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Find video protocols related to scientific articles indexed in Pubmed.
Acidification of floodplains due to river level decline during drought.
J. Contam. Hydrol.
PUBLISHED: 03-17-2014
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A severe drought from 2007 to 2010 resulted in the lowest river levels (1.75 m decline from average) in over 90 years of records at the end of the Murray-Darling Basin in South Australia. Due to the low river level and inability to apply irrigation, the groundwater depth on the adjacent agricultural flood plain also declined substantially (1-1.5 m) and the alluvial clay subsoils dried and cracked. Sulfidic material (pH>4, predominantly in the form of pyrite, FeS2) in these subsoils oxidised to form sulfuric material (pH<4) over an estimated 3300 ha on 13 floodplains. Much of the acidity in the deeply cracked contaminated soil layers was in available form (in pore water and on cation exchange sites), with some layers having retained acidity (iron oxyhydroxysulfate mineral jarosite). Post drought, the rapid raising of surface and ground water levels mobilised acidity in acid sulfate soil profiles to the floodplain drainage channels and this was transported back to the river via pumping. The drainage water exhibited low pH (2-5) with high soluble metal (Al, Co, Mn, Fe, Mn, Ni, and Zn) concentrations, in exceedance of guidelines for ecosystem protection. Irrigation increased the short-term transport of acidity, however loads were generally greater in the non-irrigation (winter) season when rainfall is highest (0.0026 tonnes acidity/ha/day) than in the irrigation (spring-summer) season (0.0013 tonnes acidity/ha/day). Measured reductions in groundwater acidity and increases in pH have been observed over time but severe acidification persisted in floodplain sediments and waters for over two years post-drought. Results from 2-dimensional modelling of the river-floodplain hydrological processes were consistent with field measurements during the drying phase and illustrated how the declining river levels led to floodplain acidification. A modelled management scenario demonstrated how river level stabilisation and limited irrigation could have prevented, or greatly lessened the severity of the acidification.
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Synthesis and biological evaluation of novel hygromycin A antibacterial agents.
Bioorg. Med. Chem. Lett.
PUBLISHED: 08-20-2010
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Novel hygromycin A derivatives bearing a variety of functionalized aminocyclitol moieties have been synthesized in an effort to increase the antibacterial activity and drug-like properties of this class of agents. A systematic study of the effect of alkylation and removal of the hydroxyls of the aminocyclitol directed us to a series of alkylated aminocyclitol derivatives with improved gram-positive activity.
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Design of selective, ATP-competitive inhibitors of Akt.
J. Med. Chem.
PUBLISHED: 05-21-2010
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This paper describes the design and synthesis of novel, ATP-competitive Akt inhibitors from an elaborated 3-aminopyrrolidine scaffold. Key findings include the discovery of an initial lead that was modestly selective and medicinal chemistry optimization of that lead to provide more selective analogues. Analysis of the data suggested that highly lipophilic analogues would likely suffer from poor overall properties. Central to the discussion is the concept of optimization of lipophilic efficiency and the ability to balance overall druglike propeties with the careful control of lipophilicity in the lead series. Discovery of the nonracemic amide series and subsequent modification produced an advanced analogue that performed well in advanced preclinical assays, including xenograft tumor growth inhibition studies, and this analogue was nominated for clinical development.
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Small molecule selectivity and specificity profiling using functional protein microarrays.
Methods Mol. Biol.
PUBLISHED: 03-11-2010
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Small molecules interact with proteins to perturb their functions, a property that has been exploited both for research applications and to produce therapeutic agents for disease treatment. Commonly utilized approaches for identifying the target proteins for a small molecule have limitations in terms of throughput and resource consumption and lack a mechanism to broadly assess the selectivity profile of the small molecule. Here we describe how protein microarray technology can be applied to the study of small molecule-protein interactions using tritiated small molecules. Protein arrays comprising thousands of full-length functional proteins facilitate target identification for those small molecules discovered in cell-based phenotypic assays and both target validation and off-target binding assessment for compounds discovered in target-based screens. The assays are highly reproducible, sensitive, and scalable, and provide an enabling technology for small molecule selectivity profiling in the context of drug development.
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Robust-linear-model normalization to reduce technical variability in functional protein microarrays.
J. Proteome Res.
PUBLISHED: 10-13-2009
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Protein microarrays are similar to DNA microarrays; both enabling the parallel interrogation of thousands of probes immobilized on a surface. Consequently, they have benefited from technologies previously developed for DNA microarrays. However, assumptions for the analysis of DNA microarrays do not always translate to protein arrays, especially in the case of normalization. Hence, we have developed an experimental and computational framework to assess normalization procedures for protein microarrays. Specifically, we profiled two sera with markedly different autoantibody compositions. To analyze intra- and interarray variability, we compared a set of control proteins across subarrays and the corresponding spots across multiple arrays, respectively. To estimate the degree to which the normalization could help reveal true biological separability, we tested the difference in the signal between the sera relative to the variability within replicates. Next, by mixing the sera in different proportions (titrations), we correlated the reactivity of proteins with serum concentration. Finally, we analyzed the effect of normalization procedures on the list of reactive proteins. We compared global and quantile normalization, techniques that have traditionally been employed for DNA microarrays, with a novel normalization approach based on a robust linear model (RLM) making explicit use of control proteins. We show that RLM normalization is able to reduce both intra- and interarray technical variability while maintaining biological differences. Moreover, in titration experiments, RLM normalization enhances the correlation of protein signals with serum concentration. Conversely, while quantile and global normalization can reduce interarray technical variability, neither is as effective as RLM normalization in maintaining biological differences. Most importantly, both introduce artifacts that distort the signals and affect the correct identification of reactive proteins, impairing their use for biomarker discovery. Hence, we show RLM normalization is better suited to protein arrays than approaches used for DNA microarrays.
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Discovery of small molecule isozyme non-specific inhibitors of mammalian acetyl-CoA carboxylase 1 and 2.
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-21-2009
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Screening Pfizers compound library resulted in the identification of weak acetyl-CoA carboxylase inhibitors, from which were obtained rACC1 CT-domain co-crystal structures. Utilizing HTS hits and structure-based drug discovery, a more rigid inhibitor was designed and led to the discovery of sub-micromolar, spirochromanone non-specific ACC inhibitors. Low nanomolar, non-specific ACC-isozyme inhibitors that exhibited good rat pharmacokinetics were obtained from this chemotype.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.