233 results on '"MacLeod, Michael"'
Search Results
202. A cloned fragment of HeLa DNA containing consensus sequences of satellite II and III DNA hybridizes with the Drosophila P-element and with the 1.8 kb family of human KpnI fragments
- Author
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Sol, Katia, Lapointe, Martine, MacLeod, Michael, Nadeau, Carole, and DuBow, Michael S.
- Published
- 1986
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- View/download PDF
203. Low absolute mutagenic efficiency but high cytotoxicity of a non-bay region diol epoxide derived from benzo[ a]pyrene
- Author
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MacLeod, Michael C., Adair, Gerald, Daylong, Anne, Lew, Linda, and Humphrey, Ronald M.
- Published
- 1991
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204. Differences in the rate of DNA adduct removal and the efficiency of mutagenesis for two benzo[ a]pyrene diol epoxides in CHO cells
- Author
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MacLeod, Michael C., Daylong, Anne, Adair, Gerald, and Humphrey, Ronald M.
- Published
- 1991
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205. Differential efficiency of mutagenesis at three genetic loci in CHO cells by a benzo[ a]pyrene diol epoxide
- Author
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MacLeod, Michael C., Adair, Gerald, and Humphrey, Ronald M.
- Published
- 1988
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206. Stabilization of a reactive, electophilic carcinogen, benzo[ a]pyrene diol epoxide, by mammalian cells
- Author
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Macleod, Michael C., Adair, Gerald, Dickson-Black, Dawn, Pevny, Tomas, and Humphrey, Ronald M.
- Published
- 1987
- Full Text
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207. Uncertainty in the determination of the molecular weight of poly(A)-containing RNA
- Author
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MacLeod, Michael C.
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- 1975
- Full Text
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208. WESTIN MISSION HILLS RESORT & SPA.
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MaCleod, Michael
- Subjects
RESORTS ,HEALTH resorts ,CONVENTION facilities - Abstract
This article offers information on the Westin Mission Hills Resort & Spa located in Rancho Mirage, California. This property boasts stylish interior, lush landscaping, divine California-style cuisine and full-service spa. It also features a 65,000-square-feet meeting space. It offers two conference centers, three ballrooms and boardrooms. According to Michael Macleod, director of sales and marketing, they maintain their business mix at about 65 percent groups versus 35 percent leisure.
- Published
- 2008
209. Innovation Is Needed, Not International Comparison.
- Author
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MacLeod, Michael
- Subjects
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LETTERS to the editor , *EDUCATIONAL planning - Abstract
A letter to the editor is presented in response to the article "A Pause Before Plunging Through the China Looking Glass," by Yong Zhao in the May 10, 2006 issue of the journal.
- Published
- 2006
210. Bilingual Parents and 'Language Confusion'
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MacLeod, Michael
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LETTERS to the editor , *FOREIGN language education - Abstract
A letter to the editor is presented in response to an article on foreign language education in the April 19, 2006 issue.
- Published
- 2006
211. Evidence From the East On Testing's Damage.
- Author
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MacLeod, Michael
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LETTERS to the editor , *EDUCATIONAL tests & measurements - Abstract
Presents a letter to the editor commenting on the article "Big Tests, Big Sticks," published in the July 13, 2005 issue.
- Published
- 2005
212. Reducing the carbon footprint of Senegalese cattle systems through improved productivity
- Author
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Salmon, Gareth Richard, Macleod, Michael, Wilson, Ron, Dexter, Kyle, Karen, Marshall, and Robinson, Timothy
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greenhouse gases ,productivity ,cattle ,Senegal ,emissions ,cost-effective - Abstract
Meat and milk from sub Saharan African cattle systems tend to have high greenhouse gas emissions intensities; this is largely due to low levels of productivity. There is a need to increase production to meet an increasing demand for livestock commodities; driven by growing populations, and growing diet variation, as incomes and urbanisation increase. Without measures to reduce the emissions intensity of production, there will be significant increases in total greenhouse gas emissions. Therefore, cost-effective ways of reducing emissions intensity, whilst increasing productivity should be identified. This thesis looks to support this by providing an assessment of low-input to semi-intensified cattle production systems in Senegal, West Africa; where cattle populations are growing and efforts are being made to increase domestic milk production. The emissions intensity of protein from current production systems is calculated using a version of the Food and Agriculture Organization’s Global Livestock Environmental Assessment Model (GLEAM). Variation in emissions intensity is observed between current systems, which can be largely linked to feed ration quality and levels of protein productivity. Productivity improving interventions suitable for the study systems are identified, and their application to current systems modelled by altering input parameters within GLEAM. It is suggested that production systems could reduce emissions intensities by applying nutritional and health related intervention packages; through which the varying production systems could abate between 10% and 20% of their total greenhouse gas emissions whilst also making financial savings. A comparison between the current systems of production also suggests that changing the lower productivity systems to match higher producing systems would also offer substantial cost-saving emissions abatement. The thesis considers the key limitation to the use of GLEAM for modelling the application of nutritional mitigation measures, in that when nutritional improvements are made animal performance does not currently increase. Predicting how animals will respond to improved nutrition is challenging. However, a methodology is discussed, and is shown to have an important effect on the emissions abatement results. Subsequently, the thesis advocates further research to experimentally substantiate animal performance responses when nutritionally limited cattle are given improved feed regimes. Despite the study livestock keepers showing aspiration to improve the productivity of their herds, with subsequent potential to reduce greenhouse gas emissions, the thesis recognises that the abatement potentials suggested by modelling would be restricted by the reality of production system context and constraints. Key barriers to a realisation of the productivity improvements include: a lack of financial means, limitations to resource access and affordability, and requirement for information and training concerning productivity improving options. For realisation of productivity improvements the current barriers would require further investigation, the thesis helps identify what form interventions should take.
