Identifying chemokines as therapeutic targets in renal disease: Lessons from antagonist studies and knockout mice

Chemokines, in concert with cytokines and adhesion molecules, play multiple roles in local and systemic immune responses. In the kidney, the temporal and spatial expression of chemokines correlates with local renal damage and accumulation of chemokine receptor-bearing leukocytes. Chemokines play important roles in leukocyte trafficking and blocking chemokines can effectively reduce renal leukocyte recruitment and subsequent renal damage. However, recent data indicate that blocking chemokine or chemokine receptor activity in renal disease may also exacerbate renal inflammation under certain conditions. An increasing amount of data indicates additional roles of chemokines in the regulation of innate and adaptive immune responses, which may adversively affect the outcome of interventional studies. This review summarizes available in vivo studies on the blockade of chemokines and chemokine receptors in kidney diseases, with a special focus on the therapeutic potential of anti-chemokine strategies, including potential side effects, in renal disease. Copyright (C) 2004 S. Karger AG, Basel

Microbial catabolic activities are naturally selected by metabolic energy harvest rate

The fundamental trade-off between yield and rate of energy harvest per unit of substrate has been largely discussed as a main characteristic for microbial established cooperation or competition. In this study, this point is addressed by developing a generalized model that simulates competition between existing and not experimentally reported microbial catabolic activities defined only based on well-known biochemical pathways. No specific microbial physiological adaptations are considered, growth yield is calculated coupled to catabolism energetics and a common maximum biomass-specific catabolism rate (expressed as electron transfer rate) is assumed for all microbial groups. Under this approach, successful microbial metabolisms are predicted in line with experimental observations under the hypothesis of maximum energy harvest rate. Two microbial ecosystems, typically found in wastewater treatment plants, are simulated, namely: (i) the anaerobic fermentation of glucose and (ii) the oxidation and reduction of nitrogen under aerobic autotrophic (nitrification) and anoxic heterotrophic and autotrophic (denitrification) conditions. The experimentally observed cross feeding in glucose fermentation, through multiple intermediate fermentation pathways, towards ultimately methane and carbon dioxide is predicted. Analogously, two-stage nitrification (by ammonium and nitrite oxidizers) is predicted as prevailing over nitrification in one stage. Conversely, denitrification is predicted in one stage (by denitrifiers) as well as anammox (anaerobic ammonium oxidation). The model results suggest that these observations are a direct consequence of the different energy yields per electron transferred at the different steps of the pathways. Overall, our results theoretically support the hypothesis that successful microbial catabolic activities are selected by an overall maximum energy harvest rate

How should performance in EBUS mediastinal staging in lung cancer be measured?

There has been a paradigm shift in mediastinal staging algorithms in non-small cell lung cancer over the last decade in the United Kingdom (UK). This has seen endoscopic nodal staging (predominantly endobronchial ultrasound, EBUS) almost replace surgical staging (predominantly mediastinoscopy) as the pathological staging procedure of first choic

Radon and material radiopurity assessment for the NEXT double beta decay experiment

The Neutrino Experiment with a Xenon TPC (NEXT), intended to investigate the neutrinoless double beta decay using a high-pressure xenon gas TPC filled with Xe enriched in 136Xe at the Canfranc Underground Laboratory in Spain, requires ultra-low background conditions demanding an exhaustive control of material radiopurity and environmental radon levels. An extensive material screening process is underway for several years based mainly on gamma-ray spectroscopy using ultra-low background germanium detectors in Canfranc but also on mass spectrometry techniques like GDMS and ICPMS. Components from shielding, pressure vessel, electroluminescence and high voltage elements and energy and tracking readout planes have been analyzed, helping in the final design of the experiment and in the construction of the background model. The latest measurements carried out will be presented and the implication on NEXT of their results will be discussed. The commissioning of the NEW detector, as a first step towards NEXT, has started in Canfranc; in-situ measurements of airborne radon levels were taken there to optimize the system for radon mitigation and will be shown too.Comment: Proceedings of the Low Radioactivity Techniques 2015 workshop (LRT2015), Seattle, March 201

Heavy sulphur compounds, higher alcohols and esters production profile of Hanseniaspora uvarum and Hanseniaspora guilliermondii grown as pure and mixed cultures in grape must

