The use of life-cycle assessment to evaluate the environmental impacts of growing genetically modified, nitrogen use-efficient canola

Agriculture, particularly intensive crop production, makes a significant contribution to environmental pollution. A variety of canola (Brassica napus) has been genetically modified to enhance nitrogen use efficiency, effectively reducing the amount of fertilizer required for crop production. A partial life-cycle assessment adapted to crop production was used to assess the potential environmental impacts of growing genetically modified, nitrogen use-efficient (GMNUE) canola in North Dakota and Minnesota compared with a conventionally bred control variety. The analysis took into account the entire production system used to produce 1 tonne of canola. This comprised raw material extraction, processing and transportation, as well as all agricultural field operations. All emissions associated with the production of 1 tonne of canola were listed, aggregated and weighted in order to calculate the level of environmental impact. The findings show that there are a range of potential environmental benefits associated with growing GMNUE canola. These include reduced impacts on global warming, freshwater ecotoxicity, eutrophication and acidification. Given the large areas of canola grown in North America and, in particular, Canada, as well as the wide acceptance of genetically modified varieties in this area, there is the potential for GMNUE canola to reduce pollution from agriculture, with the largest reductions predicted to be in greenhouse gases and diffuse water pollution.

Adjusted jackknife for imputation under unequal probability sampling without replacement

Imputation is commonly used to compensate for item non-response in sample surveys. If we treat the imputed values as if they are true values, and then compute the variance estimates by using standard methods, such as the jackknife, we can seriously underestimate the true variances. We propose a modified jackknife variance estimator which is defined for any without-replacement unequal probability sampling design in the presence of imputation and non-negligible sampling fraction. Mean, ratio and random-imputation methods will be considered. The practical advantage of the method proposed is its breadth of applicability.

Cell cycle perturbations induced by infection with the coronavirus infectious bronchitis virus and their effect on virus replication

In eukaryotic cells, cell growth and division occur in a stepwise, orderly fashion described by a process known as the cell cycle. The relationship between positive-strand RNA viruses and the cell cycle and the concomitant effects on virus replication are not clearly understood. We have shown that infection of asynchronously replicating and synchronized replicating cells with the avian coronavirus infectious bronchitis virus (IBV), a positive-strand RNA virus, resulted in the accumulation of infected cells in the G(2)/M phase of the cell cycle. Analysis of various cell cycle-regulatory proteins and cellular morphology indicated that there was a down-regulation of cyclins D1 and D2 (G(2) regulatory cyclins) and that a proportion of virus-infected cells underwent aberrant cytokinesis, in which the cells underwent nuclear, but not cytoplasmic, division. We assessed the impact of the perturbations on the cell cycle for virus-infected cells and found that IBV-infected G(2)/M-phase-synchronized cells exhibited increased viral protein production when released from the block when compared to cells synchronized in the Go phase or asynchronously replicating cells. Our data suggested that IBV induces a G(2)/M phase arrest in infected cells to promote favorable conditions for viral replication.

Forkhead (FOX) transcription factors and the cell cycle: measurement of DNA binding by FoxO and FoxM transcription factors

Certain forkhead (FOX) transcription factors have been shown to play an intrinsic role in controlling cell cycle progression. In particular, the FoxO subclass has been shown to regulate cell cycle entry and exit, whereas the expression and activity of FoxM1 is important for the correct coupling of DNA synthesis to mitosis. In this chapter, I describe a method for measuring FoxO and FoxM1 transcription factor DNA binding in nuclear extracts from mammalian cells.

Variation in pituitary expression of mRNAs encoding the putative inhibin co-receptor (betaglycan) and type-I and type-II activin receptors during the chicken ovulatory cycle

