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1.
ACS Chem Neurosci ; 14(22): 4026-4038, 2023 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-37906715

RESUMEN

Many neurodegenerative diseases involve amyloidogenic proteins forming surface-bound aggregates on anionic membranes, and the peptide amyloid ß (Aß) in Alzheimer's disease is one prominent example of this. Curcumin is a small polyphenolic molecule that provides an interesting opportunity to understand the fundamental mechanisms of membrane-mediated aggregation because it embeds into membranes to alter their structure while also altering Aß aggregation in an aqueous environment. The purpose of this work was to understand interactions among curcumin, ß-sheet-rich Aß fibrillar oligomers (FO), and a model anionic membrane. From a combination of liquid surface X-ray scattering experiments and molecular dynamics simulations, we found that curcumin embedded into an anionic 1,2-dimyristoyl-sn-glycero-3-phosphorylglycerol (DMPG) membrane to rest between the lipid headgroups and the tails, causing disorder and membrane thinning. FO accumulation on the membrane was reduced by ∼66% in the presence of curcumin, likely influenced by membrane thinning. Simulation results suggested curcumin clusters near exposed phenylalanine residues on a membrane-embedded FO structure. Altogether, curcumin inhibited FO interactions with a DMPG membrane, likely through a combination of altered membrane structure and interactions with the FO surface. This work elucidates the mechanism of curcumin as a small molecule that inhibits amyloidogenesis through a combination of both membrane and protein interactions.


Asunto(s)
Enfermedad de Alzheimer , Curcumina , Humanos , Péptidos beta-Amiloides/metabolismo , Curcumina/farmacología , Curcumina/química , Enfermedad de Alzheimer/metabolismo , Simulación de Dinámica Molecular , Amiloide/metabolismo
2.
Water Res ; 184: 116211, 2020 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-32721766

RESUMEN

The Edwards Aquifer serves as a primary source of drinking water to more than 2 million people in south-central Texas, and as a karst aquifer, is vulnerable to human and animal fecal contamination which poses a serious risk to human and environmental health. A one-year study (Jan 2018 - Feb 2019) was conducted to determine the primary sources of fecal pollution along the Balcones and Leon Creek within the Edwards Aquifer recharge and contributing zones using general (E. coli, enterococci, and universal Bacteriodales) and host-associated (human-, dog-, cow- and chicken/duck-associated Bacteriodales) microbial source tracking (MST) assays. Additionally, sites were classified based on surrounding land use as a potential source predictor and marker levels were correlated with rain events and water quality parameters. Levels for the three general indicators were highest and exhibited similar trends across the sampling sites, suggesting that the sole use of these markers is not sufficient for specific fecal source identification. Among the host-associated markers, highest concentrations were observed for the dog marker (BacCan) in the Leon Creek area and the cow marker (BacCow) in the Balcones Creek area. Additionally, Chicken/Duck-Bac, BacCan and BacCow all exhibited higher concentrations during the spring season and the end of fall/early winter. Relatively lower concentrations were observed for the human-associated markers (HF183 and BacHum), however, levels were higher in the Leon Creek area and highest following rainfall events. Additionally, relatively higher levels in HF183 and BacHum were observed at sites having greater human population and septic tank density and may be attributed to leaks or breaks in these infrastructures. This study is the first to examine and compare fecal contamination at rural and urban areas in the recharge and contributing zones of the Edwards Aquifer using a molecular MST approach targeting Bacteroidales 16S rRNA gene-based assays. The Bacteroidales marker assays, when combined with land use and weather information, can allow for a better understanding of the sources and fluxes of fecal contamination, which can help devise effective mitigation measures to protect water quality.


Asunto(s)
Escherichia coli , Agua Subterránea , Animales , Bovinos , Perros , Monitoreo del Ambiente , Heces , Femenino , Humanos , ARN Ribosómico 16S , Texas , Microbiología del Agua , Contaminación del Agua/análisis
3.
Fam Community Health ; 28(3): 239-52, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15958882

RESUMEN

Orchard workers are exposed to an array of occupational health and safety hazards that result in injury, illness, and, in some cases, death. The purpose of this qualitative study was to identify and explore factors that contribute to occupational risks related to orchard work. Twenty-five Hispanic orchard workers were interviewed. They reported that the most common type of accident was falls, usually from a ladder; and the most common injuries were strains and sprains. Three broad categories of factors that contributed to the occurrence of such injuries were Knowledge, Attitudes and Behaviors; Work-Related Factors; and Factors External to Work.


Asunto(s)
Accidentes de Trabajo/prevención & control , Agricultura , Heridas y Lesiones/prevención & control , Prevención de Accidentes/legislación & jurisprudencia , Accidentes de Trabajo/estadística & datos numéricos , Adulto , Anciano , Ambiente , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Administración de Personal , Factores de Riesgo , Washingtón/epidemiología , Heridas y Lesiones/epidemiología
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