Institution
University of Colorado Denver
Education•Denver, Colorado, United States•
About: University of Colorado Denver is a education organization based out in Denver, Colorado, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 27444 authors who have published 57213 publications receiving 2539937 citations. The organization is also known as: CU Denver & UCD.
Topics: Population, Poison control, Health care, Diabetes mellitus, Cancer
Papers published on a yearly basis
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TL;DR: It is shown that viral infection of adult hippocampal neurons induces complement-mediated elimination of presynaptic terminals in a murine WNV neuroinvasive disease model, which provides a new murine model of WNV-induced spatial memory impairment, and identifies a potential mechanism underlying neurocognitive impairment in patients recovering from WNV Neuroinvasive Disease.
Abstract: Over 50% of patients who survive neuroinvasive infection with West Nile virus (WNV) exhibit chronic cognitive sequelae. Although thousands of cases of WNV-mediated memory dysfunction accrue annually, the mechanisms responsible for these impairments are unknown. The classical complement cascade, a key component of innate immune pathogen defence, mediates synaptic pruning by microglia during early postnatal development. Here we show that viral infection of adult hippocampal neurons induces complement-mediated elimination of presynaptic terminals in a murine WNV neuroinvasive disease model. Inoculation of WNV-NS5-E218A, a WNV with a mutant NS5(E218A) protein leads to survival rates and cognitive dysfunction that mirror human WNV neuroinvasive disease. WNV-NS5-E218A-recovered mice (recovery defined as survival after acute infection) display impaired spatial learning and persistence of phagocytic microglia without loss of hippocampal neurons or volume. Hippocampi from WNV-NS5-E218A-recovered mice with poor spatial learning show increased expression of genes that drive synaptic remodelling by microglia via complement. C1QA was upregulated and localized to microglia, infected neurons and presynaptic terminals during WNV neuroinvasive disease. Murine and human WNV neuroinvasive disease post-mortem samples exhibit loss of hippocampal CA3 presynaptic terminals, and murine studies revealed microglial engulfment of presynaptic terminals during acute infection and after recovery. Mice with fewer microglia (Il34(-/-) mice with a deficiency in IL-34 production) or deficiency in complement C3 or C3a receptor were protected from WNV-induced synaptic terminal loss. Our study provides a new murine model of WNV-induced spatial memory impairment, and identifies a potential mechanism underlying neurocognitive impairment in patients recovering from WNV neuroinvasive disease.
471 citations
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Manchester Academic Health Science Centre1, Boston Children's Hospital2, Harvard University3, University of Pavia4, Necker-Enfants Malades Hospital5, University of Liverpool6, University of Florence7, University of Colorado Denver8, NHS Ayrshire and Arran9, Children's Hospital at Westmead10, Royal Hospital for Sick Children11, Katholieke Universiteit Leuven12, University of Burgundy13, University of Brescia14, French Institute of Health and Medical Research15, McMaster Children's Hospital16, Paris Descartes University17, Leeds Teaching Hospitals NHS Trust18, University of São Paulo19, University of Glasgow20, University of Milan21, Great Ormond Street Hospital22, Pierre-and-Marie-Curie University23, University of Cape Town24, Southern General Hospital25, Children's National Medical Center26
TL;DR: It is demonstrated that aberrant sensing of nucleic acids can cause immune upregulation and heterozygous mutations in the cytosolic double-stranded RNA receptor gene IFIH1 (also called MDA5) cause a spectrum of neuroimmunological features consistently associated with an enhanced interferon state.
Abstract: The type I interferon system is integral to human antiviral immunity. However, inappropriate stimulation or defective negative regulation of this system can lead to inflammatory disease. We sought to determine the molecular basis of genetically uncharacterized cases of the type I interferonopathy Aicardi-Goutieres syndrome and of other undefined neurological and immunological phenotypes also demonstrating an upregulated type I interferon response. We found that heterozygous mutations in the cytosolic double-stranded RNA receptor gene IFIH1 (also called MDA5) cause a spectrum of neuroimmunological features consistently associated with an enhanced interferon state. Cellular and biochemical assays indicate that these mutations confer gain of function such that mutant IFIH1 binds RNA more avidly, leading to increased baseline and ligand-induced interferon signaling. Our results demonstrate that aberrant sensing of nucleic acids can cause immune upregulation.
