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Institution

Northwestern University

EducationEvanston, Illinois, United States
About: Northwestern University is a education organization based out in Evanston, Illinois, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 75430 authors who have published 188857 publications receiving 9463252 citations. The organization is also known as: Northwestern & NU.


Papers
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Journal ArticleDOI
TL;DR: This article argues for design research as form of educational research because (a) design offers opportunities to learn unique lessons, (b) design research yields practical lessons that can be directly applied, and (c) designResearch engages researchers in the direct improvement of educational practice.
Abstract: Educational researchers are increasingly using design as a means of advancing their understanding Historically design in educational research has served as a way to implement theories for testing The emerging design research paradigm treats design as a strategy for developing and refining theories In this article, I discuss the lessons that can be learned from design Starting from a model that characterizes designs in terms of problem analyses, design solutions, and design processes, I describe 3 types of theories that can be developed through design research: domain theories, design frameworks, and design methodologies I present examples from a design research program investigating software supports for reflective inquiry I argue for design research as form of educational research because (a) design offers opportunities to learn unique lessons, (b) design research yields practical lessons that can be directly applied, and (c) design research engages researchers in the direct improvement of educatio

916 citations

Journal ArticleDOI
TL;DR: The hypothesis that targeting and functional disruption of particular synapses by Aβ oligomers may provide a molecular basis for the specific loss of memory function in early Alzheimer's disease is suggested.
Abstract: The cognitive hallmark of early Alzheimer's disease (AD) is an extraordinary inability to form new memories. For many years, this dementia was attributed to nerve-cell death induced by deposits of fibrillar amyloid β (Aβ). A newer hypothesis has emerged, however, in which early memory loss is considered a synapse failure caused by soluble Aβ oligomers. Such oligomers rapidly block long-term potentiation, a classic experimental paradigm for synaptic plasticity, and they are strikingly elevated in AD brain tissue and transgenic-mouse AD models. The current work characterizes the manner in which Aβ oligomers attack neurons. Antibodies raised against synthetic oligomers applied to AD brain sections were found to give diffuse stain around neuronal cell bodies, suggestive of a dendritic pattern, whereas soluble brain extracts showed robust AD-dependent reactivity in dot immunoblots. Antigens in unfractionated AD extracts attached with specificity to cultured rat hippocampal neurons, binding within dendritic arbors at discrete puncta. Crude fractionation showed ligand size to be between 10 and 100 kDa. Synthetic Aβ oligomers of the same size gave identical punctate binding, which was highly selective for particular neurons. Image analysis by confocal double-label immunofluorescence established that >90% of the punctate oligomer binding sites colocalized with the synaptic marker PSD-95 (postsynaptic density protein 95). Synaptic binding was accompanied by ectopic induction of Arc, a synaptic immediate-early gene, the overexpression of which has been linked to dysfunctional learning. Results suggest the hypothesis that targeting and functional disruption of particular synapses by Aβ oligomers may provide a molecular basis for the specific loss of memory function in early AD.

915 citations

Journal ArticleDOI
TL;DR: An up-to-date overview of the functions of nuclear lamins is provided, emphasizing their roles in epigenetics, chromatin organization, DNA replication, transcription, and DNA repair.
Abstract: Over the past few years it has become evident that the intermediate filament proteins, the types A and B nuclear lamins, not only provide a structural framework for the nucleus, but are also essential for many aspects of normal nuclear function. Insights into lamin-related functions have been derived from studies of the remarkably large number of disease-causing mutations in the human lamin A gene. This review provides an up-to-date overview of the functions of nuclear lamins, emphasizing their roles in epigenetics, chromatin organization, DNA replication, transcription, and DNA repair. In addition, we discuss recent evidence supporting the importance of lamins in viral infections.

915 citations

Journal ArticleDOI
TL;DR: This work has shown how binding specificity is determined, how ubiquitin binding is regulated, and the function of UBDs in the context of full-length proteins is controlled by studying their mechanism of action.
Abstract: Ubiquitin-binding domains (UBDs) are a collection of modular protein domains that non-covalently bind to ubiquitin. These recently discovered motifs interpret and transmit information conferred by protein ubiquitylation to control various cellular events. Detailed molecular structures are known for a number of UBDs, but to understand their mechanism of action, we also need to know how binding specificity is determined, how ubiquitin binding is regulated, and the function of UBDs in the context of full-length proteins. Such knowledge will be key to our understanding of how ubiquitin regulates cellular proteins and processes.

915 citations

Journal ArticleDOI
TL;DR: The objective is to review the Ah receptor's role in regulation of xenobiotic metabolism and use this model as a framework for understanding the less well-characterized mechanism of dioxin toxicity.
Abstract: The aryl hydrocarbon (Ah) receptor has occupied the attention of toxicologists for over two decades. Interest arose from the early observation that this soluble protein played key roles in the adaptive metabolic response to polycyclic aromatic hydrocarbons and in the toxic mechanism of halogenated dioxins and dibenzofurans. More recent investigations have provided a fairly clear picture of the primary adaptive signaling pathway, from agonist binding to the transcriptional activation of genes involved in the metabolism of xenobiotics. Structure-activity studies have provided an understanding of the pharmacology of this receptor; recombinant DNA approaches have identified the enhancer sequences through which this factor regulates gene expression; and functional analysis of cloned cDNAs has allowed the characterization of the major signaling components in this pathway. Our objective is to review the Ah receptor's role in regulation of xenobiotic metabolism and use this model as a framework for understanding the less well-characterized mechanism of dioxin toxicity. In addition, it is hoped that this information can serve as a model for future efforts to understand an emerging superfamily of related signaling pathways that control biological responses to an array of environmental stimuli.

914 citations


Authors

Showing all 76189 results

NameH-indexPapersCitations
George M. Whitesides2401739269833
Ralph B. D'Agostino2261287229636
Daniel Levy212933194778
David Miller2032573204840
Ronald M. Evans199708166722
Michael Marmot1931147170338
Robert C. Nichol187851162994
Scott M. Grundy187841231821
Stuart H. Orkin186715112182
Michael A. Strauss1851688208506
Ralph Weissleder1841160142508
Patrick O. Brown183755200985
Aaron R. Folsom1811118134044
Valentin Fuster1791462185164
Ronald C. Petersen1781091153067
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023275
20221,183
202110,513
202010,260
20199,331
20188,301