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1.
bioRxiv ; 2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37961417

RESUMO

In 2015, the largest recorded harmful algal bloom (HAB) occurred in the Northeast Pacific, causing nearly 100 million dollars in damages to fisheries and killing many protected marine mammals. Dominated by the toxic diatom Pseudo-nitzschia australis , this bloom produced high levels of the neurotoxin domoic acid (DA). Through molecular and transcriptional characterization of 52 near-weekly phytoplankton net-tow samples collected at a bloom hotspot in Monterey Bay, California, we identified active transcription of known DA biosynthesis ( dab ) genes from the three identified toxigenic species, including P. australis as the primary origin of toxicity. Elevated expression of silicon transporters ( sit1 ) during the bloom supports the previously hypothesized role of dissolved silica (Si) exhaustion in contributing to bloom physiology and toxicity. We find that co-expression of the dabA and sit1 genes serves as a robust predictor of DA one week in advance, potentially enabling the forecasting of DA-producing HABs. We additionally present evidence that low levels of iron could have co-limited the diatom population along with low Si. Iron limitation represents a previously unrecognized driver of both toxin production and ecological success of the low iron adapted Pseudo-nitzschia genus during the 2015 bloom, and increasing pervasiveness of iron limitation may fuel the escalating magnitude and frequency of toxic Pseudo-nitzschia blooms globally. Our results advance understanding of bloom physiology underlying toxin production, bloom prediction, and the impact of global change on toxic blooms. Significance: Pseudo-nitzschia diatoms form oceanic harmful algal blooms that threaten human health through production of the neurotoxin domoic acid (DA). DA biosynthetic gene expression is hypothesized to control DA production in the environment, yet what regulates expression of these genes is yet to be discovered. In this study, we uncovered expression of DA biosynthesis genes by multiple toxigenic Pseudo-nitzschia species during an economically impactful bloom along the North American West Coast, and identified genes that predict DA in advance of its production. We discovered that iron and silica co-limitation restrained the bloom and likely promoted toxin production. This work suggests that increasing iron limitation due to global change may play a previously unrecognized role in driving bloom frequency and toxicity.

3.
ISME J ; 17(12): 2147-2159, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37857709

RESUMO

Advances in bioanalytical technologies are constantly expanding our insights into complex ecosystems. Here, we highlight strategies and applications that make use of non-targeted metabolomics methods in aquatic chemical ecology research and discuss opportunities and remaining challenges of mass spectrometry-based methods to broaden our understanding of environmental systems.


Assuntos
Metabolômica , Microbiota , Espectrometria de Massas
5.
Neuroreport ; 19(13): 1271-6, 2008 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-18695506

RESUMO

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by oligodendrocytic cytoplasmic inclusions containing abnormally aggregated alpha-synuclein. This aggregation has been linked to the neurodegeneration observed in MSA. Current MSA treatments are aimed at controlling symptoms rather than tackling the underlying cause of neurodegeneration. This study investigates the ability of the antibiotic rifampicin to reduce alpha-synuclein aggregation and the associated neurodegeneration in a transgenic mouse model of MSA. We report a reduction in monomeric and oligomeric alpha-synuclein and a reduction in phosphorylated alpha-synuclein (S129) upon rifampicin treatment. This reduction in alpha-synuclein aggregation was accompanied by reduced neurodegeneration. On the basis of its anti-aggregenic properties, we conclude that rifampicin may have therapeutic potential for MSA.


Assuntos
Atrofia de Múltiplos Sistemas/tratamento farmacológico , Oligodendroglia/efeitos dos fármacos , Rifampina/uso terapêutico , alfa-Sinucleína/metabolismo , Animais , Antibióticos Antituberculose/administração & dosagem , Antibióticos Antituberculose/uso terapêutico , Western Blotting , Modelos Animais de Doenças , Humanos , Imuno-Histoquímica , Corpos de Inclusão/efeitos dos fármacos , Corpos de Inclusão/metabolismo , Injeções Intraperitoneais , Camundongos , Camundongos Transgênicos , Microscopia Confocal , Atrofia de Múltiplos Sistemas/genética , Atrofia de Múltiplos Sistemas/metabolismo , Degeneração Neural/genética , Degeneração Neural/metabolismo , Degeneração Neural/prevenção & controle , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Rifampina/administração & dosagem , Sinucleínas/metabolismo , alfa-Sinucleína/genética , beta-Sinucleína/metabolismo
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