Visualization of co-localization in Aß42-administered neuroblastoma cells reveals lysosome damage and autophagosome accumulation related to cell death.

Aß42 [amyloid-ß peptide-(1-42)] plays a central role in Alzheimer's disease and is known to have a detrimental effect on neuronal cell function and survival when assembled into an oligomeric form. In the present study we show that administration of freshly prepared Aß42 oligomers to a neuroblastoma (SH-SY5Y) cell line results in a reduction in survival, and that Aß42 enters the cells prior to cell death. Immunoconfocal and immunogold electron microscopy reveal the path of the Aß42 with time through the endosomal system and shows that it accumulates in lysosomes. A 24 h incubation with Aß results in cells that have damaged lysosomes showing signs of enzyme leakage, accumulate autophagic vacuoles and exhibit severely disrupted nuclei. Endogenous Aß is evident in the cells and the results of the present study suggest that the addition of Aß oligomers disrupts a crucial balance in Aß conformation and concentration inside neuronal cells, resulting in catastrophic effects on cellular function and, ultimately, in cell death.

Access, Use, and Preferences for Technology-Based Perinatal and Breastfeeding Support Among Childbearing Women.

We surveyed 146 postpartum women who birthed at 34-37 6/7 weeks of gestation and intended to breastfeed about their use of and preferences regarding technology to obtain perinatal and breastfeeding support. Most participants owned smartphones and used technology during pregnancy to track pregnancy data, follow fetal development, address pregnancy concerns, and obtain breastfeeding information. Internet, e-mail, apps, and multiplatform resources were the most popular technologies used and preferred. Demographic differences existed in mobile technology access and preferences for different technologies. In terms of technology-based breastfeeding support, women wanted encouragement, anticipatory guidance, and information about milk production. A nuanced understanding of the technology childbearing women use and desire has the potential to impact clinical care and inform perinatal support interventions.

A central role for dityrosine crosslinking of Amyloid-ß in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is characterized by the deposition of insoluble amyloid plaques in the neuropil composed of highly stable, self-assembled Amyloid-beta (Aß) fibrils. Copper has been implicated to play a role in Alzheimer's disease. Dimers of Aß have been isolated from AD brain and have been shown to be neurotoxic. RESULTS: We have investigated the formation of dityrosine cross-links in Aß42 formed by covalent ortho-ortho coupling of two tyrosine residues under conditions of oxidative stress with elevated copper and shown that dityrosine can be formed in vitro in Aß oligomers and fibrils and that these links further stabilize the fibrils. Dityrosine crosslinking was present in internalized Aß in cell cultures treated with oligomeric Aß42 using a specific antibody for dityrosine by immunogold labeling transmission electron microscopy. Results also revealed the prevalence of dityrosine crosslinks in amyloid plaques in brain tissue and in cerebrospinal fluid from AD patients. CONCLUSIONS: Aß dimers may be stabilized by dityrosine crosslinking. These results indicate that dityrosine cross-links may play an important role in the pathogenesis of Alzheimer's disease and can be generated by reactive oxygen species catalyzed by Cu2+ ions. The observation of increased Aß and dityrosine in CSF from AD patients suggests that this could be used as a potential biomarker of oxidative stress in AD.