Summary: Xpaths is a collection of algorithms that allow for the prediction of compound-induced molecular mechanisms of action by integrating phenotypic endpoints of different species; and proposes follow-up tests for model organisms to validate these pathway predictions. The Xpaths algorithms are applied to predict developmental and reproductive toxicity (DART) and implemented into an in silico platform, called DARTpaths.
DOCUMENT
not available
MULTIFILE
From the article: "To enable selection of novel chemicals for new processes, there is a recognized need for alternative toxicity screening assays to assess potential risks to man and the environment. For human health hazard assessment these screening assays need to be translational to humans, have high throughput capability, and from an animal welfare perspective be harmonized with the principles of the 3Rs (Reduction, Refinement, Replacement). In the area of toxicology a number of cell culture systems are available but while these have some predictive value, they are not ideally suited for the prediction of developmental and reproductive toxicology (DART). This is because they often lack biotransformation capacity, multicellular or multi- organ complexity, for example, the hypothalamus pituitary gonad (HPG) axis and the complete life cycle of whole organisms. To try to overcome some of these limitations in this study, we have used Caenorhabditis elegans (nematode) and Danio rerio embryos (zebrafish) as alternative assays for DART hazard assessment of some candidate chemicals being considered for a new commercial application. Nematodes exposed to Piperazine and one of the analogs tested showed a slight delay in development compared to untreated animals but only at high concentrations and with Piperazine as the most sensitive compound. Total brood size of the nematodes was also reduced primarily by Piperazine and one of the analogs. In zebrafish Piperazine and analogs showed developmental delays. Malformations and mortality in individual fish were also scored. Significant malformations were most sensitively identified with Piperazine, significant mortality was only observed in Piperazine and only at the higest dose. Thus, Piperazine seemed the most toxic compound for both nematodes and zebrafish. The results of the nematode and zebrafish studies were in alignment with data obtained from conventional mammalian toxicity studies indicating that these have potential as developmental toxicity screening systems. The results of these studies also provided reassurance that none of the Piperazines tested are likely to have any significant developmental and/or reproductive toxicity issues to humans when used in their commercial applications."
LINK
A series of new, easily synthesized C60-fullerene derivatives is introduced that allow for optimization of the interactions between rr-P3HT and the fullerene by systematic variation of the size of the ester group. Two compounds gave overall cell efficiencies of 4.8%, clearly outperforming [60]PCBM which gives 4.3% under identical conditions.
DOCUMENT
Climate change is undermining the importance and sustainability of cooperatives as important organizations in small holder agriculture in developing countries. To adapt, cooperatives could apply carbon farming practices to reduce greenhouse gas emissions and enhance their business by increasing yields, economic returns and enhancing ecosystem services. This study aimed to identify carbon farming practices from literature and investigate the rate of application within cooperatives in Uganda. We reviewed scholarly literature and assed them based on their economic and ecological effects and trade-offs. Field research was done by through an online survey with smallholder farmers in 28 cooperatives across 19 districts in Uganda. We identified 11 and categorized them under three farming systems: organic farming, conservation farming and integrated farming. From the field survey we found that compost is the most applied CFP (54%), crop rotations (32%) and intercropping (50%) across the three categorizations. Dilemmas about right organic amendment quantities, consistent supplies and competing claims of residues for e.g. biochar production, types of inter crops need to be solved in order to further advance the application of CFPs amongst crop cooperatives in Uganda.
DOCUMENT
Understanding taste is key for optimizing the palatability of seaweeds and other non-animal-based foods rich in protein. The lingual papillae in the mouth hold taste buds with taste receptors for the five gustatory taste qualities. Each taste bud contains three distinct cell types, of which Type II cells carry various G protein-coupled receptors that can detect sweet, bitter, or umami tastants, while type III cells detect sour, and likely salty stimuli. Upon ligand binding, receptor-linked intracellular heterotrimeric G proteins initiate a cascade of downstream events which activate the afferent nerve fibers for taste perception in the brain. The taste of amino acids depends on the hydrophobicity, size, charge, isoelectric point, chirality of the alpha carbon, and the functional groups on their side chains. The principal umami ingredient monosodium l-glutamate, broadly known as MSG, loses umami taste upon acetylation, esterification, or methylation, but is able to form flat configurations that bind well to the umami taste receptor. Ribonucleotides such as guanosine monophosphate and inosine monophosphate strongly enhance umami taste when l-glutamate is present. Ribonucleotides bind to the outer section of the venus flytrap domain of the receptor dimer and stabilize the closed conformation. Concentrations of glutamate, aspartate, arginate, and other compounds in food products may enhance saltiness and overall flavor. Umami ingredients may help to reduce the consumption of salts and fats in the general population and increase food consumption in the elderly.
