scholarly journals Pathways of toxicity after inhalation of nanoparticles

10.33540/448 ◽  
2021 ◽  
Author(s):  
◽  
Susan Dekkers
Keyword(s):  
Pathways Of Toxicity

scholarly journals Multiple pathways of toxicity induced by C9orf72 dipeptide repeat aggregates and G4C2 RNA in a cellular model

2020 ◽  
Author(s):  
Frédéric Frottin ◽  
Manuela Pérez-Berlanga ◽  
F. Ulrich Hartl ◽  
Mark S. Hipp
Keyword(s):  
Protein Transport ◽  
Protein Quality ◽  
Protein Biosynthesis ◽  
Abundant Species ◽  
Cellular Model ◽  
Protein Biogenesis ◽  
Pathways Of Toxicity ◽  
Lateral Sclerosis ◽  
Dipeptide Repeat ◽  
Pronounced Inhibition

AbstractThe most frequent genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia is a G4C2 repeat expansion in the C9orf72 gene. This expansion gives rise to translation of aggregating dipeptide repeat (DPR) proteins, including poly-GA as the most abundant species. However, gain of toxic function effects have been attributed to either the DPRs or the pathological G4C2 RNA. Here we analyzed in a cellular model the relative toxicity of DPRs and RNA. Cytoplasmic poly-GA aggregates, generated in the absence of G4C2 RNA, interfered with nucleocytoplasmic protein transport, but had little effect on cell viability. In contrast, nuclear poly-GA was more toxic, impairing nucleolar protein quality control and protein biosynthesis. Production of the G4C2 RNA strongly reduced viability independent of DPR translation and caused pronounced inhibition of nuclear mRNA export and protein biogenesis. Thus, while the toxic effects of G4C2 RNA predominate, DPRs exert additive effects that may contribute to pathology.

scholarly journals AKT-sensitive or insensitive pathways of toxicity in glial cells and neurons in Drosophila models of Huntington's disease

2007 ◽  
Vol 17 (6) ◽  
pp. 882-894 ◽  
Author(s):  
J.-C. Lievens ◽  
M. Iche ◽  
M. Laval ◽  
C. Faivre-Sarrailh ◽  
S. Birman
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Glial Cells ◽  
Pathways Of Toxicity ◽  
Drosophila Models

scholarly journals Metal pollutants have additive negative effects on honey bee cognition

2021 ◽  
Author(s):  
Coline Monchanin ◽  
Erwann Drujont ◽  
Jean-Marc Devaud ◽  
Mathieu Lihoreau ◽  
Andrew B. Barron
Keyword(s):  
Honey Bee ◽  
Memory Retrieval ◽  
Environmental Pollutants ◽  
Complex Mixtures ◽  
Negative Effects ◽  
Metal Pollutants ◽  
Major Threat ◽  
The Impact ◽  
Pathways Of Toxicity ◽  
Copper Arsenic

Environmental pollutants can exert sublethal deleterious effects on animals. These include disruption of cognitive functions underlying crucial behaviours. While agrochemicals have been identified as a major threat to pollinators, metal pollutants, which are often found in complex mixtures, have so far been overlooked. Here we assessed the impact of acute exposure to field-realistic concentrations of three common metal pollutants, lead, copper, arsenic, and their combinations, on honey bee appetitive learning and memory. All treatments involving single metals slowed down learning and disrupted memory retrieval at 24 h. Combinations of these metals had additive negative effects on both processes, suggesting common pathways of toxicity. Our results highlight the need to further assess the risks of metal pollution on invertebrates.

scholarly journals Information-dependent Enrichment Analysis Reveals Time-dependent Transcriptional Regulation of the Estrogen Pathway of Toxicity

2016 ◽  
Author(s):  
Salil N. Pendse ◽  
Alexandra Maertens ◽  
Michael Rosenberg ◽  
Dipanwita Roy ◽  
Rick A. Fasani ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Fold Change ◽  
Gene Set Enrichment Analysis ◽  
High Dose ◽  
Functional Responses ◽  
Pathways Of Toxicity