Secretion of LH and FSH from the anterior pituitary is regulated primarily by hypothalamic GnRH and ovarian steroid hormones. More recent evidence indicates regulatory roles for certain members of the transforming growth factor beta (TGF beta) superfamily including inhibin and activin. The aim of this study was to identify expression of mRNAs encoding key receptors and ligands of the inhibin/activin system in the hen pituitary gland and to monitor their expression throughout the 24-25-h ovulatory cycle. Hens maintained on long days (16 h light/8 h dark) were killed 20, 12, 6 and 2 h before predicted ovulation of a midsequence egg (n = 8 per group). Anterior pituitary glands were removed, RNA extracted and cDNA synthesized. Plasma concentrations of LH, FSH, progesterone and inhibin A were measured. Real-time quantitative PCR was used to quantify pituitary expression of mRNAs encoding betaglycan, activin receptor (ActR) subtypes (type I, IIA), GnRH receptor (GnP,H-R), LH beta subunit, FSH beta subunit and GAPDH. Levels of mRNA for inhibin/activin beta A and beta B subunits, inhibin alpha subunit, follistatin and ActRIIB mRNA in pituitary were undetectable by quantitative PCR (< 2 amol/reaction). Significant changes in expression (P < 0.05) of ActRIIA and betaglycan mRNA were found, both peaking 6 h before ovulation just prior to the preovulatory LH surge and reaching a nadir 2 h before ovulation, just after the LH surge. There were no significant changes in expression of ActRI mRNA throughout the cycle although values were correlated with mRNA levels for both ActRIIA (r=0.77; P < 0.001) and betaglycan (r=0.45; P < 0.01). Expression of GnRH-R mRNA was lowest 20 h before ovulation and highest (P < 0.05) 6 h before ovulation; values were weakly correlated with betaglycan (r=0.33; P=0.06) and ActRIIA (r=0.34; P=0.06) mRNA levels. Expression of mRNAs encoding LH beta and FSH beta subunit were both lowest (P < 0.05) after the LH surge, 2 h before ovulation. These results are consistent with an endocrine, but not a local intrapituitary, role of inhibin-related proteins in modulating gonadotroph function during the ovulatory cycle of the hen, potentially through interaction with betaglycan and ActRIIA. In contrast to mammals, intrapituitary expression of inhibin/activin subunits and follistatin appears to be extremely low or absent in the domestic fowl.

The Mammalian cell cycle: an overview

In recent years, we have witnessed major advances in our understanding of the mammalian cell cycle and how it is regulated. Normal mammalian cellular proliferation is tightly regulated at each phase of the cell cycle by the activation and deactivation of a series of proteins that constitute the cell cycle machinery. This review article describes the various phases of the mammalian cell cycle and focuses on the cell cycle regulatory molecules that act at each stage to ensure normal cellular progression.

Targeting the cell cycle machinery for the treatment of cardiovascular disease

Cardiovascular disease represents a major clinical problem affecting a significant proportion of the world's population and remains the main cause of death in the UK. The majority of therapies currently available for the treatment of cardiovascular disease do not cure the problem but merely treat the symptoms. Furthermore, many cardioactive drugs have serious side effects and have narrow therapeutic windows that can limit their usefulness in the clinic. Thus, the development of more selective and highly effective therapeutic strategies that could cure specific cardiovascular diseases would be of enormous benefit both to the patient and to those countries where healthcare systems are responsible for an increasing number of patients. In this review, we discuss the evidence that suggests that targeting the cell cycle machinery in cardiovascular cells provides a novel strategy for the treatment of certain cardiovascular diseases. Those cell cycle molecules that are important for regulating terminal differentiation of cardiac myocytes and whether they can be targeted to reinitiate cell division and myocardial repair will be discussed as will the molecules that control vascular smooth muscle cell (VSMC) and endothelial cell proliferation in disorders such as atherosclerosis and restenosis. The main approaches currently used to target the cell cycle machinery in cardiovascular disease have employed gene therapy techniques. We will overview the different methods and routes of gene delivery to the cardiovascular system and describe possible future drug therapies for these disorders. Although the majority of the published data comes from animal studies, there are several instances where potential therapies have moved into the clinical setting with promising results.

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit vascular smooth muscle cell proliferation via differential effects on the cell cycle

Abnormal vascular smooth muscle cell (VSMC) proliferation plays an important role in the pathogenesis of both atherosclerosis and restenosis. Recent studies suggest that high-dose salicylates, in addition to inhibiting cyclooxygenase activity, exert an antiproliferative effect on VSMC growth both in-vitro and in-vivo. However, whether all non-steroidal anti-inflammatory drugs (NSAIDs) exert similar anti proliferative effects on VSMCs, and do so via a common mechanism of action, remains to be shown. In this study, we demonstrate that the NSAIDs aspirin, sodium salicylate, diclofenac, ibuprofen, indometacin and sulindac induce a dose-dependent inhibition of proliferation in rat A10 VSMCs in the absence of significant cytotoxicity. Flow cytometric analyses showed that exposure of A10 cells to diclofenac, indometacin, ibuprofen and sulindac, in the presence of the mitotic inhibitor, nocodazole, led to a significant G0/G1 arrest. In contrast, the salicylates failed to induce a significant G1 arrest since flow cytometry profiles were not significantly different from control cells. Cyclin A levels were elevated, and hyperphosphorylated p107 was present at significant levels, in salicylate-treated A10 cells, consistent with a post-G1/S block, whereas cyclin A levels were low, and hypophosphorylated p107 was the dominant form, in cells treated with other NSAIDs consistent with a G1 arrest. The ubiquitously expressed cyclin-dependent kinase (CDK) inhibitors, p21 and p27, were increased in all NSAID-treated cells. Our results suggest that diclofenac, indometacin, ibuprofen and sulindac inhibit VSMC proliferation by arresting the cell cycle in the G1 phase, whereas the growth inhibitory effect of salicylates probably affects the late S and/or G2/M phases. Irrespective of mechanism, our results suggest that NSAIDs might be of benefit in the treatment of certain vasculoproliferative disorders.

