Mentation and shorter body length, apparently had no effect on the axon growth. It is apparent that all of these six chemicals show dosagedependent toxicity in essentially all the endpoints observed (Table S1). In the present study, we demonstrated that, compared to the recommended DarT endpoints, axon length, which can be observed and measured in Tg(nkx2.2a:mEGFP) fry, is about 10 fold more sensitive than the most sensitive endpoints recommended in DarT. Thus, with the ease and direct observable features of GFP expression, the Tg(nkx2.2a:mEGFP) transgenic zebrafish provides a convenient and highly sensitive tool for screening and testing neurotoxic compounds, which will be applicable in environmental monitoring and pharmaceutical production. As there are a large number of fluorescent transgenic zebrafish with fluorescent protein reporter gene expression in specific organs and tissues [10,11], our study may open a new avenue to test other useful fluorescent transgenic zebrafish for development of specific toxicological assays for different categories of chemicals. In particular, as exampled 18325633 here, all of the toxicological assays in fluorescent transgenic zebrafish can be accomplished within 5 days after fertilization and before feeding stage, which is considered an in vivo test system alternative to adult animals, thus reducing the use of animals in toxicological tests.Supporting InformationTable S1 Comparison of sensitivity of lethal andsublethal DarT endpoints and axon length measurements in Tg(nkx2.2a:mEGFP) the treatment. (DOCX)Figure 6. Lowest effective concentrations of neurotoxins for shortening of motoneuron axons. doi:10.1371/journal.pone.0055474.gTransgenic Zebrafish for Neurotoxin TestAcknowledgmentsThis work was supported by the Singapore National Clavulanate (potassium) biological activity Research Foundation under its Environmental Water Technologies Strategic Research Programme and administered by the Environment Water Industry Programme Office (EWI) of the PUB, grant number R-154-000-328-272.Author ContributionsConceived and designed the experiments: XZ ZG. Performed the experiments: XZ. Analyzed the data: XZ ZG. Contributed reagents/ materials/analysis tools: XZ ZG. Wrote the paper: XZ ZG.
White BMS 5 supplier matter lesions (WML) are clinically relevant since they are associated with a variety of neurological disorders, e. g. strokes, cognitive decline, depression, or epilepsy [1]. WML are frequently documented in brain MRI in elderly subjects. The most prominent risk factors are age and essential hypertension, followed by the remaining classical cardiovascular risk factors [2]. WML may also be detected in younger adults without typical risk factors and are occasionally associated with inflammatory, and, in particular, demyelinating diseases [3]. However, despite extensive diagnostic efforts, the underlying etiology often remains elusive in these patients. Fabry disease (FD; Online mendelian inheritance in man (OMIM) #301500) is a X-linked (Xq22.1) inborn error of glycosphingolipid catabolism resulting from deficient a-galactosidase A activity (GLA; OMIM #300644) due to mutations in the GLA coding region, leading to the systemic accumulation of globotriaoslyceramide (Gb3 or GL-3) in the plasma and cellular lysosomes of vessels, nerves, tissues, and organs [4]. Withoutenzyme replacement therapy (ERT), life span in FD patients is dramatically shortened, generally due to heart failure, renal dysfunction and cerebrovascular disease. Ischemic strokes and WML are characteristic ne.Mentation and shorter body length, apparently had no effect on the axon growth. It is apparent that all of these six chemicals show dosagedependent toxicity in essentially all the endpoints observed (Table S1). In the present study, we demonstrated that, compared to the recommended DarT endpoints, axon length, which can be observed and measured in Tg(nkx2.2a:mEGFP) fry, is about 10 fold more sensitive than the most sensitive endpoints recommended in DarT. Thus, with the ease and direct observable features of GFP expression, the Tg(nkx2.2a:mEGFP) transgenic zebrafish provides a convenient and highly sensitive tool for screening and testing neurotoxic compounds, which will be applicable in environmental monitoring and pharmaceutical production. As there are a large number of fluorescent transgenic zebrafish with fluorescent protein reporter gene expression in specific organs and tissues [10,11], our study may open a new avenue to test other useful fluorescent transgenic zebrafish for development of specific toxicological assays for different categories of chemicals. In particular, as exampled 18325633 here, all of the toxicological assays in fluorescent transgenic zebrafish can be accomplished within 5 days after fertilization and before feeding stage, which is considered an in vivo test system alternative to adult animals, thus reducing the use of animals in toxicological tests.Supporting InformationTable S1 Comparison of sensitivity of lethal andsublethal DarT endpoints and axon length measurements in Tg(nkx2.2a:mEGFP) the treatment. (DOCX)Figure 6. Lowest effective concentrations of neurotoxins for shortening of motoneuron axons. doi:10.1371/journal.pone.0055474.gTransgenic Zebrafish for Neurotoxin TestAcknowledgmentsThis work was supported by the Singapore National Research Foundation under its Environmental Water Technologies Strategic Research Programme and administered by the Environment Water Industry Programme Office (EWI) of the PUB, grant number R-154-000-328-272.Author ContributionsConceived and designed the experiments: XZ ZG. Performed the experiments: XZ. Analyzed the data: XZ ZG. Contributed reagents/ materials/analysis tools: XZ ZG. Wrote the paper: XZ ZG.
White matter lesions (WML) are clinically relevant since they are associated with a variety of neurological disorders, e. g. strokes, cognitive decline, depression, or epilepsy [1]. WML are frequently documented in brain MRI in elderly subjects. The most prominent risk factors are age and essential hypertension, followed by the remaining classical cardiovascular risk factors [2]. WML may also be detected in younger adults without typical risk factors and are occasionally associated with inflammatory, and, in particular, demyelinating diseases [3]. However, despite extensive diagnostic efforts, the underlying etiology often remains elusive in these patients. Fabry disease (FD; Online mendelian inheritance in man (OMIM) #301500) is a X-linked (Xq22.1) inborn error of glycosphingolipid catabolism resulting from deficient a-galactosidase A activity (GLA; OMIM #300644) due to mutations in the GLA coding region, leading to the systemic accumulation of globotriaoslyceramide (Gb3 or GL-3) in the plasma and cellular lysosomes of vessels, nerves, tissues, and organs [4]. Withoutenzyme replacement therapy (ERT), life span in FD patients is dramatically shortened, generally due to heart failure, renal dysfunction and cerebrovascular disease. Ischemic strokes and WML are characteristic ne.