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12,398 result(s) for "Macdonald, Ian"
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Inside politics
\"If the writing isn't prescient and perspicacious, it doesn't meet that test. This collection of columns and articles by L. Ian MacDonald--a sequel to Politics, People & Potpourri--meets that test. Much has happened in the politics of Canada and Quebec, as well as to the leaders who have defined and shaped the first two decades of the twenty-first century, since the first collection was published in 2009. The successful election campaigns of Harper and Trudeau form the political bookends of the present decade in Canada and the opening chapters of the book. Between these governments, there are the events, personalities, and issues that have shaped the political narrative and policy debate, from fiscal frameworks to clean energy and pipelines, from the Senate expense scandal and democratic reform, to national security at home and the mission against ISIS abroad. In his columns, and longer pieces from Policy Options and Policy magazines, MacDonald provides clear-minded commentary on political issues salient to all Canadians--including the election of Donald Trump in the United States. He also profiles a diverse group of political figures, and writes moving tributes to departed, nationally respected figures such as Jean Béliveau, Jim Flaherty, Jack Layton, and Tom Van Dusen. This intelligent and entertaining collection presents MacDonald at his best, and offers a captivating view of Canadian politics and life.\"- Provided by publisher.
Comparison of the Binding of Reversible Inhibitors to Human Butyrylcholinesterase and Acetylcholinesterase: A Crystallographic, Kinetic and Calorimetric Study
Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) hydrolyze the neurotransmitter acetylcholine and, thereby, function as coregulators of cholinergic neurotransmission. Although closely related, these enzymes display very different substrate specificities that only partially overlap. This disparity is largely due to differences in the number of aromatic residues lining the active site gorge, which leads to large differences in the shape of the gorge and potentially to distinct interactions with an individual ligand. Considerable structural information is available for the binding of a wide diversity of ligands to AChE. In contrast, structural data on the binding of reversible ligands to BChE are lacking. In a recent effort, an inhibitor competition approach was used to probe the overlap of ligand binding sites in BChE. Here, we extend this study by solving the crystal structures of human BChE in complex with five reversible ligands, namely, decamethonium, thioflavin T, propidium, huprine, and ethopropazine. We compare these structures to equivalent AChE complexes when available in the protein data bank and supplement this comparison with kinetic data and observations from isothermal titration calorimetry. This new information now allows us to define the binding mode of various ligand families and will be of importance in designing specific reversible ligands of BChE that behave as inhibitors or reactivators.
A comparison of three methods to assess body composition
The aim of this study was to compare the accuracy of measurements of body composition made using dual x-ray absorptiometry (DXA), analysis of computed tomography (CT) scans at the L3 vertebral level, and bioelectrical impedance analysis (BIA). DXA, CT, and BIA were performed in 47 patients recruited from two clinical trials investigating metabolic changes associated with major abdominal surgery or neoadjuvant chemotherapy for esophagogastric cancer. DXA was performed the week before surgery and before and after commencement of neoadjuvant chemotherapy. BIA was performed at the same time points and used with standard equations to calculate fat-free mass (FFM). Analysis of CT scans performed within 3 mo of the study was used to estimate FFM and fat mass (FM). There was good correlation between FM on DXA and CT (r2 = 0.6632; P < 0.0001) and FFM on DXA and CT (r2 = 0.7634; P < 0.0001), as well as FFM on DXA and BIA (r2 = 0.6275; P < 0.0001). Correlation between FFM on CT and BIA also was significant (r2 = 0.2742; P < 0.0001). On Bland–Altman analysis, average bias for FM on DXA and CT was 0.2564 with 95% limits of agreement (LOA) of –9.451 to 9.964. For FFM on DXA and CT, average bias was –0.1477, with LOA of –8.621 to 8.325. For FFM on DXA and BIA, average bias was –3.792, with LOA of –15.52 to 7.936. For FFM on CT and BIA, average bias was –2.661, with LOA of –22.71 to 17.39. Although a systematic error underestimating FFM was demonstrated with BIA, it may be a useful modality to quantify body composition in the clinical situation. •The present study compared the accuracy of measurements of body composition made using dual x-ray absorptiometry (DXA), analysis of computed tomography (CT) scans, and bioelectrical impedance analysis (BIA).•DXA, CT, and BIA were performed in 47 patients recruited from two clinical trials.•Although a systematic error underestimating fat-free mass was demonstrated with BIA, it may be a useful modality to quantify body composition in a clinical situation.
