Effects of emission reductions from the Sudbury smelters on the recovery of acid- and metal-damaged lakes

Aquatic ecosystems in a 17,000 km² area around Sudbury, Ontario, Canada, have been affected by the atmospheric deposition of pollutants from nearly a century of operations at the Sudbury area metal smelters. Effects were most severe in the lakes closest to the smelters which historically received very high deposition of both acid and metal particulates. After smelter emissions were greatly reduced in the 1970‘s, evidence began to emerge of improvements in lake water quality, and some recovery of biological communities, and the emphasis of Sudbury area monitoring programs changed from the assessment of damage to the tracking of recovery patterns. Further reductions in smelter emissions during the1990‘s have been accompanied by continuing improvements in aquatic habitat quality, but the evaluation of lake responses to emission controls is complicated by the interaction of lake acidity and metal concentrations with other factors. Weather-related variations in storage and release of sulphur from lake catchments appear to greatly influence chemical recovery. Despite the general water quality improvements observed to date, some lakes are still highly acidic and elevated levels of copper and nickel persist in the water and sediments of many lakes. Severely damaged biological communities have been slow to recover, probably reflecting a combination of continuing habitat quality limitations and restricted opportunities for dispersal. This revised version was published online in July 2006 with corrections to the Cover Date.     

τ and Microtubule-Associated Protein 2c Transfection and Neurite Outgrowth in ND 7/23 Cells

Abstract: Neuronal hybrid ND 7/23 cells, which display sensorylike properties, develop neurites when cultured in the presence of either dibutyryl cyclic AMP plus nerve growth factor (DBcAMP + NGF) or retinoic acid or a phorbol ester derivative, although they express only trace amounts of the microtubule-associated τ proteins and low levels of microtubule-associated protein 2c (MAP2c). Nondifferentiated ND cells transfected with τ cDNAs did not develop neurites, whereas very short cell processes were formed in MAP2c-transfected cells. τ and MAP2 antibodies labeled microtubule bundles displayed in a ring array underneath the surface of the transfected cells and short microtubules starting from the cell center. After differentiation in the presence of DBcAMP + NGF, the same bundle organization was observed in the transfected cells. In addition, τ and MAP2 antibodies stained a short section of the formed neurites. These data demonstrate that the expression of τ protein is not sufficient to induce neurite extension and that other proteins induced by morphogens are more important to initiate morphological differentiation of this cell line.     

Trisubstituted ureas as potent and selective mPGES-1 inhibitors

A novel series of trisubstituted ureas has been identified as potent and selective mPGES-1 inhibitors. These compounds are selective over other prostanoid enzymes such as PGF synthase and TX synthase. This series of inhibitors was developed by lead optimization of a hit from an internal HTS campaign. Lead compound 42 is potent in A549 cell assay (IC₅₀ of 0.34 μM) and in human whole blood assay (IC₅₀ of 2.1 μM). An efficient and versatile one-pot strategy for the formation of ureas, involving a reductive amination, was developed to generate these inhibitors.     

Sequential Coherence in Sentence Pairs Enhances Imagery during Comprehension: An Individual Differences Study

The present study investigates how sequential coherence in sentence pairs (events in sequence vs. unrelated events) affects the perceived ability to form a mental image of the sentences for both auditory and visual presentations. In addition, we investigated how the ease of event imagery affected online comprehension (word reading times) in the case of sequentially coherent and incoherent sentence pairs. Two groups of comprehenders were identified based on their self-reported ability to form vivid mental images of described events. Imageability ratings were higher and faster for pairs of sentences that described events in coherent sequences rather than non-sequential events, especially for high imagers. Furthermore, reading times on individual words suggested different comprehension patterns with respect to sequence coherence for the two groups of imagers, with high imagers activating richer mental images earlier than low imagers. The present results offer a novel link between research on imagery and discourse coherence, with specific contributions to our understanding of comprehension patterns for high and low imagers.     

Estimating Impacts of Climate Change Policy on Land Use: An Agent-Based Modelling Approach

Agriculture is important to New Zealand’s economy. Like other primary producers, New Zealand strives to increase agricultural output while maintaining environmental integrity. Utilising modelling to explore the economic, environmental and land use impacts of policy is critical to understand the likely effects on the sector. Key deficiencies within existing land use and land cover change models are the lack of heterogeneity in farmers and their behaviour, the role that social networks play in information transfer, and the abstraction of the global and regional economic aspects within local-scale approaches. To resolve these issues we developed the Agent-based Rural Land Use New Zealand model. The model utilises a partial equilibrium economic model and an agent-based decision-making framework to explore how the cumulative effects of individual farmer’s decisions affect farm conversion and the resulting land use at a catchment scale. The model is intended to assist in the development of policy to shape agricultural land use intensification in New Zealand. We illustrate the model, by modelling the impact of a greenhouse gas price on farm-level land use, net revenue, and environmental indicators such as nutrient losses and soil erosion for key enterprises in the Hurunui and Waiau catchments of North Canterbury in New Zealand. Key results from the model show that farm net revenue is estimated to increase over time regardless of the greenhouse gas price. Net greenhouse gas emissions are estimated to decline over time, even under a no GHG price baseline, due to an expansion of forestry on low productivity land. Higher GHG prices provide a greater net reduction of emissions. While social and geographic network effects have minimal impact on net revenue and environmental outputs for the catchment, they do have an effect on the spatial arrangement of land use and in particular the clustering of enterprises.     

Chemotherapy versus supportive care alone in pediatric palliative care for cancer: comparing the preferences of parents and health care professionals

Background:

The choice between palliative chemotherapy (defined as the use of cytotoxic medications delivered intravenously for the purpose of our study) and supportive care alone is one of the most difficult decisions in pediatric oncology, yet little is known about the preferences of parents and health care professionals. We compared the strength of these preferences by considering children’s quality of life and survival time as key attributes. In addition, we identified factors associated with the reported preferences.

