment for Artifact Analysis), a trait-based tool that allows for a systematic recording of diversity and variability in a way that is applicable to quantitative analysis and multivariate statistics. Using Gravettian assemblages from Lower Austria and Moravia as a case study, we analyze changes in the morphology as well as the design of lithic projectiles and statistically determine the amount of variation that correlates with the progression of time. We identify a slow trend towards slenderer and more pointed projectiles and a shift from laterally to latero-frontally hafted implements. Most of the analyzed traits, however, appear not to experience selective pressure and seem to be unrelated to the passage of time. We discuss these results with regard to different scales of selection, in particular individual choice vs. macroevolutionary group selection over longer periods of time and thus beyond the realm of individual intend, and we raise questions for future research

Gold amides as anticancer drugs: synthesis and activity studies

Modular gold amide chemotherapeutics: Access to modern chemotherapeutics with robust and flexible synthetic routes that are amenable to extensive customisation is a key requirement in drug synthesis and discovery. A class of chiral gold amide complexes featuring amino acid derived ligands is reported herein. They all exhibit in vitro cytotoxicity against two slow growing breast cancer cell lines with limited toxicity towards normal epithelial cells