Browsing by Subject "IDENTIFICATION"

Now showing 1 - 6 of 6
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    Comparison of US Federal and Foundation Funding of Research for Sickle Cell Disease and Cystic Fibrosis and Factors Associated With Research Productivity.
    (JAMA network open, 2020-03-02) Farooq, Faheem; Mogayzel, Peter J; Lanzkron, Sophie; Haywood, Carlton; Strouse, John J
    Importance:Sickle cell disease (SCD) and cystic fibrosis (CF) are severe autosomal recessive disorders associated with intermittent disease exacerbations that require hospitalizations, progressive chronic organ injury, and substantial premature mortality. Research funding is a limited resource and may contribute to health care disparities, especially for rare diseases that disproportionally affect economically disadvantaged groups. Objective:To compare disease-specific funding between SCD and CF and the association between funding and research productivity. Design, Setting, and Participants:This cross-sectional study examined federal and foundation funding, publications indexed in PubMed, clinical trials registered in ClinicalTrials.gov, and new drug approvals from January 1, 2008, to December 31, 2018, in an estimated US population of approximately 90 000 individuals with SCD and approximately 30 000 individuals with CF. Main Outcomes and Measures:Federal and foundation funding, publications indexed in PubMed, clinical trial registrations, and new drug approvals. Results:From 2008 through 2018, federal funding was greater per person with CF compared with SCD (mean [SD], $2807 [$175] vs $812 [$147]; P < .001). Foundation expenditures were greater for CF than for SCD (mean [SD], $7690 [$3974] vs $102 [$13.7]; P < .001). Significantly more research articles (mean [SD], 1594 [225] vs 926 [157]; P < .001) and US Food and Drug Administration drug approvals (4 vs 1) were found for CF compared with SCD, but the total number of clinical trials was similar (mean [SD], 27.3 [6.9] vs 23.8 [6.3]; P = .22). Conclusions and Relevance:The findings show that disparities in funding between SCD and CF may be associated with decreased research productivity and novel drug development for SCD. Increased federal and foundation funding is needed for SCD and other diseases that disproportionately affect economically disadvantaged groups to address health care disparities.
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    Differential Expression of Coding and Long Noncoding RNAs in Keratoconus-Affected Corneas.
    (Investigative ophthalmology & visual science, 2018-06) Khaled, Mariam Lofty; Bykhovskaya, Yelena; Yablonski, Sarah ER; Li, Hanzhou; Drewry, Michelle D; Aboobakar, Inas F; Estes, Amy; Gao, X Raymond; Stamer, W Daniel; Xu, Hongyan; Allingham, R Rand; Hauser, Michael A; Rabinowitz, Yaron S; Liu, Yutao
    Keratoconus (KC) is the most common corneal ectasia. We aimed to determine the differential expression of coding and long noncoding RNAs (lncRNAs) in human corneas affected with KC.From the corneas of 10 KC patients and 8 non-KC healthy controls, 200 ng total RNA was used to prepare sequencing libraries with the SMARTer Stranded RNA-Seq kit after ribosomal RNA depletion, followed by paired-end 50-bp sequencing with Illumina Sequencer. Differential analysis was done using TopHat/Cufflinks with a gene file from Ensembl and a lncRNA file from NONCODE. Pathway analysis was performed using WebGestalt. Using the expression level of differentially expressed coding and noncoding RNAs in each sample, we correlated their expression levels in KC and controls separately and identified significantly different correlations in KC against controls followed by visualization using Cytoscape.Using |fold change| ≥ 2 and a false discovery rate ≤ 0.05, we identified 436 coding RNAs and 584 lncRNAs with differential expression in the KC-affected corneas. Pathway analysis indicated the enrichment of genes involved in extracellular matrix, protein binding, glycosaminoglycan binding, and cell migration. Our correlation analysis identified 296 pairs of significant KC-specific correlations containing 117 coding genes enriched in functions related to cell migration/motility, extracellular space, cytokine response, and cell adhesion. Our study highlighted the potential roles of several genes (CTGF, SFRP1, AQP5, lnc-WNT4-2:1, and lnc-ALDH3A2-2:1) and pathways (TGF-β, WNT signaling, and PI3K/AKT pathways) in KC pathogenesis.Our RNA-Seq-based differential expression and correlation analyses have identified many potential KC contributing coding and noncoding RNAs.
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    Imagined communities of fandom: sport, spectatorship, meaning and alienation in late capitalism
    (Sport in Society, 2020-01-01) Kalman-Lamb, N
    © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group. This article accounts for the allure of sports spectatorship in late capitalism by theorizing spectatorial communities as imagined communities. Building on the work of Benedict Anderson and others, and drawing on discourse around fandom in popular culture and the media, it argues that imagined communities of fandom function as sites of meaning and community within the alienating and individualist context of late capitalism. These communities are invented and continuously rehearsed through fetish spectacle and ritualistic practice and produce Manichean understandings of social relations that can lead to marginalization and violence.
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    Integrative Regulatory Mapping Indicates that the RNA-Binding Protein HuR Couples Pre-mRNA Processing and mRNA Stability
    (MOLECULAR CELL, 2011-08-05) Mukherjee, Neelanjan; Corcoran, David L; Nusbaum, Jeffrey D; Reid, David W; Georgiev, Stoyan; Hafner, Markus; Ascano, Manuel; Tuschl, Thomas; Ohler, Uwe; Keene, Jack D
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    Protein prenylation restrains innate immunity by inhibiting Rac1 effector interactions.
    (Nature communications, 2019-09-04) Akula, Murali K; Ibrahim, Mohamed X; Ivarsson, Emil G; Khan, Omar M; Kumar, Israiel T; Erlandsson, Malin; Karlsson, Christin; Xu, Xiufeng; Brisslert, Mikael; Brakebusch, Cord; Wang, Donghai; Bokarewa, Maria; Sayin, Volkan I; Bergo, Martin O
    Rho family proteins are prenylated by geranylgeranyltransferase type I (GGTase-I), which normally target proteins to membranes for GTP-loading. However, conditional deletion of GGTase-I in mouse macrophages increases GTP-loading of Rho proteins, leading to enhanced inflammatory responses and severe rheumatoid arthritis. Here we show that heterozygous deletion of the Rho family gene Rac1, but not Rhoa and Cdc42, reverses inflammation and arthritis in GGTase-I-deficient mice. Non-prenylated Rac1 has a high affinity for the adaptor protein Ras GTPase-activating-like protein 1 (Iqgap1), which facilitates both GTP exchange and ubiquitination-mediated degradation of Rac1. Consistently, inactivating Iqgap1 normalizes Rac1 GTP-loading, and reduces inflammation and arthritis in GGTase-I-deficient mice, as well as prevents statins from increasing Rac1 GTP-loading and cytokine production in macrophages. We conclude that blocking prenylation stimulates Rac1 effector interactions and unleashes proinflammatory signaling. Our results thus suggest that prenylation normally restrains innate immune responses by preventing Rac1 effector interactions.
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    Understanding the Social Learning Effect in Contagious Switching Behavior
    (Management Science, 2019-10) Hu, MM; Yang, S; Xu, DY