University of Kentucky

About: University of Kentucky is a education organization based out in Lexington, Kentucky, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 43933 authors who have published 92195 publications receiving 3256087 citations. The organization is also known as: UK.

DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration

Abstract: Geographic atrophy (GA), an untreatable advanced form of age-related macular degeneration, results from retinal pigmented epithelium (RPE) cell degeneration. Here we show that the microRNA (miRNA)-processing enzyme DICER1 is reduced in the RPE of humans with GA, and that conditional ablation of Dicer1, but not seven other miRNA-processing enzymes, induces RPE degeneration in mice. DICER1 knockdown induces accumulation of Alu RNA in human RPE cells and Alu-like B1 and B2 RNAs in mouse RPE. Alu RNA is increased in the RPE of humans with GA, and this pathogenic RNA induces human RPE cytotoxicity and RPE degeneration in mice. Antisense oligonucleotides targeting Alu/B1/B2 RNAs prevent DICER1 depletion-induced RPE degeneration despite global miRNA downregulation. DICER1 degrades Alu RNA, and this digested Alu RNA cannot induce RPE degeneration in mice. These findings reveal a miRNA-independent cell survival function for DICER1 involving retrotransposon transcript degradation, show that Alu RNA can directly cause human pathology, and identify new targets for a major cause of blindness.

Organizational Social Network Research: Core Ideas and Key Debates

Abstract: Given the growing popularity of the social network perspective across diverse organizational subject areas, this review examines the coherence of the research tradition (in terms of leading ideas from which the diversity of new research derives) and appraises current directions and controversies. The leading ideas at the heart of the organizational social network research program include: an emphasis on relations between actors; the embeddedness of exchange in social relations; the assumption that dyadic relationships do not occur in isolation, but rather form a complex structural pattern of connectivity and cleavage beyond the dyad; and the belief that social network connections matter in terms of outcomes to both actors and groups of actors across a range of indicators. These leading ideas are articulated in current debates that center on issues of actor characteristics, agency, cognition, cooperation versus competition, and boundary specification. To complement the review, we provide a glossar...

Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models.

Abstract: The goal of this review is to discuss how behavioral tests in mice relate to the pathological and neuropsychological features seen in human Alzheimer’s disease (AD), and present a comprehensive analysis of the temporal progression of behavioral impairments in commonly used AD mouse models that contain mutations in amyloid precursor protein. We provide a brief overview of neuropathological changes seen in AD brain, and some of the clinical neuropsychological assessments used to measure cognitive deficits. This is followed by a critical assessment of behavioral tasks that are used in AD mice to model the cognitive changes seen in humans. Behavioral tests discussed include spatial memory tests (Morris water maze, radial arm water maze, Barnes maze), associative learning tasks (passive avoidance, fear conditioning), alternation tasks (Y-Maze/T-Maze), recognition memory tasks (Novel Object Recognition), attentional tasks (3 & 5 choice serial reaction time), set-shifting tasks, and reversal learning tasks. We discuss the strengths and weaknesses of each of these tests, and how they may correlate with clinical assessments in humans. Finally, the temporal progression of both cognitive and non-cognitive deficits in ten AD mouse models (PDAPP, TG2576, APP23, TgCRND8, J20, APP/PS1, TG2576 + PS1(M146L), APP/PS1 KI, 5xFAD and 3xTg-AD) are discussed. Mouse models of AD and the behavioral tasks used in conjunction with those models are immensely important in contributing to our knowledge of disease progression, and are useful tools to study AD pathophysiology and the resulting cognitive deficits. However, investigators need to be aware of the potential weaknesses of the available preclinical models in terms of their ability to model cognitive changes observed in human AD. It is our hope that this review will assist investigators in selecting an appropriate mouse model, and accompanying behavioral paradigms to investigate different aspects of AD pathology and disease progression.

Outcomes of patients with differentiated thyroid carcinoma following initial therapy.

Abstract: This analysis was performed to determine the effect of initial therapy on the outcomes of thyroid cancer patients. The study setting was a prospectively followed multi-institutional registry. Patients were stratified as low risk (stages I and II) or high risk (stages III and IV). Treatments employed included near-total thyroidectomy, administration of radioactive iodine, and thyroid hormone suppression therapy. Outcome measures were overall survival, disease-specific survival, and disease-free survival. Near-total thyroidectomy, radioactive iodine, and aggressive thyroid hormone suppression therapy were each independently associated with longer overall survival in high-risk patients. Near-total thyroidectomy followed by radioactive iodine therapy, and moderate thyroid hormone suppression therapy, both predicted improved overall survival in stage II patients. No treatment modality, including lack of radioactive iodine, was associated with altered survival in stage I patients. Based on our overall survival data, we confirm that near-total thyroidectomy is indicated in high-risk patients. We also conclude that radioactive iodine therapy is beneficial for stage II, III, and IV patients. Importantly, we show for the first time that superior outcomes are associated with aggressive thyroid hormone suppression therapy in high-risk patients, but are achieved with modest suppression in stage II patients. We were unable to show any impact, positive or negative, of specific therapies in stage I patients.

Metatriangulation: Building Theory from Multiple Paradigms

Abstract: Multiparadigm approaches aid exploration of particularly complex and paradoxical phenomena by helping theorists employ disparate theoretical perspectives. In this article we provide an extensive guide to multiparadigm exemplars and then link their varied approaches within a metatriangulation theory-building strategy. Our process addresses the challenges theorists face as they select a research topic, collect and analyze data, theorize, and evaluate resulting theory using multiple paradigms. A concluding discussion of the advantages, limitations, and potential applications of metatriangulation positions it within the wider realm of organization theory.