- Published
- 2017
213. Revisiting the “10% rule” in breast cancer sentinel lymph node biopsy: an approach to minimize the number of sentinel lymph nodes removed
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Dutta, Ranjan, Kluftinger, Andreas, MacLeod, Michael, Kindrachuk, Gary, and Baliski, Chris
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BREAST cancer , *SENTINEL lymph nodes , *BIOPSY , *RETROSPECTIVE studies , *STATISTICS , *DATA analysis - Abstract
Abstract: Background: Sentinel lymph node (SLN) biopsy (SLNB) is an accurate and proven axillary staging procedure for early breast cancer. The aim of this study was to determine if the “10% rule” is applicable to the performance of SLNB at the investigators'' institution and if the criteria used for SLNB at their institution could be refined to minimize the number of SLNs removed. Methods: Retrospective analysis was conducted of a prospectively collected breast cancer SLNB database. Standard statistical methods were used for data analysis. Results: Five hundred nine patients underwent a SLNB for breast cancer over a 5 year period. A mean of 2.5 SLNs were removed per patient. All patients with SLN metastasis were identified within the 1st 4 SLNs removed. Conclusions: The “10% rule” is best used as a guide at the investigators'' institution. Strict adherence to this rule appears to result in the removal of an excessive number of lymph nodes, which may contribute to excessive health care costs and patient morbidity. [Copyright &y& Elsevier]
- Published
- 2012
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214. The Evolution of Legislative Jurisdictions.
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Baumgartner, Frank R., Jones, Bryan D., and MacLeod, Michael C.
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TWENTIETH century , *LEGISLATIVE bodies , *POLITICAL science - Abstract
Presents a study which examined the clarity of the jurisdictions of the committees of the United States Congress over the entire post-war period. Model of jurisdictional clarity; Results from a new dataset on all congressional hearings between 1947 and 1994; Implications of the findings for models of legislative behavior and government decision-making.
- Published
- 2000
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215. Review of the reviews.
- Author
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MacLeod, Michael
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RESORTS ,HOSPITALITY industry - Abstract
A review is offered for Portavadie Marinaspa resort located in Loch Fyne, on the west coast of Argyll and Bute, Scotland.
- Published
- 2015
216. Achieving cleaner growth in agriculture: Establishing feasible mitigation through a bottom-up approach.
- Author
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Barnes, Andrew P., Stockdale, Elizabeth, Norton, Lisa, Eory, Vera, Macleod, Michael, and Buys, Gwen
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- *
GREENHOUSE gas mitigation , *AGRICULTURAL industries - Abstract
Achieving greenhouse gas emission reductions to meet the 1.5 °C target by 2050 is particularly challenging for the agricultural sector. Cleaner Growth Mitigation Measures (CG-MM) are practices and technologies which balance food production with greenhouse gas abatement and are also identified as being economically acceptable. This paper explores a large number of CG-MMs to assess their feasibility using a novel participatory filtering process. Each measure is explored through a series of mapping exercises with supply chain actors to identify the impact on greenhouse gases and their applicability to different farming systems. These are then refined in a series of farmer workshops to identify which measures were considered feasible. Results show that acceptance of CG-MMs by the industry and the farmers themselves is limited. A pessimistic estimate of 50–60% of potential abatement could be lost due to lack of acceptance of currently available CG-MMs within farming. This impacts expectations on decarbonisation trajectories for the agricultural sector to reach net zero by 2050. This also argues for targeted approaches in order to capture some of the lost abatement. • Cleaner growth mitigation measures are assessed at farming systems level. • Half of the potential abatement from cost-effective measures is considered feasible for farmers. • Agricultural support needs to be targeted to capture lost abatement from cleaner growth measures. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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217. Challenges and priorities for modelling livestock health and pathogens in the context of climate change.
- Author
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Özkan, Şeyda, Vitali, Andrea, Lacetera, Nicola, Amon, Barbara, Bannink, André, Bartley, Dave J., Blanco-Penedo, Isabel, de Haas, Yvette, Dufrasne, Isabelle, Elliott, John, Eory, Vera, Fox, Naomi J., Garnsworthy, Phil C., Gengler, Nicolas, Hammami, Hedi, Kyriazakis, Ilias, Leclère, David, Lessire, Françoise, Macleod, Michael, and Robinson, Timothy P.
