Patients with AD had less density of retinal microvascular networks than controls. Our findings suggest the presence of retinal microvascular dysfunction in AD.

No abstract

Keratins that are overexpressed selectively in human carcinomas may offer diagnostic and prognostic utility. In this study, we show that high expression of keratin-17 (K17) predicts poor outcome in patients with cervical cancer, at early or late stages of disease, surpassing in accuracy either tumor staging or loss of p27 KIP1 as a negative prognostic marker in this setting. We investigated the mechanistic basis for the biologic impact of K17 through loss-and gain-of-function experiments in human cervix, breast, and pancreatic cancer cells. Specifically, we determined that K17 functions as an oncoprotein by regulating the subcellular localization and degradation of p27 KIP1 . We found that K17 was released from intermediate filaments and translocated into the nucleus via a nuclear localization signal (NLS), specific among keratins, where it bound p27 KIP1 during G 1 phase of the cell cycle. p27 KIP1 lacks a nuclear export signal (NES) and requires an adaptor for CRM1 binding for nuclear export. In K17, we defined and validated a leucine-rich NES that mediated CRM1 binding for export. Cervical cancer cells expressing K17 mutations in its NLS or NES signals exhibited an increase in levels of nuclear p27 KIP1 , whereas cells expressing wild-type K17 exhibited a depletion in total endogenous p27 KIP1 . In clinical specimens of cervical cancer, we confirmed that the expressions of K17 and p27 KIP1 were inversely correlated, both across tumors and within individual tumors. Overall, our findings establish that K17 functions specially among keratins as an oncoprotein by controlling the ability of p27 KIP1 to influence cervical cancer pathogenesis. Cancer Res; 75(17); 3650-62. Ó2015 AACR.

Focal thinning of the GCIPL was visualized and quantified by detailed partitions in AD and MCI, which provides specific information about neurodegeneration in MCI and AD.

Researchers evaluated results using a disability studies framework of empowerment which recognizes the role of environment, gender, race/ethnicity, and social status in the experience of disability. Participants reported increased independence, community access, and participation. They took action in multiple arenas with changes observed and reported in areas of intrapersonal, interpersonal, and behavioral functioning that indicated greater personal empowerment.