Use of quercetin in animal feed : effects on the P-gp expression and pharmacokinetics of orally administrated enrofloxacin in chicken

Modulation of P-glycoprotein (P-gp, encoded by Mdr1) by xenobiotics plays central role in pharmacokinetics of various drugs. Quercetin has a potential to modulate P-gp in rodents, however, its effects on P-gp modulation in chicken are still unclear. Herein, study reports role of quercetin in modulation of P-gp expression and subsequent effects on the pharmacokinetics of enrofloxacin in broilers. Results show that P-gp expression was increased in a dose-dependent manner following exposure to quercetin in Caco-2 cells and tissues of chicken. Absorption rate constant and apparent permeability coefficient of rhodamine 123 were decreased, reflecting efflux function of P-gp in chicken intestine increased by quercetin. Quercetin altered pharmacokinetic of enrofloxacin by decreasing area under curve, peak concentration, and time to reach peak concentration and by increasing clearance rate. Molecular docking shows quercetin can form favorable interactions with binding pocket of chicken xenobiotic receptor (CXR). Results provide convincing evidence that quercetin induced P-gp expression in tissues by possible interaction with CXR, and consequently reducing bioavailability of orally administered enrofloxacin through restricting its intestinal absorption and liver/kidney clearance in broilers. The results can be further extended to guide reasonable use of quercetin to avoid drug-feed interaction occurred with co-administered enrofloxacin or other similar antimicrobials.Peer reviewedFinal Published versio

DADA: data assimilation for the detection and attribution of weather and climate-related events

A new nudging method for data assimilation, delay‐coordinate nudging, is presented. Delay‐coordinate nudging makes explicit use of present and past observations in the formulation of the forcing driving the model evolution at each time step. Numerical experiments with a low‐order chaotic system show that the new method systematically outperforms standard nudging in different model and observational scenarios, also when using an unoptimized formulation of the delay‐nudging coefficients. A connection between the optimal delay and the dominant Lyapunov exponent of the dynamics is found based on heuristic arguments and is confirmed by the numerical results, providing a guideline for the practical implementation of the algorithm. Delay‐coordinate nudging preserves the easiness of implementation, the intuitive functioning and the reduced computational cost of the standard nudging, making it a potential alternative especially in the field of seasonal‐to‐decadal predictions with large Earth system models that limit the use of more sophisticated data assimilation procedures

Extragalactic Results from the Infrared Space Observatory

More than a decade ago the IRAS satellite opened the realm of external galaxies for studies in the 10 to 100 micron band and discovered emission from tens of thousands of normal and active galaxies. With the 1995-1998 mission of the Infrared Space Observatory the next major steps in extragalactic infrared astronomy became possible: detailed imaging, spectroscopy and spectro-photometry of many galaxies detected by IRAS, as well as deep surveys in the mid- and far- IR. The spectroscopic data reveal a wealth of detail about the nature of the energy source(s) and about the physical conditions in galaxies. ISO's surveys for the first time explore the infrared emission of distant, high-redshift galaxies. ISO's main theme in extragalactic astronomy is the role of star formation in the activity and evolution of galaxies.Comment: 106 pages, including 17 figures. Ann.Rev.Astron.Astrophys. (in press), a gzip'd pdf file (667kB) is also available at http://www.mpe.mpg.de/www_ir/preprint/annrev2000.pdf.g

Responses of marine benthic microalgae to elevated CO<inf>2</inf>

Increasing anthropogenic CO2 emissions to the atmosphere are causing a rise in pCO2 concentrations in the ocean surface and lowering pH. To predict the effects of these changes, we need to improve our understanding of the responses of marine primary producers since these drive biogeochemical cycles and profoundly affect the structure and function of benthic habitats. The effects of increasing CO2 levels on the colonisation of artificial substrata by microalgal assemblages (periphyton) were examined across a CO2 gradient off the volcanic island of Vulcano (NE Sicily). We show that periphyton communities altered significantly as CO2 concentrations increased. CO2 enrichment caused significant increases in chlorophyll a concentrations and in diatom abundance although we did not detect any changes in cyanobacteria. SEM analysis revealed major shifts in diatom assemblage composition as CO2 levels increased. The responses of benthic microalgae to rising anthropogenic CO2 emissions are likely to have significant ecological ramifications for coastal systems. © 2011 Springer-Verlag

Regionalization by fuzzy expert system based approach optimized by genetic algorithm.