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ANIMAL health , *CLIMATE change & health , *ANIMAL welfare , *GREENHOUSE gases & the environment , *ANIMAL adaptation - Abstract
Climate change has the potential to impair livestock health, with consequences for animal welfare, productivity, greenhouse gas emissions, and human livelihoods and health. Modelling has an important role in assessing the impacts of climate change on livestock systems and the efficacy of potential adaptation strategies, to support decision making for more efficient, resilient and sustainable production. However, a coherent set of challenges and research priorities for modelling livestock health and pathogens under climate change has not previously been available. To identify such challenges and priorities, researchers from across Europe were engaged in a horizon-scanning study, involving workshop and questionnaire based exercises and focussed literature reviews. Eighteen key challenges were identified and grouped into six categories based on subject-specific and capacity building requirements. Across a number of challenges, the need for inventories relating model types to different applications (e.g. the pathogen species, region, scale of focus and purpose to which they can be applied) was identified, in order to identify gaps in capability in relation to the impacts of climate change on animal health. The need for collaboration and learning across disciplines was highlighted in several challenges, e.g. to better understand and model complex ecological interactions between pathogens, vectors, wildlife hosts and livestock in the context of climate change. Collaboration between socio-economic and biophysical disciplines was seen as important for better engagement with stakeholders and for improved modelling of the costs and benefits of poor livestock health. The need for more comprehensive validation of empirical relationships, for harmonising terminology and measurements, and for building capacity for under-researched nations, systems and health problems indicated the importance of joined up approaches across nations. The challenges and priorities identified can help focus the development of modelling capacity and future research structures in this vital field. Well-funded networks capable of managing the long-term development of shared resources are required in order to create a cohesive modelling community equipped to tackle the complex challenges of climate change. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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218. 2,6-Dithiopurine, a nucleophilic scavenger, protects against mutagenesis in mouse skin treated in vivo with 2-(chloroethyl) ethyl sulfide, a mustard gas analog
- Author
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Boulware, Stephen, Fields, Tammy, McIvor, Elizabeth, Powell, K. Leslie, Abel, Erika L., Vasquez, Karen M., and MacLeod, Michael C.
- Subjects
- *
PURINES , *NUCLEOPHILIC reactions , *MUTAGENESIS , *SULFIDES , *MUSTARD gas , *DNA damage , *CHEMICAL warfare , *LABORATORY mice - Abstract
Abstract: Sulfur mustard [bis(2-chloroethyl)sulfide, SM] is a well-known DNA-damaging agent that has been used in chemical warfare since World War I, and is a weapon that could potentially be used in a terrorist attack on a civilian population. Dermal exposure to high concentrations of SM produces severe, long-lasting burns. Topical exposure to high concentrations of 2-(chloroethyl) ethyl sulfide (CEES), a monofunctional analog of SM, also produces severe skin lesions in mice. Utilizing a genetically engineered mouse strain, Big Blue, that allows measurement of mutation frequencies in mouse tissues, we now show that topical treatment with much lower concentrations of CEES induces significant dose- and time-dependent increases in mutation frequency in mouse skin; the mutagenic exposures produce minimal toxicity as determined by standard histopathology and immunohistochemical analysis for cytokeratin 6 and the DNA-damage induced phosphorylation of histone H2AX (γ-H2AX). We attempted to develop a therapeutic that would inhibit the CEES-induced increase in mutation frequency in the skin. We observe that multi-dose, topical treatment with 2,6-dithiopurine (DTP), a known chemical scavenger of CEES, beginning 1h post-exposure to CEES, completely abolishes the CEES-induced increase in mutation frequency. These findings suggest the possibility that DTP, previously shown to be non-toxic in mice, may be useful as a therapeutic agent in accidental or malicious human exposures to SM. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF
219. Protection against 2-chloroethyl ethyl sulfide (CEES) — induced cytotoxicity in human keratinocytes by an inducer of the glutathione detoxification pathway
- Author
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Abel, Erika L., Bubel, Jennifer D., Simper, Melissa S., Powell, Leslie, McClellan, S. Alex, Andreeff, Michael, MacLeod, Michael C., and DiGiovanni, John
- Subjects
- *
MUSTARD gas , *SULFIDES , *CELL-mediated cytotoxicity , *KERATINOCYTES , *CHEMICAL warfare agents , *GLUTATHIONE transferase , *DIMETHYL sulfoxide , *ETHYLENEDIAMINETETRAACETIC acid , *SALICYLIC acid , *CELL membranes , *EPIDERMIS - Abstract
Abstract: Sulfur mustard (SM or mustard gas) was first used as a chemical warfare agent almost 100years ago. Due to its toxic effects on the eyes, lungs, and skin, and the relative ease with which it may be synthesized, mustard gas remains a potential chemical threat to the present day. SM exposed skin develops fluid filled bullae resulting from potent cytotoxicity of cells lining the basement membrane of the epidermis. Currently, there are no antidotes for SM exposure; therefore, chemopreventive measures for first responders following an SM attack are needed. Glutathione (GSH) is known to have a protective effect against SM toxicity, and detoxification of SM is believed to occur, in part, via GSH conjugation. Therefore, we screened 6 potential chemopreventive agents for ability to induce GSH synthesis and protect cultured human keratinocytes against the SM analog, 2-chloroethyl ethyl sulfide (CEES). Using NCTC2544 human keratinocytes, we found that both sulforaphane and methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO-Me) stimulated nuclear localization of Nrf2 and induced expression of the GSH synthesis gene, GCLM. Additionally, we found that treatment with CDDO-Me elevated reduced GSH content of NCTC2544 cells and preserved their viability by ~3-fold following exposure to CEES. Our data also suggested that CDDO-Me may act additively with 2,6-dithiopurine (DTP), a nucleophilic scavenging agent, to increase the viability of keratinocytes exposed to CEES. These results suggest that CDDO-Me is a promising chemopreventive agent for SM toxicity in the skin. [Copyright &y& Elsevier]
- Published
- 2011
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220. Coastal dune conservation on an Irish commonage: community-based management or tragedy of the commons?