Hanseniaspora guilliermondii and Hanseniaspora uvarum were tested in grape must fermentations as pure and mixed starter cultures with Saccharomyces cerevisiae. In pure cultures, the specific growth rates found were 0.29 h⁻¹ for H. uvarum, 0.23 h⁻¹ for H. guilliermondii and 0.18 h⁻¹ for S. cerevisiae. No significant differences were observed between these values and those obtained in mixed cultures. Results presented in this work show that growth of apiculate yeasts during the first days of fermentation enhances the production of desirable compounds, such as esters, and may not have a negative influence on the production of higher alcohols and undesirable heavy sulphur compounds. Growth of apiculate yeasts reduced the total content of higher alcohols in wines, when compared to those produced by a pure culture of S. cerevisiae. Furthermore, the highest levels of 2-phenylethyl acetate were obtained when H. guilliermondii was inoculated in grape musts, whereas H. uvarum increased the isoamyl acetate content of wines. Apiculate yeasts produced high amounts of ethyl acetate; however, the level of this compound decreased in mixed cultures of apiculate yeasts and S. cerevisiae. When S. cerevisiae was used as a starter culture, wines showed higher concentrations of glycerol, 2-phenylethanol and ethyl hexanoate. In mixed cultures of apiculate yeasts and S. cerevisiae, wines presented amounts of methionol, acetic acid-3-(methylthio)propyl ester, 4-(methylthio)-1-butanol, 2-mercaptoethanol and cis-2-methyltetrahydro-thiophen-3-ol similar to those produced by a pure culture of S. cerevisiae. An increase in the amounts of 3-(ethylthio)-1-propanol, trans-2-methyltetrahydro-thiophen-3-ol and 3- mercapto-1-propanol was obtained in wines produced from mixed cultures with H. guilliermondii

The chicken or the egg? Exploring bi-directional associations between Newcastle disease vaccination and village chicken flock size in rural Tanzania

Newcastle disease (ND) is a viral disease of poultry with global importance, responsible for the loss of a potential source of household nutrition and economic livelihood in many low-income food-deficit countries. Periodic outbreaks of this endemic disease result in high mortality amongst free-ranging chicken flocks and may serve as a disincentive for rural households to invest time or resources in poultry-keeping. Sustainable ND control can be achieved through vaccination using a thermotolerant vaccine administered via eyedrop by trained "community vaccinators". This article evaluates the uptake and outcomes of fee-for-service ND vaccination programs in eight rural villages in the semi-arid central zone of Tanzania. It represents part of an interdisciplinary program seeking to address chronic undernutrition in children through improvements to existing poultry and crop systems. Newcastle disease vaccination uptake was found to vary substantially across communities and seasons, with a significantly higher level of vaccination amongst households participating in a longitudinal study of children's growth compared with non-participating households (p = 0.009). Two multivariable model analyses were used to explore associations between vaccination and chicken numbers, allowing for clustered data and socioeconomic and cultural variation amongst the population. Results demonstrated that both (a) households that undertook ND vaccination had a significantly larger chicken flock size in the period between that vaccination campaign and the next compared with those that did not vaccinate (p = 0.018); and (b) households with larger chicken flocks at the time of vaccination were significantly more likely to participate in vaccination programs (p < 0.001). Additionally, households vaccinating in all three vaccination campaigns held over 12 months were identified to have significantly larger chicken flocks at the end of this period (p < 0.001). Opportunities to understand causality and complexity through quantitative analyses are limited, and there is a role for qualitative approaches to explore decisions made by poultry-keeping households and the motivations, challenges and priorities of community vaccinators. Evidence of a bi-directional relationship, however, whereby vaccination leads to greater chicken numbers, and larger flocks are more likely to be vaccinated, offers useful insights into the efficacy of fee-for-service animal health programs. This article concludes that attention should be focused on ways of supporting the participation of vulnerable households in ND vaccination campaigns, and encouraging regular vaccination throughout the year, as a pathway to strengthen food security, promote resilience and contribute to improved human nutrition

Distribution and abundance of Pleuronectiformes larvae off Southeastern Brazil

The objective of this study was the description of the composition, abundance and density in horizontal and vertical distribution of Pleuronectiformes larvae on the southeastern Brazilian continental shelf. The samples were collected with bongo nets and a Multi Plankton Sampler (MPS), both in summer and winter 2002. A total of 352 flatfishes larvae were collected in summer and 343 in winter, representing three families and a total of 13 taxa: Paralichthyidae (Citharichthys cornutus, C. spilopterus, Citharichthys sp., Cyclopsetta chittendeni, Syacium spp., Etropus spp. and Paralichthys spp.), Bothidae (Bothus ocellatus and Monolene antillarum) and Cynoglossidae (Symphurus trewavasae, S. jenynsi, S. plagusia and S. ginsburgi). The most abundant taxa were Etropus spp., Syacium spp. and Bothus ocellatus. Etropus spp. occurred mainly as far out as the 200 m isobath and Syacium spp. from 100 m. B. ocellatus was present mainly in the oceanic zone between Ubatuba and Rio de Janeiro as from the 200 m isobath. The greatest average densities of these species occurred in the strata from 0 to 20 m depth in summer and between 20 and 40 m in winter