Assessing the combined toxicity of the natural toxins, aflatoxin B₁, fumonisin B₁ and microcystin-LR by high content analysis

As human co-exposure to natural toxins through food and water is inevitable, risk assessments to safeguard health are necessary. Aflatoxin B1 and fumonisin B1, frequent co-contaminants of maize and microcystin-LR, produced in freshwater by cyanobacteria are all naturally occurring potent toxins that threaten human health. Populations in the poorest regions of the world may suffer repeated simultaneous exposure to these contaminants. Using High Content Analysis, multiple cytotoxicity endpoints were measured for the individual toxins and mixtures in various cell lines. Results highlighted that significant cytotoxic effects were observed for aflatoxin B1 in all cell lines while no cytotoxic effects were observed for fumonisin B1 or microcystin-LR. Aflatoxin B1/microcystin-LR was cytotoxic in the order HepG2 &gt; Caco-2 &gt; MDBK. Fumonisin B1/microcystin-LR affected MDBK cells. The ternary mixture was cytotoxic to all cell lines. Most combinations were additive, however antagonism was observed for binary and ternary mixtures in HepG2 and MDBK cell lines at low and high concentrations. Synergy was observed in all cell lines, including at low concentrations. The combination of these natural toxins may pose a significant risk to populations in less developed countries. Furthermore, the study highlights the complexity around trying to regulate for human exposure to multiple contaminants.</p

Pragmatic engagement in a low trust supply chain: Beef farmers’ perceptions of power, trust and agency

The academic discussion of power in supply chains has changed from a discussion of the use of coercive power to one which emphasizes the role of trust in embedding co-operation and disincentivizing opportunism. Whilst a number of empirical studies have suggested the former is alive and well, this paper argues that power relations may also be constituted by the self-perceptions of weaker actors as much as by the explicit actions of more powerful ones. This study explores the role of power through the perceptions of subjugated actors, which set the ‘rules of the game’. Our case centres on perceptions of Northern Irish beef farmers and their reflections on their ‘powerlessness’ in relation to the larger, more consolidated processors that they sell to. We find that the way farmers make sense of the power relations they encounter is influenced by the individuating character of the power relations exercised by the processors, which debilitates their ability to collaborate and resist collectively. What emerges is a story about the process of accommodation whereby farmers pragmatically resign themselves to play by ‘the rules of the game’ to remain ‘part of the game’

Synchronization and Control in Intrinsic and Designed Computation: An Information-Theoretic Analysis of Competing Models of Stochastic Computation

We adapt tools from information theory to analyze how an observer comes to synchronize with the hidden states of a finitary, stationary stochastic process. We show that synchronization is determined by both the process's internal organization and by an observer's model of it. We analyze these components using the convergence of state-block and block-state entropies, comparing them to the previously known convergence properties of the Shannon block entropy. Along the way, we introduce a hierarchy of information quantifiers as derivatives and integrals of these entropies, which parallels a similar hierarchy introduced for block entropy. We also draw out the duality between synchronization properties and a process's controllability. The tools lead to a new classification of a process's alternative representations in terms of minimality, synchronizability, and unifilarity.Comment: 25 pages, 13 figures, 1 tabl

Identification of systemic immune response markers through metabolomic profiling of plasma from calves given an intra-nasally delivered respiratory vaccine