- Author
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Mc Kenna, John, O'Hagan, Anne Marie, Power, James, Macleod, Michael, and Cooper, Andrew
- Subjects
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AGRICULTURE , *HABITAT conservation , *NATURE conservation , *ENVIRONMENTAL degradation - Abstract
In Ireland ‘commonage’ refers to lands jointly owned by several individuals who have grazing rights. Commonage can provide the low-intensity grazing regime regarded as optimal for habitat conservation, and it is also unlikely to suffer the negative impacts of building development or coastal engineering. Today, however, the traditional control systems of coastal commonage are generally moribund, leading to habitat degradation. The only viable future management model is likely to be one based on local community control. Community management would have the legitimacy to counter the negative perceptions of external authority that generate environmental degradation. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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221. Quantitative high-throughput measurement of gene expression with sub-zeptomole sensitivity by capillary electrophoresis
- Author
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Spyres, Lea, Gaddis, Sally, Bedford, Ella, Arantes, Stacey, Liburd, Nikki, Powell, K. Leslie, Thames, Howard, Mitchell, David, Walborg, Earl, Rouabhia, Mahmoud, Aldaz, C. Marcelo, and MacLeod, Michael C.
- Subjects
- *
GEL electrophoresis , *GENE expression , *HEREDITY , *MESSENGER RNA - Abstract
Abstract: Microarray technologies have provided the ability to monitor the expression of whole genomes rapidly. However, concerns persist with regard to quantitation and reproducibility, and the detection limits for individual genes in particular arrays are generally unknown. This article describes a semiautomated PCR-based technology, Q-RAGE, which rapidly provides measurements of mRNA abundance with extremely high sensitivity using fluorescent detection of specific products separated by capillary electrophoresis. A linear relationship between template concentration and fluorescent signal can be demonstrated down to template concentrations in the low aM region, corresponding to approximately 0.04zmol (24 molecules) per reaction. The technique is shown to be quantitative over five orders of magnitude of template concentration, and average mRNA abundances of approximately 0.01 molecule per cell can be detected. A single predefined set of 320 primers provides 90–95% coverage of all eukaryotic genomes. Analysis of a set of 19 p53-regulated genes in untreated cultures of normal human epithelial cells, derived from three different tissues, revealed a 600-fold range of apparent constitutive expression levels. For most of the genes assayed, good correlations were observed among the expression levels in normal mammary, bronchial, and epidermal epithelial cells. [Copyright &y& Elsevier]
- Published
- 2005
- Full Text
- View/download PDF
222. Soil organic carbon sequestration rates in vineyard agroecosystems under different soil management practices: A meta-analysis.
- Author
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Payen, Florian Thomas, Sykes, Alasdair, Aitkenhead, Matt, Alexander, Peter, Moran, Dominic, and MacLeod, Michael
- Subjects
- *
CARBON sequestration , *SOIL management , *CARBON in soils , *VINEYARDS , *AGRICULTURAL ecology , *CLIMATE change mitigation - Abstract
Vineyards are usually cultivated in soils characterised by low soil organic carbon (SOC) content and have high risks of soil erosion and degradation. Increasing SOC stocks in these cropping systems has the potential to contribute to climate change mitigation through SOC sequestration and to enhance soil quality. We conducted a meta-analysis and compared the SOC stock response ratio, the SOC stock rate of change, and the SOC sequestration rate in vineyards under different SOC sequestration (SCS) practices relative to conventional management. SCS practices included organic amendments (OA), biochar amendments (BC), returning pruning residues to the soil (PR), no-tillage (NT), cover cropping (CC), and several combinations of these practices. The average SOC sequestration rate of SCS management was 7.53 Mg CO 2 -eq. ha−1 yr−1 to a 30-cm soil depth. The highest SOC sequestration rate (11.06 Mg CO 2 -eq. ha−1 yr−1) was achieved under a combination of OA+NT and the lowest (2.82 Mg CO 2 -eq. ha−1 yr−1) was observed under PR treatments. Field experiments performed in particularly hot and dry bioclimatic zones were associated with lower SOC sequestration rates relative to those performed in more temperate areas. The high SOC sequestration rates obtained for many SCS practices, and the large land area dedicated to viticulture worldwide (7.45 Mha), imply that the adoption of SCS practices in vineyards can contribute to the global efforts to offset atmospheric greenhouse gas concentrations via SOC sequestration to mitigate climate change. • Effects of soil carbon sequestration (SCS) practices were assessed in vineyards using a meta-analysis. • All SCS practices led to soil organic carbon (SOC) accumulation in viticultural soils. • The average SOC sequestration rate was 7.53 Mg CO 2 -eq. ha−1 yr−1. • The impact of SCS management on SOC stocks was climate-dependent. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
