Increasing the fungicidal action of Amphotericin B by inhibiting the Nitric Oxide-Dependent tolerance pathway

Amphotericin B (AmB) induces oxidative and nitrosative stresses, characterized by production of reactive oxygen and nitrogen species, in fungi. Yet, how these toxic species contribute to AmB-induced fungal cell death is unclear. We investigated the role of superoxide and nitric oxide radicals in AmB's fungicidal activity in Saccharomyces cerevisiae, using a digital microfluidic platform, which enabled monitoring individual cells at a spatiotemporal resolution, and plating assays. The nitric oxide synthase inhibitor L-NAME was used to interfere with nitric oxide radical production. L-NAME increased and accelerated AmB-induced accumulation of superoxide radicals, membrane permeabilization, and loss of proliferative capacity in S. cerevisiae. In contrast, the nitric oxide donor S-nitrosoglutathione inhibited AmB's action. Hence, superoxide radicals were important for AmB's fungicidal action, whereas nitric oxide radicals mediated tolerance towards AmB. Finally, also the human pathogens Candida albicans and Candida glabrata were more susceptible to AmB in the presence of L-NAME, pointing to the potential of AmB-L-NAME combination therapy to treat fungal infections.Kim Vriens acknowledges the receipt of a predoctoral grant from the Flanders Innovation & Entrepeneurship Agency (IWT-SB 111016); Karin Thevissen acknowledges the receipt of a mandate of Industrial Research Fund (KU Leuven). In addition, the research leading to these results has received funding from the Research Foundation - Flanders (FWO G086114N and G080016N) and the KU Leuven (OT 13/ 058 and IDO 10/012, IOF KP/12/009 Atheromix, IOF KP/ 12/002 Nanodiag). This work was partially developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). Belém Sampaio-Marques is supported by the fellowship SFRH/BPD/90533/2012 funded by Fundação para a Ciência e Tecnologia (FCT, Portugal).info:eu-repo/semantics/publishedVersio

Embry-Riddle Fly Paper 1943-01-15

https://commons.erau.edu/fly-paper/1159/thumbnail.jp

Designing the appearance of environmentally sustainable products

The study presented in this paper uses a mathematical model to measure the degree in which a product will be perceived as environmentally friendly from its physical attributes. A model based on genetic algorithms and neural networks was developed to predict the judgement of the users about environmental friendliness of different tables. Opinions of real users about a large set of tables were used to train the model. The results of the study suggest that, using this procedure in advanced stages of product design process, designers can determine the set of product's physical attributes that best convey the idea of environmentally sustainable to the customer. The analysis of the obtained model allows establishing how different product's attributes influence users' perception. From these results, the utilization of users' affective response models to design the appearance of environmentally sustainable products is discussed.Diego-Mas, JA.; Poveda Bautista, R.; Alcaide Marzal, J. (2016). Designing the appearance of environmentally sustainable products. Journal of Cleaner Production. 135(1):784-793. doi:10.1016/j.jclepro.2016.06.173S784793135

The cyclin‐dependent kinase G group defines a thermo‐sensitive alternative splicing circuit modulating the expression of Arabidopsis ATU2AF65A

The ability to adapt growth and development to temperature variations is crucial to generate plant varieties resilient to predicted temperature changes. However, the mechanisms underlying plant response to progressive increases in temperature have just started to be elucidated. Here, we report that the Cyclin?dependent Kinase G1 (CDKG1) is a central element in a thermo?sensitive mRNA splicing cascade that transduces changes in ambient temperature into differential expression of the fundamental spliceosome component, ATU2AF65A. CDKG1 is alternatively spliced in a temperature?dependent manner. We found that this process is partly dependent on both the Cyclin?dependent Kinase G2 (CDKG2) and the interacting co?factor CYCLIN L1 resulting in two distinct messenger RNAs. Relative abundance of both CDKG1 transcripts correlates with ambient temperature and possibly with different expression levels of the associated protein isoforms. Both CDKG1 alternative transcripts are necessary to fully complement the expression of ATU2AF65A across the temperature range. Our data support a previously unidentified temperature?dependent mechanism based on the alternative splicing of CDKG1 and regulated by CDKG2 and CYCLIN L1. We propose that changes in ambient temperature affect the relative abundance of CDKG1 transcripts and this in turn translates into differential CDKG1 protein expression coordinating the alternative splicing of ATU2AF65AauthorsversionPeer reviewe

Citral Sensing by TRANSient Receptor Potential Channels in Dorsal Root Ganglion Neurons

Transient receptor potential (TRP) ion channels mediate key aspects of taste, smell, pain, temperature sensation, and pheromone detection. To deepen our understanding of TRP channel physiology, we require more diverse pharmacological tools. Citral, a bioactive component of lemongrass, is commonly used as a taste enhancer, as an odorant in perfumes, and as an insect repellent. Here we report that citral activates TRP channels found in sensory neurons (TRPV1 and TRPV3, TRPM8, and TRPA1), and produces long-lasting inhibition of TRPV1–3 and TRPM8, while transiently blocking TRPV4 and TRPA1. Sustained citral inhibition is independent of internal calcium concentration, but is state-dependent, developing only after TRP channel opening. Citral's actions as a partial agonist are not due to cysteine modification of the channels nor are they a consequence of citral's stereoisoforms. The isolated aldehyde and alcohol cis and trans enantiomers (neral, nerol, geranial, and geraniol) each reproduce citral's actions. In juvenile rat dorsal root ganglion neurons, prolonged citral inhibition of native TRPV1 channels enabled the separation of TRPV2 and TRPV3 currents. We find that TRPV2 and TRPV3 channels are present in a high proportion of these neurons (94% respond to 2-aminoethyldiphenyl borate), consistent with our immunolabeling experiments and previous in situ hybridization studies. The TRPV1 activation requires residues in transmembrane segments two through four of the voltage-sensor domain, a region previously implicated in capsaicin activation of TRPV1 and analogous menthol activation of TRPM8. Citral's broad spectrum and prolonged sensory inhibition may prove more useful than capsaicin for allodynia, itch, or other types of pain involving superficial sensory nerves and skin

How should the completeness and quality of curated nanomaterial data be evaluated?

Nanotechnology is of increasing significance. Curation of nanomaterial data into electronic databases offers opportunities to better understand and predict nanomaterials' behaviour. This supports innovation in, and regulation of, nanotechnology. It is commonly understood that curated data need to be sufficiently complete and of sufficient quality to serve their intended purpose. However, assessing data completeness and quality is non-trivial in general and is arguably especially difficult in the nanoscience area, given its highly multidisciplinary nature. The current article, part of the Nanomaterial Data Curation Initiative series, addresses how to assess the completeness and quality of (curated) nanomaterial data. In order to address this key challenge, a variety of related issues are discussed: the meaning and importance of data completeness and quality, existing approaches to their assessment and the key challenges associated with evaluating the completeness and quality of curated nanomaterial data. Considerations which are specific to the nanoscience area and lessons which can be learned from other relevant scientific disciplines are considered. Hence, the scope of this discussion ranges from physicochemical characterisation requirements for nanomaterials and interference of nanomaterials with nanotoxicology assays to broader issues such as minimum information checklists, toxicology data quality schemes and computational approaches that facilitate evaluation of the completeness and quality of (curated) data. This discussion is informed by a literature review and a survey of key nanomaterial data curation stakeholders. Finally, drawing upon this discussion, recommendations are presented concerning the central question: how should the completeness and quality of curated nanomaterial data be evaluated