159 research outputs found

    Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans

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    Background Physiologically based modelling using DEBtox (dynamic energy budget in toxicology) and transcriptional profiling were used in Caenorhabditis elegans to identify how physiological modes of action, as indicated by effects on system level resource allocation were associated with changes in gene expression following exposure to three toxic chemicals: cadmium, fluoranthene (FA) and atrazine (AZ). Results For Cd, the physiological mode of action as indicated by DEBtox model fitting was an effect on energy assimilation from food, suggesting that the transcriptional response to exposure should be dominated by changes in the expression of transcripts associated with energy metabolism and the mitochondria. While evidence for effect on genes associated with energy production were seen, an ontological analysis also indicated an effect of Cd exposure on DNA integrity and transcriptional activity. DEBtox modelling showed an effect of FA on costs for growth and reproduction (i.e. for production of new and differentiated biomass). The microarray analysis supported this effect, showing an effect of FA on protein integrity and turnover that would be expected to have consequences for rates of somatic growth. For AZ, the physiological mode of action predicted by DEBtox was increased cost for maintenance. The transcriptional analysis demonstrated that this increase resulted from effects on DNA integrity as indicated by changes in the expression of genes chromosomal repair. Conclusions Our results have established that outputs from process based models and transcriptomics analyses can help to link mechanisms of action of toxic chemicals with resulting demographic effects. Such complimentary analyses can assist in the categorisation of chemicals for risk assessment purposes

    Continuous evaluation of large-scale information access systems : a case for living labs

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    A/B testing is currently being increasingly adopted for the evaluation of commercial information access systems with a large user base since it provides the advantage of observing the efficiency and effectiveness of information access systems under real conditions. Unfortunately, unless university-based researchers closely collaborate with industry or develop their own infrastructure or user base, they cannot validate their ideas in live settings with real users. Without online testing opportunities open to the research communities, academic researchers are unable to employ online evaluation on a larger scale. This means that they do not get feedback for their ideas and cannot advance their research further. Businesses, on the other hand, miss the opportunity to have higher customer satisfaction due to improved systems. In addition, users miss the chance to benefit from an improved information access system. In this chapter, we introduce two evaluation initiatives at CLEF, NewsREEL and Living Labs for IR (LL4IR), that aim to address this growing “evaluation gap” between academia and industry. We explain the challenges and discuss the experiences organizing these living labs

    The ZIP6/ZIP10 heteromer is essential for the zinc-mediated trigger of mitosis

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    Zinc has been known to be essential for cell division for over 40 years but the molecular pathways involved remain elusive. Cellular zinc import across biological membranes necessitates the help of zinc transporters such as the SLC39A family of ZIP transporters. We have discovered a molecular process that explains why zinc is required for cell division, involving two highly regulated zinc transporters, as a heteromer of ZIP6 and ZIP10, providing the means of cellular zinc entry at a specific time of the cell cycle that initiates a pathway resulting in the onset of mitosis. Crucially, when the zinc influx across this heteromer is blocked by ZIP6 or ZIP10 specific antibodies, there is no evidence of mitosis, confirming the requirement for zinc influx as a trigger of mitosis. The zinc that influxes into cells to trigger mitosis additionally changes the phosphorylation state of STAT3 converting it from a transcription factor to a protein that complexes with this heteromer and pS38Stathmin, the form allowing microtubule rearrangement as required in mitosis. This discovery now explains the specific cellular role of ZIP6 and ZIP10 and how they have special importance in the mitosis process compared to other ZIP transporter family members. This finding offers new therapeutic opportunities for inhibition of cell division in the many proliferative diseases that exist, such as cancer

    Plant productivity enhancement in a simulated Amazonian Dark Earth (Terra Preta Nova).

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    Amazonian Dark Earths (ADEs) are highly fertile human-made soils, commonly found in Amazonia. These soils have a unique soil biota and a high content of charcoal, organic C, available P and Ca as a result of repeated burning and additions of bone and organic matter (OM) over centuries of Amerindian occupation. ?Terra Preta Nova? techniques aim to replicate these soils by adding ADE components, but little is known of their single and synergistic impacts on plant productivity. We replicated an ADE by adding five distinct components and studying their single and interactive effects on maize production in the greenhouse. Earthworms (Pontoscolex corethrurus), OM (horse manure), biochar (from Brazil nut), ground fish bones and pottery sherds were added to a nutrient poor soil, and after 60 days plant height, above and below-ground (root) biomass, root length, and soil fertility levels were assessed. The main components affecting plant productivity were earthworms, OM and fish bone meal, with significant synergistic effects, while biochar and pottery, although significant, were not as important for plant growth and soil fertility

    Pesticides in a case study on no-tillage farming systems and surrounding forest patches in Brazil.

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    With the growing global concern on pesticide management, the relationship between its environmental recalcitrance, food security and human health has never been more relevant. Pesticides residues are known to cause significant environmental contamination. Here, we present a case study on long-term no-tillage farming systems in Brazil, where Glyphosate (GLY) has been applied for more than 35 years. GLY and its main breakdown product, aminomethylphosphonic acid (AMPA) were determined in topsoil (0–10 cm) samples from no-tillage fields and nearby subtropical secondary forests by high-performance liquid chromatography coupled with a fluorescence detector. In addition, the presence of carbamates, organochlorines, organophosphates and triazines were also screened for. GLY and AMPA were present in all soil samples, reaching values higher than those described for soils so far in the literature. A significant decrease for AMPA was observed only between the secondary forest and the farm’s middle slope for site B. GLY and AMPA were observed respectively at peak concentrations of 66.38 and 26.03 mg/kg soil. GLY was strongly associated with forest soil properties, while AMPA associated more with no-tillage soil properties. Soil texture was a significant factor contributing to discrimination of the results as clay and sand contents affect GLY and AMPA retention in soils. This was the first study to report DDT and metabolites in consolidated no-tillage soils in Brazil (a pesticide fully banned since 2009). Based on human risk assessment conducted herein and the potential risk of GLY to local soil communities, this study offers a baseline for future studies on potential adverse effects on soil biota, and mechanistic studies

    VarLOCK - sequencing independent, rapid detection of SARS-CoV-2 variants of concern for point-of-care testing, qPCR pipelines and national wastewater surveillance

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    The COVID-19 pandemic continues to pose a threat to the general population. The ongoing vaccination programs provide protection to individuals and facilitate the opening of society and a return to normality. However, emergent and existing SARS-CoV-2 variants capable of evading the immune system endanger the efficacy of the vaccination strategy. To preserve the efficacy of SARS-CoV-2 vaccination globally, aggressive and effective surveillance for known and emerging SARS-CoV-2 Variants of Concern (VOC) is required. Rapid and specific molecular diagnostics can provide speed and coverage advantages compared to genomic sequencing alone, benefitting the public health response and facilitating VOC containment. In this work, we expand the recently developed SARS-CoV-2 CRISPR-Cas detection technology (SHERLOCK) to allow rapid and sensitive discrimination of VOCs, that can be used at point of care and/or implemented in the pipelines of small or large testing facilities, and even determine proportion of VOCs in pooled population-level wastewater samples. This technology aims to complement the ongoing sequencing efforts to allow facile and, crucially, rapid identification of individuals infected with VOCs to help break infection chains. Here, we show the optimisation of our VarLOCK assays (Variant-specific SHERLOCK) for multiple specific mutations in the S gene of SARS-CoV-2 and validation with samples from the Cardiff University Testing Service. We also show the applicability of VarLOCK to national wastewater surveillance of SARS-CoV-2 variants. In addition, we show the rapid adaptability of the technique for new and emerging VOCs such as Omicron
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