Institution
University of Arizona
Education•Tucson, Arizona, United States•
About: University of Arizona is a education organization based out in Tucson, Arizona, United States. It is known for research contribution in the topics: Population & Galaxy. The organization has 63805 authors who have published 155998 publications receiving 6854915 citations. The organization is also known as: UA & U of A.
Topics: Population, Galaxy, Star formation, Redshift, Planet
Papers published on a yearly basis
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TL;DR: Major advances in understanding of age-related changes in the medial temporal lobe and prefrontal cortex are discussed and how these changes in functional plasticity contribute to behavioural impairments in the absence of significant pathology.
Abstract: The mechanisms involved in plasticity in the nervous system are thought to support cognition, and some of these processes are affected during normal ageing. Notably, cognitive functions that rely on the medial temporal lobe and prefrontal cortex, such as learning, memory and executive function, show considerable age-related decline. It is therefore not surprising that several neural mechanisms in these brain areas also seem to be particularly vulnerable during the ageing process. In this review, we discuss major advances in our understanding of age-related changes in the medial temporal lobe and prefrontal cortex and how these changes in functional plasticity contribute to behavioural impairments in the absence of significant pathology.
1,358 citations
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TL;DR: The scope of this review will be limited to highlighting the actions of 1,25(OH)2D3 mediated by nuclear VDR and discussing new developments in the structure/function analysis of the receptor, including the phenotype of VDR knockout mice and the biochemical classification of patients with point mutations in the receptor.
Abstract: IN THE DECADE SINCE THE VITAMIN D RECEPTOR (VDR) was cloned and recognized as a member of the superfamily of nuclear receptors that regulate gene expression in a ligand-dependent manner, the central role of VDR in the biology of vitamin D action has been illuminated and is being defined at the molecular level. Following renal production as the hormonal metabolite of vitamin D, 1a,25-dihydroxyvitamin D3 (1,25(OH)2D3) functions as the ligand for VDR, with the hormone–receptor complex inducing calcemic and phosphatemic effects that result in normal bone mineralization and remodeling. VDR not only mediates the action of 1,25(OH)2D3 in calcium/phosphate translocating tissues, primarily intestine, but also elicits a myriad of apparent bioactivities in other major cell systems in the organism, including immune, neural, epithelial, and endocrine. The scope of this review will be limited to highlighting the actions of 1,25(OH)2D3 mediated by nuclear VDR and discussing new developments in the structure/function analysis of the receptor, including the phenotype of VDR knockout mice and the biochemical classification of patients with point mutations in the receptor. These new advances, along with other recent research, will be interpreted to update our understanding of the molecular role of VDR, ranging from characterization of its natural gene and clinically significant polymorphisms, through its DNA contact sites and protein partners, to novel ligand analogs that hold the promise of influencing VDR conformation in a therapeutically beneficial fashion. VDR BIOLOGY
1,358 citations
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James Hutton Institute1, University of Adelaide2, University of California, Riverside3, Iowa State University4, Leibniz Association5, University of Tsukuba6, Okayama University7, University of Helsinki8, University of Haifa9, Institut national de la recherche agronomique10, National Institutes of Health11, University of Turin12, University of Udine13, University of Arizona14, Kansas State University15, University of Dundee16
TL;DR: An integrated and ordered physical, genetic and functional sequence resource that describes the barley gene-space in a structured whole-genome context and suggests that post-transcriptional processing forms an important regulatory layer.
Abstract: Barley (Hordeum vulgare L.) is among the world's earliest domesticated and most important crop plants. It is diploid with a large haploid genome of 5.1 gigabases (Gb). Here we present an integrated and ordered physical, genetic and functional sequence resource that describes the barley gene-space in a structured whole-genome context. We developed a physical map of 4.98 Gb, with more than 3.90 Gb anchored to a high-resolution genetic map. Projecting a deep whole-genome shotgun assembly, complementary DNA and deep RNA sequence data onto this framework supports 79,379 transcript clusters, including 26,159 'high-confidence' genes with homology support from other plant genomes. Abundant alternative splicing, premature termination codons and novel transcriptionally active regions suggest that post-transcriptional processing forms an important regulatory layer. Survey sequences from diverse accessions reveal a landscape of extensive single-nucleotide variation. Our data provide a platform for both genome-assisted research and enabling contemporary crop improvement.
