Platelet-mediated metabolism of the common dietary flavonoid, quercetin.

BACKGROUND: Flavonoid metabolites remain in blood for periods of time potentially long enough to allow interactions with cellular components of this tissue. It is well-established that flavonoids are metabolised within the intestine and liver into methylated, sulphated and glucuronidated counterparts, which inhibit platelet function. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate evidence suggesting platelets which contain metabolic enzymes, as an alternative location for flavonoid metabolism. Quercetin and a plasma metabolite of this compound, 4'-O-methyl quercetin (tamarixetin) were shown to gain access to the cytosolic compartment of platelets, using confocal microscopy. High performance liquid chromatography (HPLC) and mass spectrometry (MS) showed that quercetin was transformed into a compound with a mass identical to tamarixetin, suggesting that the flavonoid was methylated by catechol-O-methyl transferase (COMT) within platelets. CONCLUSIONS/SIGNIFICANCE: Platelets potentially mediate a third phase of flavonoid metabolism, which may impact on the regulation of the function of these cells by metabolites of these dietary compounds

Differential transcriptional modulation of duplicated fatty acid-binding protein genes by dietary fatty acids in zebrafish (Danio rerio): evidence for subfunctionalization or neofunctionalization of duplicated genes

<p>Abstract</p> <p>Background</p> <p>In the Duplication-Degeneration-Complementation (DDC) model, subfunctionalization and neofunctionalization have been proposed as important processes driving the retention of duplicated genes in the genome. These processes are thought to occur by gain or loss of regulatory elements in the promoters of duplicated genes. We tested the DDC model by determining the transcriptional induction of fatty acid-binding proteins (Fabps) genes by dietary fatty acids (FAs) in zebrafish. We chose zebrafish for this study for two reasons: extensive bioinformatics resources are available for zebrafish at zfin.org and zebrafish contains many duplicated genes owing to a whole genome duplication event that occurred early in the ray-finned fish lineage approximately 230-400 million years ago. Adult zebrafish were fed diets containing either fish oil (12% lipid, rich in highly unsaturated fatty acid), sunflower oil (12% lipid, rich in linoleic acid), linseed oil (12% lipid, rich in linolenic acid), or low fat (4% lipid, low fat diet) for 10 weeks. FA profiles and the steady-state levels of <it>fabp </it>mRNA and heterogeneous nuclear RNA in intestine, liver, muscle and brain of zebrafish were determined.</p> <p>Result</p> <p>FA profiles assayed by gas chromatography differed in the intestine, brain, muscle and liver depending on diet. The steady-state level of mRNA for three sets of duplicated genes, <it>fabp1a/fabp1b.1/fabp1b.2</it>, <it>fabp7a/fabp7b</it>, and <it>fabp11a</it>/<it>fabp11b</it>, was determined by reverse transcription, quantitative polymerase chain reaction (RT-qPCR). In brain, the steady-state level of <it>fabp7b </it>mRNAs was induced in fish fed the linoleic acid-rich diet; in intestine, the transcript level of <it>fabp1b.1 </it>and <it>fabp7b </it>were elevated in fish fed the linolenic acid-rich diet; in liver, the level of <it>fabp7a </it>mRNAs was elevated in fish fed the low fat diet; and in muscle, the level of <it>fabp7a </it>and <it>fabp11a </it>mRNAs were elevated in fish fed the linolenic acid-rich or the low fat diets. In all cases, induction of the steady-state level of <it>fabp </it>mRNAs by dietary FAs correlated with induced levels of hnRNA for a given <it>fabp </it>gene. As such, up-regulation of the steady-state level of <it>fabp </it>mRNAs by FAs occurred at the level of initiation of transcription. None of the sister duplicates of these <it>fabp </it>genes exhibited an increase in their steady-state transcript levels in a specific tissue following feeding zebrafish any of the four experimental diets.</p> <p>Conclusion</p> <p>Differential induction of only one of the sister pair of duplicated <it>fabp </it>genes by FAs provides evidence to support the DDC model for retention of duplicated genes in the zebrafish genome by either subfunctionalization or neofunctionalization.</p

Developing component models for automated functional testing

Reference models developed from first principles and empirical relationships are used to represent correct operation of air-handling units. The models are incorporated into software capable of comparing actual system output measurements with model outputs and detecting deviations from correct operation. Tests of the model-based system with data from a real system, operating with and without introduced faults, are reported

Application of fault detection and diagnosis techniques to automated functional testing

Extensive research in the field of fault detection and diagnosis has produced useful tools and techniques that have been applied to continuously operating building HVAC systems. A few researchers have applied some of these to commissioning of new buildings. This paper reports on a project that adapted or developed models of air-handling unit components and controls and combined them into an automated functional testing tool. Operation of the tool is demonstrated in testing a real air-handling unit