223. ATF3-Induced Mammary Tumors Exhibit Molecular Features of Human Basal-Like Breast Cancer.
- Author
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Yan, Leqin, Gaddis, Sally, Coletta, Luis Della, Repass, John, Powell, Katherine Leslie, Simper, Melissa S., Chen, Yueping, Byrom, Michelle, Zhong, Yi, Lin, Kevin, Liu, Bin, Lu, Yue, Shen, Jianjun, MacLeod, Michael C., and Nicolini, Andrea
- Subjects
- *
BREAST cancer , *RAS oncogenes , *CANCER genes , *MAMMARY glands , *GENES , *TUMORS , *CATENINS - Abstract
Basal-like breast cancer (BLBC) is an aggressive and deadly subtype of human breast cancer that is highly metastatic, displays stem-cell like features, and has limited treatment options. Therefore, developing and characterizing preclinical mouse models with tumors that resemble BLBC is important for human therapeutic development. ATF3 is a potent oncogene that is aberrantly expressed in most human breast cancers. In the BK5.ATF3 mouse model, overexpression of ATF3 in the basal epithelial cells of the mammary gland produces tumors that are characterized by activation of the Wnt/β-catenin signaling pathway. Here, we used RNA-Seq and microRNA (miRNA) microarrays to better define the molecular features of BK5.ATF3-derived mammary tumors. These analyses showed that these tumors share many characteristics of human BLBC including reduced expression of Rb1, Esr1, and Pgr and increased expression of Erbb2, Egfr, and the genes encoding keratins 5, 6, and 17. An analysis of miRNA expression revealed reduced levels of Mir145 and Mir143, leading to the upregulation of their target genes including both the pluripotency factors Klf4 and Sox2 as well as the cancer stem-cell-related gene Kras. Finally, we show through knock-down experiments that ATF3 may directly modulate MIR145/143 expression. Taken together, our results indicate that the ATF3 mouse mammary tumor model could provide a powerful model to define the molecular mechanisms leading to BLBC, identify the factors that contribute to its aggressiveness, and, ultimately, discover specific genes and gene networks for therapeutic targeting. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
224. Marine aquaculture can deliver 40% lower carbon footprints than freshwater aquaculture based on feed, energy and biogeochemical cycles.
- Author
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Shen L, Wu L, Wei W, Yang Y, MacLeod MJ, Lin J, Song G, Yuan J, Yang P, Wu L, Li M, and Zhuang M
- Subjects
- Greenhouse Gases analysis, Methane analysis, Animals, Seawater chemistry, Nitrous Oxide analysis, Aquaculture methods, Carbon Footprint statistics & numerical data, Fresh Water, Animal Feed analysis
- Abstract
Freshwater aquaculture is an increasingly important source of blue foods but produces substantial methane and nitrous oxide emissions. Marine aquaculture, also known as mariculture, is a smaller sector with a large growth potential, but its climate impacts are challenging to accurately quantify. Here we assess the greenhouse gas emissions from mariculture's aquatic environment in global potentially suitable areas at 10 km resolution on the basis of marine biogeochemical cycles, greenhouse gas measurements from research cruises and satellite-observed net primary productivity. Mariculture's aquatic emissions intensities are estimated to be 1-6 g CH
4 kg-1 carcass weight and 0.05-0.2 g N2 O kg-1 carcass weight, >98% and >80% lower than freshwater systems. Using a life-cycle assessment approach, we show that mariculture's carbon footprints are ~40% lower than those of freshwater aquaculture based on feed, energy use and the aquatic environment emissions. Adoption of mariculture alongside freshwater aquaculture production could offer considerable climate benefits to meet future dietary protein and nutritional needs., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2024
- Full Text
- View/download PDF
225. A comprehensive quantification of global nitrous oxide sources and sinks.
- Author
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Tian H, Xu R, Canadell JG, Thompson RL, Winiwarter W, Suntharalingam P, Davidson EA, Ciais P, Jackson RB, Janssens-Maenhout G, Prather MJ, Regnier P, Pan N, Pan S, Peters GP, Shi H, Tubiello FN, Zaehle S, Zhou F, Arneth A, Battaglia G, Berthet S, Bopp L, Bouwman AF, Buitenhuis ET, Chang J, Chipperfield MP, Dangal SRS, Dlugokencky E, Elkins JW, Eyre BD, Fu B, Hall B, Ito A, Joos F, Krummel PB, Landolfi A, Laruelle GG, Lauerwald R, Li W, Lienert S, Maavara T, MacLeod M, Millet DB, Olin S, Patra PK, Prinn RG, Raymond PA, Ruiz DJ, van der Werf GR, Vuichard N, Wang J, Weiss RF, Wells KC, Wilson C, Yang J, and Yao Y
- Subjects
- Agriculture, Atmosphere chemistry, Crops, Agricultural metabolism, Human Activities, Internationality, Nitrogen analysis, Nitrogen metabolism, Nitrous Oxide analysis, Nitrous Oxide metabolism
- Abstract
Nitrous oxide (N
2 O), like carbon dioxide, is a long-lived greenhouse gas that accumulates in the atmosphere. Over the past 150 years, increasing atmospheric N2 O concentrations have contributed to stratospheric ozone depletion1 and climate change2 , with the current rate of increase estimated at 2 per cent per decade. Existing national inventories do not provide a full picture of N2 O emissions, owing to their omission of natural sources and limitations in methodology for attributing anthropogenic sources. Here we present a global N2 O inventory that incorporates both natural and anthropogenic sources and accounts for the interaction between nitrogen additions and the biochemical processes that control N2 O emissions. We use bottom-up (inventory, statistical extrapolation of flux measurements, process-based land and ocean modelling) and top-down (atmospheric inversion) approaches to provide a comprehensive quantification of global N2 O sources and sinks resulting from 21 natural and human sectors between 1980 and 2016. Global N2 O emissions were 17.0 (minimum-maximum estimates: 12.2-23.5) teragrams of nitrogen per year (bottom-up) and 16.9 (15.9-17.7) teragrams of nitrogen per year (top-down) between 2007 and 2016. Global human-induced emissions, which are dominated by nitrogen additions to croplands, increased by 30% over the past four decades to 7.3 (4.2-11.4) teragrams of nitrogen per year. This increase was mainly responsible for the growth in the atmospheric burden. Our findings point to growing N2 O emissions in emerging economies-particularly Brazil, China and India. Analysis of process-based model estimates reveals an emerging N2 O-climate feedback resulting from interactions between nitrogen additions and climate change. The recent growth in N2 O emissions exceeds some of the highest projected emission scenarios3,4 , underscoring the urgency to mitigate N2 O emissions.- Published
