Project description:REACH, the EU regulation on chemicals and their safe use, stipulates that about 30,000 chemical substances are to be assessed on their possible risks. Toxicological evaluation of these compounds will at least partly be based on animal testing. Especially reproductive toxicity is one of the most complicated, time-consuming and expensive in vivo endpoints. Introducing microarray-based endpoints can potentially refine in vivo toxicity testing. If compounds from a distinct chemical class induce reproducible gene-expression responses with a recognizable overlap, these gene-expression signatures may indicate intrinsic features of certain compounds, including toxicity. In the present study, we investigated this theory for the reproductive toxicity of phthalates. Male rats were treated with a single dose of either reprotoxic or non-reprotoxic phthalates and sacrificed 24h thereafter. Subsequently, histopathological and gene-expression profiling analyses were performed. Despite ambiguous histopathological observations, we were able to distinguish the reprotoxic from the non-reprotoxic phthalates based on differential gene expression. This shows that differences in gene expression indicative for the type of exposure can be detected earlier, or at lower doses, than phenotypic tissue damage. These findings are promising for ’early warning’ biomarker analyses and for using toxicogenomics in a category approach.
Project description:Lipoic acid induced endoplasmic reticulum stress-mediated apoptosis in rat hepatoma cells:identification of new ER stress aggravator (ERSA)
Project description:Toxicogenomics profiling of bone marrow from rats treated with topotecan in combination with oxaliplatin: a mechanistic strategy to inform combination toxicity.
Project description:The Norway rat has important impacts on our life. They are amongst the most used research subjects, resulting in ground-breaking advances. At the same time, wild rats live in close association with us, leading to various adverse interactions. In face of this relevance, it is surprising how little is known about their natural behaviour. While recent laboratory studies revealed their complex social skills, little is known about their social behaviour in the wild. An integration of these different scientific approaches is crucial to understand their social life, which will enable us to design more valid research paradigms, develop more effective management strategies, and to provide better welfare standards. Hence, I first summarise the literature on their natural social behaviour. Second, I provide an overview of recent developments concerning their social cognition. Third, I illustrate why an integration of these areas would be beneficial to optimise our interactions with them.
Project description:BackgroundMurine kobuviruses (MuKV) are newly recognized picornaviruses first detected in murine rodents in the USA in 2011. Little information on MuKV epidemiology in murine rodents is available. Therefore, we conducted a survey of the prevalence and genomic characteristics of rat kobuvirus in Guangdong, China.ResultsFecal samples from 223 rats (Rattus norvegicus) were collected from Guangdong and kobuviruses were detected in 12.6% (28) of samples. Phylogenetic analysis based on partial 3D and complete VP1 sequence regions showed that rat kobuvirus obtained in this study were genetically closely related to those of rat/mouse kobuvirus reported in other geographical areas. Two near full-length rat kobuvirus genomes (MM33, GZ85) were acquired and phylogenetic analysis of these revealed that they shared very high nucleotide/amino acids identity with one another (95.4%/99.4%) and a sewage-derived sequence (86.9%/93.5% and 87.5%/93.7%, respectively). Comparison with original Aichivirus A strains, such human kobuvirus, revealed amino acid identity values of approximately 80%.ConclusionOur findings indicate that rat kobuvirus have distinctive genetic characteristics from other Aichivirus A viruses. Additionally, rat kobuvirus may spread via sewage.
Project description:REACH, the EU regulation on chemicals and their safe use, stipulates that about 30,000 chemical substances are to be assessed on their possible risks. Toxicological evaluation of these compounds will at least partly be based on animal testing. Especially reproductive toxicity is one of the most complicated, time-consuming and expensive in vivo endpoints. Introducing microarray-based endpoints can potentially refine in vivo toxicity testing. If compounds from a distinct chemical class induce reproducible gene-expression responses with a recognizable overlap, these gene-expression signatures may indicate intrinsic features of certain compounds, including toxicity. In the present study, we investigated this theory for the reproductive toxicity of phthalates. Male rats were treated with a single dose of either reprotoxic or non-reprotoxic phthalates and sacrificed 24h thereafter. Subsequently, histopathological and gene-expression profiling analyses were performed. Despite ambiguous histopathological observations, we were able to distinguish the reprotoxic from the non-reprotoxic phthalates based on differential gene expression. This shows that differences in gene expression indicative for the type of exposure can be detected earlier, or at lower doses, than phenotypic tissue damage. These findings are promising for ’early warning’ biomarker analyses and for using toxicogenomics in a category approach. Male rats were treated with a single dose of either reprotoxic (DMP, DEP, DPrP, DOP) or non-reprotoxic phthalates (DBP, DPeP, DHP, DEHP, MEHP), positive control (2-ME) or negative control (vehicle) and killed 24 h thereafter. Rat testes were preserved for RNA extraction and hybridization on Affymetrix microarrays.
Project description:Inflammation is a key component of pathological angiogenesis. Here we induce cornea neovascularisation using sutures placed into the cornea, and sutures are removed to induce a regression phase. We used whole transcriptome microarray to monitor gene expression profies of several genes