Project description:safety versus fear conditioning. Mice were trained with 4 unpaired (Safety) or paired (Fear) CS-US presentations over 3 days. Mice were killed by decapitation 4hrs after the last training session.
Project description:Oocyte vitrification has been introduced into clinical settings without pre-clinical safety testing. In this study, we analyzed the safety of human oocyte
Project description:Food safety evaluation of new, genetically modified (GM) plant varieties has led to basic questions regarding the safety assessment of new plant varieties and whole foods derived thereof. An important part of the hazard identification in the European approach is a targeted compositional analysis of new GM plant varieties compared to one or more conventional reference varieties. Comparative analysis will become much more informative with unbiased analytical approaches, such as omics profiling. Analysis tools that estimate the similarity of new varieties to the reference would in turn greatly facilitate hazard identification. Further in-depth biological, functional and eventually toxicological analysis of the data would then only be necessary for varieties that fall outside the scale of those with a history of safe human consumption. For this purpose, the use of a one-class classifier tool was explored in this study to assess and classify transcriptome profiles of potato varieties. Five potato varieties were grown in the Netherlands during the same year (NL samples) and included four biological replicates for four varieties or two biological replicates for the fifth one. They were all analysed in 2011. A sixth variety was grown in the UK in a previous study and a previous year, for which the data are submitted in E-MTAB-605. The two UK samples were analysed in the original study in 2008 and again together with the NL samples in the present study, resulting in four profiles for two samples.
Project description:Regulatable CAR platforms could circumvent toxicities associated with CAR-T therapy, but existing systems have shortcomings including leakiness and attenuated activity. Here, we present SNIP-CARs, a novel protease-based platform for regulating CAR activity using an FDA-approved small molecule. Design iterations yielded CAR-T cells that manifest full functional capacity with drug and no leaky activity in the absence of drug. In numerous models, SNIP CAR-T cells were more potent than constitutive CAR-T cells and showed diminished T cell exhaustion and greater stemness. In a ROR1-based CAR lethality model, drug cessation following toxicity onset reversed toxicity, thereby credentialling the platform as a safety switch. In the same model, reduced drug dosing opened a therapeutic window that resulted in tumor eradication in the absence of toxicity. SNIP-CARs enable remote tuning of CAR activity, which provides solutions to safety and efficacy barriers currently limiting progress in using CAR T cells to treat solid tumors.
Project description:Brucellosis, caused by Brucella spp, is an important zoonotic disease leading to enormous economic losses in livestock and posing great threat to public health worldwide. The live attenuated Brucella suis (B. suis) strain S2 is a safe and effective vaccine, and it is most widely used in animals in China. However, S2 vaccination in animals may raise debates and concerns in terms of safety to primates, particularly human. In this study, using cynomolgus monkey as an animal model, we evaluated the safety of the S2 vaccine strain on primate, in addition, we performed transcriptome analysis to determine gene expression profiling on cynomolgus monkeys immunized with the S2 vaccine. Our results suggested that the S2 vaccine was safe to cynomolgus monkeys. Transcriptome analysis identified 663 differentially expressed genes (DEGs), of which 348 were significantly up-regulated and 315 were remarkably down-regulated. Gene Ontology (GO) classification and KEGG pathway analysis indicated that these DEGs were involved in various biological processes, including chemokine signaling pathway, actin cytoskeleton regulation, defense response, immune system processing, and type I interferon signaling pathway. The molecular functions of the DEGs mainly comprised of 2'-5'-oligoadenylate synthetase activity, double-stranded RNA binding and actin binding. Moreover, the cellular components of these DEGs included integrin complex, myosin II complex and blood microparticle. Our findings alleviate the concerns in safety of the S2 vaccine on primates and provide genetic basis of mammalian host response and gene regulation after vaccination with the S2 vaccine.