Novel solid networks containing Sn-H as a greener replacement for soluble alkyl Sn-H reagents in radical assisted organic synthesis

DiGrignard reagents of the form XMg(CH2)(n)MgX, where X = Br or I and n = 6, 8, 10 or 12, were allowed to react with PhSnCl3 to produce highly cross-linked Ph-Sn polymeric networks. The Sn-H moiety was incorporated into these insoluble network polymers by treatment with Br-2 and NaBH4. Excellent accessibility of the Sn-H was displayed by these solvent penetrable but insoluble networks, giving them higher Sn-H loadings than all previously reported supported reagents. These reagents were totally regenerable in NaBH4 for radical assisted organic synthesis and no detectable leaching of the Sn into solution was observed during these reactions.

Life cycle analysis of UK coal fired power plants

This paper examines the life cycle GHG emissions from existing UK pulverized coal power plants. The life cycle of the electricity Generation plant includes construction, operation and decommissioning. The operation phase is extended to upstream and downstream processes. Upstream processes include the mining and transport of coal including methane leakage and the production and transport of limestone and ammonia, which are necessary for flue gas clean up. Downstream processes, on the other hand, include waste disposal and the recovery of land used for surface mining. The methodology used is material based process analysis that allows calculation of the total emissions for each process involved. A simple model for predicting the energy and material requirements of the power plant is developed. Preliminary calculations reveal that for a typical UK coal fired plant, the life cycle emissions amount to 990 g CO2-e/kWh of electricity generated, which compares well with previous UK studies. The majority of these emissions result from direct fuel combustion (882 g/kWh 89%) with methane leakage from mining operations accounting for 60% of indirect emissions. In total, mining operations (including methane leakage) account for 67.4% of indirect emissions, while limestone and other material production and transport account for 31.5%. The methodology developed is also applied to a typical IGCC power plant. It is found that IGCC life cycle emissions are 15% less than those from PC power plants. Furthermore, upon investigating the influence of power plant parameters on life cycle emissions, it is determined that, while the effect of changing the load factor is negligible, increasing efficiency from 35% to 38% can reduce emissions by 7.6%. The current study is funded by the UK National Environment Research Council (NERC) and is undertaken as part of the UK Carbon Capture and Storage Consortium (UKCCSC). Future work will investigate the life cycle emissions from other power generation technologies with and without carbon capture and storage. The current paper reveals that it might be possible that, when CCS is employed. the emissions during generation decrease to a level where the emissions from upstream processes (i.e. coal production and transport) become dominant, and so, the life cycle efficiency of the CCS system can be significantly reduced. The location of coal, coal composition and mining method are important in determining the overall impacts. In addition to studying the net emissions from CCS systems, future work will also investigate the feasibility and technoeconomics of these systems as a means of carbon abatement.

Life cycle GHG assessment of fossil fuel power plants with carbon capture and storage

The evaluation of life cycle greenhouse gas emissions from power generation with carbon capture and storage (CCS) is a critical factor in energy and policy analysis. The current paper examines life cycle emissions from three types of fossil-fuel-based power plants, namely supercritical pulverized coal (super-PC), natural gas combined cycle (NGCC) and integrated gasification combined cycle (IGCC), with and without CCS. Results show that, for a 90% CO2 capture efficiency, life cycle GHG emissions are reduced by 75-84% depending on what technology is used. With GHG emissions less than 170 g/kWh, IGCC technology is found to be favorable to NGCC with CCS. Sensitivity analysis reveals that, for coal power plants, varying the CO2 capture efficiency and the coal transport distance has a more pronounced effect on life cycle GHG emissions than changing the length of CO2 transport pipeline. Finally, it is concluded from the current study that while the global warming potential is reduced when MEA-based CO2 capture is employed, the increase in other air pollutants such as NOx and NH3 leads to higher eutrophication and acidification potentials.