Search results for "Toxic"
showing 10 items of 6968 documents
Aβ Induces Excitotoxicity Mediated by APC/C-Cdh1 Depletion That Can Be Prevented by Glutaminase Inhibition Promoting Neuronal Survival
2016
AbstractThe E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) is activated by the fizzy-related protein homolog/CDC20-like protein 1 (cdh1) in post-mitotic neurons. Growing evidence suggests that dysregulation of APC/C-Cdh1 is involved in neurodegenerative diseases. Here we show in neurons that oligomers of amyloid beta (Aβ), a peptide related to Alzheimer’s disease, cause proteasome-dependent degradation of cdh1. This leads to a subsequent increase in glutaminase (a degradation target of APC/C-Cdh1), which causes an elevation of glutamate levels and further intraneuronal Ca2+ dysregulation, resulting in neuronal apoptosis. Glutaminase inhibition prevents glutamate excitotoxi…
Breaking BAG: The Co-Chaperone BAG3 in Health and Disease.
2016
Human BAG ( B cl-2-associated a thano g ene) proteins form a family of antiapoptotic proteins that currently consists of six members (BAG1–6) all sharing the BAG protein domain from which the name arises. Via this domain, BAG proteins bind to the heat shock protein 70 (Hsp70), thereby acting as a co-chaperone regulating the activity of Hsp70. In addition to their antiapoptotic activity, all human BAG proteins have distinct functions in health and disease, and BAG3 in particular is the focus of many investigations. BAG3 has a modular protein domain composition offering the possibility for manifold interactions with other proteins. Various BAG3 functions are implicated in disorders including …
MycoKey Round Table Discussions of Future Directions in Research on Chemical Detection Methods, Genetics and Biodiversity of Mycotoxins
2018
MycoKey, an EU-funded Horizon 2020 project, includes a series of “Roundtable Discussions” to gather information on trending research areas in the field of mycotoxicology. This paper includes summaries of the Roundtable Discussions on Chemical Detection and Monitoring of mycotoxins and on the role of genetics and biodiversity in mycotoxin production. Discussions were managed by using the nominal group discussion technique, which generates numerous ideas and provides a ranking for those identified as the most important. Four questions were posed for each research area, as well as two questions that were common to both discussions. Test kits, usually antibody based, were one major focus of the…
HLA-E-Restricted CD8+ T Lymphocytes Efficiently Control Mycobacterium tuberculosis and HIV-1 Co-Infection
2020
We investigated the contribution of human leukocyte antigen A2 (HLA-A2) and HLA-E-restricted CD8+ T cells in patients with Mycobacterium tuberculosis and human immunodeficiency virus 1 (HIV-1) coinfection. HIV-1 downregulates HLA-A, -B, and -C molecules in infected cells, thus influencing recognition by HLA class I-restricted CD8+ T cells but not by HLA-E-restricted CD8+ T cells, owing to the inability of the virus to downmodulate their expression. Therefore, antigen-specific HLA-E-restricted CD8+ T cells could play a protective role in Mycobacterium tuberculosis and HIV-1 coinfection. HLA-E- and HLA-A2-restricted Mycobacterium tuberculosis-specific CD8+ T cells were tested in vitro for cyt…
Human CD8(+) T Cells Damage Noninfected Epithelial Cells during Influenza Virus Infection In Vitro
2017
During severe influenza A virus (IAV) infections, a large amount of damage to the pulmonary epithelium is the result of the antiviral immune response. Specifically, whilst CD8+ T cells are important for killing IAV-infected cells, during a severe IAV infection, they can damage uninfected epithelial cells. At present, the mechanisms by which this occurs are unclear. Here, we used a novel in vitro coculture model of human NCl-H441 cells and CD8+ T cells to provide a new insight into how CD8+ T cells may affect uninfected epithelial cells during severe IAV infections. Using this model, we show that human IAV-specific CD8+ T cells produce soluble factors that reduce the barrier integrity of non…
Modelos animales de adicción a las drogas
2017
El desarrollo de modelos animales de refuerzo y adicción a las drogas es imprescindible para el avance en el conocimiento de las bases biológicas de este trastorno y la identificación de nuevas dianas terapéuticas. En función del componente del refuerzo que deseemos estudiar podemos servirnos de un tipo de modelos animales u otros. Podemos utilizar modelos de refuerzo basados en el efecto hedónico primario que produce el consumo de la sustancia adictiva, como los modelos de autoadministración (AA) y autoestimulación eléctrica intracraneal (AEIC), o modelos basados en el componente relacionado con el aprendizaje asociativo y la capacidad cognitiva de realizar predicciones sobre la obtención …
Cytotoxic activity of the histone deacetylase 3-Selective inhibitor Pojamide on MDA-MB-231 triple-negative breast cancer cells
2019
We examined the effects of the ferrocene-based histone deacetylase-3 inhibitor Pojamide (N1-(2-aminophenyl)-N8-ferrocenyloctanediamide) and its two derivatives N1-(2-aminophenyl)-N6-ferrocenyladipamide and N1-(2-aminophenyl)-N8-ferroceniumoctanediamide tetrafluoroborate on triple-negative MDA-MB-231 breast cancer cells. Viability/growth assays indicated that only the first two compounds at 70 &mu
Innovative Strategies to Develop Chemical Categories Using a Combination of Structural and Toxicological Properties.
2016
Interest is increasing in the development of non-animal methods for toxicological evaluations. These methods are however, particularly challenging for complex toxicological endpoints such as repeated dose toxicity. European Legislation, e.g., the European Union's Cosmetic Directive and REACH, demands the use of alternative methods. Frameworks, such as the Read-across Assessment Framework or the Adverse Outcome Pathway Knowledge Base, support the development of these methods. The aim of the project presented in this publication was to develop substance categories for a read-across with complex endpoints of toxicity based on existing databases. The basic conceptual approach was to combine str…
New Insights into the Genome Organization of Yeast Killer Viruses Based on “Atypical” Killer Strains Characterized by High-Throughput Sequencing
2017
Viral M-dsRNAs encoding yeast killer toxins share similar genomic organization, but no overall sequence identity. The dsRNA full-length sequences of several known M-viruses either have yet to be completed, or they were shorter than estimated by agarose gel electrophoresis. High-throughput sequencing was used to analyze some M-dsRNAs previously sequenced by traditional techniques, and new dsRNAs from atypical killer strains of Saccharomyces cerevisiae and Torulaspora delbrueckii. All dsRNAs expected to be present in a given yeast strain were reliably detected and sequenced, and the previously-known sequences were confirmed. The few discrepancies between viral variants were mostly located aro…
Subacute effects of ozone exposure on cultivated human respiratory mucosa.
2001
This study was designed to investigate subacute effects of long-term exposure of both healthy and chronically inflamed human respiratory mucosa to ozone. Functional and metabolic effects on ciliary beat frequency (CBF), release of interleukin 8 (IL-8), interleukin 4 (IL-4), and γ interferon (g-INF), as well as cellular viability and cytotoxicity, were monitored. Cell cultures of 60 specimens (healthy mucosa: n = 30, inflamed mucosa: n = 30) were exposed to synthetic air and to ozone-enriched synthetic air in different concentrations of WO, 500, and WOO μg/m3. Continuous expositions were performed using an air/liquid interface cell culture technique for a period of 4 weeks. CBF was monitore…