In recent years soft computing methods are being increasingly used to model complex hydrologic processes. These methods can simulate the real life processes without prior knowledge of the exact relationship between their components. The principal aim of this paper is perform hydrological regionalization based on soft computing concepts in the southern strip of the Caspian Sea basin, north of Iran. The basin with an area of 42,400 sq. km has been affected by severe floods in recent years that caused damages to human life and properties. Although some 61 hydrometric stations and 31 weather stations with 44 years of observed data (1961–2005) are operated in the study area, previous flood studies in this region have been hampered by insufficient and/or reliable observed rainfall-runoff records. In order to investigate the homogeneity (h) of catchments and overcome incompatibility that may occur on boundaries of cluster groups, a fuzzy expert system (FES) approach is used which incorporates physical and climatic characteristics, as well as flood seasonality and geographic location. Genetic algorithm (GA) was employed to adjust parameters of FES and optimize the system. In order to achieve the objective, a MATLAB programming code was developed which considers the heterogeneity criteria of less than 1 (H < 1) as the satisfying criteria. The adopted approach was found superior to the conventional hydrologic regionalization methods in the region because it employs greater number of homogeneity parameters and produces lower values of heterogeneity criteria

Cumulative subgroup analysis to reduce waste in clinical research for individualised medicine

Background: Although subgroup analyses in clinical trials may provide evidence for individualised medicine, their conduct and interpretation remain controversial. Methods: Subgroup effect can be defined as the difference in treatment effect across patient subgroups. Cumulative subgroup analysis refers to a series of repeated pooling of subgroup effects after adding data from each of related trials chronologically, to investigate the accumulating evidence for subgroup effects. We illustrated the clinical relevance of cumulative subgroup analysis in two case studies using data from published individual patient data (IPD) meta-analyses. Computer simulations were also conducted to examine the statistical properties of cumulative subgroup analysis. Results: In case study 1, an IPD meta-analysis of 10 randomised trials (RCTs) on beta blockers for heart failure reported significant interaction of treatment effects with baseline rhythm. Cumulative subgroup analysis could have detected the subgroup effect 15 years earlier, with five fewer trials and 71% less patients, than the IPD meta-analysis which first reported it. Case study 2 involved an IPD meta-analysis of 11 RCTs on treatments for pulmonary arterial hypertension that reported significant subgroup effect by aetiology. Cumulative subgroup analysis could have detected the subgroup effect 6 years earlier, with three fewer trials and 40% less patients than the IPD meta-analysis. Computer simulations have indicated that cumulative subgroup analysis increases the statistical power and is not associated with inflated false positives. Conclusions: To reduce waste of research data, subgroup analyses in clinical trials should be more widely conducted and adequately reported so that cumulative subgroup analyses could be timely performed to inform clinical practice and further research

Crustose coralline algae can contribute more than corals to coral reef carbonate production

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: Data are available at https://github.com/JayCrlt/CCA_MethodsCode availability: Codes are available at https://github.com/JayCrlt/CCA_MethodsUnderstanding the drivers of net coral reef calcium carbonate production is increasingly important as ocean warming, acidification, and other anthropogenic stressors threaten the maintenance of coral reef structures and the services these ecosystems provide. Despite intense research effort on coral reef calcium carbonate production, the inclusion of a key reef forming/accreting calcifying group, the crustose coralline algae, remains challenging both from a theoretical and practical standpoint. While corals are typically the primary reef builders of contemporary reefs, crustose coralline algae can contribute equally. Here, we combine several sets of data with numerical and theoretical modelling to demonstrate that crustose coralline algae carbonate production can match or even exceed the contribution of corals to reef carbonate production. Despite their importance, crustose coralline algae are often inaccurately recorded in benthic surveys or even entirely missing from coral reef carbonate budgets. We outline several recommendations to improve the inclusion of crustose coralline algae into such carbonate budgets under the ongoing climate crisis.French Embassy - French Related Research Projects (F2RP)Agence Nationale de la Recherche (ANR)Royal Society of New Zealand Te Apārang

The Fat Mass and Obesity Associated Gene FTO Functions in the Brain to Regulate Postnatal Growth in Mice

FTO (fat mass and obesity associated) was identified as an obesity-susceptibility gene by several independent large-scale genome association studies. A cluster of SNPs (single nucleotide polymorphism) located in the first intron of FTO was found to be significantly associated with obesity-related traits, such as body mass index, hip circumference, and body weight. FTO encodes a protein with a novel C-terminal α-helical domain and an N-terminal double-strand β-helix domain which is conserved in Fe(II) and 2-oxoglutarate-dependent oxygenase family. In vitro, FTO protein can demethylate single-stranded DNA or RNA with a preference for 3-methylthymine or 3-methyluracil. Its physiological substrates and function, however, remain to be defined. Here we report the generation and analysis of mice carrying a conditional deletion allele of Fto. Our results demonstrate that Fto plays an essential role in postnatal growth. The mice lacking Fto completely display immediate postnatal growth retardation with shorter body length, lower body weight, and lower bone mineral density than control mice, but their body compositions are relatively normal. Consistent with the growth retardation, the Fto mutant mice have reduced serum levels of IGF-1. Moreover, despite the ubiquitous expression of Fto, its specific deletion in the nervous system results in similar phenotypes as the whole body deletion, indicating that Fto functions in the central nerve system to regulate postnatal growth