1,347 citations
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National Institutes of Health1, City of Hope National Medical Center2, University of Würzburg3, Bosch4, University of British Columbia5, University of Arizona6, University of Barcelona7, University of Oslo8, University of Rochester9, Oregon Health & Science University10, Cleveland Clinic11, University of Nebraska Medical Center12
TL;DR: The dependence of ABC DLBCLs on MYD88, an adaptor protein that mediates toll and interleukin (IL)-1 receptor signalling, is described and the development of inhibitors of IRAK4 kinase and other components of this pathway for the treatment of tumours bearing oncogenic MyD88 mutations are supported.
Abstract: The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) remains the least curable form of this malignancy despite recent advances in therapy. Constitutive nuclear factor (NF)-κB and JAK kinase signalling promotes malignant cell survival in these lymphomas, but the genetic basis for this signalling is incompletely understood. Here we describe the dependence of ABC DLBCLs on MYD88, an adaptor protein that mediates toll and interleukin (IL)-1 receptor signalling, and the discovery of highly recurrent oncogenic mutations affecting MYD88 in ABC DLBCL tumours. RNA interference screening revealed that MYD88 and the associated kinases IRAK1 and IRAK4 are essential for ABC DLBCL survival. High-throughput RNA resequencing uncovered MYD88 mutations in ABC DLBCL lines. Notably, 29% of ABC DLBCL tumours harboured the same amino acid substitution, L265P, in the MYD88 Toll/IL-1 receptor (TIR) domain at an evolutionarily invariant residue in its hydrophobic core. This mutation was rare or absent in other DLBCL subtypes and Burkitt's lymphoma, but was observed in 9% of mucosa-associated lymphoid tissue lymphomas. At a lower frequency, additional mutations were observed in the MYD88 TIR domain, occurring in both the ABC and germinal centre B-cell-like (GCB) DLBCL subtypes. Survival of ABC DLBCL cells bearing the L265P mutation was sustained by the mutant but not the wild-type MYD88 isoform, demonstrating that L265P is a gain-of-function driver mutation. The L265P mutant promoted cell survival by spontaneously assembling a protein complex containing IRAK1 and IRAK4, leading to IRAK4 kinase activity, IRAK1 phosphorylation, NF-κB signalling, JAK kinase activation of STAT3, and secretion of IL-6, IL-10 and interferon-β. Hence, the MYD88 signalling pathway is integral to the pathogenesis of ABC DLBCL, supporting the development of inhibitors of IRAK4 kinase and other components of this pathway for the treatment of tumours bearing oncogenic MYD88 mutations.
1,346 citations
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TL;DR: This paper reviewed and discussed the empirical literature on interorganizational networks at the network level of analysis, or what is sometimes referred to as "whole" networks, and offered a discussion concerning what future directions might be taken by researchers hoping to expand this important, but understudied, topic.
1,340 citations
Authors
Showing all 64388 results
Name | H-index | Papers | Citations |
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Simon D. M. White | 189 | 795 | 231645 |
Julie E. Buring | 186 | 950 | 132967 |
David H. Weinberg | 183 | 700 | 171424 |
Richard Peto | 183 | 683 | 231434 |
Xiaohui Fan | 183 | 878 | 168522 |
Dennis S. Charney | 179 | 802 | 122408 |
Daniel J. Eisenstein | 179 | 672 | 151720 |
David Haussler | 172 | 488 | 224960 |
Carlos S. Frenk | 165 | 799 | 140345 |
Jian-Kang Zhu | 161 | 550 | 105551 |
Tobin J. Marks | 159 | 1621 | 111604 |
Todd Adams | 154 | 1866 | 143110 |
Jane A. Cauley | 151 | 914 | 99933 |
Wei Zheng | 151 | 1929 | 120209 |
Daniel L. Schacter | 149 | 592 | 90148 |