Strategies for Wildlife Disease Surveillance

Epidemiologic surveillance is defined by the Centers for Disease Control and Prevention (CDC) as the ongoing systematic and continuous collection, analysis, and interpretation of health data\u27: The objective of surveillance is to generate data for rapid response to the detection of a disease of concern to apply prevention, control, or eradication measures as well as to evaluate such interventions. This is distinct from disease monitoring, which usually does not involve a particular response to disease detection. Surveillance for wildlife diseases has increased in importance due to the emergence and re-emergence of wildlife diseases that are threats to human, animal, and ecosystem health, or could potentially have a negative economic impact. It has been estimated that 75% of emerging human diseases are zoonotic in origin, of which the majority originate from wildlife (Taylor et al. 2001). However, there are unique challenges concerning wildlife disease surveillance such that disease and pathogens can be very difficult to detect and measure in wild animals. These challenges have been described previously (Wobeser 2006), but one of the primary issues is that disease in wildlife often goes unrecognized, especially in remote locations. Furthermore, sick and dead animals are very difficult to detect, as animals will disguise the signs of illness or hide when diseased. Carcasses from diseased animals are also rapidly removed by scavengers or will rapidly decompose, rendering them suboptimal for diagnostic purposes. There is also a lack of validated diagnostic tests for most wildlife disease agents as well as baseline data. The paucity of laboratory capacity with expertise in wildlife disease diagnostic investigation is also an impediment. Finally, surveillance networks for wildlife diseases that perform field investigations and report disease events are under-developed in most regions of the world. Despite these challenges, a number of very important epidemiological surveillance projects have been ongoing or recently developed, and some examples are described in this chapter. The examples are mostly drawn from the experiences of the U.S. Geological Survey National Wildlife Health Center (NWHC) and are provided to illustrate the different surveillance strategies and sampling techniques that can be used and have proven successful. Some future directions for wildlife disease surveillance are also suggested

The Utility of SATA Satellite DNA Sequences for Inferring Phylogenetic Relationships an1ong the Three Major Genera of Tilapiine Cichlid Fishes

The SATA satellite DNA family of sequences, composed of three size variants of approximately 237, 230, and 209 bp, is conserved in the genomes of tilapiine and haplochromine cichlid fishes. In the present study we examined the utility of the SATA sequences for inferring phylogenetic relationships among the three major genera of tilapiine fishes, Oreochromis, Sarotherodon, and Tilapia. Hybridization of the monomer SATA repeat to genomic DNA of representative cichlid species established conservation of the sequence in the African tilapiine and haplochromine lineages and its absence from other cichlid lineages. Bootstrapped DNA parsimony and neighbor-joining analyses of derived consensus sequences revealed two distinct clades, one containing the mouthbrooding genera Oreochromis and Sarotherodon, and the other containing the substrate spawning genus Tilapia. These results are consistent with recent independent studies using mitochondrial DNA and establish the utility of the SATA satellite DNA family for phylogenetic reconstruction. Concerted evolution of the SATA sequences was also demonstrated within the tilapiine tribe

Understanding the temporal dynamics of a lowland river fish community at a hazardous intake and floodgate to inform safe operation

Entrainment and mortality of freshwater fish at hazardous pumping station intakes used for Flood Risk Management (FRM) are of global concern. Although upstream and downstream passage of diadromous fish has received considerable attention, the ecological behaviours of river-resident fish at these structures and how to protect these species from entrainment is poorly-understood. At a lowland flood-relief pumping station and floodgate situated off-channel (River Foss) to the main-river Yorkshire Ouse (York, England), multi-beam sonar (Dual-Frequency Identification Sonar: DIDSON) was used over a pluriannual (three years) period to investigate diel movements of river-resident fish in response to the variations in temperature, hydrology and pump and floodgate operation, and to determine fish-friendly management options. Diel lateral movements of thousands of river-resident fish between the main-river, floodgate operated channel (River Foss) and off-channel pump forebay were predominantly during the crepuscular period and daytime, proposing important considerations for when managers should operate pumps and associated flood infrastructure. Seasonal diel movements increased throughout winter during a baseline year (no pump operation) and overwintering behaviour was influenced by cooling river temperatures. A Generalized Linear Mixed Model (GLMM) revealed fish entered the off-channel forebay when river levels were stable and not when they were rising or falling, suggesting hydrological stability was important for the ecological function of this fish community. Two years of impact data (pumps operated) then revealed pump operations severely disrupted the ecological functions of local fish populations, which was also uniquely quantified over two independent 24h periods during which temporal fish counts were reduced by 85%. A trial period where the floodgate was lowered ahead of dawn significantly reduced fish immigration into the hazardous forebay when compared to two different hydrological periods. Modifying when the floodgate and pumps operate, including lowering the floodgate ahead of fish immigration at dawn, and starting pumps during the night (but not day), are therefore promising non-engineered management options to prevent immigration of fish into the hazardous off-channel pump forebay and to reduce entrainment and mortality risk during pump operation

Requiem for a Paradox: The Dubious Rise and Inevitable Fall of Hipster Antitrust

For antitrust practitioners, scholars, and economists—those who work with antitrust in agencies, courts, or law firms—the development of the antitrust laws over the past half century has been a remarkable and positive development for the American economy and consumers. Over the last fifty years, antitrust has developed into a coherent, principled, and workable body of law that contributes positively not only to American competitiveness and societal well-being, but also helps to export the culture of market competition around the world. Although a healthy diversity of views governs the intellectual landscape in antitrust, and there is no shortage of ideas on how to improve its performance around the margins and within the paradigm of existing doctrine, there is consensus that modern antitrust laws have the core concepts right. Most fundamentally, there is agreement that the goal of protecting consumer welfare is and should be the lodestar of modern antitrust enforcement

Marine baseline and monitoring strategies for Carbon Dioxide Capture and Storage (CCS)

The QICS controlled release experiment demonstrates that leaks of carbon dioxide (CO2) gas can be detected by monitoring acoustic, geochemical and biological parameters within a given marine system. However the natural complexity and variability of marine system responses to (artificial) leakage strongly suggests that there are no absolute indicators of leakage or impact that can unequivocally and universally be used for all potential future storage sites. We suggest a multivariate, hierarchical approach to monitoring, escalating from anomaly detection to attribution, quantification and then impact assessment, as required. Given the spatial heterogeneity of many marine ecosystems it is essential that environmental monitoring programmes are supported by a temporally (tidal, seasonal and annual) and spatially resolved baseline of data from which changes can be accurately identified. In this paper we outline and discuss the options for monitoring methodologies and identify the components of an appropriate baseline survey