New benzotriazoles generated during textile dyeing process: Synthesis, hazard, water occurrence and aquatic risk assessment

Phenylbenzotriazoles (PBTA) can be generated unintentionally during textile dyeing factories by reduction of dinitrophenylazo dyes and their subsequent chlorination in disinfection process. Eight non-chlorinated PBTAs (non-Cl PBTA) and their related chlorinated PBTAs have been found in rivers and presented mutagenic activity. No data on their aquatic toxicity are available. In this work, two new phenylbenzotriazoles, non-Cl PBTA-9 and PBTA-9, derived from the dye C.I. Disperse Violet 93 (DV93) were synthesized and chemically/toxicologically characterized. Both compounds were more mutagenic than the parental dye in the Salmonella/microsome assay in the presence of metabolic activation (S9). Mutagenicity studies in vivo with mammals would confirm their potential hazard to humans. The two compounds were acutely toxic to Daphnia similis. We developed an analytical method to simultaneously quantify non-Cl PBTA-9, PBTA-9 and DV93 in river waters. Non-Cl PBTA-9 was found in sites under influence of textile effluents but at concentrations that do not pose risk to the aquatic life according to the P-PNEC calculated based on the acute toxicity tests. PBTA-9 was not detected in any samples analyzed. More studies on the aquatic toxicity and water occurrence of PBTAs should be conducted to verify the relevance of this class of compounds as aquatic contaminants403CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP30767/2017-6sem informação2019/ 07822-

Adeno-associated viral vectors for functional intravenous gene transfer throughout the non-human primate brain

Crossing the blood-brain barrier in primates is a major obstacle for gene delivery to the brain. Adeno-associated viruses (AAVs) promise robust, non-invasive gene delivery from the bloodstream to the brain. However, unlike in rodents, few neurotropic AAVs efficiently cross the blood-brain barrier in non-human primates. Here we report on AAV.CAP-Mac, an engineered variant identified by screening in adult marmosets and newborn macaques, which has improved delivery efficiency in the brains of multiple non-human primate species: marmoset, rhesus macaque and green monkey. CAP-Mac is neuron biased in infant Old World primates, exhibits broad tropism in adult rhesus macaques and is vasculature biased in adult marmosets. We demonstrate applications of a single, intravenous dose of CAP-Mac to deliver functional GCaMP for ex vivo calcium imaging across multiple brain areas, or a cocktail of fluorescent reporters for Brainbow-like labelling throughout the macaque brain, circumventing the need for germline manipulations in Old World primates. As such, CAP-Mac is shown to have potential for non-invasive systemic gene transfer in the brains of non-human primates

Next-generation sequencing of AAV.CAP-Mac from Chuapoco et al. (2023) Nature Nanotechnology

Dataset of next-generation sequencing of enrichment of AAV.CAP-Mac in various tissues from the publication: Chuapoco, M.R., Flytzanis, N.C., Goeden, N. et al. Adeno-associated viral vectors for functional intravenous gene transfer throughout the non-human primate brain. Nat. Nanotechnol. (2023). https://doi.org/10.1038/s41565-023-01419-xThis work was funded by grants from the National Institutes of Health (NIH): NIH Pioneer DP1NS111369 (to V.G.); P51OD011107 (to the California National Primate Research Center), R01HD091325 (to L.T.); U19NS123719 (to L.T.); UG3MH120095 (to J.T.T. and B.P.L.); P51OD010425 (to the Washington National Primate Research Center); U42OD011123 (to the Washington National Primate Research Center); BRAIN Armamentarium UF1MH128336 (to V.G., T.F.S., L.T. and A.S.F.), and in part by Aligning Science Across Parkinson's (ASAP-020495 to V.G., A.S.F. and L.T.) through the Michael J. Fox Foundation for Parkinson's Research (MJFF)