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Seifert LL, Si C, Saha D, Sadic M, de Vries M, Ballentine S, Briley A, Wang G, Valero-Jimenez AM, Mohamed A, Schaefer U, Moulton HM, Garcia-Sastre A, Tripathi S, Rosenberg BR, Dittmann M
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The ETS transcription factor ELF1 regulates a broadly antiviral program distinct from the type I interferon response
PLOS PATHOGENS 2019 NOV; 15(11):? Article e1007634
Induction of vast transcriptional programs is a central event of innate host responses to viral infections. Here we report a transcriptional program with potent antiviral activity, driven by E74-like ETS transcription factor 1 (ELF1). Using microscopy to quantify viral infection over time, we found that ELF1 inhibits eight diverse RNA and DNA viruses after multi-cycle replication. Elf1 deficiency results in enhanced susceptibility to influenza A virus infections in mice. ELF1 does not feed-forward to induce interferons, and ELF1's antiviral effect is not abolished by the absence of STAT1 or by inhibition of JAK phosphorylation. Accordingly, comparative expression analyses by RNA-seq revealed that the ELF1 transcriptional program is distinct from interferon signatures. Thus, ELF1 provides an additional layer of the innate host response, independent from the action of type I interferons.
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Brodski M, Buchanan J, Caillol C, Carlsmith D, Dasu S, Dodd L, Duric S, Gomber B, Grothe M, Herndon M, Herve A, Hussain U, Klabbers P, Lanaro A, Levine A, Long K, Loveless R, Rekovic V, Ruggles T, Savin A, Smith N, Smith WH, Woods N
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Search for supersymmetry in proton-proton collisions at 13 TeV in final states with jets and missing transverse momentum
JOURNAL OF HIGH ENERGY PHYSICS 2019 OCT 25; ?(10):? Article 244
Results are reported from a search for supersymmetric particles in the final state with multiple jets and large missing transverse momentum. The search uses a sample of proton-proton collisions at root s = 13 TeV collected with the CMS detector in 2016-2018, corresponding to an integrated luminosity of 137 fb(-1), representing essentially the full LHC Run 2 data sample. The analysis is performed in a four-dimensional search region defined in terms of the number of jets, the number of tagged bottom quark jets, the scalar sum of jet transverse momenta, and the magnitude of the vector sum of jet transverse momenta. No significant excess in the event yield is observed relative to the expected background contributions from standard model processes. Limits on the pair production of gluinos and squarks are obtained in the framework of simplified models for supersymmetric particle production and decay processes. Assuming the lightest supersymmetric particle to be a neutralino, lower limits on the gluino mass as large as 2000 to 2310 GeV are obtained at 95% confidence level, while lower limits on the squark mass as large as 1190 to 1630 GeV are obtained, depending on the production scenario.
Cortes-Canteli M
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Long-Term Dabigatran Treatment Delays Alzheimer's Disease Pathogenesis
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2019 OCT 15; 74(15):1910-1923
BACKGROUND Alzheimer's disease (AD) is a multifactorial
Nachmani D
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Germline NPM1 mutations lead to altered rRNA 2 '-O-methylation and cause
NATURE GENETICS 2019 OCT; 51(10):1518-1529
RNA modifications are emerging as key determinants of gene expression.
Flores-Montoya MG
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Early chronic low-level lead exposure reduced C-C chemokine receptor 7
TOXICOLOGY LETTERS 2019 OCT 10; 314(?):106-116
Chronic low-level lead exposure alters cognitive function in young
Galea S
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Public Health and Marginalized Populations: A Public Health of
AMERICAN JOURNAL OF PUBLIC HEALTH 2019 OCT; 109(10):1327-1328
Delgobo M, Mendes DAGB, Kozlova E, Rocha EL, Rodrigues-Luiz GF, Mascarin L, Dias G, Patricio DO, Dierckx T, Bicca MA, Bretton G, de Menezes YKT, Starick MR, Rovaris D, Del Moral J, Mansur DS, Van Weyenbergh J, Bafica A
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An evolutionary recent IFN/IL-6/CEBP axis is linked to monocyte expansion and tuberculosis severity in humans
ELIFE 2019 OCT 22; 8(?):? Article e47013
Monocyte counts are increased during human tuberculosis (TB) but it has not been determined whether Mycobacterium tuberculosis (Mtb) directly regulates myeloid commitment. We demonstrated that exposure to Mtb directs primary human CD34(+) cells to differentiate into monocytes/macrophages. In vitro myeloid conversion did not require type I or type II IFN signaling. In contrast, Mtb enhanced IL-6 responses by CD34(+) cell cultures and IL-6R neutralization inhibited myeloid differentiation and decreased mycobacterial growth in vitro. Integrated systems biology analysis of transcriptomic, proteomic and genomic data of large data sets of healthy controls and TB patients established the existence of a myeloid IL-6/IL6R/CEBP gene module associated with disease severity. Furthermore, genetic and functional analysis revealed the IL6/IL6R/CEBP gene module has undergone recent evolutionary selection, including Neanderthal introgression and human pathogen adaptation, connected to systemic monocyte counts. These results suggest Mtb co-opts an evolutionary recent IFN-IL6-CEBP feed-forward loop, increasing myeloid differentiation linked to severe TB in humans.
Nussenzweig PM
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Cas9 Cleavage of Viral Genomes Primes the Acquisition of New
CELL HOST & MICROBE 2019 OCT 9; 26(4):515-526.e6
Type II CRISPR-Cas systems defend prokaryotes from bacteriophage
Kumari N, Abul Hassan M, Lu XD, Roeder RG, Biswas D
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AFF1 acetylation by p300 temporally inhibits transcription during genotoxic stress response
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2019 OCT 29; 116(44):22140-22151
Soon after exposure to genotoxic reagents, mammalian cells inhibit transcription to prevent collisions with repair machinery and to mount a proper DNA damage response. However, mechanisms underlying early transcriptional inhibition are poorly understood. In this report, we show that site-specific acetylation of super elongation complex (SEC) subunit AFF1 by p300 reduces its interaction with other SEC components and impairs P-TEFb-mediated C-terminal domain phosphorylation of RNA polymerase II both in vitro and in vivo. Reexpression of wild-type AFF1, but not an acetylation mimic mutant, restores SEC component recruitment and target gene expression in AFF1 knockdown cells. Physiologically, we show that, upon genotoxic exposure, p300-mediated AFF1 acetylation is dynamic and strongly correlated with concomitant global down-regulation of transcription-and that this can be reversed by over-expression of an acetylation-defective AFF1 mutant. Therefore, we describe a mechanism of dynamic transcriptional regulation involving p300-mediated acetylation of a key elongation factor during genotoxic stress.
Sakurai K
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Cutaneous p38 mitogen-activated protein kinase activation triggers
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 2019 OCT; 144(4):1036-1049
Background: Psoriasis is a chronic inflammatory skin disease