Free sugars
It is clear that the sugars component of the diet has potentially deleterious effects on health. In the past, the dietary sugars were collectively referred to as non-milk extrinsic sugars (UK) or added sugars. The WHO first proposed a new term, free sugars, which is rather broader than added sugars, and also includes the sugars in fruit juices and purees, as well as honey and syrups. This review considers the potential problems that free sugars represent in relation to health risks, and the recent proposals that free sugars are a more appropriate focus than added or total as far as public health initiatives are concerned. This will require major activities in relation to measurement, labelling and communication to the consumer if attempts to reduce dietary free sugars content are to be successful.
Magnitude and oxidation potential of hydrocarbon gases released from the BP oil well blowout
The deep-sea oil spill in the Gulf of Mexico released large quantities of oil and gaseous hydrocarbons into the deep ocean. Calculations using published estimates of the volume of oil released suggest that up to 500,000 t of gases such as methane were released into the deep ocean. The deep-sea hydrocarbon discharge resulting from the BP oil well blowout in the northern Gulf of Mexico released large quantities of oil and gaseous hydrocarbons such as methane into the deep ocean. So far, estimates of hydrocarbon discharge have focused on the oil released, and have overlooked the quantity, fate and environmental impact of the gas 1 . Gaseous hydrocarbons turn over slowly in the deep ocean, and microbial consumption of these gases could have a long-lasting impact on oceanic oxygen levels 2 . Here, we combine published estimates of the volume of oil released 1 , 3 , together with provisional estimates of the oil to gas ratio of the discharged fluid 4 , to determine the volume of gaseous hydrocarbons discharged during the spill. We estimate that the spill injected up to 500,000 t of gaseous hydrocarbons into the deep ocean and that these gaseous emissions comprised 40% of the total hydrocarbon discharge. Analysis of water around the wellhead revealed discrete layers of dissolved hydrocarbon gases between 1,000 and 1,300 m depth; concentrations exceeded background levels by up to 75,000 times. We suggest that microbial consumption of these gases could lead to the extensive and persistent depletion of oxygen in hydrocarbon-enriched waters.
Modifying the m6A brain methylome by ALKBH5-mediated demethylation: a new contender for synaptic tagging
Synaptic plasticity processes, which underlie learning and memory formation, require RNA to be translated local to synapses. The synaptic tagging hypothesis has previously been proposed to explain how mRNAs are available at specific activated synapses. However how RNA is regulated, and which transcripts are silenced or processed as part of the tagging process is still unknown. Modification of RNA by N6-methyladenosine (m6A/m) influences the cellular fate of mRNA. Here, by advanced microscopy, we showed that m6A demethylation by the eraser protein ALKBH5 occurs at active synaptic ribosomes and at synapses during short term plasticity. We demonstrated that at activated glutamatergic post-synaptic sites, both the YTHDF1 and YTHDF3 reader and the ALKBH5 eraser proteins increase in co-localisation to m6A-modified RNAs; but only the readers showed high co-localisation to modified RNAs during late-stage plasticity. The YTHDF1 and YTHFDF3 readers also exhibited differential roles during synaptic maturation suggesting that temporal and subcellular abundance may determine specific function. m6A-sequencing of human parahippocampus brain tissue revealed distinct white and grey matter m6A methylome profiles indicating that cellular context is a fundamental factor dictating regulated pathways. However, in both neuronal and glial cell-rich tissue, m6A effector proteins are themselves modified and m6A epitranscriptional and posttranslational modification processes coregulate protein cascades. We hypothesise that the availability m6A effector protein machinery in conjunction with RNA modification, may be important in the formation of condensed synaptic nanodomain assemblies through liquid-liquid phase separation. Our findings support that m6A demethylation by ALKBH5 is an intrinsic component of the synaptic tagging hypothesis and a molecular switch which leads to alterations in the RNA methylome, synaptic dysfunction and potentially reversible disease states.