- 2020
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- View/download PDF
226. Quantifying greenhouse gas emissions from global aquaculture.
- Author
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MacLeod MJ, Hasan MR, Robb DHF, and Mamun-Ur-Rashid M
- Abstract
Global aquaculture makes an important contribution to food security directly (by increasing food availability and accessibility) and indirectly (as a driver of economic development). In order to enable sustainable expansion of aquaculture, we need to understand aquaculture's contribution to global greenhouse gas (GHG) emissions and how it can be mitigated. This study quantifies the global GHG emissions from aquaculture (excluding the farming of aquatic plants), with a focus on using modern, commercial feed formulations for the main species groups and geographic regions. Here we show that global aquaculture accounted for approximately 0.49% of anthropogenic GHG emissions in 2017, which is similar in magnitude to the emissions from sheep production. The modest emissions reflect the low emissions intensity of aquaculture, compared to terrestrial livestock (in particular cattle, sheep and goats), which is due largely to the absence of enteric CH
4 in aquaculture, combined with the high fertility and low feed conversion ratios of finfish and shellfish.- Published
- 2020
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- View/download PDF
227. Characterising the biophysical, economic and social impacts of soil carbon sequestration as a greenhouse gas removal technology.
- Author
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Sykes AJ, Macleod M, Eory V, Rees RM, Payen F, Myrgiotis V, Williams M, Sohi S, Hillier J, Moran D, Manning DAC, Goglio P, Seghetta M, Williams A, Harris J, Dondini M, Walton J, House J, and Smith P
- Subjects
- Agriculture, Carbon, Carbon Sequestration, Greenhouse Effect, Social Change, Soil, Greenhouse Gases
- Abstract
To limit warming to well below 2°C, most scenario projections rely on greenhouse gas removal technologies (GGRTs); one such GGRT uses soil carbon sequestration (SCS) in agricultural land. In addition to their role in mitigating climate change, SCS practices play a role in delivering agroecosystem resilience, climate change adaptability and food security. Environmental heterogeneity and differences in agricultural practices challenge the practical implementation of SCS, and our analysis addresses the associated knowledge gap. Previous assessments have focused on global potentials, but there is a need among policymakers to operationalise SCS. Here, we assess a range of practices already proposed to deliver SCS, and distil these into a subset of specific measures. We provide a multidisciplinary summary of the barriers and potential incentives towards practical implementation of these measures. First, we identify specific practices with potential for both a positive impact on SCS at farm level and an uptake rate compatible with global impact. These focus on: (a) optimising crop primary productivity (e.g. nutrient optimisation, pH management, irrigation); (b) reducing soil disturbance and managing soil physical properties (e.g. improved rotations, minimum till); (c) minimising deliberate removal of C or lateral transport via erosion processes (e.g. support measures, bare fallow reduction); (d) addition of C produced outside the system (e.g. organic manure amendments, biochar addition); (e) provision of additional C inputs within the cropping system (e.g. agroforestry, cover cropping). We then consider economic and non-cost barriers and incentives for land managers implementing these measures, along with the potential externalised impacts of implementation. This offers a framework and reference point for holistic assessment of the impacts of SCS. Finally, we summarise and discuss the ability of extant scientific approaches to quantify the technical potential and externalities of SCS measures, and the barriers and incentives to their implementation in global agricultural systems., (© 2019 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)
- Published
- 2020
- Full Text
- View/download PDF
228. Designer Sinorhizobium meliloti strains and multi-functional vectors enable direct inter-kingdom DNA transfer.
- Author
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Brumwell SL, MacLeod MR, Huang T, Cochrane RR, Meaney RS, Zamani M, Matysiakiewicz O, Dan KN, Janakirama P, Edgell DR, Charles TC, Finan TM, and Karas BJ
- Subjects
- Conjugation, Genetic, Electroporation, Escherichia coli genetics, Saccharomyces cerevisiae genetics, Transformation, Genetic, DNA metabolism, Genetic Vectors, Sinorhizobium meliloti genetics, Synthetic Biology methods
- Abstract
Storage, manipulation and delivery of DNA fragments is crucial for synthetic biology applications, subsequently allowing organisms of interest to be engineered with genes or pathways to produce desirable phenotypes such as disease or drought resistance in plants, or for synthesis of a specific chemical product. However, DNA with high G+C content can be unstable in many host organisms including Saccharomyces cerevisiae. Here, we report the development of Sinorhizobium meliloti, a nitrogen-fixing plant symbioticα-Proteobacterium, as a novel host that can store DNA, and mobilize DNA to E. coli, S. cerevisiae, and the eukaryotic microalgae Phaeodactylum tricornutum. To achieve this, we deleted the hsdR restriction-system in multiple reduced genome strains of S. meliloti that enable DNA transformation with up to 1.4 x 105 and 2.1 x 103 CFU μg-1 of DNA efficiency using electroporation and a newly developed polyethylene glycol transformation method, respectively. Multi-host and multi-functional shuttle vectors (MHS) were constructed and stably propagated in S. meliloti, E. coli, S. cerevisiae, and P. tricornutum. We also developed protocols and demonstrated direct transfer of these MHS vectors via conjugation from S. meliloti to E. coli, S. cerevisiae, and P. tricornutum. The development of S. meliloti as a new host for inter-kingdom DNA transfer will be invaluable for synthetic biology research and applications, including the installation and study of genes and biosynthetic pathways into organisms of interest in industry and agriculture., Competing Interests: B.J.K. is Chief Executive Officer of Designer Microbes Inc. and holds Designer Microbes Inc. stock. P.J. also holds Designer Microbes Inc. stock. The funder provided support in the form of salaries for R.S.M., and P.J. This competing interest does not alter our adherence to PLOS ONE policies on sharing data and materials.
