Cornell University

About: Cornell University is a education organization based out in Ithaca, New York, United States. It is known for research contribution in the topics: Population & Gene. The organization has 102246 authors who have published 235546 publications receiving 12283673 citations. The organization is also known as: Cornell & CUI.

Regulation of NMDA receptor trafficking by amyloid-beta.

Abstract: Amyloid-beta peptide is elevated in the brains of patients with Alzheimer disease and is believed to be causative in the disease process. Amyloid-beta reduces glutamatergic transmission and inhibits synaptic plasticity, although the underlying mechanisms are unknown. We found that application of amyloid-beta promoted endocytosis of NMDA receptors in cortical neurons. In addition, neurons from a genetic mouse model of Alzheimer disease expressed reduced amounts of surface NMDA receptors. Reducing amyloid-beta by treating neurons with a gamma-secretase inhibitor restored surface expression of NMDA receptors. Consistent with these data, amyloid-beta application produced a rapid and persistent depression of NMDA-evoked currents in cortical neurons. Amyloid-beta-dependent endocytosis of NMDA receptors required the alpha-7 nicotinic receptor, protein phosphatase 2B (PP2B) and the tyrosine phosphatase STEP. Dephosphorylation of the NMDA receptor subunit NR2B at Tyr1472 correlated with receptor endocytosis. These data indicate a new mechanism by which amyloid-beta can cause synaptic dysfunction and contribute to Alzheimer disease pathology.

PINK1-dependent recruitment of Parkin to mitochondria in mitophagy

Abstract: Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and PARK2/Parkin mutations cause autosomal recessive forms of Parkinson's disease. Upon a loss of mitochondrial membrane potential (DeltaPsi(m)) in human cells, cytosolic Parkin has been reported to be recruited to mitochondria, which is followed by a stimulation of mitochondrial autophagy. Here, we show that the relocation of Parkin to mitochondria induced by a collapse of DeltaPsi(m) relies on PINK1 expression and that overexpression of WT but not of mutated PINK1 causes Parkin translocation to mitochondria, even in cells with normal DeltaPsi(m). We also show that once at the mitochondria, Parkin is in close proximity to PINK1, but we find no evidence that Parkin catalyzes PINK1 ubiquitination or that PINK1 phosphorylates Parkin. However, co-overexpression of Parkin and PINK1 collapses the normal tubular mitochondrial network into mitochondrial aggregates and/or large perinuclear clusters, many of which are surrounded by autophagic vacuoles. Our results suggest that Parkin, together with PINK1, modulates mitochondrial trafficking, especially to the perinuclear region, a subcellular area associated with autophagy. Thus by impairing this process, mutations in either Parkin or PINK1 may alter mitochondrial turnover which, in turn, may cause the accumulation of defective mitochondria and, ultimately, neurodegeneration in Parkinson's disease.

Authoritative sources in a hyperlinked environment

Abstract: The network structure of a hyperlinked environment can be a rich source of information about the content of the environment, provided we have eective means for understanding it. We develop a set of algorithmic tools for extracting information from the link structures of such environments, and report on experiments that demonstrate their eectiveness in a variety of contexts on the World Wide Web. The central issue we address within our framework is the distillation of broad search topics, through the discovery of \authoritative" information sources on such topics. We propose and test an algorithmic formulation of the notion of authority, based on the relationship between a set of relevant authoritative pages and the set of \hub pages" that join them together in the link structure. Our formulation has connections to the eigenvectors of certain matrices associated with the link graph; these connections in turn motivate additional heuristics for link-based analysis.

Map-based cloning of a protein kinase gene conferring disease resistance in tomato

Abstract: The Pto gene in tomato confers resistance to races of Pseudomonas syringae pv. tomato that carry the avirulence gene avrPto. A yeast artificial chromosome clone that spans the Pto region was identified and used to probe a leaf complementary DNA (cDNA) library. A cDNA clone was isolated that represents a gene family, at least six members of which genetically cosegregate with Pto. When susceptible tomato plants were transformed with a cDNA from this family, they were resistant to the pathogen. Analysis of the amino acid sequence revealed similarity to serine-threonine protein kinases, suggesting a role for Pto in a signal transduction pathway.

DIFFUSION IN ORGANIZATIONS AND SOCIAL MOVEMENTS: From Hybrid Corn to Poison Pills

Abstract: There has been rapid growth in the study of diffusion across organizations and social movements in recent years, fueled by interest in institutional arguments and in network and dynamic analysis. This research develops a sociologically grounded account of change emphasizing the channels along which practices flow. Our review focuses on characteristic lines of argument, emphasizing the structural and cultural logic of diffusion processes. We argue for closer theoretical attention to why practices diffuse at different rates and via different pathways in different settings. Three strategies for further development are proposed: broader comparative research designs, closer inspection of the content of social relations between collective actors, and more attention to diffusion industries run by the media and communities of experts.