Methods:

We included parents of children whose cancer had no reasonable chance of being cured and health care professionals in pediatric oncology as participants in our study. We administered separate interviews to parents and to health care professionals. Visual analogue scales were shown to respondents to illustrate the anticipated level of the child’s quality of life, the expected duration of survival and the probability of cure (shown only to health care professionals). Respondents were then asked which treatment option they would favour given these baseline attributes. In addition, respondents reported what factors might affect such a decision and ranked all factors identified in order of importance. The primary measure was the desirability score for supportive care alone relative to palliative chemotherapy, as obtained using the threshold technique.

Results:

A total of 77 parents and 128 health care professionals participated in our study. Important factors influencing the decision between therapeutic options were child quality-of-life and survival time among both parents and health care professionals. Hope was particularly important to parents. Parents significantly favoured chemotherapy (42/77, 54.5%) compared with health care professionals (20/128, 15.6%; p < 0.0001). The opinions of the physician and child significantly influenced the parents’ desire for supportive care; for health care professionals, the opinions of parents and children were significant factors influencing this decision.

Interpretation:

Compared with health care professionals, parents more strongly favour aggressive treatment in the palliative phase and rank hope as a more important factor for making decisions about treatment. Understanding the differences between parents and health care professionals in the relative desirability of supportive care alone may aid in communication and improve end-of-life care for children with cancer.Despite the substantial improvements in rates of cure among children with cancer, some children will have progressive or recurrent disease and will die.¹ Cancer remains the second most common cause of death for North American children between 5 and 14 years of age.^2–4 When cure becomes unlikely, parents and health care professionals are often faced with the decision to continue further aggressive treatments or to provide relief from symptoms alone.¹The choice between palliative chemotherapy and supportive care alone is one of the most important and difficult decisions for parents of children whose disease cannot be cured.⁵ At this point, the goals of therapy are usually to maximize the child’s quality and length of life and to ensure respect for the family’s and child’s preferences.⁶Given the difficult nature of this decision, it is worthwhile to compare and contrast the perspectives of parents and health care professionals. Discordance in these perspectives could heighten the anxiety felt by patients and parents and might lead to their dissatisfaction with the care received. One qualitative study that interviewed parents of children with recurrent cancer found that “fearing disagreement with staff” was an important negative factor in decision-making.⁷ However, little is known as to whether the attitudes of parents and health care professionals toward therapeutic options are congruent.The goal of this study was to compare the strength of preference between parents and health care professionals for supportive care alone versus palliative chemotherapy for children whose cancer has no reasonable chance of being cured, and to determine how specific factors affect these preferences.     

Synchrotron radiation infrared microspectroscopy to assess the activity of vancomycin against endocarditis vegetation bacteria

Infrared microspectroscopy was used to show that vancomycin alters infrared spectra of endocarditis vegetation bacteria, and that vancomycin effects on bacterial biochemical contents are unevenly distributed between peripheral and central areas of bacterial masses. Infrared microspectroscopy is useful to study the activity of antibacterial agents against bacteria in tissues.     

A major role for nonenzymatic antioxidant processes in the radioresistance of Halobacterium salinarum

Oxidative stress occurs when the generation of reactive oxygen species (ROS) exceeds the capacity of the cell's endogenous systems to neutralize them. Our analyses of the cellular damage and oxidative stress responses of the archaeon Halobacterium salinarum exposed to ionizing radiation (IR) revealed a critical role played by nonenzymatic antioxidant processes in the resistance of H. salinarum to IR. ROS-scavenging enzymes were essential for resistance to chemical oxidants, yet those enzymes were not necessary for H. salinarum's resistance to IR. We found that protein-free cell extracts from H. salinarum provided a high level of protection for protein activity against IR in vitro but did not protect DNA significantly. Compared with cell extracts of radiation-sensitive bacteria, H. salinarum extracts were enriched in manganese, amino acids, and peptides, supporting an essential role in ROS scavenging for those small molecules in vivo. With regard to chemical oxidants, we showed that the damage caused by gamma irradiation was mechanistically different than that produced by hydrogen peroxide or by the superoxide-generating redox-cycling drug paraquat. The data presented support the idea that IR resistance is most likely achieved by a "metabolic route," with a combination of tightly coordinated physiological processes.     

Predicting the effect of ions on the conformation of the H-NS dimerization domain

The histone-like nucleoid structuring protein (H-NS) is a DNA-organizing protein in bacteria. It contains a DNA-binding domain and a dimerization domain, connected by a flexible linker region. Dimerization occurs through the formation of a helical bundle, including a coiled-coil interaction motif. Two conformations have been resolved, for different sequences of Escherichia coli H-NS, resulting in an antiparallel coiled-coil for the shorter wild-type sequence, and a parallel coiled-coil for the longer C21S mutant. Because H-NS functions as a thermo- and osmosensor, these conformations may both be functionally relevant. Molecular simulation can complement experiments by modeling the dynamical time evolution of biomolecular systems in atomistic detail. We performed a molecular-dynamics study of the H-NS dimerization domain, showing that the parallel complex is sensitive to changes in salt conditions: it is unstable in absence of NaCl, but stable at physiological salt concentrations. In contrast, the stability of the antiparallel complex is not salt-dependent. The stability of the parallel complex also appears to be affected by mutation of the critical but nonconserved cysteine residue at position 21, whereas the antiparallel complex is not. Together, our simulations suggest that osmoregulation could be mediated by changes in the ratio of parallel- and antiparallel-oriented H-NS dimers.