- Published
- 2019
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229. Epidermal hyperplasia and oral carcinoma in mice overexpressing the transcription factor ATF3 in basal epithelial cells.
- Author
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Wang A, Arantes S, Conti C, McArthur M, Aldaz CM, and MacLeod MC
- Subjects
- Animals, DNA, Complementary metabolism, Genotype, Humans, Keratin-5 biosynthesis, Keratins metabolism, Mice, Mice, Transgenic, Plant Roots, Time Factors, Transcription Factors metabolism, Tumor Suppressor Protein p53 metabolism, Activating Transcription Factor 3 physiology, Gene Expression Regulation, Neoplastic, Mouth Neoplasms metabolism
- Abstract
ATF3 is a highly conserved eukaryotic transcription factor that is ubiquitously upregulated transcriptionally during cellular responses to a variety of stresses, in particular DNA damage. However, the role of ATF3 in the DNA damage response is unclear. Transgenic mice that overexpress human ATF3 in basal epithelial cells under the control of the bovine keratin 5 (K5) promoter were constructed and characterized for epidermal alterations. Strong, nuclear expression of the exogenous ATF3 protein was seen in basal cells of the epidermis, hair follicles, and oral mucosa. Hyperplastic changes in the K5-expressing, outer root sheath (ORS) cells of the hair follicle were observed in young mice, resulting in multiple layers of ORS cells in the mature follicle and large aberrantly shaped follicles. Mild hyperplasia of the interfollicular epidermis was also noted, increasing with age. However, no epidermal tumors were identified in BK5.ATF3 mice observed for 16 mo. At 16 mo of age, most transgenic mice exhibited multi-focal areas of hyperplasia and dysplasia in the oral mucosa, with cellular atypia and underlying acute inflammatory changes. Neoplastic lesions were also seen in the oral cavity of BK5.ATF3 mice, including oral squamous cell carcinoma (60% incidence) and basal cell tumors with follicular differentiation (70% incidence), but not in non-transgenic FVB/N littermates. Heterogeneous nuclear expression (or stabilization) of p53 protein was seen in some oral dysplasias, with a patchy distribution primarily in the least differentiated layers of the lesions. This represents the first indication that ATF3 may have oncogenic properties in epithelial cells., ((c) 2007 Wiley-Liss, Inc.)
- Published
- 2007
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- View/download PDF
230. High-affinity triplex-forming oligonucleotide target sequences in mammalian genomes.
- Author
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Wu Q, Gaddis SS, MacLeod MC, Walborg EF, Thames HD, DiGiovanni J, and Vasquez KM
- Subjects
- Animals, Electrophoretic Mobility Shift Assay, Humans, Mice, Promoter Regions, Genetic, DNA chemistry, Gene Targeting, Genome, Human, Mammals genetics, Oligonucleotides chemistry, Sequence Analysis, DNA methods
- Abstract
Site-specific recognition of duplex DNA by triplex-forming oligonucleotides (TFOs) provides a promising approach to manipulate mammalian genomes. A prerequisite for successful gene targeting using this approach is that the targeted gene must contain specific, high-affinity TFO target sequences (TTS). To date, TTS have been identified and characterized in only approximately 37 human or rodent genes, limiting the application of triplex-directed gene targeting. We searched the complete human and mouse genomes using an algorithm designed to identify high-affinity TTS. The resulting data set contains 1.9 million potential TTS for each species. We found that 97.8% of known human and 95.2% of known mouse genes have at least one potential high-affinity TTS in the promoter and/or transcribed gene regions. Importantly, 86.5% of known human and 83% of the known mouse genes have at least one TTS that is unique to that gene. Thus, it is possible to target the majority of human and mouse genes with specific TFOs. We found substantially more potential TTS in the promoter sequences than in the transcribed gene sequences or intergenic sequences in both genomes. We selected 12 mouse genes and 2 human genes critical for cell signaling, proliferation, and/or carcinogenesis, identified potential TTS in each, and determined TFO binding affinities to these sites in vitro. We identified at least one high-affinity, specific TFO binding site within each of these genes. Using this information, many genes involved in mammalian cell proliferation and carcinogenesis can now be targeted., (Copyright 2006 Wiley-Liss, Inc.)
- Published
- 2007
- Full Text
- View/download PDF
231. Expression of common chromosomal fragile site genes, WWOX/FRA16D and FHIT/FRA3B is downregulated by exposure to environmental carcinogens, UV, and BPDE but not by IR.