International audienceVaccination procedures within the cattle industry are important disease control tools to minimize economic and welfare burdens associated with respiratory pathogens. However, new vaccine, antigen and carrier technologies are required to combat emerging viral strains and enhance the efficacy of respiratory vaccines, particularly at the point of pathogen entry. New technologies, specifically metabolomic profiling, could be applied to identify metabolite immune-correlates representative of immune protection following vaccination aiding in the design and screening of vaccine candidates. This study for the first time demonstrates the ability of untargeted UPLC-MS metabolomic profiling to identify metabolite immune correlates characteristic of immune responses following mucosal vaccination in calves. Male Holstein Friesian calves were vaccinated with Pfizer Rispoval® PI3 + RSV intranasal vaccine and metabolomic profiling of post-vaccination plasma revealed 12 metabolites whose peak intensities differed significantly from controls. Plasma levels of glycocholic acid, N-[(3α,5β,12α)-3,12-Dihydroxy-7,24-dioxocholan-24-yl]glycine, uric acid and biliverdin were found to be significantly elevated in vaccinated animals following secondary vaccine administration, whereas hippuric acid significantly decreased. In contrast, significant upregulation of taurodeoxycholic acid and propionylcarnitine levels were confined to primary vaccine administration. Assessment of such metabolite markers may provide greater information on the immune pathways stimulated from vaccine formulations and benchmarking early metabolomic responses to highly immunogenic vaccine formulations could provide a means for rapidly assessing new vaccine formulations. Furthermore, the identification of metabolic systemic immune response markers which relate to specific cell signaling pathways of the immune system could allow for targeted vaccine design to stimulate key pathways which can be assessed at the metabolic level

Exoplanet Characterization by Proxy: a Transiting 2.15 R_Earth Planet Near the Habitable Zone of the Late K dwarf Kepler-61

We present the validation and characterization of Kepler-61b: a 2.15 R_Earth planet orbiting near the inner edge of the habitable zone of a low-mass star. Our characterization of the host star Kepler-61 is based upon a comparison with the set of spectroscopically similar stars with directly-measured radii and temperatures. We apply a stellar prior drawn from the weighted mean of these properties, in tandem with the Kepler photometry, to infer a planetary radius for Kepler-61b of 2.15+/-0.13 R_Earth and an equilibrium temperature of 273+/-13 K (given its period of 59.87756+/-0.00020 days and assuming a planetary albedo of 0.3). The technique of leveraging the physical properties of nearby "proxy" stars allows for an independent check on stellar characterization via the traditional measurements with stellar spectra and evolutionary models. In this case, such a check had implications for the putative habitability of Kepler-61b: the planet is 10% warmer and larger than inferred from K-band spectral characterization. From the Kepler photometry, we estimate a stellar rotation period of 36 days, which implies a stellar age of >1 Gyr. We summarize the evidence for the planetary nature of the Kepler-61 transit signal, which we conclude is 30,000 times more likely to be due to a planet than a blend scenario. Finally, we discuss possible compositions for Kepler-61b with a comparison to theoretical models as well as to known exoplanets with similar radii and dynamically measured masses.Comment: 23 pages, 12 figures. Accepted for publication in Ap

Non-thermal Plasma Exposure Rapidly Attenuates Bacterial AHL-Dependent Quorum Sensing and Virulence.

The antimicrobial activity of atmospheric pressure non-thermal plasma has been exhaustively characterised, however elucidation of the interactions between biomolecules produced and utilised by bacteria and short plasma exposures are required for optimisation and clinical translation of cold plasma technology. This study characterizes the effects of non-thermal plasma exposure on acyl homoserine lactone (AHL)-dependent quorum sensing (QS). Plasma exposure of AHLs reduced the ability of such molecules to elicit a QS response in bacterial reporter strains in a dose-dependent manner. Short exposures (30–60 s) produce of a series of secondary compounds capable of eliciting a QS response, followed by the complete loss of AHL-dependent signalling following longer exposures. UPLC-MS analysis confirmed the time-dependent degradation of AHL molecules and their conversion into a series of by-products. FT-IR analysis of plasma-exposed AHLs highlighted the appearance of an OH group. In vivo assessment of the exposure of AHLs to plasma was examined using a standard in vivo model. Lettuce leaves injected with the rhlI/lasI mutant PAO-MW1 alongside plasma treated N-butyryl-homoserine lactone and n-(3-oxo-dodecanoyl)-homoserine lactone, exhibited marked attenuation of virulence. This study highlights the capacity of atmospheric pressure non-thermal plasma to modify and degrade AHL autoinducers thereby attenuating QS-dependent virulence in P. aeruginosa

