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1.
iScience ; 26(5): 106631, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37168567

RESUMO

Mycobacterium tuberculosis (Mtb) is the most common infection among people with HIV (PWH). Mtb disease-associated inflammation could affect HIV-directed immune responses in PWH. We show that HIV antibodies are broader and more potent in PWH in the presence as compared to the absence of Mtb disease. With co-existing Mtb disease, the virus in PWH also encounters unique antibody selection pressure. The Mtb-linked HIV antibody enhancement associates with specific mediators important for B cell and antibody development. This Mtb humoral augmentation does not occur due to cross-reactivity, a generalized increase in all antibodies, or differences in duration or amount of antigen exposure. We speculate that the co-localization of Mtb and HIV in lymphatic tissues leads to the emergence of potent HIV antibodies. PWH's Mtb disease status has implications for the future use of HIV broadly neutralizing antibodies as prophylaxis or treatment and the induction of better humoral immunity.

2.
J Toxicol Environ Health A ; 81(18): 924-938, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30102137

RESUMO

The widespread use of lead (Pb) shot in shooting activities, including at former shooting ranges, continues to pose environmental risks. The La Crosse River Marsh (located in Wisconsin, USA) is a biologically diverse urban riparian wetland with a legacy of Pb-contaminated sediment resulting from its use as a trap shooting range from 1929-1963. Within the shot fall zone, shot densities exceed 43,000 pellets/m2 and surface sediments exceed 25,000 mg/kg in some areas. This study used the Zebrafish as a model to determine the acute toxicity of these contaminated sediments. Zebrafish were exposed to sediments containing approximately 13 to 13,450 mg/kg Pb for 5 days (8-120 hr post-fertilization). The toxic responses to sediments were non-monotonic. Only exposure to sediments containing "mid-range" concentrations of Pb (4580 mg/kg) induced mild skeletal malformations and a sluggish C-start response indicating that Pb was marginally bioavailable. Expression of δ-aminolevulinic acid dehydratase (ALA-D) also indicated the potential for uptake of Pb from sediments. Our findings suggest that Pb within the La Crosse River Marsh sediments is not readily bioavailable to Zebrafish, and while this metal poses a minimal acute toxicological risk, toxicity due to chronic exposure of low concentrations of Pb is possible. Further, our data demonstrated that induction of ALA-D gene expression in Zebrafish embryos shows promise as an alternative to ALA-D enzyme activity as a biomarker for acute Pb exposure under lab conditions.


Assuntos
Osso e Ossos/anormalidades , Chumbo/toxicidade , Nitratos/toxicidade , Sintase do Porfobilinogênio/genética , Reflexo de Sobressalto/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia , Animais , Biomarcadores/metabolismo , Osso e Ossos/efeitos dos fármacos , Relação Dose-Resposta a Droga , Monitoramento Ambiental , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Sedimentos Geológicos/análise , Sintase do Porfobilinogênio/metabolismo , Testes de Toxicidade Aguda , Áreas Alagadas , Peixe-Zebra/anatomia & histologia , Peixe-Zebra/metabolismo
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