- Author
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Thavathiru E, Ludes-Meyers JH, MacLeod MC, and Aldaz CM
- Subjects
- Acid Anhydride Hydrolases genetics, Cell Line, Tumor, Down-Regulation radiation effects, Gene Expression Regulation, Neoplastic drug effects, Gene Expression Regulation, Neoplastic radiation effects, Humans, Neoplasm Proteins genetics, Oxidoreductases genetics, Radiation, Ionizing, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Proteins, WW Domain-Containing Oxidoreductase, 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide pharmacology, Acid Anhydride Hydrolases metabolism, Carcinogens, Environmental pharmacology, Chromosome Fragile Sites genetics, Down-Regulation drug effects, Neoplasm Proteins metabolism, Oxidoreductases metabolism, Ultraviolet Rays
- Abstract
Common chromosomal fragile sites are unstable genomic loci susceptible to breakage, rearrangement, and are highly recombinogenic. Frequent alterations at these loci in tumor cells led to the hypothesis that they may contribute to cancer development. The two most common chromosomal fragile sites FRA16D and FRA3B which harbor WWOX and FHIT genes, respectively, are frequently altered in human cancers. Here we report that environmental carcinogens, ultraviolet (UV) light, and Benzo[a]pyrene diol epoxide (BPDE), significantly downregulate expression of both genes. On the other hand, we observe that ionizing radiation (IR) does not affect expression of these genes, suggesting that the effect of repression exerted by UV and BPDE is not just a consequence of DNA damage but may be a result of different signaling pathways triggered by specific DNA lesions. Such downregulation correlates with an induction of an S-phase delay in the cell cycle. Treatment of UV-irradiated cells with caffeine abrogates the S-phase delay while concomitantly overcoming the repression phenomenon. This suggests the involvement of unique cell cycle checkpoint mechanisms in the observed repression. Therefore, it is hypothesized that protracted downregulation of the putative tumor suppressor genes WWOX and FHIT by environmental carcinogens may constitute an additional mechanism of relevance in the initiation of tumorigenesis., (Copyright 2005 Wiley-Liss, Inc)
- Published
- 2005
- Full Text
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232. Late cornified envelope family in differentiating epithelia--response to calcium and ultraviolet irradiation.
- Author
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Jackson B, Tilli CM, Hardman MJ, Avilion AA, MacLeod MC, Ashcroft GS, and Byrne C
- Subjects
- Cell Differentiation, Cells, Cultured, Epidermis drug effects, Epidermis radiation effects, Humans, Terminology as Topic, Ultraviolet Rays, Calcium pharmacology, Epidermis metabolism, Gene Expression Regulation drug effects, Gene Expression Regulation radiation effects, Multigene Family
- Abstract
The late cornified envelope (LCE) gene cluster within the epidermal differentiation complex on human chromosome one (mouse chromosome three) contains multiple conserved genes encoding stratum-corneum proteins. Within the LCE cluster, genes form "groups" based on chromosomal position and protein homology. We link a recently accepted nomenclature for the LCE cluster (formerly XP5, small proline-rich-like, late-envelope protein genes) to gene structure, groupings, and chromosomal organization, and carry out a pan-cluster quantitative expression analysis in a variety of tissues and environmental conditions. This analysis shows that (i) the cluster organizes into two "skin" expressing groups and a third group with low-level, tissue-specific expression patterns in all barrier-forming epithelia tested, including internal epithelia; (ii) LCE genes respond "group-wise" to environmental stimuli such as calcium levels and ultraviolet (UV) light, highlighting the functional significance of groups; (iii) in response to UV stimulation there is massive upregulation of a single, normally quiescent, non-skin LCE gene; and (iv) heterogeneity occurs between individuals with one individual lacking expression of an LCE skin gene without overt skin disease, suggesting LCE genes affect subtle attributes of skin function. This quantitative and pan-cluster expression analysis suggests that LCE groups have distinct functions and that within groups regulatory diversification permits specific responsiveness to environmental challenge.
- Published
- 2005
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233. Response of human mammary epithelial cells to DNA damage induced by BPDE: involvement of novel regulatory pathways.
- Author
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Wang A, Gu J, Judson-Kremer K, Powell KL, Mistry H, Simhambhatla P, Aldaz CM, Gaddis S, and MacLeod MC
- Subjects
- 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide metabolism, Breast cytology, Breast metabolism, Cell Cycle drug effects, Cyclin-Dependent Kinase Inhibitor p21, Cyclins metabolism, DNA Adducts metabolism, Epithelial Cells drug effects, Epithelial Cells metabolism, Gene Expression Profiling, Humans, Tumor Suppressor Protein p53 metabolism, 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide toxicity, Breast drug effects, Carcinogens toxicity, DNA drug effects, DNA Damage
- Abstract
The responses of a line of normal human mammary epithelial cells, HME87, to treatment with the ultimate carcinogen benzo[a]pyrene diol epoxide (BPDE) were analyzed using a directed gene expression analysis technique, RAGE. Under conditions where cell number was decreased by 50% 24 or 48 h post-treatment, flow cytometry demonstrated no establishment of a G(1)/S arrest nor induction of apoptosis; cells continued to enter S phase from G(1) for at least 24 h but were blocked at G(2)/M. Using the RAGE technique, changes in gene expression were assayed for over 1000 genes, and multiple time-point data were collected for approximately 90 genes. In accord with the cell cycle studies, expression of the p21-WAF1 gene, the major mediator of p53-dependent G(1)/S arrest, did not increase until 24 h post-treatment. The expression of other target genes for transactivation by p53 was increased at early time points, including GADD45, an effector of the G(2)/M checkpoint, and WIP1. Analyses of proteins in treated cells indicated that p53 was phosphorylated at Ser15 but not at Ser20 within 30 min of treatment, and this correlated with an increase in the total amount of p53 protein. Significant expression changes were noted in a number of transcription factor genes, including ATF3 and E2A, genes that have not been previously connected to a response to DNA damage involving bulky chemical adducts. In addition, expression of the XPC gene was induced by BPDE treatment; the XPC product is thought to be involved in recognition of DNA damage by the nucleotide excision repair system.
- Published
- 2003
- Full Text
- View/download PDF
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