MULTIFILE
Polycyclic aromatic hydrocarbons (PAHs) are a group of more than hundred compounds that are ubiquitous in our environment. Some of these PAHs are known to be carcinogenic, mutagenic and teratogenic. PAHs have been detected in dried herbs that were cultured in The Netherlands as well as in other European countries above the maximum levels in dried herbs set by the EU (EU, 2015) for benzo(a)pyrene and the sum of the following four PAHs benzo(a)pyrene, benzo[a]anthracene, benzo[b]fluoranteen and chrysene. The origin of these PAHs in herbs is unknown. VNK cultivates, harvests and dries herbs including valerian and would like to identify the source of PAHs to comply to the EU limits for PAHs in herbs. The goal of the present study was to identify the source of PAHs found in valerian root, and to identify possible measures to reduce the concentration of PAHs in valerian root.
DOCUMENT
To study the ways in which compounds can induce adverse effects, toxicologists have been constructing Adverse Outcome Pathways (AOPs). An AOP can be considered as a pragmatic tool to capture and visualize mechanisms underlying different types of toxicity inflicted by any kind of stressor, and describes the interactions between key entities that lead to the adverse outcome on multiple biological levels of organization. The construction or optimization of an AOP is a labor intensive process, which currently depends on the manual search, collection, reviewing and synthesis of available scientific literature. This process could however be largely facilitated using Natural Language Processing (NLP) to extract information contained in scientific literature in a systematic, objective, and rapid manner that would lead to greater accuracy and reproducibility. This would support researchers to invest their expertise in the substantive assessment of the AOPs by replacing the time spent on evidence gathering by a critical review of the data extracted by NLP. As case examples, we selected two frequent adversities observed in the liver: namely, cholestasis and steatosis denoting accumulation of bile and lipid, respectively. We used deep learning language models to recognize entities of interest in text and establish causal relationships between them. We demonstrate how an NLP pipeline combining Named Entity Recognition and a simple rules-based relationship extraction model helps screen compounds related to liver adversities in the literature, but also extract mechanistic information for how such adversities develop, from the molecular to the organismal level. Finally, we provide some perspectives opened by the recent progress in Large Language Models and how these could be used in the future. We propose this work brings two main contributions: 1) a proof-of-concept that NLP can support the extraction of information from text for modern toxicology and 2) a template open-source model for recognition of toxicological entities and extraction of their relationships. All resources are openly accessible via GitHub (https://github.com/ontox-project/en-tox).
DOCUMENT
Sinds 2010 produceert NieuWater ultrapuur water uit effluent van de RWZI Emmen. Dit water wordt als proceswater geleverd aan de NAM in Schoonebeek. De biologische actieve koolfiltratie met zuurstofdosering (BODAC), die als voorzuivering gebruikt wordt, lijkt ook een veelbelovende techniek om geneesmiddelen te verwijderen.
DOCUMENT
From the article: Abstract Sub-chronic toxicity studies of 163 non-genotoxic chemicals were evaluated in order to predict the tumour outcome of 24-month rat carcinogenicity studies obtained from the EFSA and ToxRef databases. Hundred eleven of the 148 chemicals that did not induce putative preneoplastic lesions in the sub-chronic study also did not induce tumours in the carcinogenicity study (True Negatives). Cellular hypertrophy appeared to be an unreliable predictor of carcinogenicity. The negative predictivity, the measure of the compounds evaluated that did not show any putative preneoplastic lesion in de sub-chronic studies and were negative in the carcinogenicity studies, was 75%, whereas the sensitivity, a measure of the sub-chronic study to predict a positive carcinogenicity outcome was only 5%. The specificity, the accuracy of the sub-chronic study to correctly identify non-carcinogens was 90%. When the chemicals which induced tumours generally considered not relevant for humans (33 out of 37 False Negatives) are classified as True Negatives, the negative predictivity amounts to 97%. Overall, the results of this retrospective study support the concept that chemicals showing no histopathological risk factors for neoplasia in a sub-chronic study in rats may be considered non-carcinogenic and do not require further testing in a carcinogenicity study.
DOCUMENT