Evaluation of an alternative spectroscopic approach for aflatoxin analysis: Comparative analysis of food and feed samples with UPLC-MS/MS

Increasing research has highlighted the effects of changing climates on the occurrence and prevalence of toxigenic Aspergillus species producing aflatoxins. There is concern of the toxicological effects to human health and animal productivity following acute and chronic exposure that may affect the future ability to provide safe and sufficient food globally. Considerable research has focused on the detection of these toxins, based on the physicochemical and biochemical properties of the aflatoxin compounds, in agricultural products for human and animal consumption. As improvements in food security continue more regulations for acceptable levels of aflatoxins have arisen globally; the most stringent in Europe. These regulations are important for developing countries as aflatoxin occurrence is high significantly effecting international trade and the economy. In developed countries analytical approaches have become highly sophisticated, capable of attaining results with high precision and accuracy, suitable for regulatory laboratories. Regrettably, many countries that are affected by aflatoxin contamination do not have resources for high tech HPLC and MS instrumentation and require more affordable, yet robust equally accurate alternatives that may be used by producers, processors and traders in emerging economies. It is especially important that those companies wishing to exploit the opportunities offered by lucrative but highly regulated markets in the developed world, have access to analytical methods that will ensure that their exports meet their customers quality and safety requirements. This work evaluates the ToxiMet system as an alternative approach to UPLC–MS/MS for the detection and determination of aflatoxins relative to current European regulatory standards. Four commodities: rice grain, maize cracked and flour, peanut paste and dried distillers grains were analysed for natural aflatoxin contamination. For B1 and total aflatoxins determination the qualitative correlation, above or below the regulatory limit, was good for all commodities with the exception of the dried distillers grain samples for B1 for which no calibration existed. For B1 the quantitative R2 correlations were 0.92, 0.92, 0.88 (<250 μg/kg) and 0.7 for rice, maize, peanuts and dried distillers grain samples respectively whereas for total aflatoxins the quantitative correlation was 0.92, 0.94, 0.88 and 0.91. The ToxiMet system could be used as an alternative for aflatoxin analysis for current legislation but some consideration should be given to aflatoxin M1 regulatory levels for these commodities considering the high levels detected in this study especially for maize and peanuts. (Résumé d'auteur

Validation of Twelve Small Kepler Transiting Planets in the Habitable Zone

We present an investigation of twelve candidate transiting planets from Kepler with orbital periods ranging from 34 to 207 days, selected from initial indications that they are small and potentially in the habitable zone (HZ) of their parent stars. Few of these objects are known. The expected Doppler signals are too small to confirm them by demonstrating that their masses are in the planetary regime. Here we verify their planetary nature by validating them statistically using the BLENDER technique, which simulates large numbers of false positives and compares the resulting light curves with the Kepler photometry. This analysis was supplemented with new follow-up observations (high-resolution optical and near-infrared spectroscopy, adaptive optics imaging, and speckle interferometry), as well as an analysis of the flux centroids. For eleven of them (KOI-0571.05, 1422.04, 1422.05, 2529.02, 3255.01, 3284.01, 4005.01, 4087.01, 4622.01, 4742.01, and 4745.01) we show that the likelihood they are true planets is far greater than that of a false positive, to a confidence level of 99.73% (3 sigma) or higher. For KOI-4427.01 the confidence level is about 99.2% (2.6 sigma). With our accurate characterization of the GKM host stars, the derived planetary radii range from 1.1 to 2.7 R_Earth. All twelve objects are confirmed to be in the HZ, and nine are small enough to be rocky. Excluding three of them that have been previously validated by others, our study doubles the number of known rocky planets in the HZ. KOI-3284.01 (Kepler-438b) and KOI-4742.01 (Kepler-442b) are the planets most similar to the Earth discovered to date when considering their size and incident flux jointly.Comment: 27 pages in emulateapj format, including tables and figures. To appear in The Astrophysical Journa