The twenty-first century vision for toxicology involves a transition away from high-dose animal studies and into in vitro and computational models. This movement requires mapping pathways of toxicity through an understanding of how in vitro systems respond to chemical perturbation. Uncovering transcription factors responsible for gene expression patterns is essential for defining pathways of toxicity, and ultimately, for determining chemical mode of action, through which a toxicant acts. Traditionally this is achieved via chromatin immunoprecipitation studies and summarized by calculating, which transcription factors are statistically associated with the up- and down-regulated genes. These lists are commonly determined via statistical or fold-change cutoffs, a procedure that is sensitive to statistical power and may not be relevant to determining transcription factor associations. To move away from an arbitrary statistical or fold-change based cutoffs, we have developed in the context of the Mapping the Human Toxome project, a novel enrichment paradigm called Information Dependent Enrichment Analysis (IDEA) to guide identification of the transcription factor network. We used the test case of endocrine disruption of MCF-7 cells activated by 17β estradiol (E2). Using this new approach, we were able to establish a time course for transcriptional and functional responses to E2. ERα and ERβ are associated with short-term transcriptional changes in response to E2. Sustained exposure leads to the recruitment of an additional ensemble of transcription factors and alteration of cell-cycle machinery. TFAP2C and SOX2 were the transcription factors most highly correlated with dose. E2F7, E2F1 and Foxm1, which are involved in cell proliferation, were enriched only at 24h. IDEA is, therefore, a novel tool to identify candidate pathways of toxicity, clearly outperforming Gene-set Enrichment Analysis but with similar results as Weighted Gene Correlation Network Analysis, which helps to identify genes not annotated to pathways.

scholarly journals Heavy metal pollutants have additive negative effects on honey bee cognition

2020 ◽  
Author(s):  
Coline Monchanin ◽  
Erwann Drujont ◽  
Jean-Marc Devaud ◽  
Mathieu Lihoreau ◽  
Andrew B Barron
Keyword(s):  
Heavy Metal ◽  
Honey Bee ◽  
Memory Retrieval ◽  
Environmental Pollutants ◽  
Negative Effects ◽  
Metal Pollutants ◽  
Major Threat ◽  
Heavy Metal Pollutants ◽  
The Impact ◽  
Pathways Of Toxicity

Environmental pollutants can exert sublethal deleterious effects on animals. These include disruption of cognitive functions underlying crucial behaviours. While agrochemicals have been identified as a major threat to pollinators, other compounds, such as heavy metals that are often found in complex mixtures, have largely been overlooked. Here, we assessed the impact of acute exposure to field-realistic concentrations of lead, copper, arsenic, and their combinations, on honey bee learning and memory. All treatments involving single metals slowed down appetitive learning and disrupted memory retrieval at 24 h. Importantly, combinations of these metals induced additive negative effects on both processes, suggesting common pathways of toxicity. Our results highlight the need to further assess the risks of heavy metal pollution on invertebrates and to their associated ecosystem services.

Investigations of the pathways of toxicity of methyl iodide in the rat nasal cavity

Toxicology ◽  
1998 ◽  
Vol 129 (2-3) ◽  
pp. 169-181 ◽  
Author(s):  
Mark P. Chamberlain ◽  
Edward A. Lock ◽  
Celia J. Reed
Keyword(s):  
Nasal Cavity ◽  
Methyl Iodide ◽  
Pathways Of Toxicity

Early pathways of toxicity triggered by 3,4-methylene-dioxypyrovalerone unveiled by in vivo toxicometabolomics

2021 ◽  
Vol 350 ◽  
pp. S130-S131
Author(s):  
A.M. Araújo ◽  
M. Carvalho ◽  
V.M. Costa ◽  
J.A. Duarte ◽  
R.J. Dinis-Oliveira ◽  
...  
Keyword(s):  
Pathways Of Toxicity
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