470 citations
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University of Michigan1, Harvard University2, University of Washington3, University of Colorado Denver4, University of Wisconsin-Madison5, St James's University Hospital6, University of California, San Francisco7, Georgetown University8, Cross Cancer Institute9, Wayne State University10, University of Southern California11, Carolinas Healthcare System12, Fred Hutchinson Cancer Research Center13, University of Texas Health Science Center at San Antonio14
TL;DR: In patients with metastatic hormone-sensitive prostate cancer, the confidence interval for survival exceeded the upper boundary for noninferiority, suggesting that the authors cannot rule out a 20% greater risk of death with intermittent therapy than with continuous therapy, but too few events occurred to rule out significant inferiority of intermittent therapy.
Abstract: Background Castration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving androgen-deprivation therapy. Replacing androgens before progression of the disease is hypothesized to prolong androgen dependence. Methods Men with newly diagnosed, metastatic, hormone-sensitive prostate cancer, a performance status of 0 to 2, and a prostate-specific antigen (PSA) level of 5 ng per milliliter or higher received a luteinizing hormone–releasing hormone analogue and an antiandrogen agent for 7 months. We then randomly assigned patients in whom the PSA level fell to 4 ng per milliliter or lower to continuous or intermittent androgen deprivation, with patients stratified according to prior or no prior hormonal therapy, performance status, and extent of disease (minimal or extensive). The coprimary objectives were to assess whether intermittent therapy was noninferior to continuous therapy with respect to survival, with a one-sided test with an upper boundary of the haza...
470 citations
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TL;DR: The use of moderated multiple regression (MMR) has become pervasive in numerous management specialties such as organizational behavior, human resources management, and strategy, to name a few as mentioned in this paper.
469 citations
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TL;DR: The science rationale for the targeting of the TRK oncogene family, which encodes the TRKA, TRKB, and TRKC receptor tyrosine kinases across multiple tumor types, is discussed here.
Abstract: The use of high-throughput next-generation sequencing techniques in multiple tumor types during the last few years has identified NTRK1 , 2 , and 3 gene rearrangements encoding novel oncogenic fusions in 19 different tumor types to date. These recent developments have led us to revisit an old oncogene, Trk (originally identified as OncD ), which encodes the TPM3 – NTRK1 gene fusion and was one of the first transforming chromosomal rearrangements identified 32 years ago. However, no drug has yet been approved by the FDA for cancers harboring this oncogene. This review will discuss the biology of the TRK family of receptors, their role in human cancer, the types of oncogenic alterations, and drugs that are currently in development for this family of oncogene targets.
Significance: Precision oncology approaches have accelerated recently due to advancements in our ability to detect oncogenic mutations in tumor samples. Oncogenic alterations, most commonly gene fusions, have now been detected for the genes encoding the TRKA, TRKB, and TRKC receptor tyrosine kinases across multiple tumor types. The scientific rationale for the targeting of the TRK oncogene family will be discussed here. Cancer Discov; 5(1); 25–34. ©2014 AACR.
469 citations
Authors
Showing all 27683 results
Name | H-index | Papers | Citations |
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Matthew Meyerson | 194 | 553 | 243726 |
Charles A. Dinarello | 190 | 1058 | 139668 |
Gad Getz | 189 | 520 | 247560 |
Gordon B. Mills | 187 | 1273 | 186451 |
Jasvinder A. Singh | 176 | 2382 | 223370 |
David Haussler | 172 | 488 | 224960 |
Donald G. Truhlar | 165 | 1518 | 157965 |
Charles M. Perou | 156 | 573 | 202951 |
David Cella | 156 | 1258 | 106402 |
Bruce D. Walker | 155 | 779 | 86020 |
Marco A. Marra | 153 | 620 | 184684 |
Thomas E. Starzl | 150 | 1625 | 91704 |
Marc Humbert | 149 | 1184 | 100577 |
Rajesh Kumar | 149 | 4439 | 140830 |
Martin J. Blaser | 147 | 820 | 104104 |